PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES
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1 PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES CENTRAL NERVOUS SYSTEM MEDULLOBLASTOMA AND PNET
2 CNS Site Group Medulloblastoma and PNET Author: Dr. Norm Laperriere 1. INTRODUCTION 3 2. PREVENTION 3 3. SCREENING AND EARLY DETECTION 3 4. DIAGNOSIS AND PATHOLOGY 3 5. MANAGEMENT MANAGEMENT ALGORITHMS SURGERY CHEMOTHERAPY RADIATION THERAPY 5 6. ONCOLOGY NURSING PRACTICE 5 7. SUPPORTIVE CARE PATIENT EDUCATION PSYCHOSOCIAL CARE SYMPTOM MANAGEMENT CLINICAL NUTRITION PALLIATIVE CARE REHABILITATION 6 8. FOLLOW-UP CARE 5 Last Revision Date July
3 Medulloblastoma and PNET 1. Introduction this guideline is exclusively for medulloblastoma and PNET occurring in ADULTS medulloblastomas originate in the cerebellum, PNETs although histologically similar originate elsewhere in the CNS, but are biologically more aggressive age distribution of medulloblastoma is predominantly in children, with about 10% of cases occurring in young adults PNETs are far less common than medulloblastomas, but treatment is similar, although less effective medulloblastomas account for < 2% of intracranial malignancies in adults This document is intended for use by members of the Central Nervous System site group of the Princess Margaret Hospital/University Health Network. The guidelines in this document are meant as a guide only, and are not meant to be prescriptive. There exists a multitude of individual factors, prognostic factors and peculiarities in any individual case, and for that reason the ultimate decision as to the management of any individual patient is at the discretion of the staff physician in charge of that particular patient s care. 2. Prevention No specific prevention available 3. Screening and Early Detection No screening available 4. Diagnosis and Pathology WHO grade IV tumours medulloblastomas are associated with Gorlin s and Turcot s syndrome, usually as the first manifestation of either syndrome both entities have a high likelihood of spread via CSF typical imaging demonstrates heterogeneously enhancing tumour of post fossa laterally occurring in cerebellar hemispheres in adults (as opposed to midline vermis in children) often associated with hydrocephalus low intensity on T1 and CT it is highly recommended that MRI of spine be done prior to surgery, as post-operative MRI of spine may be difficult to interpret related to post-operative blood and inflammatory effects in spine post-operative MRI of brain is recommended to be done within hrs of surgery to best assess extent of locally residual disease and extent of resection it is recommended that hydrocephalus be dealt with via resection of primary tumour rather than a CSF shunt evidence of CSF spread assessed by MRI brain and spine, AND a lumbar puncture done no sooner than 14 days post-operatively these are highly cellular neoplasms that are composed of cells with small- to mediumsized, hyperchromatic nuclei and little apparent cytoplasm nucleoli are not typically prominent, except in the large-cell/anaplastic variant mitoses are usually plentiful, as is the necrosis (apoptosis) of individual cells in the form of nuclear pyknosis, fragmentation, or karyorrhexis Homer Wright ("neuroblastic") rosettes may be found in about 40% of cases Last Revision Date July
4 immunohistochemistry: synaptophysin, neuron-specific enolase, MAP-2, and class-iii beta tubulin will be at least focally immunoreactive in most medulloblastomas expression of nuclear beta-catenin occurs in 15-20% of medulloblastomas and is considered to correlate with activation of the WNT signaling pathway and a better patient prognosis the MYCC gene is amplified in around 10% of medulloblastomas and is most often observed in anaplastic variants of medulloblastoma other molecular alterations associated with a poor prognosis include chromosome 1q gain, MYCN amplification, C-ERBB2 overexpression, and p53 mutation/expression loss of chromosome 6 and TRK-C expression are related to a better prognosis histologic subgroups of medulloblastoma: classic desmoplastic/nodular large cell anaplastic prognostic scales based on extent of locally residual tumour post-surgery and presence or absence of CSF spread low or average risk: < 1.5 cm3 of tumour at primary site post-operatively AND no evidence of CSF