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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/pdqcis/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-pdqcis-lrg.png" alt="Cover of PDQ Cancer Information Summaries" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>PDQ Cancer Information Summaries [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK65746_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65746_dtls__"><div>Bethesda (MD): <a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>; 2002-.</div></div><div class="half_rhythm"></div><div class="bk_noprnt"><form method="get" action="/books/n/pdqcis/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK65746_"><span class="title" itemprop="name">Laryngeal Cancer Treatment (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contrib-group"><span itemprop="author">PDQ Adult Treatment Editorial Board</span>.</p><p class="small">Published online: December 21, 2016.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062922__431">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of laryngeal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062922__432">This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062922__1"><h2 id="_CDR0000062922__1_">General Information About Laryngeal Cancer</h2><div id="CDR0000062922__299"><h3>Incidence and Mortality</h3><p id="CDR0000062922__300">Estimated new cases and deaths from laryngeal cancer in the United States in 2016:[<a class="bk_pop" href="#CDR0000062922_rl_1_1">1</a>]</p><ul id="CDR0000062922__225"><li class="half_rhythm"><div>New cases: 13,430.</div></li><li class="half_rhythm"><div>Deaths: 3,620.</div></li></ul></div><div id="CDR0000062922__317"><h3>Anatomy</h3><p id="CDR0000062922__2">The larynx is divided into the following three anatomical regions: </p><ul id="CDR0000062922__283"><li class="half_rhythm"><div>The supraglottic larynx
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includes the epiglottis, false vocal cords, ventricles, aryepiglottic folds,
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and arytenoids.</div></li><li class="half_rhythm"><div>The glottis includes the true vocal cords and the anterior and
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posterior commissures.</div></li><li class="half_rhythm"><div>The subglottic region begins about 1 cm below
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the true vocal cords and extends to the lower border of the cricoid cartilage
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or the first tracheal ring.
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</div></li></ul><p id="CDR0000062922__3">The supraglottic area is rich in lymphatic drainage. After penetrating the
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pre-epiglottic space and thyrohyoid membrane, lymphatic drainage is initially
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to the jugulodigastric and midjugular nodes. About 25% to 50% of patients
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present with involved lymph nodes. The precise figure depends on the T stage. The
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true vocal cords are devoid of lymphatics. As a result, vocal cord cancer
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confined to the true cords rarely, if ever, presents with involved lymph nodes.
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Extension above or below the cords may, however, lead to lymph node
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involvement. Primary subglottic cancers, which are quite rare, drain through
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the cricothyroid and cricotracheal membranes to the pretracheal, paratracheal,
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and inferior jugular nodes, and occasionally to mediastinal nodes.[<a class="bk_pop" href="#CDR0000062922_rl_1_2">2</a>]
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|
</p></div><div id="CDR0000062922__318"><h3>Risk Factors</h3><p id="CDR0000062922__4">A clear association has been made between smoking, excess alcohol ingestion,
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and the development of squamous cell cancers of the upper aerodigestive
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tract.[<a class="bk_pop" href="#CDR0000062922_rl_1_3">3</a>] For smokers, the risk of the development of laryngeal cancer decreases after the cessation of smoking but remains elevated even years later when compared to that of nonsmokers.[<a class="bk_pop" href="#CDR0000062922_rl_1_4">4</a>] If a patient who has had a single cancer continues to smoke and drink
|
|
alcoholic beverages, the likelihood of a cure for the initial cancer, by any
|
|
modality, is diminished, and the risk of second tumor is enhanced. Because of clinical problems related to smoking and alcohol use in this
|
|
population, many patients succumb to intercurrent illness rather than to the
|
|
primary cancer. </p></div><div id="CDR0000062922__320"><h3>Clinical Features</h3><p id="CDR0000062922__5">Supraglottic cancers typically present with sore throat, painful swallowing,
|
|
referred ear pain, change in voice quality, or enlarged neck nodes. Early
|
|
vocal cord cancers are usually detected because of hoarseness. By the time
|
|
they are detected, cancers arising in the subglottic area commonly involve the
|
|
vocal cords; thus, symptoms usually relate to contiguous spread.
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|
</p></div><div id="CDR0000062922__321"><h3>Prognostic Factors</h3><p id="CDR0000062922__6">The most important adverse prognostic factors for laryngeal cancers include
|
|
increasing T stage and N stage. Other prognostic factors may include sex, age,
|
|
performance status, and a variety of pathologic features of the tumor,
|
|
including grade and depth of invasion.[<a class="bk_pop" href="#CDR0000062922_rl_1_5">5</a>]
|
|
</p><p id="CDR0000062922__7">Prognosis for small laryngeal cancers that have not spread to lymph nodes is
|
|
very good with cure rates of 75% to 95% depending on the site, tumor bulk,[<a class="bk_pop" href="#CDR0000062922_rl_1_6">6</a>]
|
|
and degree of infiltration. Although most early lesions can be cured by either
|
|
radiation therapy or surgery, radiation therapy may be reasonable to preserve
|
|
the voice, leaving surgery for salvage. Patients with a preradiation
|
|
hemoglobin level higher than 13 g/dL have higher local control
|
|
and survival rates than patients who are anemic.[<a class="bk_pop" href="#CDR0000062922_rl_1_7">7</a>] </p><p id="CDR0000062922__8">Locally advanced lesions are treated with combined modality treatment involving radiation and chemotherapy with or without surgery, the aim of which is laryngeal preservation in appropriately selected candidates.[<a class="bk_pop" href="#CDR0000062922_rl_1_8">8</a>] Distant metastases are also common, even if the primary
|
|
tumor is controlled.
|
|
</p><p id="CDR0000062922__9">Intermediate lesions have intermediate prognoses, depending on site, T stage,
|
|
N stage, and performance status. Therapy recommendations for patients with
|
|
these lesions are based on a variety of complex anatomic, clinical, and social
|
|
factors, which should be individualized and discussed in multidisciplinary
|
|
consultation (surgery, radiation therapy, and dental and oral surgery) prior to
|
|
prescribing therapy.
|
|
</p></div><div id="CDR0000062922__333"><h3>Follow-up and Survivorship</h3><p id="CDR0000062922__334">Second
|
|
primary tumors, often in the aerodigestive tract, have been reported in as many as
|
|
25% of patients whose initial lesion is controlled. A study has shown that
|
|
daily treatment of these patients with moderate doses of isotretinoin
|
|
(i.e., 13-cis-retinoic acid) for 1 year can significantly reduce the incidence of
|
|
second tumors.[<a class="bk_pop" href="#CDR0000062922_rl_1_9">9</a>] No survival advantage has been demonstrated, partially because of recurrence and death from the primary malignancy.</p><p id="CDR0000062922__335">Patients treated for laryngeal cancers are at the highest risk of recurrence in the
|
|
first 2 to 3 years. Recurrences after 5 years are rare and usually represent
|
|
new primary malignancies. Close, regular follow-up is crucial to maximize the
|
|
chance for salvage. Careful clinical examination and repetition of any
|
|
abnormal staging study are included in follow-up, along with attention to any
|
|
treatment-related toxic effect or complication.
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|
</p></div><div id="CDR0000062922_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_1_1">American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. <a href="https://old.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed July 13, 2017.</div></li><li><div class="bk_ref" id="CDR0000062922_rl_1_2">Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis. Int J Radiat Oncol Biol Phys 13 (7): 963-8, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3597159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3597159</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_1_3">Spitz MR: Epidemiology and risk factors for head and neck cancer. Semin Oncol 21 (3): 281-8, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8209260" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8209260</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_1_4">Bosetti C, Garavello W, Gallus S, et al.: Effects of smoking cessation on the risk of laryngeal cancer: an overview of published studies. Oral Oncol 42 (9): 866-72, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16931120" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16931120</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_1_5">Yilmaz T, Hoşal S, Gedikoglu G, et al.: Prognostic significance of depth of invasion in cancer of the larynx. Laryngoscope 108 (5): 764-8, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9591560" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9591560</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_1_6">Reddy SP, Mohideen N, Marra S, et al.: Effect of tumor bulk on local control and survival of patients with T1 glottic cancer. Radiother Oncol 47 (2): 161-6, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9683364" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9683364</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_1_7">Fein DA, Lee WR, Hanlon AL, et al.: Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx. J Clin Oncol 13 (8): 2077-83, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7636551" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7636551</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_1_8">Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013. [<a href="/pmc/articles/PMC3577950/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3577950</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23182993" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23182993</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_1_9">Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2202902" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2202902</span></a>]</div></li></ol></div></div><div id="CDR0000062922__11"><h2 id="_CDR0000062922__11_">Cellular Classification of Laryngeal Cancer</h2><p id="CDR0000062922__12">The vast majority of laryngeal cancers are of squamous cell histology.
|
|
Squamous cell subtypes include keratinizing and nonkeratinizing and well-differentiated to poorly differentiated grade. A variety of nonsquamous cell
|
|
laryngeal cancers also occur.[<a class="bk_pop" href="#CDR0000062922_rl_11_1">1</a>] These are not staged using the American Joint
|
|
Cancer Committee staging system, and their management, which is not discussed here, can
|
|
differ from that of squamous cell laryngeal cancers. <i>In situ</i> squamous cell
|
|
carcinoma of the larynx is usually managed by a conservative surgical procedure
|
|
such as mucosal stripping or superficial laser excision. Radiation therapy may
|
|
also be appropriate treatment of selected patients with <i>in situ</i> carcinoma of
|
|
the glottic larynx.
