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 Campus

Grosshadern

Germany

Disclosures

Consultant

MerckSerono, Roche, medac, BrainLab

Grants

Deutsche Forschungsgemeinschaft (DFG)

German Cancer Research Foundation

(Deutsche Krebshilfe)

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 110:156–162 (2009)

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

Reoperation for recurrent high-grade glioma:

a current perspective of the literature Hervey-Jumper SL et al: Neurosurgery. 2014;75(5):491-9

• Review 1980 - 2013: 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

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

An extent of resection threshold for recurrent

glioblastoma and its risk for neurological morbidity Oppenlander ME et al, J Neurosurg. 2014;120(4):846-53

• 170 consecutive pts (2001-2011), 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 cm3 (1.7 cm diameter!)

• after Re-OP: median tumor volume 3.1 cm3 (87.4% EOR)

• median overall survival: 19.0 months, median PRS 5.2 months

• Cox proportional hazards analysis and RPA:

age, KPS, EOR (p = 0.0001)

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

An extent of resection threshold for recurrent

glioblastoma and its risk for neurological morbidity Oppenlander ME et al, J Neurosurg. 2014;120(4):846-53

• 7 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 = 0.0049)

- disparity did not endure beyond 30 days postoperatively (p = 0.1279)

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

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. 2015 Feb 5. [Epub ahead of print]

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

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. 2015 Feb 5. [Epub ahead of print]

Reoperation: 61

No re-OP: 44

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

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):3117-23

n= 222, all pts with EORTC/NCIC protocol

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

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)

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

Extent of the Tumor ?

LMU

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

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!

Klinikum der Universität München • Großhadern • Neurochirurgische Klinik und Poliklinik

http://neurochirurgie.klinikum.uni-muenchen.de

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 !