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class="bkr_bib"><h1 id="_NBK559941_"><span itemprop="name">Preoperative chemotherapy for non-metastatic colon cancer</span></h1><div class="subtitle">Colorectal cancer (update)</div><p><b>Evidence review C7</b></p><p><i>NICE Guideline, No. 151</i></p><p class="contrib-group"><h4>Authors</h4><span itemprop="author">National Guideline Alliance (UK)</span>.</p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2020 Jan</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-3657-1</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2020.</div></div><div class="bkr_clear"></div></div><div id="ch9.s1"><h2 id="_ch9_s1_">Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h2><p>This evidence review supports <a href="/books/n/niceng151/?report=reader" class="toc-item">recommendation 1.3.13</a>.</p><div id="ch9.s1.1"><h3>Review question</h3><p>Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</p><div id="ch9.s1.1.1"><h4>Introduction</h4><p>Localised and resectable non-metastatic colon cancer has traditionally required an aggressive therapeutic approach through complete oncologic resection with post-operative chemotherapy, with extensive surgical resection needed to achieve negative margins. While preoperative chemotherapy is commonly used for localised oesophageal, gastric and rectal cancers, its use is not well-established for colon cancer as of yet. Preoperative chemotherapy has the potential to provide earlier and more effective eradication of occult micrometastatic disease, minimise the extent of surgery and debulk tumours to reduce the frequency of tumour cell shedding during surgery. Therefore, the aim of this review was to determine which people with non-metastatic colon cancer would benefit from preoperative chemotherapy.</p></div><div id="ch9.s1.1.2"><h4>Summary of the protocol</h4><p>Please see <a class="figpopup" href="/books/NBK559941/table/ch9.tab1/?report=objectonly" target="object" rid-figpopup="figch9tab1" rid-ob="figobch9tab1">Table 1</a> for a summary of the population, intervention, comparison and outcomes (PICO) characteristics of this review.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch9tab1"><a href="/books/NBK559941/table/ch9.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figch9tab1" rid-ob="figobch9tab1"><img class="small-thumb" src="/books/NBK559941/table/ch9.tab1/?report=thumb" src-large="/books/NBK559941/table/ch9.tab1/?report=previmg" alt="Table 1. Summary of the protocol (PICO table)." /></a><div class="icnblk_cntnt"><h4 id="ch9.tab1"><a href="/books/NBK559941/table/ch9.tab1/?report=objectonly" target="object" rid-ob="figobch9tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">Summary of the protocol (PICO table). </p></div></div><p>For further details see the review protocol in <a href="#ch9.appa">appendix A</a>.</p></div><div id="ch9.s1.1.3"><h4>Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>
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<u>2014</u>. Methods specific to this review question are described in the review protocol in <a href="#ch9.appa">appendix A</a>.</p><p>Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy until 31 March 2018. From 1 April 2018, declarations of interest were recorded according to NICE’s 2018 <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">conflicts of interest policy</a>. Those interests declared until April 2018 were reclassified according to NICE’s 2018 conflicts of interest policy (see Register of Interests).</p></div><div id="ch9.s1.1.4"><h4>Clinical evidence</h4><div id="ch9.s1.1.4.1"><h5>Included studies</h5><p>Two studies were included in this review (<a class="bibr" href="#ch9.s1.1.ref1" rid="ch9.s1.1.ref1">FOxTROT trial [Agbamu 2012]</a>; <a class="bibr" href="#ch9.s1.1.ref2" rid="ch9.s1.1.ref2">Dehal 2017</a>).</p><p>The clinical studies included in this evidence review are summarised in <a class="figpopup" href="/books/NBK559941/table/ch9.tab2/?report=objectonly" target="object" rid-figpopup="figch9tab2" rid-ob="figobch9tab2">Table 2</a>.</p><p>One pilot RCT (<a class="bibr" href="#ch9.s1.1.ref1" rid="ch9.s1.1.ref1">FOxTROT 2012 [Agbamu 2012]</a>) compared preoperative chemotherapy + surgery + postoperative chemotherapy to surgery + postoperative chemotherapy and 1 retrospective cohort study (<a class="bibr" href="#ch9.s1.1.ref2" rid="ch9.s1.1.ref2">Dehal 2017</a>) compared preoperative chemotherapy + surgery to surgery + postoperative chemotherapy.</p></div><div id="ch9.s1.1.4.2"><h5>Expert evidence</h5><p>The published evidence base is weak and relies on one retrospective study and the pilot phase of the FOxTROT trial. The FOxTROT trial is an international, mainly UK-based, phase III randomised trial that investigates the efficacy of neoadjuvant chemotherapy in colon cancer and is the only trial in the topic to date. The results from FOxTROT were presented to the guideline committee as academic in confidence data by one of the FOxTROT trialists as expert witness evidence. Where outcomes were reported in both the pilot trial and expert evidence presentation, data from the expert evidence presentation were used as these data were most recent and more mature (longer follow-up). Since the expert witness presentation, the results of the trial have been presented in a conference making them publicly available, although not peer-reviewed.</p><p>See the summary of expert evidence in <a href="#ch9.appm">appendix M</a>.</p></div><div id="ch9.s1.1.4.3"><h5>Excluded studies</h5><p>Studies not included in this review and their reasons for exclusion are listed in <a href="#ch9.appk">appendix K</a>.</p></div></div><div id="ch9.s1.1.5"><h4>Summary of clinical studies included in the evidence review</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch9tab2"><a href="/books/NBK559941/table/ch9.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figch9tab2" rid-ob="figobch9tab2"><img class="small-thumb" src="/books/NBK559941/table/ch9.tab2/?report=thumb" src-large="/books/NBK559941/table/ch9.tab2/?report=previmg" alt="Table 2. Summary of included studies." /></a><div class="icnblk_cntnt"><h4 id="ch9.tab2"><a href="/books/NBK559941/table/ch9.tab2/?report=objectonly" target="object" rid-ob="figobch9tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of included studies. </p></div></div><p>See the full evidence tables in <a href="#ch9.appd">appendix D</a> and the forest plots in <a href="#ch9.appe">appendix E</a>.</p></div><div id="ch9.s1.1.6"><h4>Quality assessment of clinical outcomes included in the evidence review</h4><p>See the clinical evidence profiles in <a href="#ch9.appf">appendix F</a>.</p></div><div id="ch9.s1.1.7"><h4>Economic evidence</h4><div id="ch9.s1.1.7.1"><h5>Included studies</h5><p>A systematic review of the economic literature was conducted but no economic studies were identified which were applicable to this review question.</p></div><div id="ch9.s1.1.7.2"><h5>Excluded studies</h5><p>A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information.</p></div></div><div id="ch9.s1.1.8"><h4>Economic model</h4><p>No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.</p></div><div id="ch9.s1.1.9"><h4>Evidence statements</h4><div id="ch9.s1.1.9.1"><h5>Clinical evidence statements</h5><div id="ch9.s1.1.9.1.1"><h5>Comparison 1: Preoperative chemotherapy versus no preoperative chemotherapy</h5><div id="ch9.s1.1.9.1.1.1"><h5>Critical outcomes</h5><div id="ch9.s1.1.9.1.1.1.1"><h5>Disease-free survival</h5><p>No evidence was identified to inform this outcome.</p></div><div id="ch9.s1.1.9.1.1.1.2"><h5>Overall survival</h5><div id="ch9.s1.1.9.1.1.1.2.1"><h5>T3 patients</h5><ul id="ch9.l8"><li id="ch9.lt20" class="half_rhythm"><div>Very low quality evidence from 1 retrospective cohort study (N=27,575) showed no clinically important difference in 3-year overall survival between those receiving preoperative chemotherapy + surgery compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.1.1.1.2.2"><h5>T4a patients</h5><ul id="ch9.l9"><li id="ch9.lt21" class="half_rhythm"><div>Very low quality evidence from 1 retrospective cohort study (N=27,575) showed no clinically important difference in 3-year overall survival between those receiving preoperative chemotherapy + surgery compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.1.1.1.2.3"><h5>T4b patients</h5><ul id="ch9.l10"><li id="ch9.lt22" class="half_rhythm"><div>Very low quality evidence from 1 retrospective cohort study (N=27,575) showed a clinically important increase in 3-year overall survival between those receiving preoperative chemotherapy + surgery compared to surgery + postoperative chemotherapy.</div></li></ul></div></div><div id="ch9.s1.1.9.1.1.1.3"><h5>Resection margins</h5><div id="ch9.s1.1.9.1.1.1.3.1"><h5>T4b patients</h5><ul id="ch9.l11"><li id="ch9.lt23" class="half_rhythm"><div>Very low quality evidence from 1 retrospective cohort study (N=27,575) showed a clinically important decrease in resection margins between those receiving preoperative chemotherapy + surgery compared to surgery + postoperative chemotherapy.</div></li></ul></div></div></div><div id="ch9.s1.1.9.1.1.2"><h5>Important outcomes</h5><div id="ch9.s1.1.9.1.1.2.1"><h5>Any Grade 3 or 4 adverse events</h5><div id="ch9.s1.1.9.1.1.2.1.1"><h5>Grade ≥3 adverse events</h5><ul id="ch9.l12"><li id="ch9.lt24" class="half_rhythm"><div>Very low quality evidence from 1 RCT (N=150) showed no clinically important difference in Grade ≥3 adverse events within 6, 12, 18, or 24 weeks between those receiving preoperative chemotherapy + surgery + postoperative chemotherapy compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.1.1.2.1.2"><h5>Anastomotic leak</h5><ul id="ch9.l13"><li id="ch9.lt25" class="half_rhythm"><div>More recent data for this outcome were available in the expert evidence summary.</div></li></ul></div><div id="ch9.s1.1.9.1.1.2.1.3"><h5>Wound infection with or without intra-abdominal abscess</h5><ul id="ch9.l14"><li id="ch9.lt26" class="half_rhythm"><div>Very low quality evidence from 1 RCT (N=150) showed no clinically important difference in wound infection with or without intra-abdominal abscess between those receiving preoperative chemotherapy + surgery + postoperative chemotherapy compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.1.1.2.1.4"><h5>Bronchopneumonia</h5><ul id="ch9.l15"><li id="ch9.lt27" class="half_rhythm"><div>Very low quality evidence from 1 RCT (N=150) showed no clinically important difference in bronchopneumonia between those receiving preoperative chemotherapy + surgery + postoperative chemotherapy compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.1.1.2.1.5"><h5>Deep vein thrombosis</h5><ul id="ch9.l16"><li id="ch9.lt28" class="half_rhythm"><div>Very low quality evidence from 1 RCT (N=150) showed no clinically important difference in deep vein thrombosis between those receiving preoperative chemotherapy + surgery + postoperative chemotherapy compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.1.1.2.1.6"><h5>Neutropenia</h5><ul id="ch9.l17"><li id="ch9.lt29" class="half_rhythm"><div>Very low quality evidence from 1 RCT (N=150) showed no clinically important difference in neutropenia between those receiving preoperative chemotherapy + surgery + postoperative chemotherapy compared to surgery + postoperative chemotherapy.</div></li></ul></div></div><div id="ch9.s1.1.9.1.1.2.2"><h5>Overall quality of life</h5><p>No evidence was identified to inform this outcome.</p></div><div id="ch9.s1.1.9.1.1.2.3"><h5>Treatment-related mortality</h5><ul id="ch9.l18"><li id="ch9.lt30" class="half_rhythm"><div>More recent data for this outcome were available in the expert evidence summary.</div></li></ul></div><div id="ch9.s1.1.9.1.1.2.4"><h5>Local recurrence</h5><p>No evidence was identified to inform this outcome.</p></div></div></div></div><div id="ch9.s1.1.9.2"><h5>Expert evidence statements</h5><div id="ch9.s1.1.9.2.1"><h5>Comparison 1: Preoperative chemotherapy versus no preoperative chemotherapy</h5><div id="ch9.s1.1.9.2.1.1"><h5>Critical outcomes</h5><div id="ch9.s1.1.9.2.1.1.1"><h5>Disease-free survival</h5><ul id="ch9.l19"><li id="ch9.lt31" class="half_rhythm"><div>Moderate quality evidence from 1 RCT (N=1052) showed a clinically important decrease in recurrence between those receiving preoperative chemotherapy + surgery + postoperative chemotherapy compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.2.1.1.2"><h5>Overall survival</h5><p>No evidence was identified to inform this outcome.</p></div><div id="ch9.s1.1.9.2.1.1.3"><h5>Resection margins</h5><p>No evidence was identified to inform this outcome.</p></div></div><div id="ch9.s1.1.9.2.1.2"><h5>Important outcomes</h5><div id="ch9.s1.1.9.2.1.2.1"><h5>Any Grade 3 or 4 adverse events</h5><div id="ch9.s1.1.9.2.1.2.1.1"><h5>Anastomotic leak</h5><ul id="ch9.l20"><li id="ch9.lt32" class="half_rhythm"><div>Moderate quality evidence from 1 RCT (N=1052) showed a clinically important decrease in anastomotic leak between those receiving preoperative chemotherapy + surgery + postoperative chemotherapy compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.2.1.2.1.2"><h5>Wound infection with or without intra-abdominal abscess</h5><ul id="ch9.l21"><li id="ch9.lt33" class="half_rhythm"><div>No evidence was identified to inform this outcome.