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Published on January 19, 2016

Author: ishajaiswal169


1. Management Of Gliomas Made By: Dr. Isha Jaiswal Guided By Prof. Kamal Sahni Date:13 January 2016

2. Topics to be covered General management Management of low grade gliomas: overview Pilocytic astrocytoma non pilocytic/diffuse infiltrating gliomas Management of high grade gliomas: overview Anaplastic gliomas Glioblastoma multiformae

3. Medical management For Cerebral oedema: Glucocorticoids used :Dexamethasone preferred because of minimal mineral-corticoid effects. Lower doses :shown to be as effective as higher doses-2 to 4 mg bd preferred should be discontinued or tapered to the lowest dose necessary, as soon as possible. taper is necessary to prevent rebound in cerebral edema and also to allow the pituitary– adrenal axis to recover.

4. For seizures Patients with seizures require anticonvulsants. Levetiracetam preferred: non–hepatic isozymes inducing carbamazepine, phenobarbital, and phenytoin (induce hepatic cytochrome P450 isozymes) reduce the efficacy of corticosteroids & chemotherapy. Prophylactic anticonvulsant use remains controversial American Academy of Neurology recommended against it because of lack of efficacy and potential side effects like cognitive impairment, myelosuppression, liver dysfunction, and dermatologic reactions. FOR PATIENT WHO HAVE UNDERGONE ANY TREATMENT…ANY FORM OF SURGERY,BIPSY OR RR: prophylactic anticonvulsant given for shortest period of time *Glantz MJ, Cole BF, Forsyth PA, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;54:1886– 1893.

5. Definitive treatment of gliomas: options • Surgery: • Resection For Cure • Surgical Debulking • Biopsy • CSF Diversion Procedures • Radiotherapy • Chemotherapy


7. Goals: • Prolong progression-free survival & overall survival • Improve, maintain, slow the decline in neurological function • Minimize treatment-related effects Treatment Options: • Observation • Surgery • Radiation • Chemotherapy

8. Observation: • Includes MRI monitoring at regular intervals (e.g., every 6 months) to detect radiologic progression before new signs and symptoms occur. PROS: • Low grade Gliomas: considered relatively favourable natural history compared o high grade • lack of proven benefit for surgery or radiation therapy in improving overall survival • No treatment associated morbidities CONS: • Natural history is significantly worse than that of an age- and sex matched control population

9. Based on this observation is under treatment Maximal Safe Surgical Resection followed by PORT improve survival , and may cure pts. Survival curves for pts with various subtypes of low-grade glioma compared age and sex matched control population. ,Adapted from Shaw EG: The low-grade glioma debate. Evidence defending the position of early radiation therapy. Clin Neurosurg 42:488-494, 1995.

10. Surgery Pros: • benefits of surgery on seizures / raised ICT are fairly dramatic • Early Surgery delays reappearance of symptoms and tumor growth • Imaging can be misleading in upto 40% cases ,surgery provides histological confirmation • Survival advantage to gross resection in retrospective literature Cons: • Possibility of complications in a minimally symptomatic person

11. With advancement in technology ,morbidity of surgery has decreased hence surgery is the mainstay of treatment Observation with MRI monitoring :can be reserved for very few patients with ≤ 1cm tumor and minimal symptoms Extent of resection :No prospective randomized trials to assess the impact of maximal tumor resection so maximal safe resection preferred

12. Adjuvant Radiation (RT) • Timing • Dose • Treatment volume

13. Adjuvant radiotherapy PROS Improves outcome in unresectable & partially resectable tumors increased Progression Free Survival RT does not decrease seizure CONS No improvement in overall survival Increased morbidity especially in young pt :neurocognitive decline , dementia , behavioural changes, vasculopathy, development of 2nd malignancy.

