Hypofractionated radiation therapy and temozolomide in patients with glioblastoma and poor prognostic factors. A prospective, single-institution experience

Abstract

Background Hypofractionated radiation therapy is a feasible and safe treatment option in elderly and frail patients with glioblastoma. The aim of this study was to evaluate the effectiveness of hypofractionated radiation therapy with concurrent temozolomide in terms of feasibility and disease control in primary glioblastoma patients with poor prognostic factors other than advanced age, such as post-surgical neurological complications, high tumor burden, unresectable or multifocal lesions, and potential low treatment compliance due to social factors or rapidly progressive disease. Material and methods GTV included the surgical cavity plus disease visible in T1WI-MRI, FLAIR-MRI and in the MET-uptake. The CTV was defined as the GTV plus 1.5–2 cm margin; the PTV was the CTV+0.3 cm margin. Forty, fourty-five, and fifty grays in 15 fractions were prescribed to 95% of PTV, CTV, and GTV, respectively. Treatment was delivered using IMRT or the VMAT technique. Simultaneously, 75 mg/m 2 /day of temozolomide were administered. Results Between January 2010 and November 2017, we treated a total of 17 patients. The median age at diagnosis was 68-years; median KPS was 50–70%. MGMT -methylation status was negative in 5 patients, and 8 patients were IDH -wildtype. Eight of 18 patients were younger than 65-years. Median tumor volume was 26.95cc; median PTV volume was 322cc. Four lesions were unresectable; 6 patients underwent complete surgical resection. Median residual volume was 1.14cc. Progression-free survival was 60% at 6 months, 33% at 1-year and 13% at 2-years (median OS = 7 months). No acute grade 3–5 toxicities were documented. Symptomatic grade 3 radiation necrosis was observed in one patient. Conclusions Patients with poor clinical factors other than advanced age can be selected for hypofractionated radiotherapy. The OS and PFS rates obtained in our series are similar to those in patients treated with standard fractionation, assuring good treatment adherence, low rates of toxicity and probable improved cost-effectiveness.

Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis

“…Twenty one non-comparative studies assessed the impact of hypofractionation in newly diagnosed glioblastoma patients in 22 treatment arms [4,6,8,11,12,20,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] (Additional file 3). Outcomes were compared with the ones of the Stupp trial, which is currently considered as the reference in the management of first-line glioblastoma [2].…”

“…Among the 22 treatment arms, 11 tested a concurrent chemoradiation (temozolomide or temozolomide-bevacizumab) [11,[26][27][28][29][30][31][32][33][34]40]. Radiotherapy was hSRT in 2 arms whereas 9 arms used conventional techniques.…”

“…In addition to important heterogeneities in radiation characteristics, patients were treated for various disease status (first line treatment or relapse). The results of such studies were contradictory which made the impact of fractionation on glioblastoma prognosis hard to figure out [8,[10][11][12]. A comprehensive analysis of all data about the impact of radiation characteristics on GBM prognosis has never been carried out.…”

Poor-Prognosis Patients Affected by Glioblastoma: Retrospective Study of Hypofractionated Radiotherapy with Simultaneous Integrated Boost and Concurrent/Adjuvant Temozolomide

“…However, few data have been produced for GBM patients with poor prognostic factors such as high tumor burden, unresectable or multifocal lesions, low Karnofsky performance status (KPS) or the presence of significant comorbidities [15,17].…”

“…In the setting of poor-prognosis patients, no standard of care is available, suggesting that RT alone, TMZ alone or best supportive care could be proposed. However, in this setting, several results were correlated only with elderly and frail people, for whom the reduction of RT fractions could represent a valid option with a median OS of 6-8 months [11,[14][15][16][17][18][19][20][21][22][23][24][25][26][27].…”