P14.116 Lack of correlation between incidental ipsilateral subventricular zone radiation dose and overall survival in glioblastoma patients
Authors: Hallaert G , Pinson H , Vanhauwaert D , Staelens L , Vandenbroecke C , Van Roost D , Kalala J , Boterberg T 
Published: September 2019

Abstract

BACKGROUND
The role of the subventricular zone (SVZ) in glioblastoma (GBM) is controversial. The past decade, several retrospective studies were published concerning the potential correlation between incidental radiation of the SVZ and survival in GBM patients. Although these publications showed conflicting results, a large study claimed an overall survival (OS) benefit for GBM patients after gross total resection if the ipsilateral SVZ received a higher dose than 40 Gy. We investigated this finding in our own population of GBM patients.

MATERIAL AND METHODS
A multicenter retrospective study was conducted including all adult patients treated for histologically proven GBM from 2003–2014. All patients received 60 Gy radiation therapy after surgery and concomitant temozolomide. Exclusion criteria were: infratentorial GBM; presence of other neoplasm(s); known previous history of low grade glioma; incomplete radiotherapy data. Demographic data were collected from the patient charts. O6-methylguanin-DNA-methyltransferase-promotor-gene (MGMT) methylation was determined on stored tumor samples using semi quantitative methylation-specific polymerase chain reaction (qMSP). SVZs (ipsilateral, contralateral and bilateral) were contoured on radiotherapy treatment plans. Multivariate Cox regression analysis was used to study the correlation between incidental SVZ radiation dose and OS. Age (cut-off 65 years), Karnofsky Performance Score (KPS; cut-off 70), methylation of the MGMT-promotor gene and extent of resection (biopsy; subtotal resection, groos total resection) were used as covariates. Patients alive at time of database closure were censored for analysis.

RESULTS
183 patients were eligible for analysis. Mean age at diagnosis was 62 years, with an average KPS of 70. In 34% of patients, gross total resection (GTR) was achieved, while in 28% only a biopsy was taken. MGMT-promoter gene methylation was present in 39% of cases. Median ipsilateral, contralateral and bilateral SVZ doses were 46.1 Gy, 25.35 Gy and 34.8 Gy resp. In multivariate Cox regression, all covariates (age, P = 0.011; KPS, P = 0.001; MGMT methylation, P = 0.000; extent of resection, P = 0.000) were significantly associated with OS. Mean OS was 23 months, but median OS 13 months. There was no correlation between incidental radiation dose of the ipsilateral SVZ and OS for 46 Gy or 40 Gy (hazard ratio 0.82 (0.6–1.1), P = 0.225 and 0.89 (0.63–1.23), P = 0.52 resp.) for the whole group nor for the subgroup of gross total resection.

CONCLUSION
In this group of GBM patients, age, KPS, extent of resection and methylation of the MGMT-promotor gene were significantly correlated with OS, but not incidental ipsilateral SVZ radiation dose. The previously published positive results may result from bias, possibly arising from lack of inclusion of MGMT-promotor gene methylation as an important independent prognostic factor.