14. total 362 eligible pts accrued between 1998 and 2002.  Median follow-up time 4 years. For 111 favourable pts observed on Arm 1,  OS at 2- and 5-yrs is 99% and 94%.  PFS at 2- and 5-yrs is 82% and 50% Risk Factors predictive of a poorer PFS 1. Pre-operative tumor diameter of >/=4 cm 2. Astrocytoma histology 3. Residual tumor of >/=1 cm2 on Postop MR Patients with: All 3 unfavorable factors- PFS at 5years -13% None of the three factors- PFS at 5years -70% RT vs observation A Phase II Study Of Observation In Favourable Low-grade Glioma And A Phase III Study Of Radiation With Or Without PCV Chemotherapy In Unfavorable Low-grade Glioma

15. Indications for observation So, on the basis of above data Observation after surgery can be a reasonable strategy for the most favorable subset i.e.  age ≤ 40 years  Preoperative tumor diameter <4 cm  Oligodendroglioma histology  gross total resection (GTR).  <1 cm residual tumor

16. • phase III trial :311 pts (WHO 1–2, 51% astro., 14% oligo., 13% mixed oligo-astro) • treated with surgery (42% GTR, 19% STR,35% biopsy) • randomized to observation f/b RT at progression vs. post-op RT to 54 Gy. • RT improved median PFS (5.3 year vs. 3.4 year hazard ratio 0.59, p<0.0001) but not OS median survival 7.4 years RT arm vs. 7.2 in observation arm p=0.872). • 65% pts in observation arm received salvage RT. • Better seizure control rates at 1 year with early RT • No difference in rate of malignant transformation (66–72%). • QOL not studied whether time to progression reflects clinical deterioration not known • CONCLUSION:  early radiotherapy improves symptoms control & PFS but no improvement in OS  delayed radiotherapy does not jeopardize survival EORTC 22845 (Karim et al. 2002; van den Bent et al. 2005)

17. • prognostic factor analysis done on Phase III adult LGG trials (EORTC 22844 and 22845): • Risk Factors identified from EORTC 22844 & Validated in EORTC 22845 • Patients with pilocytic astrocytoma were excluded • Multivariate analysis showed that unfavorable prognostic factors for survival were  age ≥ 40 years,  astrocytoma histology subtype  largest diameter of the tumor > or = 6 cm  tumor crossing the midline  presence of neurologic deficit before surgery • Low Risk Patient: </= 2 factors (Median Survival- 7.7 years) High Risk: 3 or more factors (Median Survival- 3.2 years) • Low risk patients are typically observed postoperatively and given RT at disease progression or recurrence

18. Flaws in pignatti score • KPS ,Extent of resection not taken into account • No weightage of individual prognostic factors


20. Timing of RT : Early vs. delayed Immediate, if significant mass or symptoms For incompletely resected unresectable or only biopsy tumors presence of ≥3 “high-risk” features on the basis of Pignatti score Delayed, if minimal mass or symptoms after gross total resection ≤ 2 high-risk” features on the basis of Pignatti score

21. DOSE OF RT:THREE PHASE III TRIALS RT improved median PFS (5.3 year vs. 3.4 year)(p<.001) but not overall survival. Consequently, low-dose radiotherapy, 45 -54 Gy in 1.8 Gy-2Gy per fractions, has become an accepted practice

22. CTV= T2 FLAIR IMAGES +1-2 cm MARGIN may be used. PTV = CTV +0.5cm LGG Gliomas Do Not Enhance On Mri If Enhancing Treated As Hgg Target Volume For Radiotherapy in LGG .

23. Chemotherapy for Low Grade Gliomas • Previously no role for chemotherapy in adult patients with low-grade gliomas

24. INT/RTOG 9802 trial  From 1998 to 2002,  251 patients  median follow up 6 years  RESULTS  5-year OS rates for RT versus RT/PCV were 7.5 years versus not reached respectively (hazard ratio [HR] = 0.72, p = 0.33)  trend toward improved 5 year PFS 63 vs. 46%(p = 0.06)  acute grade 3/4 toxicity occurred in 67% in RT plus PCV, vs. 9% in RT alone. Phase III Study Of Radiation With Or Without PCV Chemotherapy In Unfavorable Low-grade Glioma Initial results 2006 Conclusion: PCV do not provide a survival advantage over RT alone