</div></li></ul></div><div id="ch9.s1.1.9.2.1.2.1.3"><h5>Bronchopneumonia</h5><ul id="ch9.l22"><li id="ch9.lt34" class="half_rhythm"><div>No evidence was identified to inform this outcome.</div></li></ul></div><div id="ch9.s1.1.9.2.1.2.1.4"><h5>Pulmonary embolism ± deep vein thrombosis</h5><ul id="ch9.l23"><li id="ch9.lt35" class="half_rhythm"><div>No evidence was identified to inform this outcome.</div></li></ul></div></div><div id="ch9.s1.1.9.2.1.2.2"><h5>Overall quality of life</h5><p>No evidence was identified to inform this outcome.</p></div><div id="ch9.s1.1.9.2.1.2.3"><h5>Treatment-related mortality</h5><ul id="ch9.l24"><li id="ch9.lt36" class="half_rhythm"><div>Moderate quality evidence from 1 RCT (N=1052) showed no clinically important difference in treatment-related mortality (postoperative mortality) between those receiving preoperative chemotherapy + surgery + postoperative chemotherapy compared to surgery + postoperative chemotherapy.</div></li></ul></div><div id="ch9.s1.1.9.2.1.2.4"><h5>Local recurrence</h5><p>No evidence was identified to inform this outcome.</p></div></div></div></div><div id="ch9.s1.1.9.3"><h5>Economic evidence statements</h5><p>No economic evidence was identified which was applicable to this review question.</p></div></div><div id="ch9.s1.1.10"><h4>The committee’s discussion of the evidence</h4><div id="ch9.s1.1.10.1"><h5>Interpreting the evidence</h5><div id="ch9.s1.1.10.1.1"><h5>The outcomes that matter most</h5><p>Disease-free survival and overall survival were considered critical outcomes for decision making because disease progression suggests ineffective control of the localised colon cancer, potentially requiring further treatment and affecting overall survival. Resection margins were also critical as they are indicative of whether further treatment, likely surgical, is needed.</p><p>Quality of life was an important outcome because of the impact that different treatment options can have on patients’ functioning and the potential long term adverse effects. Any grade 3 or 4 adverse events and treatment-related mortality were also important outcomes, as they are indicative of the complications of treatments. Additionally, local recurrence was an important outcome because lesions that extend into surrounding structures and organs indicate the need for further surgical resection.</p></div><div id="ch9.s1.1.10.1.2"><h5>The quality of the evidence</h5><p>Evidence was available from 1 pilot RCT comparing preoperative chemotherapy + surgery + postoperative chemotherapy to surgery + postoperative chemotherapy and 1 retrospective cohort study comparing preoperative chemotherapy + surgery to surgery + postoperative chemotherapy.</p><p>Evidence was available for overall survival, resection margins, any grade 3 or 4 adverse events and treatment-related mortality. There was no evidence for quality of life or local recurrence. The quality of the evidence was assessed using GRADE and was of very low quality. The quality of evidence was downgraded because of methodological limitations affecting the risk of bias and imprecision around the risk estimate.</p><p>Methodological limitations leading to risk of bias were due to confounding from differences in baseline characteristics, lack of blinding and allocation concealment.</p><p>Indirectness in the study interventions was attributable to numerous protocol violations in both arms of the RCT that potentially diluted the effectiveness of the interventions.</p><p>Uncertainty around the risk estimate was due to low event rates and small sample sizes.</p><p>An expert witness presented academic in confidence results of the FoXTROT trial which provided expert evidence for the comparison of preoperative chemotherapy + surgery + postoperative chemotherapy versus surgery + postoperative surgery. Evidence was available for disease-free survival, any grade 3 or 4 adverse events and treatment-related mortality. This evidence was assessed using GRADE as moderate quality.</p><p>The range in quality of the evidence and lack of evidence for many comparisons and outcomes impacted the decision-making and the strength of the recommendation as there was insufficient evidence to make a strong recommendation or to make recommendations for all subgroups within the population.</p></div><div id="ch9.s1.1.10.1.3"><h5>Benefits and harms</h5><p>The evidence indicated that there were benefits for disease-free survival, overall survival and clear resection margins for patients with more advanced (T4b) colonic tumours who received preoperative chemotherapy. No benefit on overall survival was found for patients with T3 or T4a colonic tumours. However, the committee agreed that differentiating between T4a and T4b tumours would be difficult in preoperative clinical staging (imaging), therefore, based on their clinical experience and knowledge they agreed that the recommendation to consider preoperative therapy should cover patients with T4 tumours.</p><p>While the expert evidence showed that there was a clinically important decrease in anastomotic leak, otherwise the clinical evidence did not show any clinically important difference between treatment groups in terms of adverse events or treatment-related mortality. From their clinical experience, the committee noted that there is a potential for harm from increased surgical morbidity. The committee was not aware of any evidence regarding treatment decision-making pertaining to the extent of surgical resection (that is, whether decisions should be based on pre- or post-chemotherapy imaging). However, they noted that most clinicians would base their decisions on the extent of surgery on pre-chemotherapy imaging.</p></div></div><div id="ch9.s1.1.10.2"><h5>Cost effectiveness and resource use</h5><p>A systematic review of the economic literature was conducted but no relevant studies were identified which were applicable to this review question.</p><p>The committee considered that the addition of preoperative chemotherapy would not increase costs for patients with T4 colon cancer as postoperative chemotherapy is current standard of care and costs between pre and post would be similar given the almost identical regimens. The committee acknowledged that preoperative chemotherapy was already being done in some centres and that it would only represent a change for some centres. There would also be increases in overall survival and quality of life through reduced surgical morbidity.</p></div><div id="ch9.s1.1.10.3"><h5>Other factors the committee took into account</h5><p>The committee acknowledged the FOxTROT trial, which compares preoperative plus post-operative chemotherapy (+/− panitumumab) with standard post-operative chemotherapy. Results from the earlier feasibility trial (<a class="bibr" href="#ch9.s1.1.ref1" rid="ch9.s1.1.ref1">FOxTROT trial [Agbamu 2012]</a>) were included in this review. Primary outcomes include 2-year recurrence-free survival and pathological down-staging and secondary outcomes include disease-specific survival and overall survival at 2 years and quality of life by EORTC QLQ C-30 and EuroQol EQ-5D before surgery, before the first post-operative chemotherapy and 1 year post-randomisation. The committee considered expert evidence about the unpublished results of the FOxTROT trial from the primary randomisation (preoperative-and-postoperative chemotherapy versus standard postoperative chemotherapy) to neoadjuvant treatment as data analysis for the substudy (patients with <i>KRAS</i>-wild type tumours randomised 1:1 to preoperative-and-postoperative chemotherapy +/− panitumumab) was not complete. Moderate quality evidence from the primary randomisation phase showed that complete clinical response and tumour downstaging are more likely in those who receive preoperative chemotherapy, although follow-up is not yet long enough to assess long-term outcomes. The results presented to the committee as academic in confidence were since presented at an international conference. See more details in <a href="#ch9.appm">appendix M</a>.</p></div></div><div id="ch9.rl.r1"><h4>References</h4><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="ch9.s1.1.ref1"><p id="p-93">
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<strong>FOxTROT trial [Agbamu 2012]</strong>
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</p>Agbamu
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D, Day
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N, Walsh
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C, et al. (2012) Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: The pilot phase of a randomised controlled trial. Lancet Oncology
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13(11): 1152–1160 [<a href="/pmc/articles/PMC3488188/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3488188</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23017669" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23017669</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="ch9.s1.1.ref2"><p id="p-94">
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<strong>Dehal 2017</strong>
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</p>Dehal
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A, Vuong
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B, Graff-Baker
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A, et al. (2017) Neoadjuvant chemotherapy improves survival in patients with clinical T4B colon cancer. Gastroenterology
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152 (5): S1209</div></p></li></ul></div></div></div><div id="appendixesappgroup9"><h2 id="_appendixesappgroup9_">Appendices</h2><div id="ch9.appa"><h3>Appendix A. Review protocol</h3><div id="ch9.appa.s1"><h4>Review protocol for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p id="ch9.appa.tab1"><a href="/books/NBK559941/table/ch9.appa.tab1/?report=objectonly" target="object" rid-ob="figobch9appatab1" class="figpopup">Table 3. Review protocol for pre-operative chemotherapy for people with non-metastatic colon cancer</a></p></div></div><div id="ch9.appb"><h3>Appendix B. Literature search strategies</h3><div id="ch9.appb.s1"><h4>Literature search strategies for review question: Which people with non-meta static colon cancer would benefit from preoperative chemotherapy?</h4><div id="ch9.appb.s1.1"><h5>Databases: Embase/Medline</h5><p>Last searched on: 31/10/2018</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch9appbtab1"><a href="/books/NBK559941/table/ch9.appb.tab1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figch9appbtab1" rid-ob="figobch9appbtab1"><img class="small-thumb" src="/books/NBK559941/table/ch9.appb.tab1/?report=thumb" src-large="/books/NBK559941/table/ch9.appb.tab1/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ch9.appb.tab1"><a href="/books/NBK559941/table/ch9.appb.tab1/?report=objectonly" target="object" rid-ob="figobch9appbtab1">Table</a></h4></div></div></div><div id="ch9.appb.s1.2"><h5>Database: Cochrane Library</h5><p>Last searched on: 31/10/2018</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch9appbtab2"><a href="/books/NBK559941/table/ch9.appb.tab2/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figch9appbtab2" rid-ob="figobch9appbtab2"><img class="small-thumb" src="/books/NBK559941/table/ch9.appb.tab2/?report=thumb" src-large="/books/NBK559941/table/ch9.appb.tab2/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="ch9.appb.tab2"><a href="/books/NBK559941/table/ch9.appb.tab2/?report=objectonly" target="object" rid-ob="figobch9appbtab2">Table</a></h4></div></div></div></div></div><div id="ch9.appc"><h3>Appendix C. Clinical evidence study selection</h3><div id="ch9.appc.s1"><h4>Clinical study selection for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p id="ch9.appc.fig1"><a href="/books/NBK559941/figure/ch9.appc.fig1/?report=objectonly" target="object" rid-ob="figobch9appcfig1" class="figpopup">Figure 1. Study selection flow chart</a></p></div></div><div id="ch9.appd"><h3>Appendix D. Clinical evidence tables</h3><div id="ch9.appd.s1"><h4>Clinical evidence tables for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p id="ch9.appd.et1"><a href="/books/NBK559941/bin/ch9-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 4. Clinical evidence tables</a><span class="small"> (PDF, 384K)</span></p></div></div><div id="ch9.appe"><h3>Appendix E. Forest plots</h3><div id="ch9.appe.s1"><h4>Forest plots for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p id="ch9.appe.fig1"><a href="/books/NBK559941/figure/ch9.appe.fig1/?report=objectonly" target="object" rid-ob="figobch9appefig1" class="figpopup">Figure 2. Preoperative chemotherapy versus no preoperative chemotherapy - 3-year overall survival; event is death from any cause</a></p><p id="ch9.appe.fig2"><a href="/books/NBK559941/figure/ch9.appe.fig2/?report=objectonly" target="object" rid-ob="figobch9appefig2" class="figpopup">Figure 3. Preoperative chemotherapy versus no preoperative chemotherapy - Positive resection margins, T4b patients</a></p><p id="ch9.appe.fig3"><a href="/books/NBK559941/figure/ch9.appe.fig3/?report=objectonly" target="object" rid-ob="figobch9appefig3" class="figpopup">Figure 4. Preoperative chemotherapy versus no preoperative chemotherapy – Any Grade 3 or 4 events and wound infection with or without intra-abdominal abscess</a></p><p id="ch9.appe.fig4"><a href="/books/NBK559941/figure/ch9.appe.fig4/?report=objectonly" target="object" rid-ob="figobch9appefig4" class="figpopup">Figure 5. Preoperative chemotherapy versus no preoperative chemotherapy – Grade 3 or 4 events; bronchopneumonia, neutropenia, deep vein thrombosis</a></p></div></div><div id="ch9.appf"><h3>Appendix F. GRADE tables</h3><div id="ch9.appf.s1"><h4>GRADE tables for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p id="ch9.appf.tab1"><a href="/books/NBK559941/table/ch9.appf.tab1/?report=objectonly" target="object" rid-ob="figobch9appftab1" class="figpopup">Table 5. Clinical evidence profile for comparison preoperative chemotherapy versus no preoperative chemotherapy</a></p></div></div><div id="ch9.appg"><h3>Appendix G. Economic evidence study selection</h3><div id="ch9.appg.s1"><h4>Economic evidence study selection for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy</h4><p>A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information.