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|
</p><div id="CDR0000062922_rl_11"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_11_1">Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.</div></li></ol></div></div><div id="CDR0000062922__13"><h2 id="_CDR0000062922__13_">Stage Information for Laryngeal Cancer</h2><p id="CDR0000062922__14">The staging system for laryngeal cancer is clinical and based on the best possible estimate of the
|
|
extent of disease before treatment. The assessment of the primary tumor is
|
|
based on inspection and palpation when possible and by fiberoptic laryngoscopy. Panendoscopy under anesthesia ensures careful clinical examination to determine clinical extent of local disease. The tumor must be confirmed
|
|
histologically, and any other pathological data obtained on biopsy may be
|
|
included. Head and neck magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography
|
|
should be done before therapy to supplement inspection and palpation.[<a class="bk_pop" href="#CDR0000062922_rl_13_1">1</a>]
|
|
Additional radiographic studies may be included. The appropriate nodal
|
|
drainage areas in the neck should be examined by careful palpation.
|
|
</p><div id="CDR0000062922__280"><h3>Definitions of TNM</h3><p id="CDR0000062922__261">The American Joint Committee on Cancer has designated staging by TNM
|
|
classification to define laryngeal cancer.[<a class="bk_pop" href="#CDR0000062922_rl_13_2">2</a>]</p><div id="CDR0000062922__259" class="table"><h3><span class="title">Table 1. Primary Tumor (T)<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65746.3/table/CDR0000062922__259/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062922__259_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">TX</td><td colspan="1" rowspan="1" style="vertical-align:top;">Primary tumor cannot be assessed.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No evidence of primary tumor.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tis</td><td colspan="1" rowspan="1" style="vertical-align:top;">Carcinoma <i>in situ</i>.</td></tr><tr><td colspan="2" rowspan="1" style="text-align:center;vertical-align:top;"><b><i>Supraglottis</i></b></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor limited to one subsite of supraglottis with normal vocal cord mobility.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, and/or medial wall of pyriform sinus) without fixation of the larynx.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre-epiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage.</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Moderately advanced local disease.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus).</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Very advanced local disease.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.</td></tr><tr><td colspan="2" rowspan="1" style="text-align:center;vertical-align:top;"><b><i>Glottis</i></b></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor limited to one vocal cord.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor involves both vocal cords.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor extends to supraglottis and/or subglottis and/or with impaired vocal cord mobility.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor limited to the larynx with vocal cord fixation and/or invasion of paraglottic space and/or inner cortex of the thyroid cartilage.</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Moderately advanced local disease.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus).</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Very advanced local disease.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.</td></tr><tr><td colspan="2" rowspan="1" style="text-align:center;vertical-align:top;"><b><i>Subglottis</i></b></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor limited to the subglottis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor extends to vocal cord(s) with normal or impaired mobility.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor limited to larynx with vocal cord fixation.</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Moderately advanced local disease.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus).</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Very advanced local disease.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.</p></div></dd></dl></div></div></div><div id="CDR0000062922__253" class="table"><h3><span class="title">Table 2. Regional Lymph Nodes<sup>a</sup><sup>b</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65746.3/table/CDR0000062922__253/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062922__253_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">NX</td><td colspan="1" rowspan="1" style="vertical-align:top;">Regional lymph nodes cannot be assessed. </td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No regional lymph node metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension.</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N2a</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N2b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension. </td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N2c</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N3</td><td colspan="1" rowspan="1" style="vertical-align:top;">Metastasis in a lymph node, >6 cm in greatest dimension.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>b</sup>Metastases at level VII are considered regional lymph node metastases.</p></div></dd></dl></div></div></div><div id="CDR0000062922__254" class="table"><h3><span class="title">Table 3. Distant Metastasis (M)<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65746.3/table/CDR0000062922__254/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062922__254_lrgtbl__"><table class="no_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td><td colspan="1" rowspan="1" style="vertical-align:top;">No distant metastasis.</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">M1</td><td colspan="1" rowspan="1" style="vertical-align:top;">Distant metastasis.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.</p></div></dd></dl></div></div></div><div id="CDR0000062922__255" class="table"><h3><span class="title">Table 4. Anatomic Stage/Prognostic Groups</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65746.3/table/CDR0000062922__255/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062922__255_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">T</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">N</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">M</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> 0</td><td colspan="1" rowspan="1" style="vertical-align:top;">Tis</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> I</td><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> II</td><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="4" style="vertical-align:top;"> III</td><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="6" style="vertical-align:top;"> IVA</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N0</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N1</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T1</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T2</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T3</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T4a</td><td colspan="1" rowspan="1" style="vertical-align:top;">N2</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;"> IVB</td><td colspan="1" rowspan="1" style="vertical-align:top;">T4b</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any N</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Any T</td><td colspan="1" rowspan="1" style="vertical-align:top;">N3</td><td colspan="1" rowspan="1" style="vertical-align:top;">M0</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"> IVC</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any T</td><td colspan="1" rowspan="1" style="vertical-align:top;">Any N</td><td colspan="1" rowspan="1" style="vertical-align:top;">M1</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Laryngeal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-67.</p></div></dd></dl></div></div></div></div><div id="CDR0000062922_rl_13"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_13_1">Thabet HM, Sessions DG, Gado MH, et al.: Comparison of clinical evaluation and computed tomographic diagnostic accuracy for tumors of the larynx and hypopharynx. Laryngoscope 106 (5 Pt 1): 589-94, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8628086" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8628086</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_13_2">Larynx. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 57-62.</div></li></ol></div></div><div id="CDR0000062922__66"><h2 id="_CDR0000062922__66_">Treatment Option Overview for Laryngeal Cancer</h2><p id="CDR0000062922__285">Small superficial cancers without laryngeal fixation or lymph node involvement
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are successfully treated by radiation therapy or surgery alone, including laser
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excision surgery. Radiation therapy may be selected to preserve the voice
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and to reserve surgery for salvaging failures. The radiation field and dose are
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determined by the location and size of the primary tumor. A variety of
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curative surgical procedures are also recommended for laryngeal cancers, some
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of which preserve vocal function. An appropriate surgical procedure must be
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considered for each patient, given the anatomic problem, performance status,
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and clinical expertise of the treatment team. Advanced laryngeal cancers are
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often treated by combining radiation with concurrent chemotherapy for larynx preservation and total laryngectomy for bulky T4 disease or salvage.[<a class="bk_pop" href="#CDR0000062922_rl_66_1">1</a>-<a class="bk_pop" href="#CDR0000062922_rl_66_3">3</a>]</p><p id="CDR0000062922__286">Evaluation of treatment outcome can be reported in various ways: locoregional
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control, disease-free survival, determinate survival, and overall survival (OS) at 2
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to 5 years. Preservation of voice is an important parameter to evaluate.
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Outcome should be reported after initial surgery, initial radiation, planned
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combined treatment, or surgical salvage of radiation failures. Primary source
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material should be consulted to review these differences.
