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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="#__NBK65944_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65944_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="_NBK65944_"><span class="title" itemprop="name">Childhood Astrocytomas Treatment (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contrib-group"><span itemprop="author">PDQ Pediatric Treatment Editorial Board</span>.</p><p class="small">Published online: December 9, 2016.</p><p class="small">Created: <span itemprop="datePublished">August 21, 2009</span>.</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="CDR0000614165__450">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood astrocytomas. 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="CDR0000614165__451">This summary is reviewed regularly and updated as necessary by the PDQ Pediatric 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="CDR0000614165__4"><h2 id="_CDR0000614165__4_">General Information About Childhood Astrocytomas</h2><p id="CDR0000614165__12">The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization (WHO) classification of nervous system tumors.[<a class="bk_pop" href="#CDR0000614165_rl_4_1">1</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_2">2</a>] For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062680/">Childhood Brain and Spinal Cord Tumors Treatment Overview</a>.</p><p id="CDR0000614165__13">Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[<a class="bk_pop" href="#CDR0000614165_rl_4_3">3</a>] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000343584/">Late Effects of Treatment for Childhood Cancer</a> for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.</p><p id="CDR0000614165__14">Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification. </p><p id="CDR0000614165__275">Gliomas are thought to arise from glial precursor cells that are present in the brain and spinal cord. Gliomas are named according to their clinicopathologic and histologic subtype. For example, astrocytomas originate from astrocytes, oligodendroglial tumors from oligodendrocytes, and mixed gliomas from a mix of oligodendrocytes, astrocytes, and ependymal cells. Astrocytoma is the most commonly diagnosed type of glioma in children. According to the WHO classification of brain tumors, gliomas are classified further as low-grade (grades I and II) or high-grade (grades III and IV) tumors. Children with low-grade tumors have a relatively favorable prognosis, especially when the tumors can be completely resected. Children with high-grade tumors generally have a less favorable prognosis, but this is somewhat dependent on subtype.</p><div id="CDR0000614165__289"><h3>Anatomy
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</h3><p id="CDR0000614165__375">Childhood astrocytomas can occur anywhere in the central nervous system (CNS). Refer to <a class="figpopup" href="/books/NBK65944.6/table/CDR0000614165__113/?report=objectonly" target="object" rid-figpopup="figCDR0000614165113" rid-ob="figobCDR0000614165113">Table 3</a> for the most common CNS location for each tumor type.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figCDR0000614165355" co-legend-rid="figlgndCDR0000614165355"><a href="/books/NBK65944.6/figure/CDR0000614165__355/?report=objectonly" target="object" title="Figure" class="img_link icnblk_img figpopup" rid-figpopup="figCDR0000614165355" rid-ob="figobCDR0000614165355"><img class="small-thumb" src="/books/NBK65944.6/bin/CDR0000748659.gif" src-large="/books/NBK65944.6/bin/CDR0000748659.jpg" alt="Anatomy of the inside of the brain, showing the cerebrum, cerebellum, brain stem, spinal cord, optic nerve, hypothalamus, and other parts of the brain" /></a><div class="icnblk_cntnt" id="figlgndCDR0000614165355"><h4 id="CDR0000614165__355"><a href="/books/NBK65944.6/figure/CDR0000614165__355/?report=objectonly" target="object" rid-ob="figobCDR0000614165355">Figure</a></h4><p class="float-caption no_bottom_margin">Anatomy of the inside of the brain, showing the cerebrum, cerebellum, brain stem, spinal cord, optic nerve, hypothalamus, and other parts of the brain. </p></div></div></div><div id="CDR0000614165__291"><h3>Clinical Features
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</h3><p id="CDR0000614165__292">Presenting symptoms for childhood astrocytomas depend on the following:</p><ul id="CDR0000614165__394"><li class="half_rhythm"><div>CNS location.</div></li><li class="half_rhythm"><div>Size of the tumor.</div></li><li class="half_rhythm"><div>Rate of tumor growth.</div></li><li class="half_rhythm"><div>Chronologic and developmental age of the child.</div></li></ul><p id="CDR0000614165__293">In infants and young children, low-grade astrocytomas presenting in the hypothalamus may result in diencephalic syndrome, which is manifested by failure to thrive in an emaciated, seemingly euphoric child. Such children may have little in the way of other neurologic findings, but can have macrocephaly, intermittent lethargy, and visual impairment.[<a class="bk_pop" href="#CDR0000614165_rl_4_4">4</a>] </p></div><div id="CDR0000614165__294"><h3>Diagnostic Evaluation</h3><p id="CDR0000614165__295">The diagnostic evaluation for astrocytoma is often limited to a magnetic resonance imaging (MRI) of the brain or spine. Spinal MRI is sometimes performed in conjunction with the initial brain MRI to exclude neuraxis metastases. Computed tomography (CT) scans and positron emission tomography (PET) scans are not typically used for characterization of suspected gliomas. Similarly, lumbar punctures examining the cerebrospinal fluid for circulating tumor cells are not commonly performed in this disease.</p></div><div id="CDR0000614165__105"><h3>Clinicopathologic Classification of Childhood Astrocytomas and Other Tumors of Glial Origin</h3><p id="CDR0000614165__106">The pathologic classification of pediatric brain tumors is a specialized area that is evolving. Examination of the diagnostic tissue by a neuropathologist who has particular expertise in this area is strongly recommended. </p><p id="CDR0000614165__107">Tumor types are based on the putative glial cell type of origin: </p><ul id="CDR0000614165__278"><li class="half_rhythm"><div>Astrocytomas (astrocytes).</div></li><li class="half_rhythm"><div>Oligodendroglial tumors (oligodendrocytes).</div></li><li class="half_rhythm"><div>Mixed gliomas (cell types of origin include oligodendrocytes, astrocytes, and ependymal cells).</div></li><li class="half_rhythm"><div>Mixed neuronal-glial tumors.</div></li></ul><div id="CDR0000614165__279"><h4>WHO histologic grade</h4><p id="CDR0000614165__280">According to the WHO histologic typing of CNS tumors, childhood astrocytomas and other tumors of glial origin are classified according to clinicopathologic and histologic subtype and are graded (grade I to IV).[<a class="bk_pop" href="#CDR0000614165_rl_4_1">1</a>] </p><p id="CDR0000614165__108">WHO histologic grades are commonly referred to as low-grade gliomas or high-grade gliomas (refer to Table 1).</p><p id="CDR0000614165__466">The 2016 WHO criteria began to utilize molecular data in the diagnosis of some tumors because of the accumulation of published evidence supporting that tumor behavior is typically driven by common biological alterations. Within glial CNS tumors, this was most evident in changes in the classification of the diffuse gliomas, which were grouped together based on genetic driver mutations rather than histopathological similarities.[<a class="bk_pop" href="#CDR0000614165_rl_4_2">2</a>] Two diffuse gliomas are no longer considered distinct entities: fibrillary astrocytoma and protoplasmic astrocytoma. Epithelioid glioblastoma is a new, provisionally included variant that is categorized as one subtype of <i>IDH</i>-wildtype glioblastoma. </p><div id="CDR0000614165__109" class="table"><h3><span class="title">Table 1. World Health Organization (WHO) Histologic Grade and Corresponding Classification for Tumors of the Central Nervous System</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65944.6/table/CDR0000614165__109/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000614165__109_lrgtbl__"><table class="no_top_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">WHO Histologic Grade</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Grade Classification</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">I</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Low grade </td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">II</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Low grade </td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">III</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">High grade </td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">IV</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">High grade </td></tr></tbody></table></div></div><div id="CDR0000614165__111" class="table"><h3><span class="title">Table 2. 2016 World Health Organization (WHO) Classification and Histologic Grade of Astrocytic Tumors<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65944.6/table/CDR0000614165__111/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000614165__111_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:left;vertical-align:top;">Type</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">WHO Histologic Grade</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><b>Diffuse Astrocytic Tumors:</b></td><td colspan="1" rowspan="1" style="vertical-align:top;"></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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—Diffuse astrocytoma, <i>IDH</i>-mutant</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">II</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Anaplastic astrocytoma, <i>IDH</i>-mutant</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">III</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Glioblastoma, <i>IDH</i>-wildtype</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">IV</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Glioblastoma, <i>IDH</i>-mutant</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">IV</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—<i>IDH</i>-mutant</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">II</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Diffuse midline glioma, <i>H3K27M</i>-mutant</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">IV</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><b>Other Astrocytic Tumors: </b></td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;"></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Pilocytic astrocytoma</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">I</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Pilomyxoid astrocytoma</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Grade uncertain<sup>b</sup></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Pleomorphic xanthoastrocytoma</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">II</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Anaplastic pleomorphic xanthoastrocytoma</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">III</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Subependymal giant cell astrocytoma</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">I</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><b>Other Gliomas:</b></td><td colspan="1" rowspan="1" style="vertical-align:top;"></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Angiocentric glioma</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">I</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Choroid glioma of the third ventricle</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">II</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—Astroblastoma</td><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Grade uncertain<sup>b</sup></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Adapted from Louis et al.[<a class="bk_pop" href="#CDR0000614165_rl_4_2">2</a>]</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>b</sup>In 2007, the WHO determined that the pilomyxoid variant of pilocytic astrocytoma may be an aggressive variant that is more likely to disseminate, and it was reclassified as a grade II tumor.[<a class="bk_pop" href="#CDR0000614165_rl_4_1">1</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_2">2</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_5">5</a>] In 2016, the WHO suggested not grading the pilomyxoid variant until further studies clarify their behavior.[<a class="bk_pop" href="#CDR0000614165_rl_4_2">2</a>]</p></div></dd></dl></div></div></div></div><div id="CDR0000614165__281"><h4>CNS location</h4><p id="CDR0000614165__112">Childhood astrocytomas and other tumors of glial origin can occur anywhere in the CNS, although each tumor type tends to have common CNS locations (refer to Table 3).