</p></div></div><div id="ch9.apph"><h3>Appendix H. Economic evidence tables</h3><div id="ch9.apph.s1"><h4>Economic evidence tables for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy</h4><p>No economic evidence was identified which was applicable to this review question. 5</p></div></div><div id="ch9.appi"><h3>Appendix I. Economic evidence profiles</h3><div id="ch9.appi.s1"><h4>Economic evidence profiles for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p>No economic evidence was identified which was applicable to this review question.</p></div></div><div id="ch9.appj"><h3>Appendix J. Economic analysis</h3><div id="ch9.appj.s1"><h4>Economic analysis for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p>No economic analysis was conducted for this review question. 5</p></div></div><div id="ch9.appk"><h3>Appendix K. Excluded studies</h3><div id="ch9.appk.s1"><h4>Excluded clinical studies for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p id="ch9.appk.tab1"><a href="/books/NBK559941/table/ch9.appk.tab1/?report=objectonly" target="object" rid-ob="figobch9appktab1" class="figpopup">Table 6. Excluded studies and reasons for their exclusion</a></p></div></div><div id="ch9.appl"><h3>Appendix L. Research recommendations</h3><div id="ch9.appl.s1"><h4>Research recommendations for review question: Which people with non-meta static colon cancer would benefit from preoperative chemotherapy?</h4><p>No research recommendations were made for this review question.</p></div></div><div id="ch9.appm"><h3>Appendix M. Expert evidence</h3><div id="ch9.appm.s1"><h4>Expert evidence for review question: Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</h4><p id="ch9.appm.et1"><a href="/books/NBK559941/bin/ch9-appm-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Table 7. Expert evidence: Preliminary findings from the FOxTROT trial</a><span class="small"> (PDF, 216K)</span></p><p id="ch9.appm.tab2"><a href="/books/NBK559941/table/ch9.appm.tab2/?report=objectonly" target="object" rid-ob="figobch9appmtab2" class="figpopup">Table 8. Gaps addressed and recommendations supported by expert evidence</a></p><p id="ch9.appm.fig1"><a href="/books/NBK559941/figure/ch9.appm.fig1/?report=objectonly" target="object" rid-ob="figobch9appmfig1" class="figpopup">Figure 6. Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Disease-free survival</a></p><p id="ch9.appm.fig2"><a href="/books/NBK559941/figure/ch9.appm.fig2/?report=objectonly" target="object" rid-ob="figobch9appmfig2" class="figpopup">Figure 7. Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Grade 3 or 4 adverse events: anastomotic leak</a></p><p id="ch9.appm.fig3"><a href="/books/NBK559941/figure/ch9.appm.fig3/?report=objectonly" target="object" rid-ob="figobch9appmfig3" class="figpopup">Figure 8. Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Treatment-related mortality</a></p><p id="ch9.appm.tab3"><a href="/books/NBK559941/table/ch9.appm.tab3/?report=objectonly" target="object" rid-ob="figobch9appmtab3" class="figpopup">Table 9. Quality assessment of expert evidence</a></p></div></div></div></div><div class="fm-sec"><div><p>Final</p></div><div><p>Evidence reviews</p><p>Developed by the National Guideline Alliance part of the Royal College of Obstetricians and Gynaecologists</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2020.</div><div class="small"><span class="label">Bookshelf ID: NBK559941</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/32730008" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">32730008</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobch9tab1"><div id="ch9.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">Summary of the protocol (PICO table)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.tab1_lrgtbl__"><table><tbody><tr><th id="hd_b_ch9.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_ch9.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Adults with localised, resectable, non-metastatic colon cancer</p>
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<p>Non-metastatic cancer defined as:
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<ul id="ch9.l1"><li id="ch9.lt1" class="half_rhythm"><div>Tany N1-2</div></li><li id="ch9.lt2" class="half_rhythm"><div>T3</div></li><li id="ch9.lt3" class="half_rhythm"><div>T4</div></li><li id="ch9.lt4" class="half_rhythm"><div>M0</div></li></ul>
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Subgroups by:
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<ul id="ch9.l2"><li id="ch9.lt5" class="half_rhythm"><div>Disease characteristics:
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<ul id="ch9.l3" class="circle"><li id="ch9.lt6" class="half_rhythm"><div>Radiological T stage</div></li><li id="ch9.lt7" class="half_rhythm"><div>Radiological N stage</div></li></ul></div></li><li id="ch9.lt8" class="half_rhythm"><div>Tumour location</div></li><li id="ch9.lt9" class="half_rhythm"><div>Colonic obstruction status (no/complete/partly)</div></li></ul></p>
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</td></tr><tr><th id="hd_b_ch9.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><td headers="hd_b_ch9.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Preoperative chemotherapy</td></tr><tr><th id="hd_b_ch9.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparison</th><td headers="hd_b_ch9.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No preoperative chemotherapy</td></tr><tr><th id="hd_b_ch9.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><td headers="hd_b_ch9.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Critical</b>
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<ul id="ch9.l4"><li id="ch9.lt10" class="half_rhythm"><div>Disease-free survival</div></li><li id="ch9.lt11" class="half_rhythm"><div>Overall survival</div></li><li id="ch9.lt12" class="half_rhythm"><div>Resection margins</div></li></ul>
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<b>Important</b>
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<ul id="ch9.l5"><li id="ch9.lt13" class="half_rhythm"><div>Any grade 3 or 4 adverse events</div></li><li id="ch9.lt14" class="half_rhythm"><div>Overall quality of life</div></li><li id="ch9.lt15" class="half_rhythm"><div>Treatment-related mortality</div></li><li id="ch9.lt16" class="half_rhythm"><div>Local recurrence</div></li></ul></td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch9tab2"><div id="ch9.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of included studies</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch9.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_ch9.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Population</th><th id="hd_h_ch9.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention/Comparison</th><th id="hd_h_ch9.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th></tr></thead><tbody><tr><td headers="hd_h_ch9.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>FOxTROT trial</p>
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<p>[<a class="bibr" href="#ch9.s1.1.ref1" rid="ch9.s1.1.ref1">Agbamu 2012</a>]</p>
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<p>Pilot RCT</p>
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<p>UK</p>
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</td><td headers="hd_h_ch9.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N=150 patients with locally advanced (T4 or T3 with extramural depth ≥ 5mm) adenocarcinoma of the colon with staging determined preoperatively by either spiral or multidetector CT</td><td headers="hd_h_ch9.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Preoperative chemotherapy + surgery + postoperative chemotherapy versus surgery + postoperative chemotherapy</td><td headers="hd_h_ch9.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch9.l6"><li id="ch9.lt17" class="half_rhythm"><div>Grade 3 or 4 adverse events</div></li></ul>
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</td></tr><tr><td headers="hd_h_ch9.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<a class="bibr" href="#ch9.s1.1.ref2" rid="ch9.s1.1.ref2">Dehal 2017</a>
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</p>
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<p>Retrospective cohort study</p>
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<p>US</p>
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</td><td headers="hd_h_ch9.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N=27,575 patients with clinically staged T3 or T4, non-metastatic primary colon cancer who had both surgery and chemotherapy and a tumour with a mucinous, signet ring cell, or adenocarcinoma</td><td headers="hd_h_ch9.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Preoperative chemotherapy + surgery versus surgery + postoperative chemotherapy</td><td headers="hd_h_ch9.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch9.l7"><li id="ch9.lt18" class="half_rhythm"><div>Overall survival</div></li><li id="ch9.lt19" class="half_rhythm"><div>Positive resection margins</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CT: computed tomography; N: number; RCT: randomised controlled trial; T: tumour stage</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch9appatab1"><div id="ch9.appa.tab1" class="table"><h3><span class="label">Table 3</span><span class="title">Review protocol for pre-operative chemotherapy for people with non-metastatic colon cancer</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.appa.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.appa.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Field (based on <a href="http://www.prisma-statement.org/Extensions/Protocols.aspx" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PRISMA</a>)</th><th id="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Content</th></tr></thead><tbody><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review question in guideline</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Which people with non-metastatic colon cancer would benefit from preoperative chemotherapy?</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type of review question</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Objective of the review</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To determine which people with non-metastatic colon cancer would benefit from preoperative chemotherapy.</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – population/disease/condition/issue/domain</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Adults with localised, resectable, non-metastatic colon cancer</p>
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<p>Non-metastatic cancer defined as:
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<ul id="ch9.l25"><li id="ch9.lt37" class="half_rhythm"><div>Tany N1-2</div></li><li id="ch9.lt38" class="half_rhythm"><div>T3</div></li><li id="ch9.lt39" class="half_rhythm"><div>T4</div></li><li id="ch9.lt40" class="half_rhythm"><div>M0</div></li></ul>
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Subgroups according to (analysed separately):
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<ul id="ch9.l26"><li id="ch9.lt41" class="half_rhythm"><div>Disease characteristics:
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<ul id="ch9.l27" class="circle"><li id="ch9.lt42" class="half_rhythm"><div>Radiological T stage</div></li><li id="ch9.lt43" class="half_rhythm"><div>Radiological N stage</div></li></ul></div></li><li id="ch9.lt44" class="half_rhythm"><div>Tumour location</div></li><li id="ch9.lt45" class="half_rhythm"><div>Colonic obstruction status (no/com-plete/partly)</div></li></ul></p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – intervention(s)/exposure(s)/prognostic factor(s)</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Preoperative chemotherapy</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – comparator(s)/control or reference (gold) standard</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No preoperative chemotherapy</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes and prioritisation</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><b>Critical outcomes:</b>