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</p><p id="CDR0000062922__67">A review of published clinical
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results of radical radiation therapy for head and neck cancer suggests a
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significant loss of local control when the administration of radiation therapy
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was prolonged; therefore, lengthening of standard treatment schedules should be
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avoided whenever possible.[<a class="bk_pop" href="#CDR0000062922_rl_66_4">4</a>,<a class="bk_pop" href="#CDR0000062922_rl_66_5">5</a>]
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</p><p id="CDR0000062922__323">Direct comparison of the results of radiation therapy versus endolaryngeal surgery (with or without laser) has not been made for patients with early stage laryngeal cancer. The evidence is insufficient to show a clear difference in the results between treatment options in regard to local control or OS. Retrospective data suggests that in comparison with surgery, radiation therapy might cause less perturbation of voice quality without a significant difference in patient perception.[<a class="bk_pop" href="#CDR0000062922_rl_66_6">6</a>] </p><p id="CDR0000062922__324">A direct comparison of chemotherapy followed by radiation therapy versus upfront surgery was made by The Department of Veterans Affairs (VA) Laryngeal Cancer Study Group in a trial in which 332 patients were randomly assigned to three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy or surgery and radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_66_7">7</a>] After two cycles of chemotherapy, the clinical tumor response was complete in 31% of the patients, and there was a partial response in 54% of the patients. Survival was similar in both arms; however, larynx preservation was possible in 64% of the patients in the chemotherapy-followed-by-radiation therapy arm. </p><p id="CDR0000062922__332">The VA study was followed up in a randomized study, <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=77756" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RTOG 9111</a> (<a href="https://clinicaltrials.gov/show/NCT00002496" title="Study NCT00002496" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00002496</a>), in which the laryngeal preservation arm of the VA study was compared with the concomitant chemoradiation and radiation-alone arms, and the primary endpoint was laryngectomy-free survival (LFS).[<a class="bk_pop" href="#CDR0000062922_rl_66_3">3</a>] The RTOG 9111 study evaluated 547 patients with locally advanced laryngeal cancer who were enrolled between August 1992 and May 2000, with a median follow-up for surviving patients of 10.8 years (range, 0.07–17 years). Three regimens were compared, including induction chemotherapy plus radiation therapy, concomitant chemoradiation, and radiation therapy alone. Both chemotherapy regimens improved LFS compared with radiation therapy alone (induction chemotherapy vs. radiation therapy alone, hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59–0.95; <i>P </i>= .02; concomitant chemotherapy vs. radiation therapy alone, HR, 0.78; 95% CI, 0.78–0.98; <i>P</i> = .03).</p><p id="CDR0000062922__325">Concurrent radiation therapy plus cisplatin resulted in a statistically significantly higher percentage of patients with an intact larynx at 10 years (67.5% for patients who had induction chemotherapy; 81.7% for patients who had concomitant chemotherapy; and 63.8% for patients who received radiation alone); 80% of laryngectomies were performed during the first 2 years (84 laryngectomies during year 1 and 35 laryngectomies during year 2).</p><p id="CDR0000062922__326">Concomitant cisplatin with radiation therapy resulted in a 41% reduction in risk of locoregional failure compared with radiation therapy alone (HR, 0.59; 95% CI, 0.43–0.82; <i>P</i> = .0015) and a 34% reduction in risk compared with induction chemotherapy (HR, 0.66; 95% CI, 0.48–0.92; <i>P</i> = .004). Both chemotherapy regimens had a lower incidence of distant metastases, although this did not reach statistical significance compared with radiation therapy alone.
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</p><p id="CDR0000062922__327">The 10-year cumulative rates of late toxicity (grades 3–5) were 30.6% for induction chemotherapy, 33.3% for concomitant chemotherapy, and 38% for radiation alone, and were not significantly different between the arms.
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</p><p id="CDR0000062922__328">OS was not significantly different between the groups, although there was possibly a worse outcome in the concomitant groups compared with the induction chemotherapy group (HR, 1.25; 95% CI, 0.98–1.61; <i>P</i> = .08). The OS rates were 58% (5 year) and 39% (10 year) for induction chemotherapy, 55% (5 year) and 28% (10 year) for concomitant chemoradiation, and 54% (5 year) and 32% (10 year) for radiation alone. The number of deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% vs. 20.8% with induction chemotherapy and 16.9% with radiation alone), because after approximately 4.5 years, the survival curves began to separate and favor induction, although the difference was not statistically significant.[<a class="bk_pop" href="#CDR0000062922_rl_66_3">3</a>]
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</p><p id="CDR0000062922__68">The risk of lymph node metastases in patients with stage I glottic cancer
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ranges from 0% to 2%, and for more advanced disease, such as stage II and stage
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III glottic, the incidence is only 10% and 15%, respectively. Thus, there is
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no need to treat glottic cancer cervical lymph nodes electively in patients
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with stage I tumors and small stage II tumors. Elective neck radiation should be considered for T3 or T4 glottic tumors or T1 to T4 supraglottic tumors.[<a class="bk_pop" href="#CDR0000062922_rl_66_8">8</a>]
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</p><p id="CDR0000062922__69">For patients with cancer of the subglottis, combined modality therapy is
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generally preferred for the uncommon small lesions (i.e., stage I or stage
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II); however, radiation therapy alone may be used.
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</p><p id="CDR0000062922__70">Patients who smoke during radiation therapy appear to have lower response rates
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and shorter survival durations than those who do not;[<a class="bk_pop" href="#CDR0000062922_rl_66_9">9</a>] therefore, patients
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|
should be counseled on smoking cessation before beginning radiation therapy.
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</p><p id="CDR0000062922__71">Accumulating evidence has demonstrated a high incidence (i.e., >30%–40%) of
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hypothyroidism in patients who have received external-beam radiation to the
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entire thyroid gland or to the pituitary gland. Thyroid-junction testing of
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patients should be considered prior to therapy and as part of posttreatment
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follow-up.[<a class="bk_pop" href="#CDR0000062922_rl_66_10">10</a>,<a class="bk_pop" href="#CDR0000062922_rl_66_11">11</a>]
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</p><div id="CDR0000062922_rl_66"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_66_1">Silver CE, Ferlito A: Surgery for Cancer of the Larynx and Related Structures. 2nd ed. Philadelphia, Pa: Saunders, 1996.</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_2">Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_3">Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013. [<a href="/pmc/articles/PMC3577950/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3577950</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23182993" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23182993</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_4">Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1534082" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1534082</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_5">Hansen O, Overgaard J, Hansen HS, et al.: Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation. Radiother Oncol 43 (1): 47-51, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9165136" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9165136</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_6">Yoo J, Lacchetti C, Hammond JA, et al.: Role of endolaryngeal surgery (with or without laser) compared with radiotherapy in the management of early (T1) glottic cancer: a clinical practice guideline. Curr Oncol 20 (2): e132-5, 2013. [<a href="/pmc/articles/PMC3615864/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3615864</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23559880" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23559880</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_7">Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 324 (24): 1685-90, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/2034244" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2034244</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_8">Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis. Int J Radiat Oncol Biol Phys 13 (7): 963-8, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3597159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3597159</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_9">Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8417381" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8417381</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_10">Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7836081" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7836081</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_66_11">Constine LS: What else don't we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7836099" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7836099</span></a>]</div></li></ol></div></div><div id="CDR0000062922__73"><h2 id="_CDR0000062922__73_">Stage I Laryngeal Cancer Treatment</h2><p id="CDR0000062922__360">Selection of treatment should include an evaluation of voice function and quality after treatment. Endoscopic CO2 laser resections may also achieve similar results in terms of local control and function [<a class="bk_pop" href="#CDR0000062922_rl_73_1">1</a>] compared with radiation therapy, although no randomized studies have been performed.[<a class="bk_pop" href="#CDR0000062922_rl_73_2">2</a>] A meta-analysis of 22 consecutive case series to examine oncologic control demonstrated no clear differences between transoral CO2 laser excision and external beam radiation therapy in terms of local control (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.51–1.3 and laryngectomy-free survival [OR, 0.84, 95% CI, 0.42–1.66]). There was a trend for improved posttreatment voice quality with radiation therapy. Transoral CO2 laser–excision surgery dominates radiotherapy from a cost-utility standpoint.[<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335134/" class="def">Level of Evidence: 2C</a>] </p><div id="CDR0000062922__74"><h3>Supraglottis</h3><p id="CDR0000062922__75"><b>Standard treatment options:
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</b></p><ol id="CDR0000062922__177"><li class="half_rhythm"><div>External-beam radiation therapy alone.
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</div></li><li class="half_rhythm"><div>Supraglottic laryngectomy. Total laryngectomy may be reserved for patients
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unable to tolerate potential respiratory complications of surgery or the
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supraglottic laryngectomy. </div></li></ol></div><div id="CDR0000062922__78"><h3>Glottis</h3><p id="CDR0000062922__79"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__178"><li class="half_rhythm"><div>Radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_73_3">3</a>-<a class="bk_pop" href="#CDR0000062922_rl_73_6">6</a>]
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</div></li><li class="half_rhythm"><div>Cordectomy for very carefully selected patients with limited and superficial
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T1 lesions.[<a class="bk_pop" href="#CDR0000062922_rl_73_7">7</a>,<a class="bk_pop" href="#CDR0000062922_rl_73_8">8</a>]</div></li><li class="half_rhythm"><div>Partial or hemilaryngectomy or total laryngectomy, depending on anatomic
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considerations.
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</div></li><li class="half_rhythm"><div>Endoscopic CO2 laser excision.[<a class="bk_pop" href="#CDR0000062922_rl_73_9">9</a>]
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</div></li></ol></div><div id="CDR0000062922__84"><h3>Subglottis</h3><p id="CDR0000062922__85"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__289"><li class="half_rhythm"><div>Lesions can be treated successfully by radiation therapy alone with
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preservation of normal voice. </div></li><li class="half_rhythm"><div>Surgery is reserved for failure of radiation
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therapy or for patients who cannot be easily assessed for radiation therapy.