spread high risk: > 1.5 cm3 of tumour at primary site post-operatively OR evidence of CSF spread all anaplastic & large cell histologies all PNETs new molecular classification currently being validated 5. Management 5.1 Management Algorithms in low risk medulloblastomas, the craniospinal RT dose has been able to be reduced from 36 Gy to 23.4 Gy with the addition of cisplatin based chemotherapy, but this has been found to be too toxic in adults, and accordingly craniospinal RT only is the recommended approach in adults with low risk medulloblastoma in high risk medulloblastomas and all PNETs, cisplatin based chemotherapy has been added to craniospinal RT at Gy, although no benefit has been demonstrated in randomized trials, all based on phase II data, but it has been found to be too toxic in adults, and accordingly RT only is currently recommended in adults 5.2 Surgery the major goals of surgery are to attempt a gross total resection of the primary tumour and address the issue of hydrocephalus, hopefully without the need for a VP shunt 5.3 Chemotherapy chemotherapy is currently not recommended as part of initial management of adults with medulloblastoma or PNET at recurrence, a variety of chemotherapy regimens may be considered, simple oral approaches such as temozolomide, CCNU, procarbazine, cyclophosphamide, and more intensive regimens that are cisplatin based, although no standard of care exists in this situation, all are non-curative Last Revision Date July
5 5.4 Radiation Therapy Craniospinal Component immobilization: supine position, thermoplastic S frame imaging: CT brain and whole spine, MRI T1 gad and flair of brain 2D planning all intracranial contents and cervical cord via lateral opposed pair, gantry rotated at approx degrees to match divergence of posterior whole spine field single post spine field accomplished at extended SSD if necessary, divergence of superior border of field matches gantry rotation of lateral brain/cervical cord fields junction is an electronic match on a bb placed on midline anterior neck of thermoplastic S frame inferior border of post spine field is cm caudal to distal thecal sac in upper sacrum, usually in region of S3 vertebrae Dose: 36 Gy/20 in all cases, possibly 39.6 Gy/22 for high risk cases Boost to primary tumour GTV: surgical cavity plus residual tumour, taking into account any CPA extension preoperatively CTV: 1 cm PTV: 3-5 mm Boost to 55.8 Gy/31 fractions to primary site, 54 Gy/30 to metastatic gross areas of disease (both for intracranial and spinal regions) 6. Oncology Nursing Practice Refer to general oncology nursing practices 7. Supportive Care 7.1 Patient Education Driving possible restriction Seizures education about seizures what to do when a seizure occurs how to take seizure medications possible side effects of seizure medications avoid heights, taking baths or swimming alone Raised Intracranial Pressure: Steroids symptoms of raised intracranial pressure side effects of steroids titration of steroids for optimal dose When to call multidisciplinary team change in seizure pattern new or progressive neurologic loss symptoms of raised intracranial pressure Last Revision Date July
6 7.2 Psychosocial Care assess family finances assess for possible disability applications assess possible depression/anxiety presence or absence of drug program, apply for provincial assistance if necessary possible need for assistive devices or services in the home 7.3 Symptom Management seizures raised intracranial pressure neurologic loss visual loss depression psychosis anger issues poor memory 7.4 Clinical Nutrition recommend normal diet as per recommendations of Canadian Cancer Society diabetic diet if elevation of blood glucose secondary to steroids 7.5 Palliative Care make referral in cases of progressive disease for which there is no further active therapy recommended management of uncontrolled symptoms 7.6 Rehabilitation in cases of neurologic loss, assess for possible rehabilitation OT/PT assess for supportive devices in the home 8. Follow-up Care q4-6 monthly with MRI brain (for low risk disease) + MRI spine for known prior gross disease for first 2 years q6 monthly until 5 years post-treatment q 12 months between 5-10 years post treatment q24 months beyond 10 years post treatment Last Revision Date July
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