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<ul id="ch9.l28"><li id="ch9.lt46" class="half_rhythm"><div>Disease-free survival (minimally important difference [MID]: statistical significance)</div></li><li id="ch9.lt47" class="half_rhythm"><div>Overall survival (MID: statistical significance)</div></li><li id="ch9.lt48" class="half_rhythm"><div>Resection margins (MID: statistical significance)</div></li></ul>
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<b>Important outcomes:</b>
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<ul id="ch9.l29"><li id="ch9.lt49" class="half_rhythm"><div>Any Grade 3 or 4 adverse events (MID: statistical significance)</div></li><li id="ch9.lt50" class="half_rhythm"><div>Overall quality of life measured using validated scales (MID: published MIDs from literature, see below)</div></li><li id="ch9.lt51" class="half_rhythm"><div>Treatment-related mortality (MID: statistical significance)</div></li><li id="ch9.lt52" class="half_rhythm"><div>Local recurrence (MID: statistical significance)</div></li></ul>
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Quality of Life MIDs from the literature:
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<ul id="ch9.l30"><li id="ch9.lt53" class="half_rhythm"><div>EORTC QLQ-C30: 5 points</div></li><li id="ch9.lt54" class="half_rhythm"><div>EORTC QLQ-CR29: 5 points</div></li><li id="ch9.lt55" class="half_rhythm"><div>EORTC QLQ-CR38: 5 points</div></li><li id="ch9.lt56" class="half_rhythm"><div>EQ-5D: 0.09 using FACT-G quintiles</div></li><li id="ch9.lt57" class="half_rhythm"><div>FACT-C: 5 points</div></li><li id="ch9.lt58" class="half_rhythm"><div>FACT-G: 5 points</div></li><li id="ch9.lt59" class="half_rhythm"><div>SF-12: > 3.77 for the mental component summary (MCS) and > 3.29 for the physical component summary (PCS) of the Short Form SF-12 (SF-12)</div></li><li id="ch9.lt60" class="half_rhythm"><div>SF-36: > 7.1 for the physical functioning scale, > 4.9 for the bodily pain scale, and > 7.2 for the PCS</div></li></ul></td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – study design</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="ch9.l31"><li id="ch9.lt61" class="half_rhythm"><div>Systematic reviews</div></li><li id="ch9.lt62" class="half_rhythm"><div>Randomised controlled trials</div></li><li id="ch9.lt63" class="half_rhythm"><div>Prospective or retrospective comparative cohort studies will only be considered if eligible RCTs are not available</div></li></ul>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other inclusion exclusion criteria</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inclusion:
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<ul id="ch9.l32"><li id="ch9.lt64" class="half_rhythm"><div>English-language</div></li><li id="ch9.lt65" class="half_rhythm"><div>All settings will be considered that consider medications and treatments available in the UK</div></li><li id="ch9.lt66" class="half_rhythm"><div>Studies published post-2005</div></li></ul>
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Studies conducted post-2005 will be considered for this review question because the guideline committee considered that treatment techniques have evolved and evidence prior to 2005 would no longer be relevant.</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Proposed sensitivity/sub-group analysis, or meta-regression</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cohort studies should include multivariate analysis controlling for the following confounding factors:
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<ul id="ch9.l33"><li id="ch9.lt67" class="half_rhythm"><div>Patient characteristics (i.e. age [life expectancy], comorbidities)</div></li><li id="ch9.lt68" class="half_rhythm"><div>Type of chemotherapy</div></li><li id="ch9.lt69" class="half_rhythm"><div>Tumour characteristics
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<ul id="ch9.l34" class="circle"><li id="ch9.lt70" class="half_rhythm"><div>T stage</div></li><li id="ch9.lt71" class="half_rhythm"><div>Tumour location</div></li></ul></div></li></ul></td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Selection process – duplicate screening/selection/analysis</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Sifting, data extraction, appraisal of methodological quality and GRADE assessment will be performed by the systematic reviewer. Resolution of any disputes will be with the senior systematic reviewer and the Topic Advisor. Quality control will be performed by the senior systematic reviewer.</p>
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<p>Dual sifting will be undertaken for this question for a random 10% sample of the titles and abstracts identified by the search.</p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data management (software)</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Pairwise meta-analyses will be performed using Cochrane Review Manager (RevMan5). ‘GRADEpro’ will be used to assess the quality of evidence for each outcome.</p>
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<p>NGA STAR software will be used for study sifting, data extraction, recording quality assessment using checklists and generating bibliographies/citations.</p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Information sources – databases and dates</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Potential sources to be searched: Medline, Medline In-Process, CCTR, CDSR, DARE, HTA, Embase</p>
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<p>Limits (e.g. date, study design):
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<ul id="ch9.l35"><li id="ch9.lt72" class="half_rhythm"><div>Apply standard animal/non-English language exclusion</div></li><li id="ch9.lt73" class="half_rhythm"><div>Limit to RCTs and systematic reviews in first instance, but download all results</div></li><li id="ch9.lt74" class="half_rhythm"><div>Dates: from 2005</div></li></ul></p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Identify if an update</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not an update</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Author contacts</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p><a href="https://www.nice.org.uk/guidance/indevelopment/gid-ng10060" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.nice.org<wbr style="display:inline-block"></wbr>​.uk/guidance/indevelopment/gid-ng10060</a> Developer: NGA</p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Highlight if amendment to previous protocol</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see section 4.5 of <a href="https://www.nice.org.uk/article/pmg20/chapter/4-Developing-review-questions-and-planning-the-evidence-review#planning-the-evidence-review" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a></td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Search strategy – for one database</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see <a href="#ch9.appb">appendix B</a></td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data collection process – forms/duplicate</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A standardised evidence table format will be used, and published as <a href="#ch9.appd">appendix D</a> (clinical evidence tables) or <a href="#ch9.apph">H</a> (economic evidence tables).</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data items – define all variables to be collected</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see evidence tables in <a href="#ch9.appd">appendix D</a> (clinical evidence tables) or <a href="#ch9.apph">H</a> (economic evidence tables).</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Methods for assessing bias at outcome/study level</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Standard study checklists were used to critically appraise individual studies. For details please see section 6.2 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a></p>
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<p>Appraisal of methodological quality:</p>
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<p>The methodological quality of each study will be assessed using an appropriate checklist:
|
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<ul id="ch9.l36"><li id="ch9.lt75" class="half_rhythm"><div>ROBIS for systematic reviews</div></li><li id="ch9.lt76" class="half_rhythm"><div>Cochrane risk of bias tool for RCTs</div></li><li id="ch9.lt77" class="half_rhythm"><div>ROBINS-I for non-randomised studies</div></li></ul>
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The quality of the evidence for an outcome (i.e. across studies) will be assessed using GRADE.</p>
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<p>The risk of bias across all available evidence was evaluated for each outcome using an adaptation of the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE) toolbox’ developed by the international GRADE working group <a href="http://www.gradeworkinggroup.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www<wbr style="display:inline-block"></wbr>​.gradeworkinggroup.org/</a></p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Criteria for quantitative synthesis (where suitable)</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see section 6.4 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a></td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Methods for analysis – combining studies and exploring (in)consistency</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<b>Synthesis of data:</b>
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</p>
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<p>Pairwise meta-analysis of randomised trials will be conducted where appropriate.</p>
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<p>When meta-analysing continuous data, final and change scores will be pooled if baselines are comparable. If any studies report both, the method used in the majority of studies will be analysed.</p>
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<p>
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<b>Minimally important differences:</b>
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</p>
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<p>The guideline committee identified statistically significant differences as appropriate indicators for clinical significance for all outcomes except quality of life for which published MIDs from literature will be used (see outcomes section for more information).</p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Meta-bias assessment – publication bias, selective reporting bias</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>For details please see section 6.2 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</p>
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<p>If sufficient relevant RCT evidence is available, publication bias will be explored using RevMan software to examine funnel plots.</p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Assessment of confidence in cumulative evidence</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see sections 6.4 and 9.1 of <a href="https://www.nice.org.uk/article/pmg20/chapter/1-Introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a></td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rationale/context – Current management</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see the introduction to the evidence review.</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Describe contributions of authors and guarantor</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>A multidisciplinary committee developed the guideline. The committee was convened by The NGA and chaired by Peter Hoskin in line with section 3 of <a href="https://www.nice.org.uk/article/pmg20/chapter/1%20Introduction%20and%20overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</p>
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<p>Staff from The National Guideline Alliance undertook systematic literature searches, appraised the evidence, conducted meta-analysis and cost-effectiveness analysis where appropriate, and drafted the guideline in collaboration with the committee. For details please see Supplement 1: methods.</p>