</p><div id="CDR0000614165__113" class="table"><h3><span class="title">Table 3. Common Central Nervous System (CNS) Locations for Childhood Astrocytomas and Other Tumors of Glial Origin</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65944.6/table/CDR0000614165__113/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000614165__113_lrgtbl__"><table class="no_top_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Tumor Type</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Common CNS Location</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Pilocytic astrocytoma</td><td colspan="1" rowspan="1" style="vertical-align:top;">Optic nerve, optic chiasm/hypothalamus, thalamus and basal ganglia, cerebral hemispheres, cerebellum, and brain stem; and spinal cord (rare)</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Pleomorphic xanthoastrocytoma</td><td colspan="1" rowspan="1" style="vertical-align:top;">Superficial location in cerebrum (temporal lobe preferentially)</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Diffuse astrocytoma</td><td colspan="1" rowspan="1" style="vertical-align:top;">Cerebrum (frontal and temporal lobes), brain stem, spinal cord, optic nerve, optic chiasm, optic pathway, hypothalamus, and thalamus</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Anaplastic astrocytoma, glioblastoma </td><td colspan="1" rowspan="1" style="vertical-align:top;">Cerebrum; occasionally cerebellum, brain stem, and spinal cord</td></tr></tbody></table></div></div><p id="CDR0000614165__114">More than 80% of astrocytomas located in the <b>cerebellum</b> are low grade (pilocytic grade I) and often cystic; most of the remainder are diffuse grade II astrocytomas. Malignant astrocytomas in the cerebellum are rare.[<a class="bk_pop" href="#CDR0000614165_rl_4_1">1</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_2">2</a>] The presence of certain histologic features (e.g., MIB-1 rate, anaplasia) has been used retrospectively to predict event-free survival for pilocytic astrocytomas arising in the cerebellum or other location.[<a class="bk_pop" href="#CDR0000614165_rl_4_6">6</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_8">8</a>]</p><p id="CDR0000614165__234">Astrocytomas arising in the <b>brain stem</b> may be either high grade or low grade, with the frequency of either type being highly dependent on the location of the tumor within the brain stem.[<a class="bk_pop" href="#CDR0000614165_rl_4_9">9</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_10">10</a>] Tumors not involving the pons are overwhelmingly low-grade gliomas (e.g., tectal gliomas of the midbrain), whereas tumors located exclusively in the pons without exophytic components are largely high-grade gliomas (e.g., diffuse intrinsic pontine gliomas with the <i>H3K27M</i>-mutant genotype).[<a class="bk_pop" href="#CDR0000614165_rl_4_9">9</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_10">10</a>] (Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062761/">Childhood Brain Stem Glioma Treatment</a> for more information.)</p><p id="CDR0000614165__297">High-grade astrocytomas are often locally invasive and extensive and tend to occur above the tentorium in the <b>cerebrum</b>.[<a class="bk_pop" href="#CDR0000614165_rl_4_11">11</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_12">12</a>] Spread via the subarachnoid space may occur. Metastasis outside of the CNS has been reported but is extremely infrequent until multiple local relapses have occurred. </p><p id="CDR0000614165__211">Gliomatosis cerebri is no longer considered a distinct entity, but rather to be a growth pattern found in some diffuse gliomas. However, this description encompasses widespread involvement of the cerebral hemispheres, often extending caudally to affect the brain stem, cerebellum, and/or spinal cord.[<a class="bk_pop" href="#CDR0000614165_rl_4_1">1</a>] It rarely arises in the cerebellum and spreads rostrally.[<a class="bk_pop" href="#CDR0000614165_rl_4_13">13</a>] The neoplastic cells are most commonly astrocytes, but in some cases, they are oligodendroglia. They may respond to treatment initially, but overall have a poor prognosis.[<a class="bk_pop" href="#CDR0000614165_rl_4_14">14</a>]</p></div><div id="CDR0000614165__282"><h4>Neurofibromatosis type 1 (NF1)</h4><p id="CDR0000614165__115">Children with NF1 have an increased propensity to develop WHO grade I and grade II astrocytomas in the visual (optic) pathway; approximately 20% of all patients with NF1 will develop an optic pathway glioma. In these patients, the tumor may be found on screening evaluations when the child is asymptomatic or has apparent static neurologic and/or visual deficits. </p><p id="CDR0000614165__395">Pathologic confirmation is frequently not obtained in asymptomatic patients; when biopsies have been performed, these tumors have been found to be predominantly pilocytic (grade I) rather than diffuse higher-grade astrocytomas.[<a class="bk_pop" href="#CDR0000614165_rl_4_2">2</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_5">5</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_15">15</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_17">17</a>]</p><p id="CDR0000614165__298">In general, treatment is not required for incidental tumors found with surveillance neuroimaging. Symptomatic lesions or those that have radiographically progressed may require treatment.[<a class="bk_pop" href="#CDR0000614165_rl_4_18">18</a>]</p></div><div id="CDR0000614165__467"><h4>Tuberous sclerosis</h4><p id="CDR0000614165__468">Patients with tuberous sclerosis have a predilection for low-grade glioma development, especially subependymal giant cell astrocytomas.[<a class="bk_pop" href="#CDR0000614165_rl_4_19">19</a>] Mutations in either <i>TSC1</i> or <i>TSC2</i> cause pathway alterations that impact the mammalian target of rapamycin (mTOR) pathway, leading to increases in proliferation. Subependymal giant cell astrocytomas have been sensitive to targeted approaches via inhibition of the mTOR pathway.[<a class="bk_pop" href="#CDR0000614165_rl_4_20">20</a>]</p></div></div><div id="CDR0000614165__283"><h3>Genomic Alterations</h3><div id="CDR0000614165__284"><h4>Low-grade gliomas</h4><p id="CDR0000614165__sm_CDR0000779371_210"><div class="milestone-start" id="CDR0000614165__sm_CDR0000779371_457"></div>Genomic alterations involving activation of <i>BRAF</i> and the ERK/MAPK pathway are very common in sporadic cases of pilocytic astrocytoma, a type of low-grade glioma. </p><p id="CDR0000614165__sm_CDR0000779371_406"><i>BRAF</i> activation in pilocytic astrocytoma occurs most commonly through a <i>BRAF</i>-<i>KIAA1549</i> gene fusion, producing a fusion protein that lacks the BRAF regulatory domain.[<a class="bk_pop" href="#CDR0000614165_rl_4_21">21</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_25">25</a>] This fusion is seen in most infratentorial and midline pilocytic astrocytomas, but is present at lower frequency in supratentorial (hemispheric) tumors.[<a class="bk_pop" href="#CDR0000614165_rl_4_21">21</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_22">22</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_26">26</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_30">30</a>] </p><p id="CDR0000614165__sm_CDR0000779371_407">Presence of the <i>BRAF-KIAA1549</i> fusion predicted a better clinical outcome (progression-free survival [PFS] and overall survival [OS]) in one report that described children with incompletely resected low-grade gliomas.[<a class="bk_pop" href="#CDR0000614165_rl_4_30">30</a>] However, other factors such as p16 deletion, whole chromosome 7 gain, and tumor location may modify the impact of the <i>BRAF</i> mutation on outcome.[<a class="bk_pop" href="#CDR0000614165_rl_4_31">31</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_4_32">32</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>] Progression to high-grade glioma is rare for pediatric low-grade glioma with the <i>BRAF-KIAA1549</i> fusion.[<a class="bk_pop" href="#CDR0000614165_rl_4_33">33</a>]</p><p id="CDR0000614165__sm_CDR0000779371_408"><i>BRAF</i> activation through the <i>BRAF-KIAA1549</i> fusion has also been described in other pediatric low-grade gliomas (e.g., pilomyxoid astrocytoma).[<a class="bk_pop" href="#CDR0000614165_rl_4_29">29</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_30">30</a>]</p><p id="CDR0000614165__sm_CDR0000779371_409"> Other genomic alterations in pilocytic astrocytomas that can activate the ERK/MAPK pathway (e.g., alternative <i>BRAF</i> gene fusions, <i>RAF1</i> rearrangements, <i>RAS</i> mutations, and <i>BRAF</i> V600E point mutations) are less commonly observed.[<a class="bk_pop" href="#CDR0000614165_rl_4_22">22</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_24">24</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_25">25</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_34">34</a>] <i>BRAF</i> V600E point mutations are also observed in nonpilocytic pediatric low-grade gliomas, including ganglioglioma, desmoplastic infantile ganglioglioma, and approximately two-thirds of pleomorphic xanthoastrocytomas.[<a class="bk_pop" href="#CDR0000614165_rl_4_35">35</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_37">37</a>] One retrospective study of 53 children with gangliogliomas demonstrated <i>BRAF</i> V600E staining in approximately 40% of tumors. Five-year recurrence-free survival was worse in the V600E-mutated tumors (about 60%) than in tumors that did not stain for V600E (about 80%).[<a class="bk_pop" href="#CDR0000614165_rl_4_38">38</a>] Similarly, children with diencephalic low-grade astrocytomas with a <i>BRAF</i> V600E mutation had a 5-year PFS of 22%, compared with a 52% PFS in children who were <i>BRAF</i> wildtype.[<a class="bk_pop" href="#CDR0000614165_rl_4_39">39</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>] The frequency of the <i>BRAF </i>V600E mutation was significantly higher in pediatric low-grade glioma that transformed to high-grade glioma (8 of 18 cases) than was the frequency of mutation in cases that did not transform (10 of 167 cases).[<a class="bk_pop" href="#CDR0000614165_rl_4_33">33</a>]</p><p id="CDR0000614165__sm_CDR0000779371_461">Angiocentric gliomas have been noted to largely harbor <i>MYB</i>-<i>QKI</i> fusions, a putative driver mutation for this relatively rare class of gliomas.[<a class="bk_pop" href="#CDR0000614165_rl_4_40">40</a>]</p><p id="CDR0000614165__sm_CDR0000779371_378">As with neurofibromatosis type 1 (NF1) deficiency in activating the ERK/MAPK pathway, activating <i>BRAF</i> genomic alterations are uncommon in pilocytic astrocytoma associated with NF1.[<a class="bk_pop" href="#CDR0000614165_rl_4_28">28</a>] </p><p id="CDR0000614165__sm_CDR0000779371_373">Activating mutations in <i>FGFR1</i>, <i>PTPN11</i>, and in <i>NTRK2</i> fusion genes have also been identified in noncerebellar pilocytic astrocytomas.[<a class="bk_pop" href="#CDR0000614165_rl_4_41">41</a>] In pediatric grade II diffuse astrocytomas, the most common alterations reported (up to 53% of tumors) are rearrangements in the MYB family of transcription factors.[<a class="bk_pop" href="#CDR0000614165_rl_4_42">42</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_43">43</a>]</p><p id="CDR0000614165__sm_CDR0000779371_398">Most children with tuberous sclerosis have a mutation in one of two tuberous sclerosis genes (<i>TSC1</i>/hamartin or <i>TSC2</i>/tuberin). Either of these mutations results in an overexpression of the mammalian target of rapamycin (mTOR) complex 1. These children are at risk of developing subependymal giant cell astrocytomas, cortical tubers, and subependymal nodules. <div class="milestone-end"></div></p></div><div id="CDR0000614165__285"><h4>High-grade gliomas</h4><p id="CDR0000614165__sm_CDR0000779372_271"><div class="milestone-start" id="CDR0000614165__sm_CDR0000779372_460"></div>Pediatric high-grade gliomas, especially glioblastoma multiforme, are biologically distinct from those arising in adults.[<a class="bk_pop" href="#CDR0000614165_rl_4_44">44</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_47">47</a>] Pediatric high-grade gliomas have <i>PTEN</i> and<i> EGFR</i> genomic alterations less frequently and <i>PDGF/PDGFR</i> genomic alterations and mutations in <i>histone H3.3</i> genes more frequently than do adult tumors. Although it was believed that pediatric glioblastoma multiforme tumors were more closely related to adult <i>secondary</i> glioblastoma multiforme tumors in which there is stepwise transformation from lower-grade into higher-grade gliomas and in which most tumors have<i> IDH1</i> and <i>IDH2</i> mutations, the latter mutations are rarely observed in childhood glioblastoma multiforme tumors.