25.  median follow-up time is 11.9 years.  RT followed by PCV yielded significantly longer median survival (MST) compared to RT alone (13.3 vs. 7.8 years, p = 0.03; HR = 0.59)  improvement in PFS (10.4 vs. 4.0 years, p = 0.002; HR = 0.50).  Treatment arm was identified as a prognostic variable in favour of RT + PCV for both OS (p = 0.003; HR = 0.59) and PFS (p < 0.001; HR = 0.49).  Molecular markers were not pre-specified; post-hoc analysis of these is ongoing. International Journal of Radiation Oncology • Biology • Physics , Volume 90 , Issue 1 , S37 - S38 Conclusion: PCV provided significant survival advantage over RT alone


27. Role of temozolomide • more preferable option compared to PCV chemotherapy • oral administration • better toxicity profile • Retrospective series and small phase II studies showed objective response in disease progression 1-3 • First-line treatment with TMZ compared to RT did not improve PFS in high-risk LGG patients (EORTC 22033) • Further phase III trials needed 1. Hoang-Xuan K, Capelle L, Kujas M, et al. Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions. J Clin Oncol 2004;22:3133–3138 2. Brada M, Viviers L, Abson C, et al. Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas. Ann Oncol 2003;14:1715–1721. 3. Quinn JA, Reardon DA, Friedman AH, et al. Phase II trial of temozolomide in patients with progressive low-grade glioma. J Clin Oncol 2003;21:646–651.

28. Conclusion for chemotherapy in high risk LGG* • RTOG 9802 (1998-2002) shows significant survival advantage with PCV chemotherapy • However, in the intervening decade novel molecular markers as well as newer chemotherapy agents such as temozolomide have been developed. • So optimal parameter for selecting patients for adjuvant PCV has yet to be decided • And It is still unclear if temozolomide can replace PCV • Hence further trials needed *Van den Bent MJ. Practice changing mature results of RTOG study 9802: another positive PCV trial makes adjuvant chemotherapy part of standard of care in low-grade glioma. Neuro-Oncology. 2014;16(12):1570-1574. *Radiation Therapy Oncology Group 9802: Controversy or Consensus in the Treatment of Newly Diagnosed Low-Grade Glioma? Seminars in Radiation Oncology Volume 25, Issue 3, July 2015, Pages 197–202

29. SUMMARY Grade I Gliomas • Complete resection: offers excellent survival, :majority (>90%) cured of the tumor; no adjuvant therapy is necessary. • Incomplete resection: associated with long-term survival rates of 70% to 80% at 10 years hence usual recommendation is for close follow-up, • PORT: indicated in very few cases depending on the location of the tumor, the extent of residual disease, the feasibility of repeated surgical excision, and availability for follow-up

30. Grade II Gliomas • Maximal surgical resection • Postoperative radiotherapy improves progression-free survival and seizure control were superior. The typical radiotherapy dose is 45 to 54 Gy • Chemotherapy: investigational

31. High grade gliomas

32. HIGH GRADE GLIOMAS • WHO grade III • Anaplastic astrocytoma • Anaplastic oligodendroglioma • Anaplastic oligoastrocytoma • WHO grade IV • Glioblastoma multiforme (GBM)

33. Prognostic Factors in HGG

34. Recursive Partitioning Analysis  Curran et al1 developed a statistical tool based on RTOG trials including 1578 pts. with malignant gliomas from 1974 to 1989 treated with RT without TMZ  identification of significant prognostic factors & classification of patients into groups with similar outcomes  six treatment-related variables were analysed.  Age & KPS are most important prognostic factor  Other prognostic factors: • Histology • Duration of mental symptoms before any treatment • Extent of resection • Mental status 1. Curran WJ Jr, Scott CB, Horton J, et al. Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 1993;85:704–710.

35. RTOG RPA OF MALIGNANT GLIOMA RPA classification retains prognostic significance in patients treated with RT+temozolomide2 as evaluated in EORTC 26981 they used age, WHO performance status, extent of surgery, and the Mini-Mental Status Examination as prognostic variable 2. Mirimanoff RO, Gorlia T, Mason W, et al. Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol 2006;24:2563–2569.

36. • More recently nomograms 3 have developed integrating variables such as MGMT promoter methylation status, age, performance status, extent of resection, and MMSE 3. Gorlia T, van den Bent MJ, Hegi ME, et al. Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 2008;9:29–38.