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</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sources of funding/support</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The NGA is funded by NICE and hosted by the Royal College of Obstetricians and Gynaecologists</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Name of sponsor</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The NGA is funded by NICE and hosted by the Royal College of Obstetricians and Gynaecologists</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Roles of sponsor</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NICE funds the NGA to develop guidelines for those working in the NHS, public health, and social care in England</td></tr><tr><td headers="hd_h_ch9.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PROSPERO registration number</td><td headers="hd_h_ch9.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not registered</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CCTR: Cochrane Central Register of Controlled Trials; CDSR: Cochrane Database of Systematic Reviews; CENTRAL: Cochrane Central Register of Controlled Trials; DARE: Database of Abstracts of Reviews of Effects; EuroQol five dimensions questionnaire; EORTC QLQ-C30: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items; EORTC QLQ-CR29: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire colorectal cancer module (29 items); EORTC QLQ-CR38: European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire colorectal cancer module (38 items); FACT-C: Functional Assessment of Cancer Therapy questionnaire (colorectal cancer); FACT-G: Functional Assessment of Cancer Therapy questionnaire (general); GRADE: Grading of Recommendations Assessment, Development and Evaluation; HTA: Health Technology Assessment; M0: no distant metastasis; MCS: mental component summary; MID: minimally important difference; N: nodal stage; NGA: National Guideline Alliance; NHS: National health service; NICE: National Institute for Health and Care Excellence; PCS: physical component summary; RCT: randomised controlled trial; RevMan5: Review Manager version 5; RoB: risk of bias; ROBINS-I: Risk Of Bias In Non-randomised Studies - of Interventions; ROBIS: risk of bias in systematic reviews; SD: standard deviation; SF-12: 12-Item Short Form Survey; SF-36: 36-Item Short Form Survey; T: tumour stage</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch9appbtab1"><div id="ch9.appb.tab1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.appb.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.appb.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#</th><th id="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Search</th></tr></thead><tbody><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp colonic neoplasms/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp colon tumor/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((colon or colonic) adj3 (adenocarcinoma* or cancer* or carcinoma* or malignan* or neoplas* or oncolog* or tumo?r*)).tw.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1-3</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(local* advanc* or locali?ed or non-metasta* or non metasta* or operable or operative or resectable).tw.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(t3 or t4 or m0 or N1 or N2).tw.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/5-6</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">preoperative chemotherapy/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">neoadjuvant chemotherapy/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neoadjuvant Therapy/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((preop* or pre?op* or neoadjuvant) adj3 (chemotherap* or therap* or treat*)).tw.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/8-11</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4 and 7 and 12</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Letter/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter.pt. or letter/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">note.pt.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial.pt.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Editorial/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">News/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Historical Article/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anecdotes as Topic/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comment/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Case Report/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/ or case study/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/14-25</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">random*.ti,ab.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/27-29</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26 not 30</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animals/ not humans/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal/ not human/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">nonhuman/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animals, Laboratory/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experimentation/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experiment/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Experimental Animal/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Models, Animal/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal model/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodentia/ use ppez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodent/ use emez</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/31-43</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13 not 44</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 45 to (yr=“2005 - current” and english language)</td></tr><tr><td headers="hd_h_ch9.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47</td><td headers="hd_h_ch9.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">remove duplicates from 46</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch9appbtab2"><div id="ch9.appb.tab2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.appb.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.appb.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#</th><th id="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Search</th></tr></thead><tbody><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Colonic Neoplasms] explode all trees</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((colon or colonic) near/3 (adenocarcinoma* or cancer* or carcinoma* or malignan* or neoplas* or oncolog* or tumo?r*)):kw,ti,ab</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1 or #2</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(local* advanc* or locali?ed or non-metasta* or non metasta* or operable or operative or resectable):kw,ti,ab</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(t3 or t4 or m0 or N1 or N2):kw,ti,ab</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#4 or #5</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Neoadjuvant Therapy] this term only</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((preop* or pre?op* or neoadjuvant) near/3 (chemotherap* or therap* or treat*)):kw,ti,ab</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7 or #8</td></tr><tr><td headers="hd_h_ch9.appb.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10</td><td headers="hd_h_ch9.appb.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#3 and #6 and #9 with Cochrane Library publication date Between Jan 2005 and Dec 2018</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobch9appcfig1"><div id="ch9.appc.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%201.%20Study%20selection%20flow%20chart.&p=BOOKS&id=559941_ch9appcf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK559941/bin/ch9appcf1.jpg" alt="Figure 1. Study selection flow chart." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 1</span><span class="title">Study selection flow chart</span></h3></div></article><article data-type="fig" id="figobch9appefig1"><div id="ch9.appe.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%202.%20Preoperative%20chemotherapy%20versus%20no%20preoperative%20chemotherapy%20-%203-year%20overall%20survival%3B%20event%20is%20death%20from%20any%20cause.&p=BOOKS&id=559941_ch9appef1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK559941/bin/ch9appef1.jpg" alt="Figure 2. Preoperative chemotherapy versus no preoperative chemotherapy - 3-year overall survival; event is death from any cause." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 2</span><span class="title">Preoperative chemotherapy versus no preoperative chemotherapy - 3-year overall survival<sup><a href="#ch9.appe.fig1.fn1">*</a></sup>; event is death from any cause</span></h3><div class="caption"><p>CI: confidence interval; CT: chemotherapy; IV: inverse variance; SE: standard error; T: tumour stage</p></div><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>*</dt><dd><div id="ch9.appe.fig1.fn1"><p class="no_top_margin">propensity score matched for age, gender, race, insurance status, comorbidity score, hospital type, tumour histology, grade, N stage, tumour location, number of nodes examined, margin, and extent of surgery</p></div></dd></dl></dl></div></div></article><article data-type="fig" id="figobch9appefig2"><div id="ch9.appe.fig2" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%203.%20Preoperative%20chemotherapy%20versus%20no%20preoperative%20chemotherapy%20-%20Positive%20resection%20margins%2C%20T4b%20patients.&p=BOOKS&id=559941_ch9appef2.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK559941/bin/ch9appef2.jpg" alt="Figure 3. Preoperative chemotherapy versus no preoperative chemotherapy - Positive resection margins, T4b patients." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 3</span><span class="title">Preoperative chemotherapy versus no preoperative chemotherapy - Positive resection margins<sup><a href="#ch9.appe.fig2.fn1">*</a></sup>, T4b patients</span></h3><div class="caption"><p>CI: confidence interval; CT: chemotherapy; IV: inverse variance; SE: standard error; T: tumour stage</p></div><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>*</dt><dd><div id="ch9.appe.fig2.fn1"><p class="no_top_margin">adjusted for age, gender, race, insurance status, comorbidity score, hospital type, tumour histology, grade, N stage, extent of surgery, and tumour location</p></div></dd></dl></dl></div></div></article><article data-type="fig" id="figobch9appefig3"><div id="ch9.appe.fig3" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%204.%20Preoperative%20chemotherapy%20versus%20no%20preoperative%20chemotherapy%20%02013%20Any%20Grade%203%20or%204%20events%20and%20wound%20infection%20with%20or%20without%20intra-abdominal%20abscess.&p=BOOKS&id=559941_ch9appef3.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK559941/bin/ch9appef3.jpg" alt="Figure 4. Preoperative chemotherapy versus no preoperative chemotherapy – Any Grade 3 or 4 events and wound infection with or without intra-abdominal abscess." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 4</span><span class="title">Preoperative chemotherapy versus no preoperative chemotherapy – Any Grade 3 or 4 events and wound infection with or without intra-abdominal abscess</span></h3><div class="caption"><p>CI: confidence interval; CT: chemotherapy; FOxTROT: Fluoropyrimidine, Oxaliplatin and Targeted-Receptor pre-Operative Therapy for patients with high-risk, operable colon cancer; M-H: Mantel Haenszel</p></div></div></article><article data-type="fig" id="figobch9appefig4"><div id="ch9.appe.fig4" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%205.%20Preoperative%20chemotherapy%20versus%20no%20preoperative%20chemotherapy%20%02013%20Grade%203%20or%204%20events%3B%20bronchopneumonia%2C%20neutropenia%2C%20deep%20vein%20thrombosis.&p=BOOKS&id=559941_ch9appef4.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK559941/bin/ch9appef4.jpg" alt="Figure 5. Preoperative chemotherapy versus no preoperative chemotherapy – Grade 3 or 4 events; bronchopneumonia, neutropenia, deep vein thrombosis." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 5</span><span class="title">Preoperative chemotherapy versus no preoperative chemotherapy – Grade 3 or 4 events; bronchopneumonia, neutropenia, deep vein thrombosis</span></h3><div class="caption"><p>CI: confidence interval; CT: chemotherapy; FOxTROT: Fluoropyrimidine, Oxaliplatin and Targeted-Receptor pre-Operative Therapy for patients with high-risk, operable colon cancer; M-H: Mantel Haenszel</p></div></div></article><article data-type="table-wrap" id="figobch9appftab1"><div id="ch9.appf.tab1" class="table"><h3><span class="label">Table 5</span><span class="title">Clinical evidence profile for comparison preoperative chemotherapy versus no preoperative chemotherapy</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.appf.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.appf.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch9.appf.tab1_1_1_1_1" colspan="7" rowspan="1" style="text-align:left;vertical-align:bottom;">Quality assessment</th><th id="hd_h_ch9.appf.tab1_1_1_1_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">No of patients</th><th id="hd_h_ch9.appf.tab1_1_1_1_3" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Effect</th><th id="hd_h_ch9.appf.tab1_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ch9.appf.tab1_1_1_1_4" style="text-align:left;vertical-align:bottom;">Quality</th><th id="hd_h_ch9.appf.tab1_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_ch9.appf.tab1_1_1_1_5" style="text-align:left;vertical-align:bottom;">Importance</th></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1" id="hd_h_ch9.appf.