Radiotherapy for intracranial meningiomas SAMO Interdisciplinary Workshop on Brain Tumors and Metastases November 2016

Transcription

1 WIR SCHAFFEN WISSEN HEUTE FÜR MORGEN PD Dr Alessia Pica, Pr Damien Charles Weber: Paul Scherrer Institut Radiotherapy for intracranial meningiomas SAMO Interdisciplinary Workshop on Brain Tumors and Metastases November 2016

2 Plan Introduction Type of radiotherapies and RTQA Management of Grade 1 Meningiomas Management of non-grade 1 Meningiomas NRG/EORTC prospective trials Conclusions

3 Introduction Apprimately 20% of brain tumors Increase with age Twice as frequent in women than in men Grade WHO grade 1+++ Atypical meningioma Mitotic rate > 4 mitotic figures/hpf Increased cellularity Small cells with high ratio nucleus (cytoplasm Prominent nucleoli Sheet-like growth pattern Geographic necrosis 3/5 features Importance of the extend of surgery Simpson D J Neurol Neurosurg Psychiatry 1957;20:22-39

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6 Introduction HUG EB, J Neuro-Oncology 2000 Milker-Sabel S IJROBP 2005

7 Introduction: the outcome of AM patients is suboptimal Relapse-Free Survival Overall Survival Perry, A. Meningiomas. McLendon R, Rosenblum M, Bigner DD (ed.) Russell & Rubinstein s Pathology of Tumors of the Nervous System. 7 th ed. Hodder Arnold (Publisher), London, England 2006, p

8 Introduction: Local Control Weber DC Int J Radiat Oncol Biol Phys 2012; 83(3):865

9 Type of Radiotherapy Many ways to administer RT EBRT with or without IM Stereotactic RT (SFRT, SRS) Proton therapy, Carbon beam therapy Weber DC Int J Radiat Oncol Biol Phys 2012; 83(3):865

10 Proton Therapy

11 Photon versus Proton Therapy Dose Distributions of the same Volume from Photon and Proton Fields Photon Therapy Proton Therapy Courtesy of A. Lomax

12 Case Study: meningioma «en plaque» Page 12

13 RTQA in RT

14 RTQA in RT

15 Management of grade 1 Meningioma Several retrospective studies have shown that RT after STR is beneficial for patients with benign meningioma (WHO Grade 1) Author Year Journal Barbaro NM et al Neurosurgery Carella RJ et al Neurosurgery Condra KS et al Int J Radiat Oncol Biol Phys DeMonte F et al Oncology Glaholm J et al Int J Radiat Oncol Biol Phys Maguire PD et al Int J Radiat Oncol Biol Phys Maire JP et al Int J Radiat Oncol Biol Phys Mesic JB et al Am J Clin Oncol Miralbell R et al J Neurooncol Pourel N et al Radiother Oncol Taylor Jr BW et al Int J Radiat Oncol Biol Phys Wenkel E et al Int J Radiat Oncol Biol Phys

16 Management of grade 1 Meningioma Debate over the timing of RT-whether it should be given postoperatively or at the time of progression. Chang EL, Radiother Oncol, 2004;71:85

17 Management of grade 1 Meningioma Phase III trial assessing the impact of radiation therapy on tumor control and QoL for patients with non-gross total resection (Simpson 3) as documented on MRI performed 1 month postoperatively. Targeted sample size of 478 patients was calculated and the protocol was activated in Weber DC, Curr Opinion Neurol 2010;23:563-79

18 Management of grade 1 Meningioma Survey BSNS Marcus HJ British J Neurosurg;2008:22(4):520-8 Potential therapeutic strategy Adjuvant RT salvage Simpson < 3 No Yes Simpson >3, Young/male Maybe Yes Simpson > 3, no FU possible Maybe NA Simpson >3, Elderly/female No Yes Simpson >3, atypical histology but nevertheless grade 1 Maybe NA Seite 18

19 Management of non-grade 1 Meningioma Weber DC, Curr Opinion Neurol 2010;23:563-79

20 Management of non-grade 1 Meningioma Dose escalation in newly diagnosed grade II/III meningioma

21 Management of non-grade 1 Meningioma

22 Management of non-grade 1 Meningioma Adjuvant Radiotherapy for Atypical and Malignant Meningiomas: A Systematic Review Atypical Meningioma Synopsis Kaur G, Sayegh ET, Larson A, Bloch O, Madden M, Sun MZ, Barani IJ, James CD, Parsa AT. Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review. Neuro-Oncology 2014;16(5): DOI: /neuronc/nou025

23 Management of non-grade 1 Meningioma Aghi MK, Carter BS, Cosgrove GR, Ojemann RG, Amin-Hanjani S, Martuza RL, Curry WT, Barker FG. Long-term recurrence rates of atypical meningiomas after GTR with or without postoperative adjuvant radiation. Neurosurgery 2009;64(1):56-60 Massachusetts General Hospital 108 atypical meningioma patients Each with Simpson Gr1 resection 48 men, 60 women, mean age 55 Mean serial imaging f/u 39 month % of Simpson grade 1 resected AMs with radiographic recurrence after resection with and without post-op RT 100% No RT (n=100) 75% RT (n=8) 8 patients received post-op FSRT Mean 60.2Gy, Gy/fraction PTV=resection bed + 1cm (mean) Mean isodose 88% 50% 25%! "#"$%&" Only RT morbidity was an enhancing abnormality in the resection cavity of 1 pt 1y after GTR, required resection, and was necrosis w/o tumor. 0% Time (yrs) * Determined from graph