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</div></li></ol></div><div id="CDR0000062922__TrialSearch_73_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062922__TrialSearch_73_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
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<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=40111&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage I laryngeal cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062922__TrialSearch_73_18">General information about clinical trials is also available from the <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062922_rl_73"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_73_1">Agrawal A, Moon J, Davis RK, et al.: Transoral carbon dioxide laser supraglottic laryngectomy and irradiation in stage I, II, and III squamous cell carcinoma of the supraglottic larynx: report of Southwest Oncology Group Phase 2 Trial S9709. Arch Otolaryngol Head Neck Surg 133 (10): 1044-50, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17938330" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17938330</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_73_2">Dey P, Arnold D, Wight R, et al.: Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer. Cochrane Database Syst Rev (2): CD002027, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12076435" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12076435</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_73_3">Mittal B, Rao DV, Marks JE, et al.: Role of radiation in the management of early vocal cord carcinoma. Int J Radiat Oncol Biol Phys 9 (7): 997-1002, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6408043" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6408043</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_73_4">Wang CC: Factors influencing the success of radiation therapy for T2 and T3 glottic carcinomas. Importance of cord mobility and sex. Am J Clin Oncol 9 (6): 517-20, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3788854" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3788854</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_73_5">Mendenhall WM, Amdur RJ, Morris CG, et al.: T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy. J Clin Oncol 19 (20): 4029-36, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11600604" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11600604</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_73_6">Foote RL, Olsen KD, Kunselman SJ, et al.: Early-stage squamous cell carcinoma of the glottic larynx managed with radiation therapy. Mayo Clin Proc 67 (7): 629-36, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1434895" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1434895</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_73_7">Steiner W: Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14 (2): 116-21, 1993 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/8484476" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8484476</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_73_8">Olsen KD, Thomas JV, DeSanto LW, et al.: Indications and results of cordectomy for early glottic carcinoma. Otolaryngol Head Neck Surg 108 (3): 277-82, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8464642" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8464642</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_73_9">Higgins KM: What treatment for early-stage glottic carcinoma among adult patients: CO2 endolaryngeal laser excision versus standard fractionated external beam radiation is superior in terms of cost utility? Laryngoscope 121 (1): 116-34, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21120828" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21120828</span></a>]</div></li></ol></div></div><div id="CDR0000062922__87"><h2 id="_CDR0000062922__87_">Stage II Laryngeal Cancer Treatment</h2><div id="CDR0000062922__88"><h3>Supraglottis</h3><p id="CDR0000062922__89"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__180"><li class="half_rhythm"><div> External-beam radiation therapy alone for the smaller lesions encompassing the primary disease and regional elective nodes.[<a class="bk_pop" href="#CDR0000062922_rl_87_1">1</a>]</div></li><li class="half_rhythm"><div>Supraglottic laryngectomy or total laryngectomy with bilateral neck dissections, depending on location of
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the lesion, clinical status of the patient, and expertise of the treatment
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team. Careful selection must be made to ensure adequate pulmonary and
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swallowing function postoperatively.
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</div></li><li class="half_rhythm"><div><a href="#CDR0000062922__434">Postoperative radiation therapy (PORT)</a> is indicated for positive or close
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surgical margins or other adverse pathological risk factors.
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</div></li></ol><p id="CDR0000062922__290">Radiation should be preferred because
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of the good results, preservation of the voice, and the possibility of surgical salvage in
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patients whose disease recurs locally.</p></div><div id="CDR0000062922__96"><h3>Glottis</h3><p id="CDR0000062922__97"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__182"><li class="half_rhythm"><div> Radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_87_1">1</a>-<a class="bk_pop" href="#CDR0000062922_rl_87_4">4</a>]
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</div></li><li class="half_rhythm"><div>Partial or hemilaryngectomy or total laryngectomy, depending on anatomic
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considerations. Under certain circumstances, laser microsurgery may be
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appropriate.[<a class="bk_pop" href="#CDR0000062922_rl_87_5">5</a>]</div></li></ol></div><div id="CDR0000062922__103"><h3>Subglottis</h3><p id="CDR0000062922__104"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__291"><li class="half_rhythm"><div>Lesions can be treated successfully by radiation therapy alone with
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preservation of normal voice.[<a class="bk_pop" href="#CDR0000062922_rl_87_1">1</a>]</div></li><li class="half_rhythm"><div>Surgery is reserved for failure of
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radiation therapy or for patients in whom follow-up is likely to be difficult.</div></li></ol><p id="CDR0000062922__435"><b><div class="milestone-start" id="CDR0000062922__434"></div>PORT With or Without Chemotherapy</b></p><p id="CDR0000062922__436">Depending on pathological findings after primary surgery, PORT or postoperative chemoradiation is used in the adjuvant setting for the following histological findings:</p><ul id="CDR0000062922__437"><li class="half_rhythm"><div> T4 disease.</div></li><li class="half_rhythm"><div>Perineural invasion.</div></li><li class="half_rhythm"><div>Lymphovascular invasion.</div></li><li class="half_rhythm"><div>Positive margins or margins less than 5 mm.</div></li><li class="half_rhythm"><div>Extracapsular extension of a lymph node.</div></li><li class="half_rhythm"><div>Two or more involved lymph nodes.</div></li></ul><p id="CDR0000062922__438">An overall survival (OS) benefit was found for patients with positive margins and extracapsular extensions based on a pooled analysis of the European Organization for the Research and Treatment of Cancer (EORTC) <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=63431" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">22931</a> [<a href="https://clinicaltrials.gov/show/NCT00002555" title="Study NCT00002555" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00002555</a>] and RTOG-9501 studies.[<a class="bk_pop" href="#CDR0000062922_rl_87_6">6</a>-<a class="bk_pop" href="#CDR0000062922_rl_87_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] The addition of chemotherapy to radiation therapy for other pathological risk factors is unclear. A postoperative randomized trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=651536" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RTOG-0920</a> ) is evaluating the use of cetuximab with adjuvant radiation therapy in the postoperative setting.[<a class="bk_pop" href="#CDR0000062922_rl_87_6">6</a>-<a class="bk_pop" href="#CDR0000062922_rl_87_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]
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<div class="milestone-end"></div></p></div><div id="CDR0000062922__TrialSearch_87_sid_6"><h3>Current Clinical Trials</h3><p id="CDR0000062922__TrialSearch_87_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
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<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=40112&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage II laryngeal cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062922__TrialSearch_87_18">General information about clinical trials is also available from the <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062922_rl_87"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_87_1">Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.</div></li><li><div class="bk_ref" id="CDR0000062922_rl_87_2">Mittal B, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53 (1): 151-61, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6689996" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6689996</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_87_3">Medini E, Medini I, Lee CK, et al.: Curative radiotherapy for stage II-III squamous cell carcinoma of the glottic larynx. Am J Clin Oncol 21 (3): 302-5, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9626804" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9626804</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_87_4">Mendenhall WM, Amdur RJ, Morris CG, et al.: T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy. J Clin Oncol 19 (20): 4029-36, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11600604" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11600604</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_87_5">Steiner W: Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14 (2): 116-21, 1993 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/8484476" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8484476</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_87_6">Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16161069" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16161069</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_87_7">Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012. [<a href="/pmc/articles/PMC3465463/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3465463</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22749632" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22749632</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_87_8">Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15128893" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15128893</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_87_9">Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15128894" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15128894</span></a>]</div></li></ol></div></div><div id="CDR0000062922__109"><h2 id="_CDR0000062922__109_">Stage III Laryngeal Cancer Treatment</h2><div id="CDR0000062922__110"><h3>Supraglottis</h3><p id="CDR0000062922__111"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__186"><li class="half_rhythm"><div><a href="#CDR0000062922__439">Chemotherapy administered concomitantly with radiation therapy</a> can
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be considered for patients who would require total laryngectomy for control of disease.[<a class="bk_pop" href="#CDR0000062922_rl_109_1">1</a>] </div></li><li class="half_rhythm"><div>
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<a href="#CDR0000062922__443">Induction chemotherapy followed by concomitant chemotherapy and radiation</a>. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[<a class="bk_pop" href="#CDR0000062922_rl_109_1">1</a>-<a class="bk_pop" href="#CDR0000062922_rl_109_6">6</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335127/" class="def">Level of evidence: 1iiC</a>] </div></li><li class="half_rhythm"><div> Definitive radiation therapy alone with <a href="#CDR0000062922__446">altered fractionation</a> in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[<a class="bk_pop" href="#CDR0000062922_rl_109_7">7</a>] </div></li><li class="half_rhythm"><div>
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<a href="#CDR0000062922__478">Surgery with or without postoperative radiation therapy (PORT)</a>.[<a class="bk_pop" href="#CDR0000062922_rl_109_8">8</a>]</div></li></ol></div><div id="CDR0000062922__120"><h3>Glottis</h3><p id="CDR0000062922__121"><b>Standard treatment options:
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</b></p><ol id="CDR0000062922__329"><li class="half_rhythm"><div><a href="#CDR0000062922__439">Chemotherapy administered concomitantly with radiation therapy</a> can
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be considered for patients who would require total laryngectomy for control of disease.[<a class="bk_pop" href="#CDR0000062922_rl_109_1">1</a>]</div></li><li class="half_rhythm"><div><a href="#CDR0000062922__444"> Induction chemotherapy followed by concomitant chemotherapy and radiation</a>. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[<a class="bk_pop" href="#CDR0000062922_rl_109_1">1</a>-<a class="bk_pop" href="#CDR0000062922_rl_109_6">6</a>] </div></li><li class="half_rhythm"><div> Definitive radiation therapy alone <a href="#CDR0000062922__446">with altered fractionation</a> in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[<a class="bk_pop" href="#CDR0000062922_rl_109_7">7</a>] </div></li><li class="half_rhythm"><div>
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<a href="#CDR0000062922__478">Surgery with or without PORT.</a>[<a class="bk_pop" href="#CDR0000062922_rl_109_8">8</a>]</div></li></ol><p id="CDR0000062922__124"><b>Treatment options under clinical evaluation:
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</b></p><ul id="CDR0000062922__425"><li class="half_rhythm"><div>Clinical trials exploring chemotherapy, radiosensitizers, or particle beam
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radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_109_9">9</a>]</div></li></ul></div><div id="CDR0000062922__130"><h3>Subglottis</h3><p id="CDR0000062922__131"><b>Standard treatment options:
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</b></p><ol id="CDR0000062922__190"><li class="half_rhythm"><div>Laryngectomy plus isolated thyroidectomy and tracheoesophageal node
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dissection usually followed by postoperative radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_109_10">10</a>]</div></li><li class="half_rhythm"><div>Treatment by radiation therapy alone is indicated for patients who are not
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candidates for surgery. Patients should be closely followed, and surgical
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salvage should be planned for recurrences that are local or in the neck.
