Glioblastoma
Delaying standard combined chemoradiotherapy after surgical resection does not impact survival in newly diagnosed glioblastoma patients

https://doi.org/10.1016/j.radonc.2016.01.001Get rights and content

Abstract

Background

To assess the influence of the time interval between surgical resection and standard combined chemoradiotherapy on survival in newly diagnosed and homogeneously treated (surgical resection plus standard combined chemoradiotherapy) glioblastoma patients; while controlling confounding factors (extent of resection, carmustine wafer implantation, functional status, neurological deficit, and postoperative complications).

Methods

From 2005 to 2011, 692 adult patients (434 men; mean of 57.5 ± 10.8 years) with a newly diagnosed glioblastoma were enrolled in this retrospective multicentric study. All patients were treated by surgical resection (65.5% total/subtotal resection, 34.5% partial resection; 36.7% carmustine wafer implantation) followed by standard combined chemoradiotherapy (radiotherapy at a median dose of 60 Gy, with daily concomitant and adjuvant temozolomide). Time interval to standard combined chemoradiotherapy was analyzed as a continuous variable and as a dichotomized variable using median and quartiles thresholds. Multivariate analyses using Cox modeling were conducted.

Results

The median progression-free survival was 10.3 months (95% CI, 10.0–11.0). The median overall survival was 19.7 months (95% CI, 18.5–21.0). The median time to initiation of combined chemoradiotherapy was 1.5 months (25% quartile, 1.0; 75% quartile, 2.2; range, 0.1–9.0). On univariate and multivariate analyses, OS and PFS were not significantly influenced by time intervals to adjuvant treatments. On multivariate analysis, female gender, total/subtotal resection and RTOG-RPA classes 3 and 4 were significant independent predictors of improved OS.

Conclusions

Delaying standard combined chemoradiotherapy following surgical resection of newly diagnosed glioblastoma in adult patients does not impact survival.

Section snippets

Patient population

Patients entered into the CASTE1 database, run by the Club de Neuro-Oncologie of the Société Française de Neurochirurgie between 2005 and 2011, constituted the study group for this article [29]. Inclusion criteria were: (1) patients older than 18 at diagnosis; (2) histologically confirmed supratentorial glioblastoma; (3) surgical resection followed by the standard combined chemoradiotherapy (radiotherapy, 60 Gy, and daily concomitant temozolomide at 75 mg/m2/day, then adjuvant temozolomide at

Results

Patients’ main characteristics are detailed in Table 1. A total of 692 patients (434 men, 258 women) were included, with a mean age of 57.5 ± 10.8 years. At diagnosis, 65.9% of patients presented with a neurological deficit, 34.2% with a Karnofsky performance status of 70 or less, and 55.1% with a RTOG-RPA class at 5 or 6. All patients underwent a surgical resection (65.5% total/subtotal resection, 34.5% partial resection), with carmustine wafer implantation in 36.7% of cases. A mean dose of

Discussion

Concern about glioblastoma regrowth [33], with the related risk of clinical degradation, has frequently led to consider a time interval of less than four to six weeks post surgical intervention as optimal in daily practice [28]. This question was initially raised in the era preceding the standard combined chemoradiotherapy. Do et al., showed on a retrospective study based on 182 patients with grade III/IV gliomas that the risk of death increased by 2% per day of waiting for radiotherapy [13].

Funding

None.

Conflict of interest

None.

Acknowledgments

Participating centers (in alphabetical order): Amiens University Hospital – University of Amiens, Angers University Hospital – Angers University, Jean-Minjoz Hospital – University of Besançon, Pellegrin Hospital – University Victor Segalen Bordeaux 2, Morvan Hospital – University of Brest, Caen University Hospital – University Caen Lower-Normandy, Pasteur Hospital in Colmar, Limoges Hospital – University of Limoges, Pierre Wertheimer Hospital – University of Lyon, La Timone Hospital –

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