24 Management of non-grade 1 Meningioma % Recurrence Komotar RJ, Iorgulescu JB, Raper DMS, Holland EC, Beal K, Bilsky MH, Brennan CW, Tabar V, Sherman JH, Yamada Y, Gutin PH. The role of radiotherapy following gross-total resection of atypical meningiomas. Journal of Neurosurgery % of gross totally resected AMs with radiologic (MRI) recurrence after resection Memorial Sloan Kettering 45 G2 meningioma patients, Each with gross total resection 20 men, 25 women, mean age 56 Mean f/u 44.1 months 13 pts received post-op CRT / IMRT Mean 59.4 Gy, Gy / fraction PTV = resection bed cm Med time to recur 19 mo w/o RT 1 pt recurred after RT at 52.5 mo All patients tolerated treatment well. with and without post-op RT GTR alone (n=32) GTR + RT (n=13) 65%* 20%* Time (yrs) p =.085 * Determined from graph Recurrences resulted in shortened OS & additional treatment burden. Our results contribute to a growing number of series in support of routine post-op RT.

25 Management of non-grade 1 Meningioma % Progression-Free Survival Impact of adjuvant radiosurgery/imrt on atypical meningioma recurrence following aggressive microsurgical Barrow Neurological Institute resection 228 atypical mening pts, Re-graded per current WHO criteria Aggressive microsurgical resection GTR (Simpson I or II) 58%, STR 42% 97 men (43%), 131 women (57%) Mean age at 1 st surg 62 (range 2-94) yr Mean post-op clin & imaging f/u 52 mo 32 patients received post-op SRS SRS after GTR in 31%, STR 69% 19 GK, median 14 Gy x 1 13 CK, Gy in 1, Gy in 3, 25 in 5 39 patients received post-op IMRT IMRT after GTR 49%, STR 51% Median 54 Gy, Gy / fraction PTV = not reported Med time to recur 20.2 mo No SRS related complications IMRT: 1 cranial wound breakdown Kaplan Meier Analysis Significant: GTR at 1 st Surg (v STR) Not Signif: SRS pgtr or STR (v No RT) IMRT pgtr or STR (v No RT) SRS v IMRT Time (yrs) GTR + SRS PFS 100% (n=10) GTR + IMRT PFS 100% (n=19) STR+IMRT STR+SRS STR alone GTR alone Hardesty DA, Wolf AB, Brachman DG, McBride HL, Youssef E, Nakaji P, Porter RW, Smith KA, Spetzler RF, Sanai N. The impact of adjuvant radiosurgery on atypical meningioma recurrence following aggressive microsurgical resection. Journal of Neurosurgery February DOI / JNS12414

26 Percent Overall Survival SEER database query Management of non-grade 1 Meningioma SEER database study of the effect of EBRT on survival with non-benign meningioma 657 patients received adjuvant RT Patients with Gr III were 41.9% more likely to receive RT after GTR and 36.7% more likely after STR Controlling for grade, resection extent, tumor size, anatomic locale, race, age, gender, & yr of diagnosis, adjuvant RT did not impact overall or disease-specific survival benefit Our data underscore the need for randomized prospective clinical trials to assess the usefulness of adjuvant EBRT and to more precisely define the subset of patients who may benefit. Overall Survival Non-Benign Meningioma (WHO Grades II & III) No RT RT p= Survival Time (months) Stessin AM, Schwartz A, Judanin G, Pannullo SC, Boockvar JA, Schwartz TH, Steig PE, Wernicke AG. Does adjuvant external-beam radiotherapy improve outcomes for nonbenign meningiomas? A Surveillence, Epidemiology, and End Results (SEER)-based analysis. Journal of Neurosurgery 2012.

27 Management of non-grade 1 Meningioma Minority of Centers Recommend RT after GTR of an Atypical Meningioma German Study (Simon et al): 9 of 56 (16%) centers recommend RT following GTR Simon M, Bostrom J, Kock P, Schromm J. Interinstitutional variance of post-operative radiotherapy and follow-up for meningiomas in Germany: Impact of changes of the WHO classification. J Neurol Neurosurg Psychiatry 2006;77: Marcus HJ British J Neurosurg;2008:22(4):520-8

28 Management of non-grade 1 Meningioma RTOG 1310 Phase III EORTC 1308 ROAM Phase III Meningioma graded by 2007 WHO Grading Extent of resection scored by neuro-surgeon (Simpson grade) confirmed by post-operative MRI. *GTR = Simpson grade I-III Central pathology and central neuro-radiology review Observation Surgery GTR* WHO Grade II Stratify: Female vs Male New vs. Recurrent NRG 1310 Simpson Grade I vs II-III R A N D O M I Z Convexity vs Non-Convexity 1 RT E MiB1 <10% vs >10% 2 IMRT: 59.4 Gy (1.8 Gy x 33) 1 Convexity will be defined as > 1 cm from dural sinus 2 Based upon Erik Sulman and Ken Aldape

29 Patients N (Grade 2) 35 (33) Mean Age 48.4 yo Initial diagnosis 54.3% Median GTV (range) 24.5 cc ( ) Dose (range) 62 Gy(RBE) (54-68) 68% 81%

30 Failure pattern N=9 (%) In field 6 (67%) Marginal 1 (11%) In field and marginal 2 (22%) Toxicity N (%) Grade 3 CTCAE 3 (9%)

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32 Conclusions Several retrospective studies have shown that RT after STR is beneficial for patients with WHO 1 grade meningioma Debate over the timing of RT-whether it should be given postoperatively or at the time of progression (WHO grade 1 meningioma ) Modification of the WHO classification Suboptimal outcome of grade 2-3 meningioma patients

33 Conclusions Dose-response of non-benign meningiomas FSRT, SRS, Protons, Carbons Failure pattern: IN FIELD Results of phase II (RTOG-EORTC) trials awaited for Q On going phase III trial for Simpson 1-3 Grade 2 meningiomas