Clinical study Determining a cut-off residual tumor volume threshold for patients with newly diagnosed glioblastoma treated with temozolomide chemoradiotherapy: A multicenter cohort study Peter Y.M. Woo a,⇑ , Jason M.K. Ho b , Teresa P.K. Tse c , Sandy W. Lam a , Calvin H.K. Mak d , Danny T.M. Chan e , Michael W.Y. Lee f , Sui-To Wong b , Kwong-Yau Chan a , Wai-Sang Poon e a Department of Neurosurgery, Kwong Wah Hospital, Hong Kong, China b Department of Neurosurgery, Tuen Mun Hospital, Hong Kong, China c Department of Neurosurgery, Princess Margaret Hospital, Hong Kong, China d Department of Neurosurgery, Queen Elizabeth Hospital, Hong Kong, China e Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, Hong Kong, China f Department of Neurosurgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China article info Article history: Received 9 October 2018 Accepted 18 January 2019 Available online xxxx Keywords: Glioblastoma Extent of resection Residual tumor volume Overall survival Temozolomide chemo-radiotherapy Volumetric analysis abstract Standard-of-care treatment of glioblastomas involves maximal safe resection and adjuvant temozolo- mide chemo-radiotherapy. Although extent of resection (EOR) is a well-known surgical predictor for overall survival most lesions cannot be completely resected. We hypothesize that in the event of incom- plete resection, residual tumor volume (RTV) may be a more significant predictor than EOR. This was a multicenter retrospective review of 147 adult glioblastoma patients (mean age 53 years) that underwent standard treatment. Semiautomatic magnetic resonance imaging segmentation was performed for pre- and postoperative scans for volumetric analysis. Cox proportional hazards regression and Kaplan-Meier survival analyses were performed for prognostic factors including: age, Karnofsky performance score (KPS), O(6)-methylguanine methyltransferase (MGMT) promoter methylation status, EOR and RTV. EOR and RTV cut-off values for improved OS were determined and internally validated by receiver operator characteristic (ROC) analysis for 12-month overall survival. Half of the tumors had MGMT promoter methylation (77, 52%). The median tumor volume, EOR and RTV were 43.20 cc, 93.5%, and 3.80 cc respec- tively. Gross total resection was achieved in 52 patients (35%). Cox proportional hazards regression, ROC and maximum Youden index analyses for RTV and EOR showed that a cut-off value of <3.50 cc (HR 0.69; 95% CI 0.48–0.98) and 84% (HR 0.64; 95% CI 0.43–0.96) respectively conferred an overall survival advan- tage. Independent overall survival predictors were MGMT promoter methylation (adjusted HR 0.35; 95% CI 0.23–0.55) and a RTV of <3.50 cc (adjusted HR 0.53; 95% CI 0.29–0.95), but not EOR for incompletely resected glioblastomas. Ó 2019 Published by Elsevier Ltd. 1. Introduction Glioblastoma patients have one of the worst prognoses among malignancies with a median overall survival (OS) of only 12–15 months in spite of multimodality care [1]. Known predictors for survival include age, Karnofsky performance status (KPS), extent of resection (EOR), temozolomide concomitant chemoradio- therapy (CCRT) and epigenetic promoter methylation of O 6 -methylguanine-methyl transferase (MGMT) [1–6]. Since the introduction of CCRT as standard-of-care adjuvant treatment, the only controllable prognostic factor has been EOR and the burden is on the neurosurgeon to maximize resection while preserving functional performance. With the advent of improved computer processing, magnetic resonance imaging (MRI) tumor volumetric analysis of pre- and postoperative scans can be conveniently performed to a high degree of precision [7]. Using imaging software tools retrospective studies have observed a stepwise improvement in OS with greater EOR [4,5,8–16]. Lacroix et al’s landmark retrospective study was one of the first to report this phenomenon and noted that a survival advantage was associated with an EOR of 98% or more [4]. However, there is a growing body of evidence supporting the https://doi.org/10.1016/j.jocn.2019.01.022 0967-5868/Ó 2019 Published by Elsevier Ltd. ⇑ Corresponding author at: Room CS11-01, 11th Floor, Kwong Wah Hospital, 25 Waterloo Road, Yaumatei, Hong Kong, China. E-mail address: wym307@ha.org.hk (P.Y.M. Woo). Journal of Clinical Neuroscience xxx (xxxx) xxx Contents lists available at ScienceDirect Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn Please cite this article as: P. Y. M. Woo, J. M. K. Ho, T. P. K. Tse et al., Determining a cut-off residual tumor volume threshold for patients with newly diag- nosed glioblastoma treated with temozolomide chemoradiotherapy: A multicenter cohort study, Journal of Clinical Neuroscience, https://doi.org/10.1016/ j.jocn.2019.01.022