Waiting times before initiation of radiotherapy might not affect outcomes for patients with glioblastoma: a French retrospective analysis of patients treated in the era of concomitant temozolomide and radiotherapy

Abstract

Purpose of this study was to determine the effect of waiting time for radiotherapy on overall survival of patients with glioblastoma treated in the EORTC-NCIC trial at 18 centers in France. A total of 400 adult patients with glioblastoma who were treated between January 1, 2006 and December 31, 2006 were included. There were 282 patients with "minimum criteria" according to the EORTC-NCIC trial: (i) concurrent chemotherapy with temozolomide; and (ii) age between 18 and 70 years old. Among these patients, 229 were treated with adjuvant temozolomide and were classified as "maximal criteria". One-hundred and eighteen patients were in the "without minimal criteria" group. Waiting time from the first symptom (FS-RT), pathology diagnosis (P-RT), multidisciplinary meeting (MM-RT), surgery (S-RT), and CT scan for delineation (CT-RT) until the start of radiotherapy were recorded. Median follow-up for all patients was 327 days. Overall, median FS-RT, P-RT, MM-RT, CT-RT, and S-RT times were 77, 36, 32, 12, and 41 days, respectively. Median, and 12 and 24-month overall survival were 409 days, and 56.3 ± 2.1 % and 27.6 ± 2.6 %, respectively. Univariate analysis failed to reveal a difference in survival, irrespective of the delay. In multivariate analysis, independent favorable prognostic factors for overall survival were age (p ≤ 0.0001) and type of surgery (p = 0.0006). In this large series treated during the EORTC-NCIC protocol period, waiting time until radiotherapy did not seem to affect patient outcome.

Waiting time to radiotherapy as a prognostic factor for glioblastoma patients in a scenario of medical disparities

“…The main limitation of that study was the inclusion in the same cohort of grade 3 and grade 4 gliomas, which are currently known to present different behaviors. Other authors 6,8,9,10,12 , already working in the era of TMZ concomitant with RT, support the result of no significant effect of longer WT to RT on OS in GBM patients. Likewise, using a huge cohort extracted from patients enrolled in the Radiation Therapy Oncology Group (RTOG) protocols, and accounting for close to 3,000 GBM patients, Blumenthal et al 7 found no reduction in survival associated with RT delay, within a temporal limit of 6 weeks.…”

“…No clear radiobiological mechanisms can be proposed to explain such phenomenon, although physician selection bias of poor performance patients has already been pointed out as an alternative reason 7 . Some authors corroborate this hypothesis suggesting that better performing patients wait longer to RT 5,9,16,18 . In our cohort, the only clinical variable that interacted with WT to RT was KPS (HR 0.128, 95%CI 0.034-0.476; p = 0.002), showing that the benefit of KPS on OS depends on the WT to RT.…”

“…The problem of delaying RT in GBM treatment has been debated more extensively because of the fast-growing nature of this tumor 13 and its ability to invade surrounding tissues, making tumor control much more difficult over time 23,24 . To date, data published on this theme are considered controversial, partially because prior studies presented diverse methodologies and patients with different characteristics 4,5,6,7,8,9,10,11,12,13,16,18 . In line with our data, previous reports failed in detecting any disadvantage in delaying RT.…”

“…Nevertheless, there is considerable evidence to support that delay of RT may have an adverse effect on patients' outcomes 1,2,3 . Glioblastoma (GBM) patients have been the subject of many clinical investigations aiming to determine the effects of waiting time (WT) for initiation of RT 4,5,6,7,8,9,10,11,12,13,14,15,16 . Much of the interest in seeking a presumable negative impact of the delay for this kind of tumor is based on its median overall survival (OS) that rarely exceeds 14 months 17 .…”

Survival impact of time to initiation of chemoradiotherapy after resection of newly diagnosed glioblastoma

“…16 Noel et al found in a cohort of 400 French patients, all of whom were treated during the modern protocol era, that there was no effect on survival associated with delay. 11 More recently, Graus et al found that in a cohort of 396 Spanish patients, initiation of radiotherapy within 42 days of surgery was associated with longer PFS but not with OS. 6 It appears there is a lack of consensus on the effects of delay to initial therapy from studies of patients treated both before and after the modern protocol era, and no studies on patients treated during the Stupp protocol era have been conducted outside of Europe.…”