37. TREATMENT OF GBM  Surgery  Concurrent Chemo-RT  Adjuvant Chemotherapy

38. SURGERY • Extent: Maximum safe surgical resection preferred. • depend on • performance status • tumor location • patient choice • surgical procedures • Other options: • surgical debulking for mass effect • Biopsy only • CSF diversion procedures for inoperable site • Extent of surgery has prognostic significance Hardesty DA, Sanai N. The Value of Glioma Extent of Resection in the Modern Neurosurgical Era. Frontiers in Neurology. 2012;3:140.

39. Radiotherapy • RCT by BTCG demonstrated a clear survival benefit to the use of RT with without nitrosoureas after surgery for malignant gliomas

40. DOSE • Standard dose:60 Gy in 30 fractions. • Walker et al. reported a dose–response analysis in BTSG Trial. • WBRT 45 vs. 50 vs. 55 vs. 60 Gy. • significant improvement in MS from 28 to 42 weeks with doses of 50 to 60 Gy • MRC study also showed a significant survival advantage with 60 Gy/30 fx. • randomized 474 patients to 45 Gy/20 fx vs. 60 Gy/30 fx. • No adjuvant chemo. • MS 12 month (60 Gy) vs. 9 month (45 Gy, p = 0.007) Walker MD, Strike TA, Sheline GE. An analysis of dose-effect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 1979;5:1725–1731 Bleehen NM, Stenning SP. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. The Medical Research Council Brain Tumour Working Party. British J Cancer 1991;64:769–774.

41. DOSE ESCALATION TECHNIQUES Rationale: • majority of tumor recurrences occurring within the irradiation field • poor outcomes associated with standard therapy • Various techniques used to deliver a larger dose to improve local control and enhance survival.  3DCRT  IMRT,  SRT boost,  brachytherapy  hyperfractionation accelerated treatment  Proton therapy & Boron neutron capture therapy • Studies have shown no benefit in median survival from dose escalation beyond 60Gy

42. Hypofrctionated radiotherapy • For patients with poor pretreatment prognostic factors • Older patients (>65 years) KPS≤50 • limited expected survival ,not able to tolerate conventional treatment of 6week • a shorter course of treatment provides good palliation • 40 Gy/15 fx Roa et al. (2004) • phase III: 100 patients with GBM age ≥60 and KPS ≤50 • randomized to 60 Gy/30 fx vs. 40 Gy/15 fx. Enhancing tumour and oedema plus 2.5 cm margin • No difference in MS (5.1 vs. 5.6 month). • Fewer patients in short course RT arm required increased steroids (23 vs. 49%). • 30 Gy/10 fx Bauman et al. (1994): • single arm prospective study. 29 pts with GBM age ≥65 and KPS ≤50 • treated with WBRT 30 Gy/10 fx • RT increased MS vs. best supportive care (10 vs.1 month).  OTHER OPTION 25Gy/5# in INDIAN studies

43. Chemotherapy in GBM

44. • Phase III trial 573 patients, age 18 -70 years WHO PS 0–2 • newly diagnosed glioblastoma (16% biopsy only, 40% GTR, 44% STR) • For 485 (85%) of 573 patients, slides or tumour tissue was available for central pathology review, glioblastoma was confirmed in 450 (93%) of these. • Randomized to RT alone 60 Gy/30 fx. vs. RT + concurrent and adjuvant TMZ • Concurrent daily (75 mg/m2/day) 7 days/week & adjuvant (150–200 mg/m2/day × 5days) q4 weeks × 6 month. • primary endpoint was overall survival EORTC/NCIC (Stupp et al. 2005, 2009) Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009;10:459–466

45. RESULT Initial results: 2005 • median follow-up of 28 months • Concurrent and adjuvant TMZ significantly improved MS (14.6 vs. 12.1 month) P<0.001 by the log-rank test) • 2-year survival rates of 26% and 6%, • Toxicity :7% grade 3/4 hematologic toxicities in Combined arm vs. none in RT alone Updated results:2009 • median follow-up of 61 months (range 11 days to 79 months). • 278 /286 (97%) pts. in RT alone & 254/287 (89%) in combined- group died during 5 years of follow-up • 5-year OS (9.8 vs. 1.9%)

