PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES

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1 PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES CENTRAL NERVOUS SYSTEM ANAPLASTIC GLIOMAS

2 CNS Site Group Anaplastic Gliomas 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 OTHER 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 6 2

3 Anaplastic Gliomas 1. Introduction anaplastic astrocytoma anaplastic oligodendroglioma anaplastic oligoastrocytoma annual incidence is approx. 0.5/100,000 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 no TMN classification typical appearance on imaging: infiltrative flair abnormality with or without several inner areas of diffuse enhancement absence of vascular proliferation and necrosis differentiates AA from GBM tumors histopathology WHO 2007 classification: WHO Grade III: anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic oligoastrocytoma (AOA) median survival: anaplastic astrocytoma 5 years anaplastic astrocytoma 2-3 years anaplastic oligoastrocytoma intermediate between above 2 LOH of 1p19q assessed in all tumours containing an oligo component co-deletion of 1p19q associated with improved prognosis and survival and chemosensitivity methylation of MGMT does confer an improvement in prognosis as in GB presence of IDH1 mutation confers a significant improvement in survival, seen in approx. 60% of patients 5. Management 5.1 Management Algorithms patients present to a neurosurgeon with typical imaging, and they will proceed to a maximal safe resection or biopsy only depending on the constellation of clinical circumstances and co-morbid conditions occasionally pre-operatively and most often post-operatively once pathology is available, all cases are reviewed at tumour board by a multidisciplinary team (neurosurgery, radiation oncology, neuro-oncology, neuropathology, neuroradiology) for a recommendation on further management 3

4 major prognostic factors include age, performance status, co-deletion of 1p19q there currently is no standard of care for this group of neoplasms post-operative options include the following: AA: RT only (54-60 Gy/30) AO: RT/concurrent & adjuvant temozolomide RT only (54-60 Gy/30) RT/concurrent & adjuvant temozolomide temozolomide only in co-deleted patients AOA: RT only (54-60 Gy/30) RT/concurrent & adjuvant temozolomide temozolomide only in co-deleted patients pseudoprogression is a frequent finding within 1-6 months following RT or RT/concurrent temozolomide in anaplastic gliomas, most often demonstrated on MRI as an increase or the appearance of new areas of enhancement with a stable or smaller area of flair abnormality MR spectroscopy, perfusion, and diffusion may be able to distinguish between true progression and pseudoprogression in about 60-70% of cases, but is not reliable enough to determine the exact situation for any individual patient for this reason, when patients have evidence of possible progression at 1-6 months post- RT/temozolomide) it is recommended that either continued observation or adjuvant temozolomide be continued until the next MRI brain some 3 months later gliomatosis cerebri: upfront temozolomide only (5 day regimen), RT reserved for progression (54 Gy/30) 5.2 Surgery maximal safe resection is recommended in all cases where possible depending on location of tumour in brain, and general medical condition of patient most studies demonstrate improved survival with gross total resection as opposed to partial resection as opposed to biopsy only, but no class 1 data exists surgery at recurrence is a useful approach where mass effect is present 5.3 Chemotherapy initial management: currently no standard of care AA: daily concurrent temozolomide (75 mg/m 2 ) during 6 week course of RT adjuvant temozolomide ( mg/m 2 ) in 5 days/28 day cycle for 12 cycles co-deleted AO or AOA: temozolomide only ( mg/m2) in 5 days/28 day cycle for 12 cycles recurrence: no standard of care exists options include: temozolomide ( mg/m 2 ) in 5 days/28 day cycle temozolomide daily continuous (50 mg/m 2 ) CCNU (lomustine) 130 mg/m² as a single oral dose every 6 weeks bevacizumab (avastin) infusion q2 weekly at either 5 or 10 mg/m Radiation Therapy immobilization: thermoplastic U/S frame Imaging: CT, MRI flair, T1 with gadolinium 4

5 GTV: surgical cavity + flair abnormality care is taken to not include surgical approach areas CTV: 1.0 cm PTV: 0.3 to 0.5 cm Technique: IMRT Dose: Gy in 30 fractions IGRT: daily cone beam CT performed, and all displacements greater than 1 mm are corrected prior to treatment delivery, and for all angular displacements greater than 3 degrees, a repeat set up is undertaken Shorter course of irradiation: Age > with poor performance status. Options: 40 Gy/15, CT/MRI based planning to partial brain 20 Gy/5 or 30 Gy/10 whole brain radiation, clinical set up 5.5 Other Therapy patients are encouraged to enter experimental trials of phase I/II studies of new agents 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 7.2 Psychosocial Care assess family finances 5

6 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 1 month post-rt with MRI brain thereafter monthly for chemotherapy with MRI q3 monthly for 1 year. thereafter q3-4 monthly with MRI 6

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