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No of studies</th><th headers="hd_h_ch9.appf.tab1_1_1_1_1" id="hd_h_ch9.appf.tab1_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Design</th><th headers="hd_h_ch9.appf.tab1_1_1_1_1" id="hd_h_ch9.appf.tab1_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Risk of bias</th><th headers="hd_h_ch9.appf.tab1_1_1_1_1" id="hd_h_ch9.appf.tab1_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inconsistency</th><th headers="hd_h_ch9.appf.tab1_1_1_1_1" id="hd_h_ch9.appf.tab1_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Indirectness</th><th headers="hd_h_ch9.appf.tab1_1_1_1_1" id="hd_h_ch9.appf.tab1_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Imprecision</th><th headers="hd_h_ch9.appf.tab1_1_1_1_1" id="hd_h_ch9.appf.tab1_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other considerations</th><th headers="hd_h_ch9.appf.tab1_1_1_1_2" id="hd_h_ch9.appf.tab1_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Preop CT</th><th headers="hd_h_ch9.appf.tab1_1_1_1_2" id="hd_h_ch9.appf.tab1_1_1_2_9" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No preop CT</th><th headers="hd_h_ch9.appf.tab1_1_1_1_3" id="hd_h_ch9.appf.tab1_1_1_2_10" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Relative (95% CI)</th><th headers="hd_h_ch9.appf.tab1_1_1_1_3" id="hd_h_ch9.appf.tab1_1_1_2_11" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Absolute</th></tr></thead><tbody><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_1_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Disease-free survival</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_3_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">3-year overall survival, event is death from any cause (propensity score matched for age, gender, race, insurance status, comorbidity score, hospital type, tumour histology, grade, N stage, tumour location, number of nodes examined, margin, and extent of surgery) - T3 patients</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">observational studies<sup>1</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>2</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15,999</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">383</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 1.15 (0.92 to 1.44)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">At 3 years no preop CT<sup>a</sup> 84.5%, preop CT 82.4% (78.5% to 85.6%)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_5_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">3-year overall survival, event is death from any cause (propensity score matched for age, gender, race, insurance status, comorbidity score, hospital type, tumour histology, grade, N stage, tumour location, number of nodes examined, margin, and extent of surgery) – T4a patients</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">observational studies<sup>1</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>2</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2,241</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 1.43 (0.85 to 2.41)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">At 3 years no preop CT<sup>a</sup> 73.2%, preop CT 64.0% (47.1% to 76.7%</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_7_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">3-year overall survival, event is death from any cause (propensity score matched for age, gender, race, insurance status, comorbidity score, hospital type, tumour histology, grade, N stage, tumour location, number of nodes examined, margin, and extent of surgery) - T4b patients</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">observational studies<sup>1</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>2</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2,330</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">273</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 0.77 (0.60 to 0.99)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">At 3 years no preop CT<sup>a</sup> 69.1%, preop CT 75.2% (69.4% to 80.1%)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_9_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Positive resection margins, T4b patients (adjusted for age, gender, race, insurance status, comorbidity score, hospital type, tumour histology, grade, N stage, extent of surgery, and tumour location)</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">observational studies</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>2</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2,987</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">350</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">OR 0.95 (0.91 to 0.99)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12 fewer per 1000 (from 24 fewer to 4 fewer)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_11_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Grade ≥ 3 toxicity within 6 weeks</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>5</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>32/94</p>
|
|
<p>(34%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>12/39</p>
|
|
<p>(30.8%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.11 (0.64 to 1.91)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34 more per 1000 (from 111 fewer to 280 more)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_13_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Grade ≥ 3 adverse events within 12 weeks</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>5</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>14/81</p>
|
|
<p>(17.3%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>9/38</p>
|
|
<p>(23.7%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 0.73 (0.35 to 1.53)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">64 fewer per 1000 (from 154 fewer to 126 more)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_15_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Grade ≥ 3 adverse events within 18 weeks</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>5</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>18/75</p>
|
|
<p>(24%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>8/34</p>
|
|
<p>(23.5%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.02 (0.49 to 2.11)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5 more per 1000 (from 120 fewer to 261 more)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_17_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Grade ≥ 3 adverse events within 24 weeks</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>5</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>47/95</p>
|
|
<p>(49.5%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>20/39</p>
|
|
<p>(51.3%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 0.96 (0.67 to 1.39)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21 fewer per 1000 (from 169 fewer to 200 more)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_19_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Wound infection with or without intra-abdominal abscess</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>5</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>13/99</p>
|
|
<p>(13.1%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>4/51</p>
|
|
<p>(7.8%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.67 (0.58 to 4.87)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53 more per 1000 (from 33 fewer to 304 more)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_21_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Bronchopneumonia</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>5</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2/99</p>
|
|
<p>(2%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>0/51</p>
|
|
<p>(0%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Peto OR 4.60 (0.24, 86.57)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20 more per 1000 (from 60 fewer to 20 more)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_23_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Neutropenia</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>5</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1/99</p>
|
|
<p>(1%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>0/51</p>
|
|
<p>(0%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Peto OR 4.55 (0.07, 285.04)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10 more per 1000 (from 30 fewer to 50 more)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_23_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_25_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events – Deep vein thrombosis</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>5</sup></td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2/99</p>
|
|
<p>(2%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>0/51</p>
|
|
<p>(0%)</p>
|
|
</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Peto OR 4.60 (0.24, 86.57)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20 more per 1000 (from 60 fewer to 20 more)</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VERY LOW</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_25_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_27_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Overall quality of life</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_27_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_h_ch9.appf.tab1_1_1_2_3 hd_h_ch9.appf.tab1_1_1_2_4 hd_h_ch9.appf.tab1_1_1_2_5 hd_h_ch9.appf.tab1_1_1_2_6 hd_h_ch9.appf.tab1_1_1_2_7 hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_h_ch9.appf.tab1_1_1_2_9 hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_h_ch9.appf.tab1_1_1_2_11 hd_h_ch9.appf.tab1_1_1_1_4 hd_h_ch9.appf.tab1_1_1_1_5" id="hd_b_ch9.appf.tab1_1_1_29_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Local recurrence</th></tr><tr><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_1 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_2 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_3 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_4 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_5 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_6 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_1 hd_h_ch9.appf.tab1_1_1_2_7 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_8 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_2 hd_h_ch9.appf.tab1_1_1_2_9 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_10 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_3 hd_h_ch9.appf.tab1_1_1_2_11 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_4 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appf.tab1_1_1_1_5 hd_b_ch9.appf.tab1_1_1_29_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CI: confidence interval; CT: chemotherapy; HR: hazard ratio; OR: odds ratio; RR: risk ratio</p></div></dd></dl><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch9.appf.tab1_1"><p class="no_margin">Subgroups based on propensity score match at a rate of 80, 70 and 78% respectively for T3, T4a, and T4b patients were used in the analysis (<a class="bibr" href="#ch9.s1.1.ref2" rid="ch9.s1.1.ref2">Dehal 2017</a>)</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="ch9.appf.tab1_2"><p class="no_margin">Quality of evidence downgraded by 1 because high risk of confounding despite use of propensity score matching and bias in the selection of participants (<a class="bibr" href="#ch9.s1.1.ref2" rid="ch9.s1.1.ref2">Dehal 2017</a>)</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="ch9.appf.tab1_3"><p class="no_margin">Quality of evidence downgraded by 2 due to lack of allocation concealment and blinding (<a class="bibr" href="#ch9.s1.1.ref1" rid="ch9.s1.1.ref1">FOxTROT trial [Agbamu 2012]</a>)</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="ch9.appf.tab1_4"><p class="no_margin">Quality of evidence downgraded by 1 due to numerous protocol violations in both arms (<a class="bibr" href="#ch9.s1.1.ref1" rid="ch9.s1.1.ref1">FOxTROT trial [Agbamu 2012]</a>)</p></div></dd></dl><dl class="bkr_refwrap"><dt>5</dt><dd><div id="ch9.appf.tab1_5"><p class="no_margin">Quality of evidence downgraded by 1 because of imprecision of the effect estimate (< 300 events for dichotomous outcomes or < 400 patients for continuous outcomes).</p></div></dd></dl><dl class="bkr_refwrap"><dt>a</dt><dd><div id="ch9.appf.tab1_6"><p class="no_margin">The absolute risk at 3 years in the control group taken from <a class="bibr" href="#ch9.s1.1.ref2" rid="ch9.s1.1.ref2">Dehal 2017</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch9appktab1"><div id="ch9.appk.tab1" class="table"><h3><span class="label">Table 6</span><span class="title">Excluded studies and reasons for their exclusion</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.appk.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.appk.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reason for exclusion</th></tr></thead><tbody><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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Anonymous, FOxTROT: safety and feasibility of neoadjuvant chemotherapy in locally advanced, resectable colon cancer based on the phase III of a randomised controlled trial, Colorectal disease. Conference: 12th scientific and annual meeting of the european society of coloproctology. Germany, 19, 3, 2017
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Waiting for full text of paper to be published in 2019; results from pilot study reported in <a class="bibr" href="#ch9.s1.1.ref1" rid="ch9.s1.1.ref1">Agbamu 2012</a></td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Arredondo
|
|
J., Gonzalez
|
|
I., Baixauli
|
|
J., Martinez
|
|
P., Rodriguez
|
|
J., Pastor
|
|
C., Ribelles
|
|
M. J., Sola
|
|
J. J., Hernandez-Lizoain
|
|
