2nd surgery in recurrent glioblastoma: when and why?

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1 CAMPUS GROSSHADERN NEUROCHIRURGISCHE KLINIK UND POLIKLINIK INTERNET: NEUROCHIRURGIE.KLINIKUM.UNI-MUENCHEN.DE 2nd surgery in recurrent glioblastoma: when and why? Jörg-Christian Tonn Dept Neurosurgery University Munich LMU Grosshadern Campus Germany

2 Disclosures Consultant MerckSerono, Roche, medac, BrainLab Grants Deutsche Forschungsgemeinschaft (DFG) German Cancer Research Foundation (Deutsche Krebshilfe)

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4 Surgery at Relapse of GBM complete resection of relapse associated with better prognosis in retrospective study improves situation for further chemotherapy? indicated for 20-30% for patients in good clinical status and with resectable tumors McGirt et al. J Neurosurg 110: (2009)

5 Reoperation for recurrent high-grade glioma: a current perspective of the literature Hervey-Jumper SL et al: Neurosurgery. 2014;75(5):491-9 Review : 31 studies glioma WHO III und IV 29/31 studies advantage of re-resection (OS /clinical status) Age, KPS (> 70), time intervall from first surgery (> 6 months), EOR patient selection reg KPS and risk factors ( Avastin< 4 weeks!) Limitations: all retrospective, non-controlled, selection-bias

6 An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity Oppenlander ME et al, J Neurosurg. 2014;120(4): consecutive pts ( ), supratentorial GB, after surgery plus EORTC/NCIC mean clinical follow-up 22.6 months - no patient lost to follow-up median preoperative tumor volume: 26.1 cm 3 (1.7 cm diameter!) after Re-OP: median tumor volume 3.1 cm 3 (87.4% EOR) median overall survival: 19.0 months, median PRS 5.2 months Cox proportional hazards analysis and RPA: age, KPS, EOR (p = )

7 An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity Oppenlander ME et al, J Neurosurg. 2014;120(4): days post re-resection: deterioration > 1 on NIH stroke scale in 39.1% of pts with EOR 80% vs 16.7% with EOR < 80% (p = ) - disparity did not endure beyond 30 days postoperatively (p = )

8 MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial Weller M et al: Clin Cancer Res Feb 5. [Epub ahead of print]

9 MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial Weller M et al: Clin Cancer Res Feb 5. [Epub ahead of print] Reoperation: 61 No re-op: 44

10 Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy Kreth, F.-W. et al.: Ann Oncol. 2013; 24(12): n= 222, all pts with EORTC/NCIC protocol

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14 What should we know about the recurrent GBM? Progression or pseudoprogression? Recurrent tumor or progression of a previous remnant? If remnant: why was it left behind?? true extension of the lesion (T2, FLAIR, PET)

15 Extent of the Tumor? LM

16 What is important? Early diagnosis of recurrent GBM to maintain the prognostically good score size KPS surgical risk regular follow-up (3 months, MRI & clinical) Decide, whom not to operate Prospective studies!

17 What is next? Tissue of re-op informative for therapy of recurrent tumor IDH 1 & LOH 1p/19q remain MGMT remains (Felsberg et al 2011) Other targets (EGFRVIII), others. Tissue of re-op informative for biology of tumor progression Material precious!