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</div></li><li class="half_rhythm"><div>Definitive radiation therapy alone with <a href="#CDR0000062922__446">altered fractionation</a> in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[<a class="bk_pop" href="#CDR0000062922_rl_109_6">6</a>,<a class="bk_pop" href="#CDR0000062922_rl_109_7">7</a>]</div></li><li class="half_rhythm"><div> Induction chemotherapy followed by <a href="#CDR0000062922__439">concomitant chemotherapy and radiation</a>. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease after radiation.[<a class="bk_pop" href="#CDR0000062922_rl_109_6">6</a>] </div></li></ol><p id="CDR0000062922__134"><b>Treatment options under clinical evaluation:</b>
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</p><ul id="CDR0000062922__426"><li class="half_rhythm"><div>Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam
|
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radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_109_9">9</a>]</div></li></ul><p id="CDR0000062922__441"><b><div class="milestone-start" id="CDR0000062922__439"></div>Concomitant Chemoradiation Therapy</b></p><p id="CDR0000062922__442">Concomitant chemoradiation therapy is a standard treatment option for locally advanced (stage III and stage IV) head and neck cancer. A meta-analysis of 93 randomized, prospective head and neck cancer trials published between 1965 and 2000 showed a 4.5% absolute survival advantage in the subset of patients receiving chemotherapy and radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_109_11">11</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335132/" class="def">Level of evidence: 2A</a>] Patients receiving concomitant chemotherapy had a greater survival benefit than those receiving induction chemotherapy.<div class="milestone-end"></div></p><p id="CDR0000062922__444"><b><div class="milestone-start" id="CDR0000062922__443"></div>Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy</b></p><p id="CDR0000062922__445">Two published randomized trials that compared concomitant chemoradiation therapy with induction chemotherapy followed by concomitant chemoradiation therapy for locally advanced head and neck cancer failed to show a survival advantage for induction chemotherapy regimens. The role of induction chemotherapy remains unclear.[<a class="bk_pop" href="#CDR0000062922_rl_109_12">12</a>,<a class="bk_pop" href="#CDR0000062922_rl_109_13">13</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335106/" class="def">Level of evidence: 1iA</a>]<div class="milestone-end"></div></p><p id="CDR0000062922__447"><b><div class="milestone-start" id="CDR0000062922__446"></div>Altered Fractionation</b></p><p id="CDR0000062922__448">Radiation therapy alone with altered fractionation may be used for patients with locally advanced head and neck cancer who are not candidates for chemotherapy. Altered fractionation radiation therapy yields a higher locoregional control rate than standard fractionated radiation therapy for patients with stage III and stage IV head and neck cancer. A long-term analysis of randomized trial <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=76475" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RTOG-9003</a> included the following four radiation therapy treatment arms: </p><ol id="CDR0000062922__449"><li class="half_rhythm"><div>Standard fractionated radiation therapy (SFX) to 70 Gy in 35 daily fractions for 7 weeks.</div></li><li class="half_rhythm"><div>Hyperfractionated radiation therapy (HFX) to 81.6 Gy in 68 twice-daily fractions for 7 weeks.</div></li><li class="half_rhythm"><div>Accelerated fractionated radiation therapy (AFX-S) to 67.2 Gy in 42 fractions for 6 weeks with a 2-week rest after 38.4 Gy.</div></li><li class="half_rhythm"><div>Accelerated continuous fractionated radiation therapy (AFX-C) to 72 Gy in 42 fractions for 6 weeks.</div></li></ol><p id="CDR0000062922__450">The three experimental arms were to be compared with SFX. Only the HFX arm showed superior locoregional control and survival at 5 years compared with the SFX arm (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62–1.00; <i>P</i> = .05). AFX-C was associated with increased late toxicity compared with SFX.[<a class="bk_pop" href="#CDR0000062922_rl_109_14">14</a>-<a class="bk_pop" href="#CDR0000062922_rl_109_19">19</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </p><p id="CDR0000062922__451">In a meta-analysis of 15 randomized trials with a total of 6,515 patients and a median follow-up of 6 years involving the assessment of HFX or AFX-S for patients with stage III and stage IV head and neck cancer, there was a significant survival benefit with altered fractionated radiation therapy and a 3.4% absolute benefit at 5 years (HR, 0.92; 95% CI, 0.86–0.97; <i>P</i> = .003). Altered fractionation improves locoregional control, and the benefit is higher in younger patients. HFX demonstrated a greater survival benefit (8% at 5 years) than AFX-S (2% with AFX-S without total dose-reduction and 1.7% with total dose-reduction at 5 years, <i>P</i> = .02).[<a class="bk_pop" href="#CDR0000062922_rl_109_20">20</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]<div class="milestone-end"></div></p><p id="CDR0000062922__479"><b><div class="milestone-start" id="CDR0000062922__478"></div>Surgery Followed by PORT or Chemoradiation Therapy</b></p><p id="CDR0000062922__480">Postoperative chemoradiation therapy for head and neck cancer squamous cell carcinoma demonstrates a locoregional control and survival benefit compared with radiation therapy alone in patients who have extracapsular extension (ECE) of a lymph node or positive margins.[<a class="bk_pop" href="#CDR0000062922_rl_109_5">5</a>,<a class="bk_pop" href="#CDR0000062922_rl_109_21">21</a>-<a class="bk_pop" href="#CDR0000062922_rl_109_23">23</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </p><p id="CDR0000062922__481">For patients with T3 and T4 disease (or stage III and stage IV disease), perineural infiltration, vascular embolisms, and clinically enlarged level IV–V lymph nodes secondary to tumors arising in the oral cavity or oropharynx; two or more histopathologically involved lymph nodes without ECE, and close margins less than 5 mm, the addition of cisplatin chemotherapy given concurrently with PORT is unclear. The addition of cetuximab with radiation therapy in the postoperative setting for these risk factors is being tested in a randomized trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=651536" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RTOG-0920</a> ).<div class="milestone-end"></div></p></div><div id="CDR0000062922__TrialSearch_109_sid_7"><h3>Current Clinical Trials</h3><p id="CDR0000062922__TrialSearch_109_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
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<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=40113&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage III laryngeal cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062922__TrialSearch_109_18">General information about clinical trials is also available from the <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062922_rl_109"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_109_1">Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013. [<a href="/pmc/articles/PMC3577950/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3577950</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23182993" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23182993</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_2">Spaulding MB, Fischer SG, Wolf GT: Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. J Clin Oncol 12 (8): 1592-9, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8040671" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8040671</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_3">Adelstein DJ, Saxton JP, Lavertu P, et al.: A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck 19 (7): 567-75, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9323144" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9323144</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_4">Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10735893" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10735893</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_5">Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15128894" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15128894</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_6">Lefebvre JL, Pointreau Y, Rolland F, et al.: Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol 31 (7): 853-9, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23341517" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23341517</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_7">MacKenzie RG, Franssen E, Balogh JM, et al.: Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: a comparison limited to patients eligible for surgery. Int J Radiat Oncol Biol Phys 47 (1): 65-71, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10758306" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10758306</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_8">Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 324 (24): 1685-90, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/2034244" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2034244</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_9">Adelstein DJ, Lavertu P, Saxton JP, et al.: Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 88 (4): 876-83, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10679658" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10679658</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_10">Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_11">Pignon JP, le Maître A, Maillard E, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92 (1): 4-14, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19446902" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19446902</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_12">Haddad R, O'Neill A, Rabinowits G, et al.: Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 14 (3): 257-64, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23414589" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23414589</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_13">Hitt R, Grau JJ, López-Pousa A, et al.: A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 25 (1): 216-25, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24256848" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24256848</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_14">Fu KK, Pajak TF, Trotti A, et al.: A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys 48 (1): 7-16, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10924966" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10924966</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_15">Overgaard J, Hansen HS, Specht L, et al.: Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 362 (9388): 933-40, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/14511925" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14511925</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_16">Overgaard J, Mohanti BK, Begum N, et al.: Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial. Lancet Oncol 11 (6): 553-60, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20382075" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20382075</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_17">Horiot JC, Le Fur R, N'Guyen T, et al.: Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol 25 (4): 231-41, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1480768" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1480768</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_18">Bourhis J, Lapeyre M, Tortochaux J, et al.: Phase III randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer: a GORTEC trial. J Clin Oncol 24 (18): 2873-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16782926" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16782926</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_19">Beitler JJ, Zhang Q, Fu KK, et al.: Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys 89 (1): 13-20, 2014. [<a href="/pmc/articles/PMC4664465/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4664465</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24613816" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24613816</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_20">Baujat B, Bourhis J, Blanchard P, et al.: Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev (12): CD002026, 2010. [<a href="/pmc/articles/PMC8407183/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8407183</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21154350" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21154350</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_21">Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15128893" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15128893</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_22">Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16161069" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16161069</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_109_23">Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012. [<a href="/pmc/articles/PMC3465463/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3465463</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22749632" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22749632</span></a>]</div></li></ol></div></div><div id="CDR0000062922__139"><h2 id="_CDR0000062922__139_">Stage IV Laryngeal Cancer Treatment</h2><div id="CDR0000062922__140"><h3>Supraglottis</h3><p id="CDR0000062922__141"><b>Standard treatment options:
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</b></p><ol id="CDR0000062922__330"><li class="half_rhythm"><div><a href="#CDR0000062922__458">Chemotherapy administered concomitantly with radiation therapy</a> can
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be considered for patients who would require total laryngectomy for control of disease, including those with nonbulky T4a disease.[<a class="bk_pop" href="#CDR0000062922_rl_139_1">1</a>]</div></li><li class="half_rhythm"><div><a href="#CDR0000062922__461"> Induction chemotherapy followed by concomitant chemotherapy and radiation</a>. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[<a class="bk_pop" href="#CDR0000062922_rl_139_1">1</a>-<a class="bk_pop" href="#CDR0000062922_rl_139_6">6</a>] </div></li><li class="half_rhythm"><div> Definitive radiation therapy alone in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[<a class="bk_pop" href="#CDR0000062922_rl_139_7">7</a>] </div></li><li class="half_rhythm"><div> For patients with bulky T4 disease,<a href="#CDR0000062922__464"> surgery with PORT</a> with or without concomitant chemotherapy based on pathological risk factors for large volume T4 disease.[<a class="bk_pop" href="#CDR0000062922_rl_139_8">8</a>]</div></li></ol><p id="CDR0000062922__144"><b>Treatment options under clinical evaluation:</b>
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</p><ul id="CDR0000062922__456"><li class="half_rhythm"><div>Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam
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radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_139_9">9</a>]</div></li></ul></div><div id="CDR0000062922__150"><h3>Glottis</h3><p id="CDR0000062922__151"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__331"><li class="half_rhythm"><div><a href="#CDR0000062922__458">Chemotherapy administered concomitantly with radiation therapy</a> can
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be considered for patients who would require total laryngectomy for control of disease, including those with nonbulky T4a disease.[<a class="bk_pop" href="#CDR0000062922_rl_139_1">1</a>]</div></li><li class="half_rhythm"><div><a href="#CDR0000062922__461"> Induction chemotherapy followed by concomitant chemotherapy and radiation</a>. Laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[<a class="bk_pop" href="#CDR0000062922_rl_139_1">1</a>-<a class="bk_pop" href="#CDR0000062922_rl_139_6">6</a>] </div></li><li class="half_rhythm"><div> Definitive radiation therapy alone in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures.[<a class="bk_pop" href="#CDR0000062922_rl_139_7">7</a>] </div></li><li class="half_rhythm"><div>For patients with bulky T4 disease, <a href="#CDR0000062922__464">total laryngectomy with postoperative radiation therapy</a> (PORT) with or without concomitant chemotherapy based on pathological risk factors for large volume T4 disease.[<a class="bk_pop" href="#CDR0000062922_rl_139_8">8</a>]</div></li></ol><p id="CDR0000062922__154"><b>Treatment options under clinical evaluation:</b>
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</p><ul id="CDR0000062922__457"><li class="half_rhythm"><div>Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam
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radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_139_9">9</a>]</div></li></ul></div><div id="CDR0000062922__160"><h3>Subglottis</h3><p id="CDR0000062922__161"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__196"><li class="half_rhythm"><div> Laryngectomy plus total thyroidectomy and bilateral tracheoesophageal node
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dissection usually followed by postoperative radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_139_10">10</a>]</div></li><li class="half_rhythm"><div>Treatment by radiation therapy alone is indicated for patients who are not
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candidates for surgery.</div></li></ol><p id="CDR0000062922__164"><b>Treatment options under clinical evaluation:</b>
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</p><ol id="CDR0000062922__197"><li class="half_rhythm"><div>Simultaneous chemotherapy and hyperfractionated radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_139_11">11</a>]</div></li><li class="half_rhythm"><div>Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam
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radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_139_9">9</a>]
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</div></li></ol><p id="CDR0000062922__459"><b><div class="milestone-start" id="CDR0000062922__458"></div>Concomitant Chemoradiation Therapy</b></p><p id="CDR0000062922__460">Concomitant chemoradiation therapy is a standard treatment option for locally advanced (stage III and stage IV) head and neck cancer. A meta-analysis of 93 randomized, prospective head and neck cancer trials published between 1965 and 2000 showed a 4.5% absolute survival advantage in the subset of patients receiving chemotherapy and radiation therapy.[<a class="bk_pop" href="#CDR0000062922_rl_139_12">12</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335132/" class="def">Level of evidence: 2A</a>] Patients receiving concomitant chemotherapy had a greater survival benefit than those receiving induction chemotherapy.<div class="milestone-end"></div></p><p id="CDR0000062922__462"><b><div class="milestone-start" id="CDR0000062922__461"></div>Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy</b></p><p id="CDR0000062922__463">Two published randomized trials that compared concomitant chemoradiation therapy with induction chemotherapy followed by concomitant chemoradiation therapy for locally advanced head and neck failed to show a survival advantage for induction chemotherapy regimens. The role of induction chemotherapy remains unclear.[<a class="bk_pop" href="#CDR0000062922_rl_139_13">13</a>,<a class="bk_pop" href="#CDR0000062922_rl_139_14">14</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335106/" class="def">Level of evidence: 1iA</a>]<div class="milestone-end"></div></p><p id="CDR0000062922__465"><b><div class="milestone-start" id="CDR0000062922__464"></div>Surgery Followed by PORT or Chemoradiation Therapy</b></p><p id="CDR0000062922__466">Postoperative chemoradiation therapy for head and neck cancer squamous cell carcinoma demonstrates a locoregional control and survival benefit compared with radiation therapy alone in patients who have extracapsular extension (ECE) of a lymph node or positive margins.[<a class="bk_pop" href="#CDR0000062922_rl_139_5">5</a>,<a class="bk_pop" href="#CDR0000062922_rl_139_15">15</a>-<a class="bk_pop" href="#CDR0000062922_rl_139_17">17</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </p><p id="CDR0000062922__467">For patients with T3 and T4 disease (or stage III and stage IV disease), perineural infiltration, vascular embolisms, and clinically enlarged level IV–V lymph nodes secondary to tumors arising in the oral cavity or oropharynx; two or more histopathologically involved lymph nodes without ECE, and close margins less than 5 mm, the addition of cisplatin chemotherapy given concurrently with PORT is unclear. The addition of cetuximab with radiation therapy in the postoperative setting for these risk factors is being tested in a randomized trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=651536" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RTOG-0920</a> ).<div class="milestone-end"></div></p></div><div id="CDR0000062922__TrialSearch_139_sid_8"><h3>Current Clinical Trials</h3><p id="CDR0000062922__TrialSearch_139_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
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<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=40114&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">stage IV laryngeal cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062922__TrialSearch_139_18">General information about clinical trials is also available from the <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062922_rl_139"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_139_1">Forastiere AA, Zhang Q, Weber RS, et al.: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 31 (7): 845-52, 2013. [<a href="/pmc/articles/PMC3577950/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3577950</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23182993" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23182993</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_2">Spaulding MB, Fischer SG, Wolf GT: Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. J Clin Oncol 12 (8): 1592-9, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8040671" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8040671</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_3">Adelstein DJ, Saxton JP, Lavertu P, et al.: A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck 19 (7): 567-75, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9323144" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9323144</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_4">Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10735893" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10735893</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_5">Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15128894" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15128894</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_6">Lefebvre JL, Pointreau Y, Rolland F, et al.: Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol 31 (7): 853-9, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23341517" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23341517</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_7">MacKenzie RG, Franssen E, Balogh JM, et al.: Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: a comparison limited to patients eligible for surgery. Int J