J. L., Tumor response assessment in locally advanced colon cancer after neoadjuvant chemotherapy, Journal of Gastrointestinal Oncology, 5, 104–111, 2014 [<a href="/pmc/articles/PMC3999636/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3999636</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24772338" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24772338</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not comparative</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Arredondo
|
|
J., Martinez
|
|
P., Baixauli
|
|
J., Pastor
|
|
C., Rodriguez
|
|
J., Pardo
|
|
F., Rotellar
|
|
F., Chopitea
|
|
A., Hernandez-Lizoain
|
|
J. L., Analysis of surgical complications of primary tumor resection after neoadjuvant treatment in stage IV colon cancer, Journal of Gastrointestinal Oncology, 5, 148–153, 2014 [<a href="/pmc/articles/PMC3999633/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3999633</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24772343" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24772343</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not comparative; population not relevant - all had liver metastases</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Arredondo
|
|
J., Pastor
|
|
C., Baixauli
|
|
J., Rodriguez
|
|
J., Gonzalez
|
|
I., Vigil
|
|
C., Chopitea
|
|
A., Hernandez-Lizoain
|
|
J. L., Preliminary outcome of a treatment strategy based on perioperative chemotherapy and surgery in patients with locally advanced colon cancer, Colorectal Disease, 15, 552–557, 2013 [<a href="https://pubmed.ncbi.nlm.nih.gov/23398577" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23398577</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not comparative</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Artac
|
|
M., Turhal
|
|
N. S., Kocer
|
|
M., Karabulut
|
|
B., Bozcuk
|
|
H., Yalcin
|
|
S., Karaagac
|
|
M., Gunduz
|
|
S., Isik
|
|
N., Uygun
|
|
K., Do high-risk features support the use of adjuvant chemotherapy in stage II colon cancer? A Turkish Oncology Group study, Tumori, 100, 143–8, 2014 [<a href="https://pubmed.ncbi.nlm.nih.gov/24852857" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24852857</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention not relevant - adjuvant chemotherapy vs no adjuvant chemotherapy</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Blencowe
|
|
N. S., Chana
|
|
P., Whistance
|
|
R. N., Stevens
|
|
D., Wong, N. A. C. S., Falk
|
|
S. J., Blazeby
|
|
J. M., Outcome reporting in neoadjuvant surgical trials: A systematic review of the literature and proposals for new standards, Journal of the National Cancer InstituteJ Natl Cancer Inst, 106 (9) (no pagination), 2014 [<a href="https://pubmed.ncbi.nlm.nih.gov/25106656" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25106656</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review - studies assessed individually</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Chaves
|
|
J. A., Neoadjuvant chemotherapy in locally advanced colon cancer -ELECLA trial, Colorectal disease. Conference: 11th scientific and annual meeting of the european society of coloproctology. Italy, 18, 126, 2016
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract - trial still in progress</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Cukier
|
|
M., Smith
|
|
A. J., Milot
|
|
L., Chu
|
|
W., Chung
|
|
H., Fenech
|
|
D., Herschorn
|
|
S., Ko
|
|
Y., Rowsell
|
|
C., Soliman
|
|
H., Ung
|
|
Y. C., Wong
|
|
C. S., Neoadjuvant chemoradiotherapy and multivisceral resection for primary locally advanced adherent colon cancer: A single institution experience, European Journal of Surgical Oncology, 38, 677–682, 2012 [<a href="https://pubmed.ncbi.nlm.nih.gov/22632848" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22632848</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not comparative</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Dehal
|
|
A., Graff-Baker
|
|
A. N., Vuong
|
|
B., Fischer
|
|
T., Klempner
|
|
S. J., Chang
|
|
S. C., Grunkemeier
|
|
G. L., Bilchik
|
|
A. J., Goldfarb
|
|
M., Neoadjuvant Chemotherapy Improves Survival in Patients with Clinical T4b Colon Cancer, Journal of Gastrointestinal Surgery, 22, 242–249, 2018 [<a href="https://pubmed.ncbi.nlm.nih.gov/28933016" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28933016</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Conference abstract, full text not available</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Deng
|
|
Y., Zhang
|
|
J., Cai
|
|
Y., Hu
|
|
H., Ling
|
|
J., Xiao
|
|
J., Huang
|
|
M., Kang
|
|
L., Wang
|
|
L., Lan
|
|
P., Wang
|
|
J., Neoadjuvant chemotherapy alone with mFOLFOXIRI in locally advanced rectal cancer: A single-arm phase II study, Journal of Clinical Oncology. Conference, 34, 2016
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract - trial still in progress</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Engstrom
|
|
P. F., Arnoletti
|
|
J. P., Benson, Iii A. B., Chen
|
|
Y. J., Choti
|
|
M. A., Cooper
|
|
H. S., Covey
|
|
A., Dilawari
|
|
R. A., Early
|
|
D. S., Enzinger
|
|
P. C., Fakih
|
|
M. G., Fleshman
|
|
Jr
|
|
J., Fuchs
|
|
C., Grem
|
|
J. L., Kiel
|
|
K., Knol
|
|
J. A., Leong
|
|
L. A., Lin
|
|
E., Mulcahy
|
|
M. F., Rao
|
|
S., Ryan
|
|
D. P., Saltz
|
|
L., Shibata
|
|
D., Skibber
|
|
J. M., Sofocleous
|
|
C., Thomas
|
|
J., Venook
|
|
A. P., Willett
|
|
C., Colon cancer, JNCCN Journal of the National Comprehensive Cancer Network, 7, 778–831, 2009 [<a href="https://pubmed.ncbi.nlm.nih.gov/19755046" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19755046</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical practice guideline</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Gray
|
|
R. G., Morton
|
|
D., Brown
|
|
G., Ferry
|
|
D. R., Magill
|
|
L., Quirke
|
|
P., Seymour
|
|
M. T., Warren
|
|
B., FOxTROT: Randomized phase II study of neoadjuvant chemotherapy with or without an anti-EGFR monoclonal antibody for locally advanced, operable colon cancer, Journal of Clinical Oncology. Conference, 28, 2010
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hansen
|
|
T. F., Kjaer-Frifeldt
|
|
S., Lindebjerg
|
|
J., Rafaelsen
|
|
S. R., Jensen
|
|
L. H., Jakobsen
|
|
A., Sorensen
|
|
F. B., Tumor-stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy, Acta Oncologica, 57, 528–533, 2018 [<a href="https://pubmed.ncbi.nlm.nih.gov/28980848" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28980848</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not comparative</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Jakobsen
|
|
A., Andersen
|
|
F., Fischer
|
|
A., Jensen
|
|
L. H., Jorgensen
|
|
J. C. R., Larsen
|
|
O., Lindebjerg
|
|
J., Ploen
|
|
J., Rafaelsen
|
|
S. R., Vilandt
|
|
J., Neoadjuvant chemotherapy in locally advanced colon cancer. A phase II trial, Acta Oncologica, 54, 17471753, 2015 [<a href="https://pubmed.ncbi.nlm.nih.gov/25920359" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25920359</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not comparative</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Karoui
|
|
M., Rullier
|
|
A., Luciani
|
|
A., Bonnetain
|
|
F., Auriault
|
|
M. L., Sarran
|
|
A., Monges
|
|
G., Trillaud
|
|
H., Le Malicot
|
|
K., Leroy
|
|
K., et al.,, Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial - the PRODIGE 22 - ECKINOXE trial, BMC Cancer, 15, 2015 [<a href="/pmc/articles/PMC4497499/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4497499</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26156156" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26156156</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract - expected study completion date February 2021</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Karoui
|
|
M., Rullier
|
|
A., Luciani
|
|
A., Bonnetain
|
|
F., Auriault
|
|
M. L., Sarran
|
|
A., Monges
|
|
G., Trillaud
|
|
H., Le Malicot
|
|
K., Leroy
|
|
K., Sobhani
|
|
I., Bardier
|
|
A., Moreau
|
|
M., Brindel
|
|
I., Seitz
|
|
J. F., Taieb
|
|
J., Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial, BMC Cancer, 15, 511, 2015 [<a href="/pmc/articles/PMC4497499/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4497499</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26156156" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26156156</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract - expected study completion date February 2021</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Karoui
|
|
M., Rullier
|
|
A., Mariette
|
|
C., Maillard
|
|
E., Bardier
|
|
A., Poizat
|
|
F., Luciani
|
|
A., Sarran
|
|
A., Legoux
|
|
J. L., De Chaisemartin
|
|
C., et al.,, Neoadjuvant FOLFOX 4 versus FOLFOX 4 plus cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a phase II multicentre randomised controlled trial (PRODIGE 22), Annals of oncology. Conference: 42nd ESMO congress, ESMO 2017. Spain, 28, v159, 2017
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract - estimated study completion date February 2021</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Nct,, Neoadjuvant Chemotherapy Verse Surgery Alone After Stent Placement for Obstructive Colonic Cancer, <a href="http://Https://clinicaltrials.gov/show/nct02972541" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Https:<wbr style="display:inline-block"></wbr>​//clinicaltrials<wbr style="display:inline-block"></wbr>​.gov/show/nct02972541</a>, 2016
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical trial entry</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Nct,, Neoadjuvant FOLFOX Chemotherapy for Patients With Locally Advanced Colon Cancer, <a href="http://Https://clinicaltrials.gov/show/nct03426904" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Https:<wbr style="display:inline-block"></wbr>​//clinicaltrials<wbr style="display:inline-block"></wbr>​.gov/show/nct03426904</a>, 2018
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical trial entry</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Nct,, Fluorouracil and Oxaliplatin With or Without Panitumumab In Treating Patients With High-Risk Colon Cancer That Can Be Removed by Surgery, <a href="http://Https://clinicaltrials.gov/show/nct00647530" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Https:<wbr style="display:inline-block"></wbr>​//clinicaltrials<wbr style="display:inline-block"></wbr>​.gov/show/nct00647530</a>, 2008
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical trial entry</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Nct,, Perioperative Versus Postoperative CapOX Chemotherapy for Locally Advanced Colon Cancer, <a href="http://Https://clinicaltrials.gov/show/nct03125980" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Https:<wbr style="display:inline-block"></wbr>​//clinicaltrials<wbr style="display:inline-block"></wbr>​.gov/show/nct03125980</a>, 2017
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical trial entry</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Nct,, Neoadjuvant Chemotherapy for the Treatment of Resectable Locally Advanced Colon Cancer, <a href="http://Https://clinicaltrials.gov/show/nct02882269" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Https:<wbr style="display:inline-block"></wbr>​//clinicaltrials<wbr style="display:inline-block"></wbr>​.gov/show/nct02882269</a>, 2016
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical trial entry</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Nct,, Neoadjuvant Chemotherapy Versus Standard Treatment in Patients With Locally Advanced Colon Cancer, <a href="http://Https://clinicaltrials.gov/show/nct01918527" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Https:<wbr style="display:inline-block"></wbr>​//clinicaltrials<wbr style="display:inline-block"></wbr>​.gov/show/nct01918527</a>, 2013
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Clinical trial entry</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Park
|
|
S., Park
|
|
J., Kim
|
|
H., Choi
|
|
G., Pilot study of neoadjuvant chemotherapy with three cycles of capox for treatment of locally advanced colon cancer, Diseases of the colon and rectum. Conference: 2018 american society of colon and rectal surgeons annual meeting, ASCRS 2018. United states, 61, e279, 2018
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Abstract - full text unavailable</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Sekiya
|
|
S., Imamura
|
|
K., Takeuchi
|
|
S., Teramura
|
|
K., Watanabe
|
|
Y., Tamoto
|
|
E., Takada
|
|
M., Kinoshita
|
|
Y., Anbo
|
|
Y., Nakamura
|
|
F., Kashimura
|
|
N., Noguchi
|
|
H., Miura
|
|
K., Hirano
|
|
S., Pathological complete response of locally advanced colon cancer after preoperative radiotherapy: a case report and narrative review of the literature, Surgical Case Reports, 4, 58, 2018 [<a href="/pmc/articles/PMC6002327/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6002327</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29904815" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29904815</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Case study and narrative review</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Tresallet
|
|
C., Benoist
|
|
S., Nordlinger
|
|
B., Adjuvant and neoadjuvant treatment in resectable and non-resectable metastatic colon cancer, European Journal of Cancer, Supplement, 3, 275–281, 2005