[<a class="bk_pop" href="#CDR0000614165_rl_4_48">48</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_50">50</a>]</p><p id="CDR0000614165__sm_CDR0000779372_272">Based on epigenetic patterns (DNA methylation), pediatric glioblastoma multiforme tumors are separated into relatively distinct subgroups with distinctive chromosome copy number gains/losses and gene mutations.[<a class="bk_pop" href="#CDR0000614165_rl_4_50">50</a>] </p><p id="CDR0000614165__sm_CDR0000779372_410">Two subgroups have identifiable recurrent <i>H3F3A</i> mutations, suggesting disrupted epigenetic regulatory mechanisms, with the most recognized subgroup having mutations at K27 (lysine 27) and the other group having mutations at G34 (glycine 34). The subgroups are the following:</p><ul id="CDR0000614165__sm_CDR0000779372_299"><li class="half_rhythm"><div><i>H3F3A</i> mutation at K27: The K27 cluster occurs predominately in mid-childhood (median age, approximately 10 years), is mainly midline (thalamus, brain stem, and spinal cord), and carries a very poor prognosis. These tumors also frequently have <i>TP53</i> mutations. Thalamic high-grade gliomas in older adolescents and young adults also show a high rate of <i>H3F3A</i> K27 mutations.[<a class="bk_pop" href="#CDR0000614165_rl_4_51">51</a>]</div></li><li class="half_rhythm"><div><i>H3F3A</i> mutation at G34: The second <i>H3F3A</i> mutation tumor cluster, the G34 grouping, is found in somewhat older children and young adults (median age, 18 years), arises exclusively in the cerebral cortex, and carries a somewhat better prognosis. The G34 clusters also have <i>TP53</i> mutations and widespread hypomethylation across the whole genome. </div></li></ul><p id="CDR0000614165__sm_CDR0000779372_300">The <i>H3F3A</i> K27 and G34 mutations appear to be unique to high-grade gliomas and have not been observed in other pediatric brain tumors.[<a class="bk_pop" href="#CDR0000614165_rl_4_52">52</a>] Both mutations induce distinctive DNA methylation patterns compared with the patterns observed in <i>IDH</i>-mutated tumors, which occur in young adults.[<a class="bk_pop" href="#CDR0000614165_rl_4_48">48</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_50">50</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_52">52</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_53">53</a>]</p><p id="CDR0000614165__sm_CDR0000779372_301">Other pediatric glioblastoma multiforme subgroups include the <i>RTK PDGFRA</i> and <i>mesenchymal </i>clusters, both of which occur over a wide age range, affecting both children and adults. The RTK PDGFRA and mesenchymal subtypes are predominantly composed of cortical tumors, with cerebellar glioblastoma multiforme tumors rarely observed; both subtypes have a poor prognosis.[<a class="bk_pop" href="#CDR0000614165_rl_4_50">50</a>]</p><p id="CDR0000614165__sm_CDR0000779372_431">Childhood secondary high-grade glioma (high-grade glioma that is preceded by a low-grade glioma) is uncommon (2.9% in a study of 886 patients). No pediatric low-grade gliomas with the <i>BRAF-KIAA1549</i> fusion transformed to a high-grade glioma, whereas low-grade gliomas with the <i>BRAF</i> V600E mutations were associated with increased risk of transformation. Seven (approximately 40%) of 18 patients with secondary high-grade glioma had <i>BRAF</i> V600E mutations, with <i>CDKN2A</i> alterations present in 8 (57%) of 14 cases.<div class="milestone-end"></div>[<a class="bk_pop" href="#CDR0000614165_rl_4_33">33</a>]</p></div></div><div id="CDR0000614165__117"><h3>Prognosis</h3><div id="CDR0000614165__118"><h4>Low-grade astrocytomas</h4><p id="CDR0000614165__119">Low-grade astrocytomas (grade I [pilocytic] and grade II) have a relatively favorable prognosis, particularly for circumscribed, grade I lesions where complete excision may be possible.[<a class="bk_pop" href="#CDR0000614165_rl_4_11">11</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_12">12</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_54">54</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_58">58</a>] Tumor spread, when it occurs, is usually by contiguous extension; dissemination to other CNS sites is uncommon, but does occur.[<a class="bk_pop" href="#CDR0000614165_rl_4_59">59</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_60">60</a>] Although metastasis is uncommon, tumors may be of multifocal origin, especially when associated with NF1.</p><p id="CDR0000614165__235">Unfavorable prognostic features for childhood low-grade astrocytomas include the following:[<a class="bk_pop" href="#CDR0000614165_rl_4_61">61</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_63">63</a>]</p><ul id="CDR0000614165__302"><li class="half_rhythm"><div>Young age.</div></li><li class="half_rhythm"><div>Diffuse histology, especially <i>IDH</i>-mutant.</div></li><li class="half_rhythm"><div>Inability to obtain a complete resection.</div></li><li class="half_rhythm"><div>Diencephalic syndrome.</div></li><li class="half_rhythm"><div>Intracranial hypertension at initial presentation.</div></li><li class="half_rhythm"><div>Metastases. When metastasis does occur, it is associated with a poorer long-term outcome.[<a class="bk_pop" href="#CDR0000614165_rl_4_64">64</a>] However, it is increasingly evident that prognosis is largely dependent on specific molecular features integrated with standard pathological grouping.</div></li></ul><p id="CDR0000614165__303">In patients with pilocytic astrocytoma, elevated MIB-1 labeling index, a marker of cellular proliferative activity, is associated with shortened PFS.[<a class="bk_pop" href="#CDR0000614165_rl_4_8">8</a>] A <i>BRAF-KIAA</i> fusion, found in pilocytic tumors, confers a better clinical outcome.[<a class="bk_pop" href="#CDR0000614165_rl_4_30">30</a>]</p><p id="CDR0000614165__304">Children with isolated optic nerve tumors have a better prognosis than those with lesions that involve the chiasm or that extend along the optic pathway.[<a class="bk_pop" href="#CDR0000614165_rl_4_65">65</a>-<a class="bk_pop" href="#CDR0000614165_rl_4_68">68</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_4_69">69</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335146/" class="def">Level of evidence: 3iiC</a>] Children with NF1 also have a better prognosis, especially when the tumor is found in asymptomatic patients at the time of screening.[<a class="bk_pop" href="#CDR0000614165_rl_4_65">65</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_70">70</a>]</p></div><div id="CDR0000614165__120"><h4>High-grade astrocytomas</h4><p id="CDR0000614165__121">Biologic markers, such as p53 overexpression and mutation status, may be useful predictors of outcome in patients with high-grade gliomas.[<a class="bk_pop" href="#CDR0000614165_rl_4_5">5</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_71">71</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_72">72</a>] MIB-1 labeling index is predictive of outcome in childhood malignant brain tumors. Both histologic classification and proliferative activity evaluation have been shown to be independently associated with survival.[<a class="bk_pop" href="#CDR0000614165_rl_4_73">73</a>] </p><p id="CDR0000614165__305">Although high-grade astrocytomas generally carry a poor prognosis in younger patients, those with anaplastic astrocytomas in whom a gross-total resection is possible may fare better,[<a class="bk_pop" href="#CDR0000614165_rl_4_56">56</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_74">74</a>,<a class="bk_pop" href="#CDR0000614165_rl_4_75">75</a>] as well as those with non-<i>H3K27M</i>–mutant tumors.</p></div></div><div id="CDR0000614165_rl_4"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000614165_rl_4_1">Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/20352473" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20352473</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_4_71">Pollack IF, Finkelstein SD, Woods J, et al.: Expression of p53 and prognosis in children with malignant gliomas. N Engl J Med 346 (6): 420-7, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11832530" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11832530</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_4_72">Rood BR, MacDonald TJ: Pediatric high-grade glioma: molecular genetic clues for innovative therapeutic approaches. J Neurooncol 75 (3): 267-72, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16195804" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16195804</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_4_73">Pollack IF, Hamilton RL, Burnham J, et al.: Impact of proliferation index on outcome in childhood malignant gliomas: results in a multi-institutional cohort. Neurosurgery 50 (6): 1238-44; discussion 1244-5, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12015841" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12015841</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_4_74">Finlay JL, Boyett JM, Yates AJ, et al.: Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. J Clin Oncol 13 (1): 112-23, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7799011" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7799011</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_4_75">Villano JL, Seery TE, Bressler LR: Temozolomide in malignant gliomas: current use and future targets. Cancer Chemother Pharmacol 64 (4): 647-55, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19543728" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19543728</span></a>]</div></li></ol></div></div><div id="CDR0000614165__33"><h2 id="_CDR0000614165__33_">Stage Information for Childhood Astrocytomas</h2><p id="CDR0000614165__34">There is no generally recognized staging system for childhood astrocytomas. For the purposes of this summary, childhood astrocytomas will be described as follows:</p><ul id="CDR0000614165__387"><li class="half_rhythm"><div>Low-grade astrocytoma—grades I and II (e.g., pilocytic astrocytomas and diffuse astrocytomas).<dl id="CDR0000614165__388" class="temp-labeled-list"><dt>-</dt><dd><p class="no_top_margin">Newly diagnosed.</p></dd><dt>-</dt><dd><p class="no_top_margin">Recurrent.</p></dd></dl></div></li><li class="half_rhythm"><div>High-grade astrocytoma—grades III and IV (anaplastic astrocytomas and glioblastoma).<dl id="CDR0000614165__389" class="temp-labeled-list"><dt>-</dt><dd><p class="no_top_margin">Newly diagnosed.</p></dd><dt>-</dt><dd><p class="no_top_margin">Recurrent.</p></dd></dl></div></li></ul></div><div id="CDR0000614165__35"><h2 id="_CDR0000614165__35_">Treatment Option Overview for Childhood Astrocytomas</h2><p id="CDR0000614165__36">Many of the improvements in survival in childhood cancer have been made as a result of clinical trials that have attempted to improve on the best available, accepted therapy. Clinical trials in pediatrics are designed to compare new therapy with therapy that is currently accepted as standard. This comparison may be done in a randomized study of two treatment arms or by evaluating a single new treatment and comparing the results with previously obtained results that assessed an existing therapy. Because of the relative rarity of cancer in children, all patients with brain tumors should be considered for entry into a clinical trial. </p><p id="CDR0000614165__37">To determine and implement optimum treatment, planning by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required. Radiation therapy of pediatric brain tumors is technically very demanding and should be carried out in centers that have experience in that area to ensure optimal results.</p><p id="CDR0000614165__38">Debilitating effects on growth and neurologic development have frequently been observed following radiation therapy, especially in younger children.[<a class="bk_pop" href="#CDR0000614165_rl_35_1">1</a>-<a class="bk_pop" href="#CDR0000614165_rl_35_3">3</a>] Also, there are other less-common complications of radiation therapy, including cerebrovascular accidents.[<a class="bk_pop" href="#CDR0000614165_rl_35_4">4</a>] For this reason, the role of chemotherapy in allowing a delay in the administration of radiation therapy is under study, and preliminary results suggest that chemotherapy can be used to delay, and sometimes obviate, the need for radiation therapy in children with benign and malignant lesions.