Radiat Oncol Biol Phys 47 (1): 65-71, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10758306" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10758306</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_8">Bernier J, Cooper JS: Chemoradiation after surgery for high-risk head and neck cancer patients: how strong is the evidence? Oncologist 10 (3): 215-24, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15793225" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15793225</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_9">Adelstein DJ, Lavertu P, Saxton JP, et al.: Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 88 (4): 876-83, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10679658" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10679658</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_10">Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_11">Weissler MC, Melin S, Sailer SL, et al.: Simultaneous chemoradiation in the treatment of advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 118 (8): 806-10, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1642831" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1642831</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_12">Pignon JP, le Maître A, Maillard E, et al.: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92 (1): 4-14, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19446902" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19446902</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_13">Haddad R, O'Neill A, Rabinowits G, et al.: Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol 14 (3): 257-64, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23414589" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23414589</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_14">Hitt R, Grau JJ, López-Pousa A, et al.: A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 25 (1): 216-25, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24256848" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24256848</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_15">Cooper JS, Pajak TF, Forastiere AA, et al.: Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350 (19): 1937-44, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15128893" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15128893</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_16">Bernier J, Cooper JS, Pajak TF, et al.: Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 27 (10): 843-50, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16161069" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16161069</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_139_17">Cooper JS, Zhang Q, Pajak TF, et al.: Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84 (5): 1198-205, 2012. [<a href="/pmc/articles/PMC3465463/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3465463</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22749632" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22749632</span></a>]</div></li></ol></div></div><div id="CDR0000062922__170"><h2 id="_CDR0000062922__170_">Recurrent Laryngeal Cancer</h2><p id="CDR0000062922__171">Treatment of recurrent supraglottic, glottic, and subglottic cancer includes
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further surgery or clinical trials.[<a class="bk_pop" href="#CDR0000062922_rl_170_1">1</a>-<a class="bk_pop" href="#CDR0000062922_rl_170_3">3</a>]
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</p><p id="CDR0000062922__172"><b>Standard treatment options:</b>
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</p><ol id="CDR0000062922__292"><li class="half_rhythm"><div>Surgery [<a class="bk_pop" href="#CDR0000062922_rl_170_4">4</a>] and/or radiation therapy. Salvage is possible for failures of surgery alone or of radiation therapy alone,
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and further surgery [<a class="bk_pop" href="#CDR0000062922_rl_170_4">4</a>] and/or radiation therapy should be attempted, as indicated.
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Selected patients may be candidates for partial laryngectomy after high-dose
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radiation therapy has failed.[<a class="bk_pop" href="#CDR0000062922_rl_170_5">5</a>]</div></li><li class="half_rhythm"><div>Radiation therapy. Re-irradiation for laryngeal salvage
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following radiation therapy failure has resulted in long-term survival in a
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small number of patients; it may be considered for small recurrences after
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radiation therapy, especially in patients who refuse or are not candidates for
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laryngectomy.[<a class="bk_pop" href="#CDR0000062922_rl_170_6">6</a>]</div></li><li class="half_rhythm"><div>Chemotherapy. A response of variable duration may be achieved after
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systemic chemotherapy.[<a class="bk_pop" href="#CDR0000062922_rl_170_7">7</a>]</div></li></ol><p id="CDR0000062922__296">Salvage after previous combined total laryngectomy and radiation therapy is
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poor.
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</p><p id="CDR0000062922__175"><b>Treatment options under clinical evaluation:</b>
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</p><ul id="CDR0000062922__199"><li class="half_rhythm"><div>Patients whose disease does not respond to combined radiation therapy and
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surgery probably are best treated by palliative chemotherapy in clinical
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trials. </div></li></ul><div id="CDR0000062922__TrialSearch_170_sid_9"><h3>Current Clinical Trials</h3><p id="CDR0000062922__TrialSearch_170_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
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<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=40115&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">recurrent laryngeal cancer</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062922__TrialSearch_170_18">General information about clinical trials is also available from the <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062922_rl_170"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062922_rl_170_1">Million RR, Cassisi NJ, eds.: Management of Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott, 1994.</div></li><li><div class="bk_ref" id="CDR0000062922_rl_170_2">Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/4051112" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4051112</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_170_3">Jacobs C, Lyman G, Velez-García E, et al.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10 (2): 257-63, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1732427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1732427</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_170_4">Wong LY, Wei WI, Lam LK, et al.: Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck 25 (11): 953-9, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/14603456" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14603456</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_170_5">Paleri V, Thomas L, Basavaiah N, et al.: Oncologic outcomes of open conservation laryngectomy for radiorecurrent laryngeal carcinoma: a systematic review and meta-analysis of English-language literature. Cancer 117 (12): 2668-76, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21287526" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21287526</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_170_6">Wang CC, McIntyre J: Re-irradiation of laryngeal carcinoma--techniques and results. Int J Radiat Oncol Biol Phys 26 (5): 783-5, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8344846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8344846</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062922_rl_170_7">Al-Sarraf M: Head and neck cancer: chemotherapy concepts. Semin Oncol 15 (1): 70-85, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3278391" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3278391</span></a>]</div></li></ol></div></div><div id="CDR0000062922__200"><h2 id="_CDR0000062922__200_">Changes to This Summary (12/21/2016)</h2><p id="CDR0000062922__201">The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
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</p><p id="CDR0000062922__405"><b><a href="#CDR0000062922__1">General Information About Laryngeal Cancer</a></b></p><p id="CDR0000062922__515">An editorial change was made to this section.</p><p id="CDR0000062922__433">Updated <a href="#CDR0000062922__300">statistics</a> with estimated new cases and deaths for 2016 (cited American Cancer Society as reference 1).</p><p id="CDR0000062922__482"><b><a href="#CDR0000062922__13">Stage Information for Laryngeal Cancer</a></b></p><p id="CDR0000062922__483">Revised <a href="#CDR0000062922__14">text</a> to state that the assessment of the primary tumor is
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based on inspection and palpation when possible and by fiberoptic laryngoscopy; also added that panendoscopy under anesthesia ensures careful clinical examination to determine the clinical extent of local disease. An additional revision states that head and neck magnetic resonance imaging, computed tomography, or positron emission tomography/computed tomography
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should be done before therapy to supplement inspection and palpation.</p><p id="CDR0000062922__484"><b><a href="#CDR0000062922__66">Treatment Option Overview for Laryngeal Cancer</a></b></p><p id="CDR0000062922__485">Added <a href="#CDR0000062922__68">text</a> to state that elective neck radiation should be considered for T3 or T4 glottic tumors or T1 to T4 supraglottic tumors.</p><p id="CDR0000062922__486"><b><a href="#CDR0000062922__73">Stage I Laryngeal Cancer Treatment</a></b></p><p id="CDR0000062922__487">Added <a href="#CDR0000062922__360">text</a> to state that selection of treatment should include an evaluation of voice function and quality after treatment; added that endoscopic CO2 laser resections may also achieve similar results in terms of local control and function (cited Agrawal et al. as reference 1) compared with radiation therapy, although no randomized studies have been performed (cited Dey et al. as reference 2). Also added that a meta-analysis of 22 consecutive case series to examine oncologic control demonstrated no clear differences between transoral CO2 laser excision and external beam radiation therapy (EBRT) in terms of local control; there was a trend for improved posttreatment voice quality with radiation therapy. Transoral CO2 laser–excision surgery dominates radiotherapy from a cost-utility standpoint (added level of evidence 2C).</p><p id="CDR0000062922__488">Added <a href="/books/NBK65746.3/#CDR0000062922__178">option</a> to list of glottis standard treatments to include endoscopic CO2 laser excision (cited Higgins as reference 11).</p><p id="CDR0000062922__489"><b><a href="#CDR0000062922__87">Stage II Laryngeal Cancer Treatment</a></b></p><p id="CDR0000062922__490">Added <a href="/books/NBK65746.3/#CDR0000062922__180">option</a> to list of supraglottis standard treatments to include EBRT alone for the smaller lesions encompassing the primary disease and regional elective nodes.</p><p id="CDR0000062922__491">Revised <a href="/books/NBK65746.3/#CDR0000062922__180">option</a> in list of supraglottis standard treatments to state supraglottic laryngectomy with bilateral neck dissections, depending on location of