46. Updated results: • benefit in all subgroup • including patients aged 60–70 years. • MGMT methylation was strongest predictor for benefit from TMZ

47. Kaplan-Meier estimates of overall survival by treatment RPA class III (A). RPA class IV (B). RPA class V (C). Benefit In class III-V Maximum in Class III

48. DOSE INTENSE TMZ • 833 pts Eligibility criteria included age > 18 yrs, KPS ≥ 60, • randomized to receive standard therapy TMZ plus RT followed by • Arm 1: standard TMZ (150-200 mg/m2 x 5 d) or Arm 2: dd TMZ (75-100 mg/m2 x 21 d) q 4 wks for 6-12 cycles. • Primary Endpoint was OS. Secondary analyses evaluated impact of MGMT status. • No statistical difference was observed between Arms 1 and 2 for median OS (16.6, 14.9 mo, p = 0.63), or median PFS (5.5, 6.7 mo, p = 0.06), or by methylation status. • MGMT methylation was associated with improved OS (21.2, 14 mo, p < 0.0001), PFS (8.7, 5.7 mo, p < 0.0001) and response (p = 0.012). • There was increased grade ≥ 3 toxicity in Arm 2 (19%, 27%, p = 0.008); mostly lymphopenia and fatigue. Gilbert MR, Wang M, Aldape KD, et al. RTOG 0525: A randomized phase III trial comparing standard adjuvant temozolomide with a dose-dense schedule in newly diagnosed glioblastoma. J Clin Oncol 2011;29:abstr 2006.

49. Management of GBM : summary • Maximal surgical resection • Postoperative radiotherapy 60 Gy in 6 weeks along with standard dose TMZ , given during and after radiotherapy

50. Anaplastic astrocytoma ( WHO GRADE 3) Anaplastic gliomas constitute approximately 25% of high-grade gliomas in adults anaplastic astrocytomas anaplastic oligodendrogliomas anaplastic mixed oligoastrocytomas Tteatemnt options Surgery Radiotherapy Chemotherapy 1p-19q co deletion is prognostic in anaplastic oligodendroglioma

51. • Maximal surgical resection is generally associated with more favorable outcome and is recommended whenever feasible. • Postoperative radiotherapy has been shown to provide a survival advantage in several clinical trials (included WHO grade III and IV tumors; no trial for only grade III tumors has been conducted) • Dose:60Gy/30# @ 2 Gy/#

52. Chemotherapy in grade III gliomas • The role and which chemotherapy to be used remains undefined. • Patients with co deletions of 1p and 19q have a more favorable prognosis and respond better to both chemotherapy and radiotherapy

53.  Between August 13, 1995, and March 3, 2002  368 patients newly diagnosed anaplastic oligodendroglioma  Central pathology review confirmed presence of an oligodendroglial tumor in 257 patients (AOD, 175; mixed AOA, 82)  randomly assigned to either 59.4 Gy of RT or same RT f/b 6 cycles of adjuvant PCV.  primary end points :overall survival (OS) and PFS.  Patients tested for 1p/19q status, IDH status, and MGMT promoter methylation status  exploratory analysis of the correlation between 1p/19q status and survival was part of study.

54.  median follow-up of 140 months  OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95).  PFS was significantly better after RT/PCV (median PFS, 24.3 months after RT/PCV v 13.2 months with RT only; HR, 0.66; 95% CI, 0.52 to 0.83; Results

55. Subgroup Analysis by 1p/19q Status: OVDERALL SURVIVAL In 80/316 cases (25%) with tissue available for 1p/19q assessment,codeletion of 1p/19q was found. In these patients with codeleted tumors, OS was not reached in the RT/PCV group versus 112 months in the RT group (HR, 0.56; 95% CI, 0.31 to 1.03; ( Fig 3A). In the patients with noncodeleted tumors, the risk reduction was less: OS of 25 versus 21 months (HR, 0.83; 95% CI, 0.62 to 1.10; (Fig 3B).