[<a class="bk_pop" href="#CDR0000614165_rl_35_5">5</a>] Long-term management of these patients is complex and requires a multidisciplinary approach. </p><div id="CDR0000614165__372" class="table"><h3><span class="title">Table 4. Standard Treatment Options for Childhood Astrocytomas</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65944.6/table/CDR0000614165__372/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000614165__372_lrgtbl__"><table class="no_top_margin"><thead><tr><th colspan="2" rowspan="1" style="vertical-align:top;">Treatment Group</th><th colspan="1" rowspan="1" style="vertical-align:top;">Standard Treatment Options</th></tr></thead><tbody><tr><td colspan="2" rowspan="1" style="vertical-align:top;"><b>Childhood low-grade astrocytomas:</b></td><td colspan="1" rowspan="1" style="vertical-align:top;"></td></tr><tr><td colspan="1" rowspan="8" style="vertical-align:top;"></td><td colspan="1" rowspan="8" style="vertical-align:top;">Newly diagnosed childhood low-grade astrocytomas</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__312">Observation</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__44">Surgery</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__310">Adjuvant therapy</a> (for tumors that are incompletely resected):</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—<a href="#CDR0000614165__177">Observation</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—<a href="#CDR0000614165__179">Radiation therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—<a href="#CDR0000614165__316">Second surgery</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—<a href="#CDR0000614165__182">Chemotherapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—<a href="#CDR0000614165__403">Targeted therapy</a> (for subependymal giant cell astrocytomas)</td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;"></td><td colspan="1" rowspan="3" style="vertical-align:top;">Recurrent childhood low-grade astrocytomas</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__361">Second surgery</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__363">Radiation therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__366">Chemotherapy</a></td></tr><tr><td colspan="2" rowspan="1" style="vertical-align:top;"><b>Childhood high-grade astrocytomas:</b></td><td colspan="1" rowspan="1" style="vertical-align:top;"></td></tr><tr><td colspan="1" rowspan="4" style="vertical-align:top;"></td><td colspan="1" rowspan="4" style="vertical-align:top;">Newly diagnosed childhood high-grade astrocytomas</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__324">Surgery</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__326">Adjuvant therapy</a>:</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—<a href="#CDR0000614165__327">Radiation therapy</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">—<a href="#CDR0000614165__329">Chemotherapy</a></td></tr><tr><td colspan="1" rowspan="4" style="vertical-align:top;"></td><td colspan="1" rowspan="4" style="vertical-align:top;">Recurrent childhood high-grade astrocytomas</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__452">Surgery</a> (not considered standard treatment)</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__452">High-dose chemotherapy with stem cell transplant</a> (not considered standard treatment)</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__452">Targeted therapy with a BRAF inhibitor, for patients with a BRAF V600E mutation</a> (not considered standard treatment)</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000614165__452">Early-phase clinical trial</a> (not considered standard treatment)</td></tr></tbody></table></div></div><div id="CDR0000614165_rl_35"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000614165_rl_35_1">Packer RJ, Sutton LN, Atkins TE, et al.: A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg 70 (5): 707-13, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2709111" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2709111</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_35_2">Johnson DL, McCabe MA, Nicholson HS, et al.: Quality of long-term survival in young children with medulloblastoma. J Neurosurg 80 (6): 1004-10, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8189255" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8189255</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_35_3">Packer RJ, Sutton LN, Goldwein JW, et al.: Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74 (3): 433-40, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1847194" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1847194</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_35_4">Bowers DC, Mulne AF, Reisch JS, et al.: Nonperioperative strokes in children with central nervous system tumors. Cancer 94 (4): 1094-101, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11920480" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11920480</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_35_5">Duffner PK, Horowitz ME, Krischer JP, et al.: Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328 (24): 1725-31, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8388548" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8388548</span></a>]</div></li></ol></div></div><div id="CDR0000614165__40"><h2 id="_CDR0000614165__40_">Treatment of Childhood Low-Grade Astrocytomas</h2><p id="CDR0000614165__41">To determine and implement optimal management, treatment is often guided by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors. </p><p id="CDR0000614165__42">In infants and young children, low-grade astrocytomas presenting in the hypothalamus make surgery difficult; consequently, biopsies are not always done. This is especially true in patients with neurofibromatosis type 1 (NF1).[<a class="bk_pop" href="#CDR0000614165_rl_40_1">1</a>] When associated with NF1, tumors may be of multifocal origin.</p><p id="CDR0000614165__43">For children with low-grade optic pathway astrocytomas, treatment options should be considered not only to improve survival but also to stabilize visual function.[<a class="bk_pop" href="#CDR0000614165_rl_40_2">2</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_3">3</a>] </p><div id="CDR0000614165__306"><h3>Treatment of Newly Diagnosed Childhood Low-Grade Astrocytomas</h3><p id="CDR0000614165__356">Standard treatment options for newly diagnosed childhood low-grade astrocytomas include the following:</p><ol id="CDR0000614165__384"><li class="half_rhythm"><div><a href="#CDR0000614165__312">Observation</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__44">Surgery</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__310">Adjuvant therapy</a>.<ul id="CDR0000614165__358"><li class="half_rhythm"><div><a href="#CDR0000614165__177">Observation</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__179">Radiation therapy</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__316">Second surgery</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__182">Chemotherapy</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__403">Targeted therapy</a> (for subependymal giant cell astrocytomas).</div></li></ul></div></li></ol><div id="CDR0000614165__312"><h4>Observation</h4><p id="CDR0000614165__313">Observation, in the absence of any intervention, is an option for patients with NF1 or incidentally found, asymptomatic masses.[<a class="bk_pop" href="#CDR0000614165_rl_40_4">4</a>-<a class="bk_pop" href="#CDR0000614165_rl_40_7">7</a>] Spontaneous regressions of optic pathway gliomas have been reported in children with and without NF1.[<a class="bk_pop" href="#CDR0000614165_rl_40_8">8</a>-<a class="bk_pop" href="#CDR0000614165_rl_40_10">10</a>]</p></div><div id="CDR0000614165__44"><h4>Surgery</h4><p id="CDR0000614165__45">Surgical resection is the primary treatment for childhood low-grade astrocytoma [<a class="bk_pop" href="#CDR0000614165_rl_40_1">1</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_4">4</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_5">5</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_11">11</a>] and surgical feasibility is determined by tumor location. </p><ul id="CDR0000614165__307"><li class="half_rhythm"><div><b>Cerebellum:</b> Complete or near-complete removal can be obtained in 90% to 95% of patients with pilocytic tumors that occur in the cerebellum.[<a class="bk_pop" href="#CDR0000614165_rl_40_11">11</a>]</div></li><li class="half_rhythm"><div><b>Optic nerve:</b> For children with isolated optic nerve lesions and progressive symptoms, complete surgical resection, while curative, generally results in blindness in the affected eye.</div></li><li class="half_rhythm"><div><b>Midline structures (hypothalamus, thalamus, brain stem, and spinal cord):</b> Low-grade astrocytomas that occur in midline structures can be aggressively resected, with resultant long-term disease control.[<a class="bk_pop" href="#CDR0000614165_rl_40_8">8</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_9">9</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_12">12</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_13">13</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335150/" class="def">Level of evidence: 3iiiA</a>] Such resection may result in significant neurologic sequelae, especially in children younger than 2 years at diagnosis.[<a class="bk_pop" href="#CDR0000614165_rl_40_8">8</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_14">14</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335140/" class="def">Level of evidence: 3iC</a>] Because of the infiltrative nature of some deep-seated lesions, extensive surgical resection may not be appropriate and biopsy only should be considered.[<a class="bk_pop" href="#CDR0000614165_rl_40_15">15</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>]</div></li><li class="half_rhythm"><div><b>Cerebrum:</b> Circumscribed, grade I hemispheric tumors are often amenable to complete surgical resection.[<a class="bk_pop" href="#CDR0000614165_rl_40_16">16</a>] </div></li><li class="half_rhythm"><div><b>Diffuse:</b> Diffuse astrocytomas may be less amenable to total resection, and this may contribute to the poorer outcome.</div></li></ul><p id="CDR0000614165__400">In some low-grade astrocytomas, surgical resection can be performed more safely.[<a class="bk_pop" href="#CDR0000614165_rl_40_17">17</a>] After resection, immediate (within 48 hours of resection per Children’s Oncology Group [COG] criteria) postoperative magnetic resonance imaging is obtained. Surveillance scans are then obtained periodically for completely resected tumors, although the value following the initial 3- to 6-month postoperative period is uncertain.[<a class="bk_pop" href="#CDR0000614165_rl_40_18">18</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_19">19</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335149/" class="def">Level of evidence: 3iiDiii</a>]</p><p id="CDR0000614165__212">Factors related to outcome for children with low-grade gliomas treated with surgery followed by observation were identified in a COG study that included 518 evaluable patients.[<a class="bk_pop" href="#CDR0000614165_rl_40_11">11</a>] Overall outcome for the entire group was 78% progression-free survival (PFS) at 8 years and 96% overall survival (OS) at 8 years. The following factors were related to prognosis:[<a class="bk_pop" href="#CDR0000614165_rl_40_11">11</a>]</p><ul id="CDR0000614165__213"><li class="half_rhythm"><div class="half_rhythm"><b>Tumor location:</b> Cerebellar and cerebral tumors showed higher PFS at 8 years compared with patients with midline and chiasmatic tumors (84% ± 1.9% versus 51% ± 5.9%).</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Histology:</b> Approximately three-fourths of patients had pilocytic astrocytoma; PFS and OS were superior for these patients when compared with children with nonpilocytic tumors.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Extent of resection:</b> Patients with gross-total resection had 8-year PFS exceeding 90% and OS of 99%. By comparison, approximately one-half of patients with any degree of residual tumor (as assessed by operative report and by postoperative imaging) showed disease progression by 8 years, although OS exceeded 90%.[<a class="bk_pop" href="#CDR0000614165_rl_40_11">11</a>]