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the lesion, clinical status of the patient, and expertise of the treatment
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team. </p><p id="CDR0000062922__492">Revised <a href="/books/NBK65746.3/#CDR0000062922__180">option</a> in list of supraglottis standard treatments to state postoperative radiation therapy (PORT) is indicated for positive or close
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surgical margins or other adverse pathological risk factors.</p><p id="CDR0000062922__493">Added <a href="#CDR0000062922__435">PORT With or Without Chemotherapy</a> as a new subsection.</p><p id="CDR0000062922__494"><b><a href="#CDR0000062922__109">Stage III Laryngeal Cancer Treatment</a></b></p><p id="CDR0000062922__495">Added Forastiere et al. as <a href="/books/NBK65746.3/#CDR0000062922__186">reference 1</a>.</p><p id="CDR0000062922__496">Added Lefebvre et al. as <a href="/books/NBK65746.3/#CDR0000062922__186">reference 6</a> and level of evidence 1iiC.</p><p id="CDR0000062922__497">Revised <a href="/books/NBK65746.3/#CDR0000062922__186">option</a> in list of supraglottis standard treatments to state definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery for salvage of radiation failures.</p><p id="CDR0000062922__513">Added <a href="/books/NBK65746.3/#CDR0000062922__186">option</a> to list of supraglottis standard treatments to include surgery with or without PORT (cited The Department of Veterans Affairs Laryngeal Cancer Study Group as reference 8).</p><p id="CDR0000062922__498"> Revised <a href="/books/NBK65746.3/#CDR0000062922__329">option</a> in list of glottis standard treatments to state definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery for salvage of radiation failures.</p><p id="CDR0000062922__514">Added <a href="/books/NBK65746.3/#CDR0000062922__329">option</a> to list of glottis standard treatments to include surgery with or without PORT.</p><p id="CDR0000062922__499">Added <a href="/books/NBK65746.3/#CDR0000062922__190">option</a> to list of subglottis standard treatments to include definitive radiation therapy alone with altered fractionation in patients who are not candidates for concomitant chemotherapy and surgery (total laryngectomy) for salvage of radiation failures. </p><p id="CDR0000062922__512">Added <a href="/books/NBK65746.3/#CDR0000062922__190">option</a> to list of subglottis standard treatments to include induction chemotherapy followed by concomitant chemotherapy and radiation. Also added that laryngectomy is reserved for patients with less than a 50% response to chemotherapy or who have persistent disease after radiation.</p><p id="CDR0000062922__500">Added <a href="#CDR0000062922__439">Concomitant Chemoradiation Therapy</a> as a new subsection.</p><p id="CDR0000062922__501">Added <a href="#CDR0000062922__443">Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy</a> as a new subsection.</p><p id="CDR0000062922__502">Added <a href="#CDR0000062922__446">Altered Fractionation</a> as a new subsection.</p><p id="CDR0000062922__503">Added <a href="#CDR0000062922__478">Surgery Followed by PORT or Chemoradiation Therapy</a> as a new subsection.</p><p id="CDR0000062922__504"><b><a href="#CDR0000062922__139">Stage IV Laryngeal Cancer Treatment</a></b></p><p id="CDR0000062922__505">Added Forastiere et al. as <a href="/books/NBK65746.3/#CDR0000062922__330">reference 1</a>.</p><p id="CDR0000062922__506">Added Lefebvre et al. as <a href="/books/NBK65746.3/#CDR0000062922__330">reference 6</a>.</p><p id="CDR0000062922__507">Revised <a href="/books/NBK65746.3/#CDR0000062922__330">option</a> in list of supraglottis standard treatments to state for patients with bulky T4 disease, surgery with PORT with or without concomitant chemotherapy based on pathological risk factors for large volume T4 disease.</p><p id="CDR0000062922__508">Revised <a href="/books/NBK65746.3/#CDR0000062922__329">option</a> in list of glottis standard treatments to state for patients with bulky T4 disease, total laryngectomy with PORT with or without concomitant chemotherapy based on pathological risk factors for large volume T4 disease.</p><p id="CDR0000062922__509">Added <a href="#CDR0000062922__458">Concomitant Chemoradiation Therapy</a> as a new subsection.</p><p id="CDR0000062922__510">Added <a href="#CDR0000062922__461">Induction Chemoradiation Therapy Followed by Concomitant Chemoradiation Therapy</a> as a new subsection.</p><p id="CDR0000062922__511">Added <a href="#CDR0000062922__464">Surgery Followed by PORT or Chemoradiation Therapy</a> as a new subsection.</p><p id="CDR0000062922__disclaimerHP_3">This summary is written and maintained by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062922__AboutThis_1">About This PDQ Summary</a> and <a href="http://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® - NCI's Comprehensive Cancer Database</a> pages.
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</p></div><div id="CDR0000062922__AboutThis_1"><h2 id="_CDR0000062922__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062922__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062922__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of laryngeal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062922__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062922__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062922__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062922__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062922__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p>The lead reviewers for Laryngeal Cancer Treatment are:</p><ul><li class="half_rhythm"><div>Scharukh Jalisi, MD, FACS (Boston University Medical Center)</div></li><li class="half_rhythm"><div>Minh Tam Truong, MD (Boston University Medical Center)</div></li></ul><p id="CDR0000062922__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062922__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062922__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a <a href="/books/n/pdqcis/CDR0000062796/">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062922__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062922__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062922__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062922__AboutThis_15">PDQ® Adult Treatment Editorial Board. PDQ Laryngeal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/types/head-and-neck/hp/laryngeal-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/types/head-and-neck/hp/laryngeal-treatment-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389189]</p><p id="CDR0000062922__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062922__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062922__AboutThis_18">Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062922__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062922__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65746.3/?report=reader">PubReader</a></li><li><a href="/books/NBK65746.3/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK65746" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK65746" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Adult Treatment Editorial Board. Laryngeal Cancer Treatment (PDQ®): Health Professional Version. 2016 Dec 21. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></div></div></li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Version History</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter shutter_closed" title="Show/hide content" remembercollapsed="true" pgsec_name="version_history" id="Shutter"></a></div><div class="portlet_content" style="display: none;"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><span class="bk_col_itm"><a href="/books/NBK65746.17/">NBK65746.17</a></span> November 25, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK65746.16/">NBK65746.16</a></span> February 9, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK65746.15/">NBK65746.15</a></span> January 31, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65746.14/">NBK65746.14</a></span> February 11, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK65746.13/">NBK65746.13</a></span> January 29, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65746.12/">NBK65746.12</a></span> January 23, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65746.11/">NBK65746.11</a></span> October 3, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65746.10/">NBK65746.10</a></span> May 17, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65746.9/">NBK65746.9</a></span> April 5, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65746.8/">NBK65746.8</a></span> February 1, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65746.7/">NBK65746.7</a></span> January 25, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65746.6/">NBK65746.6</a></span> February 8, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65746.5/">NBK65746.5</a></span> January 12, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65746.4/">NBK65746.4</a></span> July 21, 2017</li><li><span class="bk_col_itm">NBK65746.3</span> December 21, 2016 (Displayed Version)</li><li><span class="bk_col_itm"><a href="/books/NBK65746.2/">NBK65746.2</a></span> May 20, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65746.1/">NBK65746.1</a></span> July 31, 2014</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#CDR0000062922__1" ref="log$=inpage&link_id=inpage">General Information About Laryngeal Cancer</a></li><li><a href="#CDR0000062922__11" ref="log$=inpage&link_id=inpage">Cellular Classification of Laryngeal Cancer</a></li><li><a href="#CDR0000062922__13" ref="log$=inpage&link_id=inpage">Stage Information for Laryngeal Cancer</a></li><li><a href="#CDR0000062922__66" ref="log$=inpage&link_id=inpage">Treatment Option Overview for Laryngeal Cancer</a></li><li><a href="#CDR0000062922__73" ref="log$=inpage&link_id=inpage">Stage I Laryngeal Cancer Treatment</a></li><li><a href="#CDR0000062922__87" ref="log$=inpage&link_id=inpage">Stage II Laryngeal Cancer Treatment</a></li><li><a href="#CDR0000062922__109" ref="log$=inpage&link_id=inpage">Stage III Laryngeal Cancer Treatment</a></li><li><a href="#CDR0000062922__139" ref="log$=inpage&link_id=inpage">Stage IV Laryngeal Cancer Treatment</a></li><li><a href="#CDR0000062922__170" ref="log$=inpage&link_id=inpage">Recurrent Laryngeal Cancer</a></li><li><a href="#CDR0000062922__200" ref="log$=inpage&link_id=inpage">Changes to This Summary (12/21/2016)</a></li><li><a href="#CDR0000062922__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related publications</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65859/">Patient Version</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="discovery_db_links" 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href="/pubmed/29337477" ref="ordinalpos=1&linkpos=1&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Childhood Laryngeal Tumors Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Childhood Laryngeal Tumors Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Pediatric Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389244" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Lymphedema (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Lymphedema (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Supportive and Palliative Care Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ 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xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389190" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Neuroblastoma Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Neuroblastoma Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Pediatric Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389493" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Cervical Cancer Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Cervical Cancer Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ 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