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Patients had metastatic disease</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Trojan
|
|
J., Lubomierski
|
|
N., Lehnert
|
|
T., Engels
|
|
K., Zeuzem
|
|
S., Bechstein
|
|
W. O., Neoadjuvant treatment with cetuximab, 5-Fluorouracil, folinic Acid and oxaliplatin in unresectable retroperitoneal recurrent colon cancer, Zeitschrift fur Gastroenterologie, 46, 776–9, 2008 [<a href="https://pubmed.ncbi.nlm.nih.gov/18759201" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18759201</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Full text in German; case report</td></tr><tr><td headers="hd_h_ch9.appk.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Zhou
|
|
Z., Nimeiri
|
|
H. S., Benson
|
|
A. B., 3rd, Preoperative chemotherapy for locally advanced resectable colon cancer - a new treatment paradigm in colon cancer?, Annals of Translational Medicine, 1, 11, 2013 [<a href="/pmc/articles/PMC4200631/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4200631</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25332956" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25332956</span></a>]
|
|
</td><td headers="hd_h_ch9.appk.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Narrative review</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch9appmtab2"><div id="ch9.appm.tab2" class="table"><h3><span class="label">Table 8</span><span class="title">Gaps addressed and recommendations supported by expert evidence</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.appm.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.appm.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch9.appm.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Expert testimony</th><th id="hd_h_ch9.appm.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Gaps addressed</th><th id="hd_h_ch9.appm.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Recommendations supported</th></tr></thead><tbody><tr><td headers="hd_h_ch9.appm.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="ch9.l40"><li id="ch9.lt84" class="half_rhythm"><div>Preliminary findings from the FOxTROT trial</div></li></ul>
|
|
</td><td headers="hd_h_ch9.appm.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="ch9.l41"><li id="ch9.lt85" class="half_rhythm"><div>The published evidence base is weak and relies on one retrospective study and the pilot phase of the FOxTROT trial. The FOxTROT trial is a UK Phase III randomised trial that investigates the efficacy of neoadjuvant chemotherapy in colon cancer and is the only trial in the topic to date. However, the timeline of the guideline does not allow us to wait for the full results to be published later this year.</div></li></ul>
|
|
</td><td headers="hd_h_ch9.appm.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<ul id="ch9.l42"><li id="ch9.lt86" class="half_rhythm"><div>
|
|
<a href="/books/n/niceng151/?report=reader" class="toc-item">1.3.13</a>
|
|
</div></li></ul>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">FOxTROT: Fluoropyrimidine, Oxaliplatin and Targeted-Receptor pre-Operative Therapy for patients with high-risk, operable colon cancer</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobch9appmfig1"><div id="ch9.appm.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%206.%20Forest%20plot%3A%20Preoperative%20chemotherapy%20versus%20no%20preoperative%20chemotherapy%20-%20Disease-free%20survival.&p=BOOKS&id=559941_ch9appmf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK559941/bin/ch9appmf1.jpg" alt="Figure 6. Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Disease-free survival." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 6</span><span class="title">Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Disease-free survival</span></h3><div class="caption"><p>CI: confidence interval; CT: chemotherapy; E: expected; M-H: Mantel-Haenszel; O: observed; Preop: preoperative; V: variance</p></div></div></article><article data-type="fig" id="figobch9appmfig2"><div id="ch9.appm.fig2" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%207.%20Forest%20plot%3A%20Preoperative%20chemotherapy%20versus%20no%20preoperative%20chemotherapy%20-%20Grade%203%20or%204%20adverse%20events%3A%20anastomotic%20leak.&p=BOOKS&id=559941_ch9appmf2.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK559941/bin/ch9appmf2.jpg" alt="Figure 7. Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Grade 3 or 4 adverse events: anastomotic leak." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 7</span><span class="title">Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Grade 3 or 4 adverse events: anastomotic leak</span></h3><div class="caption"><p>CI: confidence interval; CT: chemotherapy; DVT: deep vein thrombosis; M-H: Mantel-Haenszel; Preop: preoperative</p></div></div></article><article data-type="fig" id="figobch9appmfig3"><div id="ch9.appm.fig3" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%208.%20Forest%20plot%3A%20Preoperative%20chemotherapy%20versus%20no%20preoperative%20chemotherapy%20-%20Treatment-related%20mortality.&p=BOOKS&id=559941_ch9appmf3.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK559941/bin/ch9appmf3.jpg" alt="Figure 8. Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Treatment-related mortality." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 8</span><span class="title">Forest plot: Preoperative chemotherapy versus no preoperative chemotherapy - Treatment-related mortality</span></h3><div class="caption"><p>CI: confidence interval; CT: chemotherapy; M-H: Mantel-Haenszel; Preop: preoperative;</p></div></div></article><article data-type="table-wrap" id="figobch9appmtab3"><div id="ch9.appm.tab3" class="table"><h3><span class="label">Table 9</span><span class="title">Quality assessment of expert evidence</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK559941/table/ch9.appm.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch9.appm.tab3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch9.appm.tab3_1_1_1_1" colspan="7" rowspan="1" style="text-align:left;vertical-align:bottom;">Quality assessment</th><th id="hd_h_ch9.appm.tab3_1_1_1_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">No of patients</th><th id="hd_h_ch9.appm.tab3_1_1_1_3" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Effect</th><th id="hd_h_ch9.appm.tab3_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ch9.appm.tab3_1_1_1_4" style="text-align:left;vertical-align:bottom;">Quality</th><th id="hd_h_ch9.appm.tab3_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_ch9.appm.tab3_1_1_1_5" style="text-align:left;vertical-align:bottom;">Importance</th></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1" id="hd_h_ch9.appm.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No of studies</th><th headers="hd_h_ch9.appm.tab3_1_1_1_1" id="hd_h_ch9.appm.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Design</th><th headers="hd_h_ch9.appm.tab3_1_1_1_1" id="hd_h_ch9.appm.tab3_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Risk of bias</th><th headers="hd_h_ch9.appm.tab3_1_1_1_1" id="hd_h_ch9.appm.tab3_1_1_2_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Inconsistency</th><th headers="hd_h_ch9.appm.tab3_1_1_1_1" id="hd_h_ch9.appm.tab3_1_1_2_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Indirectness</th><th headers="hd_h_ch9.appm.tab3_1_1_1_1" id="hd_h_ch9.appm.tab3_1_1_2_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Imprecision</th><th headers="hd_h_ch9.appm.tab3_1_1_1_1" id="hd_h_ch9.appm.tab3_1_1_2_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other considerations</th><th headers="hd_h_ch9.appm.tab3_1_1_1_2" id="hd_h_ch9.appm.tab3_1_1_2_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Preop CT</th><th headers="hd_h_ch9.appm.tab3_1_1_1_2" id="hd_h_ch9.appm.tab3_1_1_2_9" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No preop CT</th><th headers="hd_h_ch9.appm.tab3_1_1_1_3" id="hd_h_ch9.appm.tab3_1_1_2_10" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Relative (95% CI)</th><th headers="hd_h_ch9.appm.tab3_1_1_1_3" id="hd_h_ch9.appm.tab3_1_1_2_11" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Absolute</th></tr></thead><tbody><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_1_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Disease-free survival</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>95/698</p>
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<p>(13.6%)</p>
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</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>61/354</p>
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<p>(17.2%)</p>
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|
</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HR 0.74 (0.53, 1.04)</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42 fewer per 1000 (from 77 fewer to 6 more)</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MODERATE</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_3_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Overall survival</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_5_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Positive resection margins, T4b patients</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_7_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_9_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Anastomotic leak</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>32/682</p>
|
|
<p>(4.7%)</p>
|
|
</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>26/350</p>
|
|
<p>(7.4%)</p>
|
|
</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 0.63 (0.38, 1.04)</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27 fewer pre 1000 (from 68 fewer to 136 more)</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MODERATE</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_11_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events - Wound infection</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_13_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events – Bronchopneumonia</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_15_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Any Grade 3 or 4 adverse events – Pulmonary embolism ± deep vein thrombosis</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_17_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Overall quality of life</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_19_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Treatment-related mortality (postoperative death rate)</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>3/682</p>
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<p>(0.4%)</p>
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</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>1/350</p>
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<p>(0.3%)</p>
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</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.52 [0.16, 14.57]</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 more per 1000 (from 2 fewer to 387 more)</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MODERATE</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_19_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_h_ch9.appm.tab3_1_1_2_3 hd_h_ch9.appm.tab3_1_1_2_4 hd_h_ch9.appm.tab3_1_1_2_5 hd_h_ch9.appm.tab3_1_1_2_6 hd_h_ch9.appm.tab3_1_1_2_7 hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_h_ch9.appm.tab3_1_1_2_9 hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_h_ch9.appm.tab3_1_1_2_11 hd_h_ch9.appm.tab3_1_1_1_4 hd_h_ch9.appm.tab3_1_1_1_5" id="hd_b_ch9.appm.tab3_1_1_21_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Local recurrence</th></tr><tr><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_1 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_2 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No evidence available</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_3 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_4 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_5 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_6 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_1 hd_h_ch9.appm.tab3_1_1_2_7 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_8 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_2 hd_h_ch9.appm.tab3_1_1_2_9 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_10 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_3 hd_h_ch9.appm.tab3_1_1_2_11 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_4 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch9.appm.tab3_1_1_1_5 hd_b_ch9.appm.tab3_1_1_21_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMPORTANT</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">CI: confidence interval; CT: chemotherapy; HR: hazard ratio; OR: odds ratio; RR: risk ratio</p></div></dd></dl><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch9.appm.tab3_1"><p class="no_margin">Quality of evidence downgraded by 1 because of imprecision of the effect estimate (< 300 events for dichotomous outcomes or < 400 patients for continuous outcomes).</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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