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</div><div class="half_rhythm">The extent of resection necessary for cure is unknown because patients with microscopic and even gross residual tumor after surgery may experience long-term PFS without postoperative therapy.[<a class="bk_pop" href="#CDR0000614165_rl_40_1">1</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_6">6</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_11">11</a>] </div></li><li class="half_rhythm"><div class="half_rhythm"><b>Age:</b> Younger children (age <5 years) showed higher rates of tumor progression but there was no significant age effect for OS in multivariate analysis. In a retrospective review of a different series of pediatric patients, children younger than 1 year with low-grade glioma demonstrated an inferior PFS compared with children aged 1 year and older.[<a class="bk_pop" href="#CDR0000614165_rl_40_20">20</a>]</div></li></ul><p id="CDR0000614165__214">The long-term functional outcome of cerebellar pilocytic astrocytomas is relatively favorable. Full-scale mean IQs of patients with low-grade gliomas treated with surgery alone are close to the normative population. However, long-term medical, psychological, and educational deficits may be present in these patients.[<a class="bk_pop" href="#CDR0000614165_rl_40_21">21</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_22">22</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_23">23</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335152/" class="def">Level of evidence: 3iiiC</a>]</p></div><div id="CDR0000614165__310"><h4>Adjuvant therapy</h4><p id="CDR0000614165__311">Adjuvant therapy following complete resection of a low-grade glioma is generally not required unless there is a subsequent recurrence of disease. Treatment options for patients with incompletely resected tumor must be individualized and may include one or more of the following:</p><ul id="CDR0000614165__401"><li class="half_rhythm"><div><a href="#CDR0000614165__177">Observation</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__179">Radiation therapy</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__316">Second surgery</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__182">Chemotherapy</a>. </div></li><li class="half_rhythm"><div><a href="#CDR0000614165__403">Targeted therapy</a> (for subependymal giant cell astrocytomas).</div></li></ul><p id="CDR0000614165__402">A shunt or other cerebrospinal fluid diversion procedure may be needed.</p><div id="CDR0000614165__177"><h5>Observation</h5><p id="CDR0000614165__178">In selected patients in whom a portion of the tumor has been resected, the patient may be observed without further disease-directed treatment, particularly if the pace of tumor regrowth is anticipated to be very slow. Approximately 50% of patients with less-than-gross total resection may have disease that remains progression-free at 5 to 8 years, supporting the observation strategy in selected patients.[<a class="bk_pop" href="#CDR0000614165_rl_40_11">11</a>]</p></div><div id="CDR0000614165__179"><h5>Radiation therapy</h5><p id="CDR0000614165__180">Radiation therapy is usually reserved until progressive disease is documented [<a class="bk_pop" href="#CDR0000614165_rl_40_16">16</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_24">24</a>] and may be further delayed through the use of chemotherapy, a strategy that is commonly employed in young children.[<a class="bk_pop" href="#CDR0000614165_rl_40_25">25</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_26">26</a>] For children with low-grade gliomas for whom radiation therapy is indicated, approaches that contour the radiation to the tumor and avoid normal brain tissue (<a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000270731/" class="def">3-D conformal radiation therapy</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000335073/" class="def">intensity-modulated radiation therapy</a>, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000044464/" class="def">stereotactic radiation therapy</a>, and <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000534234/" class="def">proton radiation therapy [charged-particle radiation therapy]</a>) all appear effective and may potentially reduce the acute and long-term toxicities associated with these modalities.[<a class="bk_pop" href="#CDR0000614165_rl_40_27">27</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_28">28</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_29">29</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335143/" class="def">Level of evidence: 3iDiii</a>] Care must be taken in separating radiation-induced imaging changes from disease progression, which usually occurs during the first year after radiation, but may occur even after the first year, especially in patients with pilocytic astrocytomas.[<a class="bk_pop" href="#CDR0000614165_rl_40_30">30</a>-<a class="bk_pop" href="#CDR0000614165_rl_40_33">33</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_34">34</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335132/" class="def">Level of evidence: 2A</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_35">35</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335134/" class="def">Level of evidence: 2C</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_36">36</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335153/" class="def">Level of evidence: 3iiiDi</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_37">37</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335155/" class="def">Level of evidence: 3iiiDii</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_15">15</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_38">38</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>]</p><p id="CDR0000614165__314">Radiation therapy results in long-term disease control for most children with chiasmatic and posterior pathway chiasmatic gliomas, but may also result in substantial intellectual and endocrinologic sequelae, cerebrovascular damage, late death, and possibly an increased risk of secondary tumors.[<a class="bk_pop" href="#CDR0000614165_rl_40_8">8</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_39">39</a>-<a class="bk_pop" href="#CDR0000614165_rl_40_42">42</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_35">35</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335134/" class="def">Level of evidence: 2C</a>] A population-based study identified radiation therapy as the most significant risk factor associated with late mortality, although the patients who required radiation therapy may have reflected a higher-risk population.[<a class="bk_pop" href="#CDR0000614165_rl_40_42">42</a>]</p><p id="CDR0000614165__315">Radiation therapy and alkylating agents are used as last resorts for patients with NF1, given the theoretically heightened risk of inducing neurologic toxic effects and second malignancy in this population.[<a class="bk_pop" href="#CDR0000614165_rl_40_43">43</a>] Children with NF1 may be at higher risk for radiation-associated secondary tumors and morbidity due to vascular changes.</p></div><div id="CDR0000614165__316"><h5>Second surgery</h5><p id="CDR0000614165__317">An alternative to immediate radiation therapy is subtotal surgical resection, but it is unclear how many patients will have stable disease and for how long.[<a class="bk_pop" href="#CDR0000614165_rl_40_8">8</a>] </p></div><div id="CDR0000614165__182"><h5>Chemotherapy</h5><p id="CDR0000614165__183">Given the long-term side effects associated with radiation therapy, postoperative chemotherapy may be initially recommended. </p><p id="CDR0000614165__184">Chemotherapy may result in objective tumor shrinkage and delay the need for radiation therapy in most patients.[<a class="bk_pop" href="#CDR0000614165_rl_40_25">25</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_26">26</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_44">44</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_45">45</a>] Chemotherapy is also an option that may delay or avoid radiation therapy in adolescents with optic nerve pathway gliomas.[<a class="bk_pop" href="#CDR0000614165_rl_40_46">46</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335148/" class="def">Level of evidence: 3iiDii</a>] Chemotherapy has been shown to shrink tumors in children with hypothalamic gliomas and the diencephalic syndrome, resulting in weight gain in those who respond to treatment.[<a class="bk_pop" href="#CDR0000614165_rl_40_47">47</a>] </p><p id="CDR0000614165__185">The most widely used regimens to treat tumor progression or symptomatic nonresectable, low-grade gliomas are the following: </p><ul id="CDR0000614165__411"><li class="half_rhythm"><div>Carboplatin with or without vincristine.[<a class="bk_pop" href="#CDR0000614165_rl_40_25">25</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_26">26</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_48">48</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_49">49</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>]</div></li><li class="half_rhythm"><div>Combination of thioguanine, procarbazine, lomustine, and vincristine (TPCV).[<a class="bk_pop" href="#CDR0000614165_rl_40_45">45</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_50">50</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li></ul><p id="CDR0000614165__412">The COG reported the results of a randomized phase III trial (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=65394" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">COG-A9952</a>) that treated children younger than 10 years with low-grade chiasmatic/hypothalamic gliomas but without NF1 using one of two regimens: carboplatin and vincristine (CV) or TPCV. The 5-year event-free survival rate was 39% ± 4% for the CV regimen and 52% ± 5% for the TPCV regimen. Toxicity rates between the two regimens were relatively comparable.[<a class="bk_pop" href="#CDR0000614165_rl_40_50">50</a>]</p><p id="CDR0000614165__186">Other chemotherapy approaches have been employed to treat children with progressive low-grade astrocytomas, including multiagent, platinum-based regimens,[<a class="bk_pop" href="#CDR0000614165_rl_40_26">26</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_44">44</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_51">51</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_52">52</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335137/" class="def">Level of evidence: 2Diii</a>] vinblastine,[<a class="bk_pop" href="#CDR0000614165_rl_40_53">53</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_54">54</a>] and temozolomide.[<a class="bk_pop" href="#CDR0000614165_rl_40_55">55</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_56">56</a>] Reported 5-year PFS rates have ranged from approximately 35% to 60% for children receiving platinum-based chemotherapy for optic pathway gliomas,[<a class="bk_pop" href="#CDR0000614165_rl_40_26">26</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_44">44</a>] but most patients ultimately require further treatment. This is particularly true for children who initially present with hypothalamic/chiasmatic gliomas that have neuraxis dissemination.[<a class="bk_pop" href="#CDR0000614165_rl_40_57">57</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>]</p><p id="CDR0000614165__187">Among children receiving chemotherapy for optic pathway gliomas, those without NF1 have higher rates of disease progression than those with NF1, and infants have higher rates of disease progression than do children older than 1 year.[<a class="bk_pop" href="#CDR0000614165_rl_40_26">26</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_44">44</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_51">51</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_54">54</a>] Whether vision is improved with chemotherapy is unclear.[<a class="bk_pop" href="#CDR0000614165_rl_40_54">54</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_58">58</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_59">59</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335152/" class="def">Level of evidence: 3iiiC</a>]</p></div><div id="CDR0000614165__403"><h5>Targeted therapy</h5><p id="CDR0000614165__404">For children with symptomatic subependymal giant cell astrocytomas (SEGAs), agents that inhibit mammalian target of rapamycin (mTOR) (e.g., everolimus and sirolimus) have been shown in small series to cause significant reductions in the size of these tumors, often eliminating the need for surgery.[<a class="bk_pop" href="#CDR0000614165_rl_40_60">60</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_61">61</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335134/" class="def">Level of evidence: 2C</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_62">62</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587990/" class="def">Level of evidence: 3iiDiv</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_63">63</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335152/" class="def">Level of evidence: 3iiiC</a>] A multicenter, phase III, placebo-controlled trial of 117 patients confirmed these earlier findings; 35% of the patients in the everolimus group had at least a 50% reduction in the size of the SEGA, versus no reduction in the placebo group.[<a class="bk_pop" href="#CDR0000614165_rl_40_64">64</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587981/" class="def">Level of evidence: 1iDiv</a>] Whether reduction in size of the mass is durable, obviating the need for future surgery, is unknown.</p></div></div></div><div id="CDR0000614165__93"><h3>Treatment of Recurrent Childhood Low-Grade Astrocytomas</h3><p id="CDR0000614165__94">Childhood low-grade astrocytomas may recur many years after initial treatment. </p><p id="CDR0000614165__413">An individual plan needs to be tailored based on the following:</p><ul id="CDR0000614165__414"><li class="half_rhythm"><div>Patient age.</div></li><li class="half_rhythm"><div>Tumor location.</div></li><li class="half_rhythm"><div>Prior treatment.