56. In codeleted group, PFS was 157 months after RT/PCV and 50 months after RT only (HR, 0.42; 95%CI, 0.24 to 0.74; (Fig 4A). In the patients with noncodeleted tumors, PFS was 15 months in RT/PCVgroup and 9 months in RTonly group (HR, 0.73; 95% CI, 0.56 to 0.97; Fig 4B Subgroup Analysis by 1p/19q Status: PROGRESSION FREE SURVIVAL

57.  In anaplastic oligodendroglioma pt only  1994 to 2002 :291 eligible pts randomly assigned: 148 to PCV plus RT and 143 to RT.  primary end point: overall survival (OS).  At first analysis, PCV did not appear to improve survival for any subgroup.  In a recent updated analysis :survival benefit from PCV in 1p19q codeleted subset.  At median follow-up of >11 years. (range, 0.5 to 16.8 years)  median overall survival for patients receiving RT alone or RT plus PCV was similar.  Unplanned analysis showed, 126 pts with 1p19q codeleted had much longer MS than 135 pts non 1p19q codeletion: (8.7 vs 2.7 years.  1p19q codeletion predicted the benefit from adding PCV to RT.

58. 1p-19q co del in RT arm1p-19q co del in RT+CT arm OS by treatment grp OS 1p-19q non co del arm OS in 1p-19q co del arm

59. Role of Temozolomide • temozolomide has shown activity in patients with recurrent anaplastic astrocytoma. (Yung et al pahse II trial ) • this trial suggest that temozolomide has antitumor activity with an acceptable safety profile for anaplastic astrocytoma. • Role is being tested in ongoing phase III clinical trial of non–1p19q- codeleted anaplastic glioma patients • CATNON Intergroup trial: To assess whether concurrent and adjuvant temozolomide improves overall survival as compared to RT alone in patients with non-1p/19q deleted anaplastic glioma.

60. Management of Grade III glioma: summary • Maximal safe resection. • Postoperative radiotherapy 60 Gy in 6 weeks. • The role of chemotherapy remains undefined for the non-codeleted anaplastic gliomas. • Temozolomide is active in recurrent anaplastic astrocytoma and is currently being tested in the up-front setting. • PCV chemotherapy has a proven survival advantage over radiotherapy alone in 1p and 19q codeleted patients.

61. Radiotherapy techniques

62. Simulation  Position: supine  immobilization : individualized headrest & Aquaplast mask  RTP scans using i.v contrast are taken with 1–3 mm slices from the vault to the base of the skull  CECT-RTP data fused with MRI data  target volumes were defined using CT-MR fusion data set

63. Target volumes Low-grade gliomas.  Single phase treatment  EBRT dose: 1.8 Gy/fx to 50.4–54 Gy.  GTV =T2/FLAIR IMAGES  CTV = GTV + 1–2 cm margin.  PTV = CTV + 0.3–0.5 cm.

64. Whole brain RT (WBRT) vs. Partial Brain RT (PBRT) in HGG and margins WBRT Vs PBRT • RCT (n=303) of WBRT-60Gy vs WBRT -43Gy + PBRT boost-17Gy • No difference in outcome (Shapiro, J Neurosurg, 1989). Margins • Autopsy studies reveal that microscopic tumour within 2cm of enhancing margins on scan in 90% and only 3% multicentric (Hochberg FH, Pruitt A. Assumptions in the radiotherapy of glioblastoma. Neurology 1980;30:907–911) • 78% (25 of 32) of tumors recurred within 2 cm & 56% (18 of 32) in 1 cm of the initial tumor margin.( Wallner KE, Gallcich JH, Krol G, et al. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. IJROBP1989;16:1405–1409.) Standard Of Care - PBRT encompassing the enhancing tumour + 2-3 Cm Margins

65. High-grade gliomas: EBRT: 1.8–2 Gy/fx to 45–46 Gy followed by boost to 59.4–60 Gy Phase 1: • GTV1 = T1 enhancement + T2/FLAIR. • CTV1 = GTV1 + 2 cm margin. • PTV = CTV + 0.3–0.5 cm Phase 2 : • GTV2 = T1 enhancement. • CTV2 = GTV2 + 2 cm • PTV = CTV + 0.3–0.5 cm


67. Dose constraints


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