Retrospective comparison of conventional and escalated doses of radiotherapy in patients with newly diagnosed glioblastome multiforme receiving concurrent temozolomid

Purpose: Radiotherapy (RT) dose escalation has repeatedly been demonstrated to be of no benefit for glioblastome multiforme (GBM) patients in the pre-temozolomide period. However, there is lack of robust confirmation considering the conceivable advantageous impact of dose escalation on the outcomes of such patients in the era of temozolomide (TMZ). Therefore, we aimed to retrospectively compare the survival outcomes of newly diagnosed GBM patients treated with standard or escalated radiotherapy (RT) doses in presence of concurrently and adjuvantly administered TMZ. Patients and Methods: Newly diagnosed 126 patients with KPS≥70 and histopathologically proven GBM who received cranial standard or escalated doses of RT and concurrent plus adjuvant TMZ were included. In the standard RT group patients received a total of 60 Gy with 3D-conformal RT (PTV1=GTV+2 cm=40 Gy, PTV2= GTV+1 cm=60 Gy, in 30 fractions), while dose escalated group received a total of 70 Gy with simultaneous integrated boost IMRT technique (PTV1=GTV+2 cm=50 Gy, PTV2=GTV+1 cm=60 Gy, PTV3=GTV=70 Gy, in 30 fractions), respectively. During the RT course all patients received 75 mg/m2 TMZ concurrently, and adjuvantly following completion of RT. Primary endpoint was overall survival (OS). Results: The median age was 55 years for the entire cohort. Thirty-five and 91 patients received 70 Gy and 60 Gy (retrospective control group), respectively. At a median follow-up of 14.2 months 26 (20.6%) patients were still alive. The median OS for the whole group was 15.4 months (95 CI= 12.1-18.8). In comparative analysis although the 70 Gy group had numerically longer OS than the 60 Gy group this difference did not translate into statistical significance (21.9 vs. 14.9 months; p=0.45). Respective 1- and 2-year OS rates were 68.6% vs. 60.4% and 34.6% vs. 31.7%. In the univariate analysis; age group (≤50 vs. >50 years; p=0.001), KPS score (90-100 vs. 70-80; p=0.03), RPA score (3-4 vs. 5-6; p<0.001), and resection extent (gross total vs. subtotal/biopsy; p=0.04) and were found to be associated with significantly longer OS times. However, in the multivariate analysis only the RPA (p= 0.02) and resection extent (p=0.02) were demonstrated to retain their significance. Conclusion: Despite of the fact that the results of our current study did not demonstrate any statistically significant survival advantage with use of escalated RT doses beyond the standard 60 Gy even in the presence of TMZ, the achieved median OS of 21.9 months in the escalated dose suggest that our study population size, especially in the escalated dose group might have been insufficient to retrieve the possible significance. Therefore, randomized studies with larger cohorts are warranted to achieve more reliable data on this subject of paramount importance. Keywords: Glioblastome multiforme, Chemoradiotherapy, Radiotherapy, Temozolomide