</div></li></ul><p id="CDR0000614165__415">Recurrent disease is usually at the primary tumor site, although multifocal or widely disseminated disease to other intracranial sites and to the spinal leptomeninges has been documented.[<a class="bk_pop" href="#CDR0000614165_rl_40_65">65</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_66">66</a>] Most children whose low-grade fibrillary astrocytomas recur will harbor low-grade lesions; however, transformation into a higher grade tumor is possible.[<a class="bk_pop" href="#CDR0000614165_rl_40_67">67</a>] Surveillance imaging will frequently identify asymptomatic recurrences.[<a class="bk_pop" href="#CDR0000614165_rl_40_68">68</a>]</p><p id="CDR0000614165__95">At the time of recurrence, a complete evaluation to determine the extent of the relapse is indicated. Biopsy or surgical resection may be necessary for confirmation of relapse because other entities, such as secondary tumor and treatment-related brain necrosis, may be clinically indistinguishable from tumor recurrence. The need for surgical intervention must be individualized on the basis of the following: </p><ul id="CDR0000614165__318"><li class="half_rhythm"><div>Initial tumor type.</div></li><li class="half_rhythm"><div>Length of time between initial treatment and the reappearance of the mass lesion.</div></li><li class="half_rhythm"><div>Clinical picture.</div></li></ul><p id="CDR0000614165__359">Standard treatment options for recurrent childhood low-grade astrocytomas include the following:</p><ol id="CDR0000614165__385"><li class="half_rhythm"><div><a href="#CDR0000614165__361">Second surgery</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__363">Radiation therapy</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__366">Chemotherapy</a>.</div></li></ol><div id="CDR0000614165__361"><h4>Second surgery</h4><p id="CDR0000614165__362">Patients with low-grade astrocytomas who relapse after being treated with surgery alone should be considered for another surgical resection.[<a class="bk_pop" href="#CDR0000614165_rl_40_69">69</a>]</p></div><div id="CDR0000614165__363"><h4>Radiation therapy</h4><p id="CDR0000614165__365">The rationale for the use of radiation therapy is essentially the same when utilized as first-line therapy or at the time of recurrence (refer to the <a href="#CDR0000614165__179">Radiation therapy</a> subsection of the <a href="#CDR0000614165__306">Treatment of Newly Diagnosed Childhood Low-Grade Astrocytomas</a> section of this summary). If the child has never received radiation therapy, local radiation therapy may be a treatment option, although chemotherapy in lieu of radiation may be considered, depending on the child's age and the extent and location of the tumor.[<a class="bk_pop" href="#CDR0000614165_rl_40_70">70</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335138/" class="def">Level of evidence: 3iA</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_71">71</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335153/" class="def">Level of evidence: 3iiiDi</a>] </p><p id="CDR0000614165__405">For children with low-grade gliomas for whom radiation therapy is indicated, <a href="/books/n/pdqcis/glossary/def-item/glossary_CDR0000270731/" class="def">conformal radiation therapy</a> approaches appear effective and offer the potential for reducing the acute and long-term toxicities associated with this modality.[<a class="bk_pop" href="#CDR0000614165_rl_40_31">31</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_35">35</a>]</p></div><div id="CDR0000614165__366"><h4>Chemotherapy</h4><p id="CDR0000614165__367">If there is recurrence at an unresectable site that has been previously irradiated, chemotherapy should be considered.[<a class="bk_pop" href="#CDR0000614165_rl_40_72">72</a>]</p><p id="CDR0000614165__368">In patients previously treated with surgery and radiation therapy, chemotherapy should be considered. Chemotherapy may result in relatively long-term disease control.[<a class="bk_pop" href="#CDR0000614165_rl_40_26">26</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_73">73</a>] Vinblastine alone, temozolomide alone, or temozolomide in combination with carboplatin and vincristine may be useful at the time of recurrence for children with low-grade gliomas.[<a class="bk_pop" href="#CDR0000614165_rl_40_26">26</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_54">54</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_55">55</a>,<a class="bk_pop" href="#CDR0000614165_rl_40_73">73</a>]</p><p id="CDR0000614165__382">Antitumor activity has also been observed for bevacizumab given in combination with irinotecan, which, in some cases, also results in clinical or visual improvement.[<a class="bk_pop" href="#CDR0000614165_rl_40_74">74</a>] In a phase II study of bevacizumab plus irinotecan for children with recurrent low-grade gliomas, sustained partial response was observed in only two patients (5.7%), but the 6-month PFS was 85.4% (standard error [SE] ± 5.96%) and the 2-year PFS was 47.8% (SE ± 9.27%).[<a class="bk_pop" href="#CDR0000614165_rl_40_75">75</a>] A pilot study of 14 patients with recurrent low-grade gliomas also evaluated bevacizumab-based therapies and observed 12 patients (86%) with objective responses.[<a class="bk_pop" href="#CDR0000614165_rl_40_76">76</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335147/" class="def">Level of evidence: 3iiDi</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_40_77">77</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>] No patients progressed on therapy (median treatment duration, 12 months), but 13 of 14 progressed after stopping bevacizumab at a median of 5 months. Bevacizumab has also been employed for children with low-grade gliomas and symptomatic radiation-induced tumor enlargement; it produced radiographic improvement (five of five patients) and allowed weaning off steroids (four of four patients).[<a class="bk_pop" href="#CDR0000614165_rl_40_78">78</a>]</p></div><div id="CDR0000614165__469"><h4>Targeted therapy</h4><p id="CDR0000614165__470">With the identification of <i>BRAF</i> mutations driving a significant proportion of low-grade gliomas, inhibition of various elements of this molecular pathway (MEK, V600E, etc.) are actively being tested in multiple ongoing clinical trials. In a preliminary report, this approach showed positive results in a phase I study of a MEK inhibitor in recurrent pediatric low-grade gliomas.[<a class="bk_pop" href="#CDR0000614165_rl_40_79">79</a>] Other approaches include those investigating mTOR inhibitors (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=743362" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT01734512</a>). </p></div><div id="CDR0000614165__165"><h4>Treatment options under clinical evaluation</h4><p id="CDR0000614165__166">The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p><ul id="CDR0000614165__383"><li class="half_rhythm"><div><b><a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=728296" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ACNS1022 (NCT01553149)</a></b> (Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma)<b>:</b> This is a randomized phase II clinical trial comparing low-dose to high-dose lenalidomide to see how well each works in treating children with recurrent, refractory, or progressive juvenile pilocytic astrocytomas or optic nerve pathway gliomas. This clinical trial is based on results of a phase I study that observed tumor responses and long-term stable clinical disease for lenalidomide across a range of dose levels for children with recurrent low-grade gliomas.[<a class="bk_pop" href="#CDR0000614165_rl_40_80">80</a>] </div></li><li class="half_rhythm"><div><b><a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=667932" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PBTC-029 (NCT01089101)</a></b> (Selumetinib in Treating Young Patients With Recurrent or Refractory Low-Grade Glioma)<b>:</b> This is a clinical trial to determine the side effects and the best dose of the MEK inhibitor selumetinib in children with low-grade astrocytoma (phase I component). Based on activity observed in the phase I component (now completed), the study has been modified to include phase II expansion cohorts for patients with pilocytic astrocytoma and other low-grade astrocytomas with <i>BRAF</i> genomic alterations and for NF1 patients with recurrent low-grade astrocytomas.</div></li></ul><div id="CDR0000614165__TrialSearch_165_sid_15"><h5>Current Clinical Trials</h5><p id="CDR0000614165__TrialSearch_165_20">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=716330&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">recurrent childhood astrocytoma or other tumor of glial origin</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000614165__TrialSearch_165_21">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div></div></div><div id="CDR0000614165_rl_40"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000614165_rl_40_1">Due-Tønnessen BJ, Helseth E, Scheie D, et al.: Long-term outcome after resection of benign cerebellar astrocytomas in children and young adults (0-19 years): report of 110 consecutive cases. Pediatr Neurosurg 37 (2): 71-80, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12145515" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12145515</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_40_2">Nicolin G, Parkin P, Mabbott D, et al.: Natural history and outcome of optic pathway gliomas in children. Pediatr Blood Cancer 53 (7): 1231-7, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19621457" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19621457</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_40_3">Kramm CM, Butenhoff S, Rausche U, et al.: Thalamic high-grade gliomas in children: a distinct clinical subset? Neuro Oncol 13 (6): 680-9, 2011. 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[<a href="/pmc/articles/PMC3895377/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3895377</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24311632" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24311632</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_40_76">Hwang EI, Jakacki RI, Fisher MJ, et al.: Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas. Pediatr Blood Cancer 60 (5): 776-82, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/22976922" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22976922</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_40_77">Packer RJ, Jakacki R, Horn M, et al.: Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan. Pediatr Blood Cancer 52 (7): 791-5, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19165892" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19165892</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_40_78">Foster KA, Ares WJ, Pollack IF, et al.: Bevacizumab for symptomatic radiation-induced tumor enlargement in pediatric low grade gliomas. Pediatr Blood Cancer 62 (2): 240-245, 2015. [<a href="https://pubmed.ncbi.nlm.nih.gov/25382690" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25382690</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_40_79">Banerjee A, Jakacki R, Onar-Thomas A, et al.: A phase 1 study of AZD6244 in children with recurrent or refractory low-grade gliomas: a Pediatric Brain Tumor Consortium report. [Abstract] J Clin Oncol 32 (suppl 5): A-10065, 2014. <a href="http://meetinglibrary.asco.org/content/134121-144" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Also available online</a>. Last accessed November 14, 2016.</div></li><li><div class="bk_ref" id="CDR0000614165_rl_40_80">Warren KE, Goldman S, Pollack IF, et al.: Phase I trial of lenalidomide in pediatric patients with recurrent, refractory, or progressive primary CNS tumors: Pediatric Brain Tumor Consortium study PBTC-018. J Clin Oncol 29 (3): 324-9, 2011. [<a href="/pmc/articles/PMC3056466/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3056466</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21149652" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21149652</span></a>]</div></li></ol></div></div><div id="CDR0000614165__102"><h2 id="_CDR0000614165__102_">Treatment of Childhood High-Grade Astrocytomas</h2><p id="CDR0000614165__103">To determine and implement optimal management, treatment of childhood high-grade astrocytomas is often guided by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors. </p><div id="CDR0000614165__322"><h3>Treatment of Newly Diagnosed Childhood High-Grade Astrocytomas</h3><p id="CDR0000614165__323">Outcomes in high-grade gliomas occurring in childhood are often more favorable than that in adults. It is not clear whether this difference is caused by biologic variations in tumor characteristics, therapies used, tumor resectability, or other factors.