11/27/2017. Modern Treatment of Meningiomas. Disclosures. Modern is Better? No disclosures relevant to this presentation

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1 Modern Treatment of Meningiomas Michael A. Vogelbaum MD, PhD Professor of Neurosurgery Cleveland Clinic Disclosures No disclosures relevant to this presentation IP and royalties related to drug and device development for convection enhanced delivery to the brain Modern is Better? 1

2 Meningiomas a classic pathology Meningiomas Incidence 1 to 8.4 per 100,000 More recent data suggest range is 3.0 to 3.5 per 100,000 Approximately 150,000 individuals in the US Risk Factors NF2 and MEN1 account for only about 1% Prior radiation therapy Most are sporadic Hoffman et al., NeuroOncol 2008 Claus et al., NSGY 2005 Davids et al., NeuroOncol 2001 McDermott et al Meningiomas Presentation Location dependent Size dependent (size/location) Seizures reported in as many as 30% of patients at time of diagnosis Natural History Strongest predictor of growth is WHO grade Versions: Wirsching et al., NeuroOncol

3 Treatment of Meningiomas Observation Surgery Radiotherapy/radiosurgery Chemotherapy/targeted agents Treatment of Meningiomas Observation Surgery Radiotherapy/radiosurgery Chemotherapy/targeted agents Surgery for Meningioma Widely considered to be the primary treatment modality Advantages of Surgery Obtains tissue for accurate diagnosis Immediate relief of mass effect Can be curative 3

4 Surgery for Meningioma Surgery for Meningioma Surgery can provide durable tumor control Simpson, J. Neurol Neurosurg Psych 1957 Surgery for Meningioma TISSUE FOR DIAGNOSIS Grading of meningioma has been a moving target Majority of tumors are WHO grade I Grade II tumors (atypical) have ranged from 5% to 35% as the WHO criteria have evolved WHO grade III (anaplastic) remains about 3% Expectations for recurrence, and hence indications for additional treatment are tightly linked to WHO grade Perry et al., Brain Path 2003 Claus et al., NSGY 2005 Perry et al., WHO

5 Meningioma Recurrence-Free and Overall Survival by Grade (643 pts) Relapse-Free Survival Benign, n = 464 Atypical, n = 156 Atypical, n = 23 Overall Survival Atypical, n = 23 p < p < Benign, n = 464 Atypical, n = Years Years 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 Insert slides showing modern techniques for meningioma surgery Surgery for Meningioma Disadvantages of Surgery Invasive procedure General anesthesia Recovery time Risk of peri-operative seizures Risk of functional loss CSF leak/infection 5

6 Surgery for Meningioma Is surgery required for this patient s tumor? Potential advantages of SRS Non-invasive No need for general anesthesia No recovery time Lower risk of peri-operative seizures(?) Lower risk of functional loss(?) No risk of CSF leak/infection Limitations/concerns of radiosurgery No information about histology/grade Does not remove mass effect Long-term control? Radionecrosis/malignant edema 6

7 Technical considerations Dose? Safety? Efficacy? Relationship to tumor size? Biological considerations NF2 WHO grade Timing of treatment (prior RT?) When is Radiosurgery Appropriate for Meningiomas? Recurrent WHO grade II or III When is Radiosurgery Appropriate for Meningiomas? Recurrent WHO grade II or III Recurrent WHO grade I 7

8 When is Radiosurgery Appropriate for Meningiomas? Recurrent WHO grade II or III Recurrent WHO grade I Presumed meningioma History SRS initially used for recurrence or unresectable component after subtotal resection 450 patients in 7 studies Progression rates: 5 yr (37 62%) 10 yr (55 100%) 15 yr (70 91%) Rogers, Vogelbaum et al., JNSGY 2014 History Use as an upfront treatment has been more recent 8

9 Rogers, Vogelbaum et al., JNSGY 2014 Summary of Findings ~6000 patients in 35 studies Size range: 4 18 cc (e.g. 3 cm or less) Dose range: Gy F/U time: ~2 to 10 years Tumor regression: ~12 to 82% 5 yr PFS: % 10 yr PFS: 69 97% Complications: 1 23% Rogers, Vogelbaum et al., JNSGY 2014 Dosing Strategies Consistent tumor control seen with PD of Gy PD < 10 Gy not effective compared to 12 Gy PD > 16 Gy no better for LC than < 16 Gy Ganz et al., Sterotactic Func NSGY 1993 Stafford et al., Neurosurgery,

10 Dosing Strategies 145 patients with radiographic dx of meningioma Dose ranged from 10 to 24 Gy (median = 13 Gy) Optimal parameters to avoid toxicity: Conformality and Homogeniety Indices <= 2 Gradient Index >= 3 Radionecrosis/Malignant Edema Conti et al., Cureus, 2016 Radionecrosis/Malignant Edema No prospective data Most retrospective data are single center series New or worsened peritumoraledema risk appears to range from 8 to 33% (symptomatic 5 10%) Predictive factors: Pre-existing peritumoral edema Venous sinus compression/invasion Tumor volume Non-basal location Non WHO Grade I histology Conti et al., Cureus, 2016 Hoe et al., J. Korean NSGY Soc., 2015 Sheehan et al., J. NeuroOncol,

11 Impact of WHO Grade Grade II Questions remain as to target and dose Rogers, Vogelbaum et al., JNSGY 2014 Impact of WHO Grade Grade III Rogers, Vogelbaum et al., JNSGY 2014 When is Radiosurgery Appropriate for Meningiomas? Recurrent and/or residual WHO Grade I Selected cases of recurrent/residual WHO Grade II or III, especially after prior fractionated RT Poorly accessible/inaccessible, radiographically diagnosed tumors Patients with significant medical comorbidities 11

12 EANO Guidelines for the Management of Meningiomas Goldbrunner et al., Lancet Oncol WHO grade II Meningioma EANO Guidelines for the Management of Meningiomas Goldbrunner et al., Lancet Oncol NRG BN-003 Surgery GTR* WHO Grade II Newly Diagnosed Only R A N D O M I Z E Observation RT (IMRT or Protons) 59.4 Gy (1.8 Gy x 33) *GTR: gross total resection (Simpson grade 1-3, modified) Pre-randomization central pathology review, central neuro-radiology review, phh3, QOL and NCF 12

13 Thank You! 13