[<a class="bk_pop" href="#CDR0000614165_rl_102_1">1</a>] </p><p id="CDR0000614165__104">The therapy for both children and adults with supratentorial high-grade astrocytoma includes surgery, radiation therapy, and chemotherapy. </p><p id="CDR0000614165__369">Standard treatment options for newly diagnosed childhood high-grade astrocytomas include the following:</p><ol id="CDR0000614165__386"><li class="half_rhythm"><div><a href="#CDR0000614165__324">Surgery</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__326">Adjuvant therapy</a>.<ul id="CDR0000614165__371"><li class="half_rhythm"><div><a href="#CDR0000614165__327">Radiation therapy</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000614165__329">Chemotherapy</a>.</div></li></ul></div></li></ol><div id="CDR0000614165__324"><h4>Surgery</h4><p id="CDR0000614165__325">The ability to obtain a complete resection is associated with a better prognosis.[<a class="bk_pop" href="#CDR0000614165_rl_102_2">2</a>,<a class="bk_pop" href="#CDR0000614165_rl_102_3">3</a>] Among patients treated with surgery, radiation therapy, and nitrosourea (lomustine)-based chemotherapy, 5-year progression-free survival was 19% ± 3%; survival was 40% in those who had total resections.[<a class="bk_pop" href="#CDR0000614165_rl_102_4">4</a>] Similarly, in a trial of multiagent chemoradiation therapy and adjuvant chemotherapy in addition to valproic acid, 5-year event-free survival (EFS) was 13%, but for children with a complete resection of their tumor, the EFS was 48%.[<a class="bk_pop" href="#CDR0000614165_rl_102_5">5</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335132/" class="def">Level of evidence: 2A</a>] </p></div><div id="CDR0000614165__326"><h4>Adjuvant therapy</h4><div id="CDR0000614165__327"><h5>Radiation therapy</h5><p id="CDR0000614165__328">Radiation therapy is routinely administered to a field that widely encompasses the entire tumor. The radiation therapy dose to the tumor bed is usually at least 54 Gy. Despite such therapy, overall survival rates remain poor. Similarly poor survival is seen in children with spinal cord primaries and children with thalamic high-grade gliomas (i.e., diffuse midline gliomas, <i>H3K27M</i>-mutant tumors) treated with radiation therapy.[<a class="bk_pop" href="#CDR0000614165_rl_102_6">6</a>,<a class="bk_pop" href="#CDR0000614165_rl_102_7">7</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_102_8">8</a>,<a class="bk_pop" href="#CDR0000614165_rl_102_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335150/" class="def">Level of evidence: 3iiiA</a>] </p></div><div id="CDR0000614165__329"><h5>Chemotherapy</h5><p id="CDR0000614165__330">In one trial, children with glioblastoma who were treated on a prospective randomized trial with adjuvant lomustine, vincristine, and prednisone fared better than children treated with radiation therapy alone.[<a class="bk_pop" href="#CDR0000614165_rl_102_10">10</a>] Furthermore, children who received lomustine in addition to temozolomide for subtotally-resected tumors, especially glioblastoma with methylated O6-methylguanine-DNA-methyltransferase (MGMT) overexpression, had a slightly improved outcome.[<a class="bk_pop" href="#CDR0000614165_rl_102_11">11</a>] Patients with <i>IDH1</i> mutations had improved 1-year overall survival (OS) (100%) when compared with <i>IDH1</i>-wildtype tumors (1-year OS, 81%), highlighting the potential importance of underlying biological characteristics.[<a class="bk_pop" href="#CDR0000614165_rl_102_12">12</a>]</p><p id="CDR0000614165__331">The use of temozolomide to treat glioblastoma was initially investigated in adults. In adults, the addition of temozolomide during and after radiation therapy resulted in improved 2-year EFS as compared with treatment with radiation therapy alone. Adult patients with glioblastoma with a MGMT promoter benefitted from temozolomide, whereas those who did not have a methylated MGMT promoter did not benefit from temozolomide.[<a class="bk_pop" href="#CDR0000614165_rl_102_13">13</a>,<a class="bk_pop" href="#CDR0000614165_rl_102_14">14</a>] The role of temozolomide given concurrently with radiation therapy for children with supratentorial high-grade glioma appears comparable to the outcome seen in children treated with nitrosourea-based therapy [<a class="bk_pop" href="#CDR0000614165_rl_102_15">15</a>] and again demonstrated an EFS advantage for those children without MGMT overexpression. </p><p id="CDR0000614165__332">Younger children may benefit from chemotherapy or consolidation with high-dose chemotherapy to delay, modify, or, in selected cases, obviate the need for radiation therapy.[<a class="bk_pop" href="#CDR0000614165_rl_102_16">16</a>-<a class="bk_pop" href="#CDR0000614165_rl_102_19">19</a>] </p></div></div><div id="CDR0000614165__392"><h4>Treatment options under clinical evaluation</h4><p id="CDR0000614165__393">Early-phase therapeutic trials may be available for selected patients. These trials may be available via the Children's Oncology Group (COG), the Pediatric Brain Tumor Consortium (PBTC), or other entities. Information about ongoing clinical trials is available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p><div id="CDR0000614165__TrialSearch_392_sid_8"><h5>Current Clinical Trials</h5><p id="CDR0000614165__TrialSearch_392_20">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=716318&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">childhood high-grade untreated astrocytoma or other tumor of glial origin</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000614165__TrialSearch_392_21">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div></div></div><div id="CDR0000614165__90"><h3>Treatment of Recurrent Childhood High-Grade Astrocytomas</h3><p id="CDR0000614165__91">Most patients with high-grade astrocytomas or gliomas will eventually have tumor recurrence, usually within 3 years of original diagnosis, but some patients recur many years after initial treatment. Disease may recur at the primary tumor site, at the margin of the resection/radiation bed, or at noncontiguous central nervous system sites. Systemic relapse rarely occurs. </p><p id="CDR0000614165__334">At the time of recurrence, a complete evaluation for extent of relapse is indicated for all malignant tumors. Biopsy or surgical resection may be necessary for confirmation of relapse because other entities, such as secondary tumor and treatment-related brain necrosis, may be clinically indistinguishable from tumor recurrence. </p><p id="CDR0000614165__452">Treatment options for recurrent childhood high-grade astrocytomas include the following:</p><ol id="CDR0000614165__453"><li class="half_rhythm"><div>Surgery.</div></li><li class="half_rhythm"><div>High-dose chemotherapy with stem cell transplant (SCT).</div></li><li class="half_rhythm"><div>Targeted therapy with a <i>BRAF</i> inhibitor, for patients with a <i>BRAF</i> V600E mutation.</div></li><li class="half_rhythm"><div>Early-phase clinical trial.</div></li></ol><p id="CDR0000614165__454">The utility of surgical intervention must be individualized on the basis of the following: </p><ul id="CDR0000614165__335"><li class="half_rhythm"><div>Initial tumor type.</div></li><li class="half_rhythm"><div>Length of time between initial treatment and the reappearance of the mass lesion.</div></li><li class="half_rhythm"><div>Location of the recurrent tumor.</div></li><li class="half_rhythm"><div>Consideration of therapeutics based on the requirement for fresh tumor tissue or to deliver therapy to the operative bed.</div></li></ul><p id="CDR0000614165__92">Patients for whom initial treatment fails may benefit from additional treatment, including entry into clinical trials of novel therapeutic approaches.[<a class="bk_pop" href="#CDR0000614165_rl_102_20">20</a>] High-dose, marrow-ablative chemotherapy with hematopoietic SCT may be effective in a highly selected subset of patients with minimal residual disease at time of recurrence.[<a class="bk_pop" href="#CDR0000614165_rl_102_21">21</a>]; [<a class="bk_pop" href="#CDR0000614165_rl_102_22">22</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335150/" class="def">Level of evidence: 3iiiA</a>] However, the results of previous clinical trials that tested various targeted and combination chemotherapies have largely failed to demonstrate convincing benefits for enrolled patients.[<a class="bk_pop" href="#CDR0000614165_rl_102_23">23</a>-<a class="bk_pop" href="#CDR0000614165_rl_102_25">25</a>]</p><p id="CDR0000614165__433">Molecular targets for recurrent high-grade gliomas are limited. <i>BRAF</i> V600E mutations are present in a small subset of these patients, and a small number of cases have responded to <i>BRAF</i> inhibitors. A case report documented a complete response to the <i>BRAF</i> inhibitor vemurafenib in a patient with recurrent <i>BRAF</i> V600–mutated glioblastoma.[<a class="bk_pop" href="#CDR0000614165_rl_102_26">26</a>] A phase I study reported in an abstract that eight children with progressive <i>BRAF</i> V600E high-grade gliomas were treated with dabrafenib and demonstrated three complete responses, three partial responses, and two progressive disease responses.[<a class="bk_pop" href="#CDR0000614165_rl_102_27">27</a>]</p><div id="CDR0000614165__136"><h4>Treatment options under clinical evaluation</h4><p id="CDR0000614165__137">Early-phase therapeutic trials may be available for selected patients. These trials may be available via the COG, the PBTC, or other entities. Information about ongoing clinical trials is available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p><div id="CDR0000614165__TrialSearch_136_sid_11"><h5>Current Clinical Trials</h5><p id="CDR0000614165__TrialSearch_136_20">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=716330&tt=1&format=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">recurrent childhood astrocytoma or other tumor of glial origin</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000614165__TrialSearch_136_21">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div></div></div><div id="CDR0000614165_rl_102"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000614165_rl_102_1">Rasheed BK, McLendon RE, Herndon JE, et al.: Alterations of the TP53 gene in human gliomas. Cancer Res 54 (5): 1324-30, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8118823" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8118823</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_2">Wisoff JH, Boyett JM, Berger MS, et al.: Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group trial no. CCG-945. J Neurosurg 89 (1): 52-9, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9647172" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9647172</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_3">Yang T, Temkin N, Barber J, et al.: Gross total resection correlates with long-term survival in pediatric patients with glioblastoma. World Neurosurg 79 (3-4): 537-44, 2013 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/23017588" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23017588</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_4">Fouladi M, Hunt DL, Pollack IF, et al.: Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945. Cancer 98 (6): 1243-52, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12973849" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12973849</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_5">Wolff JE, Driever PH, Erdlenbruch B, et al.: Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the HIT-GBM-C protocol. Cancer 116 (3): 705-12, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/19957326" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19957326</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_6">Kramm CM, Butenhoff S, Rausche U, et al.: Thalamic high-grade gliomas in children: a distinct clinical subset? Neuro Oncol 13 (6): 680-9, 2011. [<a href="/pmc/articles/PMC3107103/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3107103</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21636712" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21636712</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_7">Tendulkar RD, Pai Panandiker AS, Wu S, et al.: Irradiation of pediatric high-grade spinal cord tumors. Int J Radiat Oncol Biol Phys 78 (5): 1451-6, 2010. [<a href="/pmc/articles/PMC5095924/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5095924</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20346593" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20346593</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_8">Wolff B, Ng A, Roth D, et al.: Pediatric high grade glioma of the spinal cord: results of the HIT-GBM database. J Neurooncol 107 (1): 139-46, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/21964697" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21964697</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_9">Ononiwu C, Mehta V, Bettegowda C, et al.: Pediatric spinal glioblastoma multiforme: current treatment strategies and possible predictors of survival. Childs Nerv Syst 28 (5): 715-20, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22307824" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22307824</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_10">Sposto R, Ertel IJ, Jenkin RD, et al.: The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group. J Neurooncol 7 (2): 165-77, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2550594" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2550594</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_11">Jakacki RI, Cohen KJ, Buxton A, et al.: Phase 2 study of concurrent radiotherapy and temozolomide followed by temozolomide and lomustine in the treatment of children with high-grade glioma: a report of the Children's Oncology Group ACNS0423 study. Neuro Oncol 18 (10): 1442-50, 2016. [<a href="/pmc/articles/PMC5035517/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5035517</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27006176" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27006176</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_12">Pollack IF, Hamilton RL, Sobol RW, et al.: IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children's Oncology Group. Childs Nerv Syst 27 (1): 87-94, 2011. [<a href="/pmc/articles/PMC3014378/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3014378</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20725730" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20725730</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_13">Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15758009" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15758009</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_14">Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352 (10): 997-1003, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15758010" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15758010</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_15">Cohen KJ, Pollack IF, Zhou T, et al.: Temozolomide in the treatment of high-grade gliomas in children: a report from the Children's Oncology Group. Neuro Oncol 13 (3): 317-23, 2011. [<a href="/pmc/articles/PMC3064602/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3064602</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21339192" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21339192</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_16">Duffner PK, Horowitz ME, Krischer JP, et al.: Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328 (24): 1725-31, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8388548" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8388548</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_17">Duffner PK, Krischer JP, Burger PC, et al.: Treatment of infants with malignant gliomas: the Pediatric Oncology Group experience. J Neurooncol 28 (2-3): 245-56, 1996 May-Jun. [<a href="https://pubmed.ncbi.nlm.nih.gov/8832466" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8832466</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_18">Dufour C, Grill J, Lellouch-Tubiana A, et al.: High-grade glioma in children under 5 years of age: a chemotherapy only approach with the BBSFOP protocol. Eur J Cancer 42 (17): 2939-45, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16962317" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16962317</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_19">Espinoza JC, Haley K, Patel N, et al.: Outcome of young children with high-grade glioma treated with irradiation-avoiding intensive chemotherapy regimens: Final report of the Head Start II and III trials. Pediatr Blood Cancer 63 (10): 1806-13, 2016. [<a href="/pmc/articles/PMC5598351/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5598351</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27332770" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27332770</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_20">Warren KE, Gururangan S, Geyer JR, et al.: A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. J Neurooncol 106 (3): 643-9, 2012. [<a href="/pmc/articles/PMC3518022/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3518022</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21968943" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21968943</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_21">McCowage GB, Friedman HS, Moghrabi A, et al.: Activity of high-dose cyclophosphamide in the treatment of childhood malignant gliomas. Med Pediatr Oncol 30 (2): 75-80, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9403013" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9403013</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_22">Finlay JL, Dhall G, Boyett JM, et al.: Myeloablative chemotherapy with autologous bone marrow rescue in children and adolescents with recurrent malignant astrocytoma: outcome compared with conventional chemotherapy: a report from the Children's Oncology Group. Pediatr Blood Cancer 51 (6): 806-11, 2008. [<a href="/pmc/articles/PMC2844080/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2844080</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18802947" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18802947</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_23">Fouladi M, Nicholson HS, Zhou T, et al.: A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: a Children's Oncology Group study. Cancer 110 (11): 2535-41, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17932894" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17932894</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_24">Nicholson HS, Kretschmar CS, Krailo M, et al.: Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer 110 (7): 1542-50, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17705175" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17705175</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_25">Wetmore C, Daryani VM, Billups CA, et al.: Phase II evaluation of sunitinib in the treatment of recurrent or refractory high-grade glioma or ependymoma in children: a children's Oncology Group Study ACNS1021. Cancer Med 5 (7): 1416-24, 2016. [<a href="/pmc/articles/PMC4944867/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4944867</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27109549" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27109549</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_26">Robinson GW, Orr BA, Gajjar A: Complete clinical regression of a BRAF V600E-mutant pediatric glioblastoma multiforme after BRAF inhibitor therapy. BMC Cancer 14: 258, 2014. [<a href="/pmc/articles/PMC3996187/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3996187</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24725538" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24725538</span></a>]</div></li><li><div class="bk_ref" id="CDR0000614165_rl_102_27">Kieran MW, Hargrave DR, Cohen KJ, et al.: Phase 1 study of dabrafenib in pediatric patients (pts) with relapsed or refractory BRAF V600E high- and low-grade gliomas (HGG, LGG), Langerhans cell histiocytosis (LCH), and other solid tumors (OST). [Abstract] J Clin Oncol 33 (15 Suppl): A-10004, 2015.</div></li></ol></div></div><div id="CDR0000614165__78"><h2 id="_CDR0000614165__78_">Changes to this Summary (12/09/2016)</h2><p id="CDR0000614165__153">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.</p><p id="CDR0000614165__471">This summary was comprehensively reviewed and extensively revised.</p><p id="CDR0000614165__disclaimerHP_3">This summary is written and maintained by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/pediatric-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Pediatric 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="#CDR0000614165__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="CDR0000614165__AboutThis_1"><h2 id="_CDR0000614165__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000614165__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000614165__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood astrocytomas. 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="CDR0000614165__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000614165__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="http://www.cancer.gov/publications/pdq/editorial-boards/pediatric-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Pediatric 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="CDR0000614165__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000614165__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="CDR0000614165__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 Childhood Astrocytomas Treatment are:</p><ul><li class="half_rhythm"><div>Kenneth J. Cohen, MD, MBA (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital)</div></li><li class="half_rhythm"><div>Louis S. Constine, MD (James P. Wilmot Cancer Center at University of Rochester Medical Center)</div></li><li class="half_rhythm"><div>Karen J. Marcus, MD (Dana-Farber Cancer Institute/Boston Children's Hospital)</div></li><li class="half_rhythm"><div>Roger J. Packer, MD (Children's National Medical Center)</div></li><li class="half_rhythm"><div>Malcolm A. Smith, MD, PhD (National Cancer Institute)</div></li></ul><p id="CDR0000614165__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="http://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="CDR0000614165__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000614165__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 Pediatric 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="CDR0000614165__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000614165__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="CDR0000614165__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000614165__AboutThis_15">PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Astrocytomas Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="http://www.cancer.gov/types/brain/hp/child-astrocytoma-treament-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www.cancer.gov/types/brain/hp/child-astrocytoma-treament-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389382]</p><p id="CDR0000614165__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="http://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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<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/NBK65944.6/?report=reader">PubReader</a></li><li><a href="/books/NBK65944.6/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK65944" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK65944" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Pediatric Treatment Editorial Board. 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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="#CDR0000614165__4" ref="log$=inpage&link_id=inpage">General Information About Childhood Astrocytomas</a></li><li><a href="#CDR0000614165__33" ref="log$=inpage&link_id=inpage">Stage Information for Childhood Astrocytomas</a></li><li><a href="#CDR0000614165__35" ref="log$=inpage&link_id=inpage">Treatment Option Overview for Childhood Astrocytomas</a></li><li><a href="#CDR0000614165__40" ref="log$=inpage&link_id=inpage">Treatment of Childhood Low-Grade Astrocytomas</a></li><li><a href="#CDR0000614165__102" ref="log$=inpage&link_id=inpage">Treatment of Childhood High-Grade Astrocytomas</a></li><li><a href="#CDR0000614165__78" ref="log$=inpage&link_id=inpage">Changes to this Summary (12/09/2016)</a></li><li><a href="#CDR0000614165__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/NBK65954/">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" id="Shutter"></a></div><div class="portlet_content"><ul><li class="brieflinkpopper"><a class="brieflinkpopperctrl" 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xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Childhood Ependymoma 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 Ependymoma 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/26389330" 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Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389243" 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> Childhood Rhabdomyosarcoma 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 Rhabdomyosarcoma 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" 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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></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=26389382" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=26389382" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="recent_activity" id="Shutter"></a></div><div class="portlet_content"><div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" 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