Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2)

• Published in: Frontiers in oncology Vol. 10; p. 626400
• Main Authors: Ferro, Marica, Ferro, Milena, Macchia, Gabriella, Cilla, Savino, Buwenge, Milly, Re, Alessia, Romano, Carmela, Boccardi, Mariangela, Picardi, Vincenzo, Cammelli, Silvia, Cucci, Eleonora, Mignogna, Samantha, Di Lullo, Liberato, Valentini, Vincenzo, Morganti, Alessio Giuseppe, Deodato, Francesco
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.02.2021
• Subjects: adjuvant treatment; glioblastoma multiforme; Oncology; simultaneous integrated boost; temozolomide; volumetric modulated arc therapy; temozolomide; simultaneous integrated boost; glioblastoma multiforme; adjuvant treatment; volumetric modulated arc therapy
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2020.626400

Glioblastoma Multiforme (GBM) is the most common primary brain cancer and one of the most lethal tumors. Theoretically, modern radiotherapy (RT) techniques allow dose-escalation due to the reduced irradiation of healthy tissues. This study aimed to define the adjuvant maximum tolerated dose (MTD) using volumetric modulated arc RT with simultaneous integrated boost (VMAT-SIB) plus standard dose temozolomide (TMZ) in GBM. A Phase I clinical trial was performed in operated GBM patients using VMAT-SIB technique with progressively increased total dose. RT was delivered in 25 fractions (5 weeks) to two planning target volumes (PTVs) defined by adding a 5-mm margin to the clinical target volumes (CTVs). The CTV was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV was the CTV plus 20-mm margin. Only PTV dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV dose remained unchanged (45 Gy/1.8 Gy). Concurrent and sequential TMZ was prescribed according to the EORTC/NCIC protocol. Dose-limiting toxicities (DLTs) were defined as any G ≥ 3 non-hematological acute toxicity or any G ≥ 4 acute hematological toxicities (RTOG scale) or any G ≥ 2 late toxicities (RTOG-EORTC scale). Thirty-seven patients (M/F: 21/16; median age: 59 years; median follow-up: 12 months) were enrolled and treated as follows: 6 patients (72.5 Gy), 10 patients (75 Gy), 10 patients (77.5 Gy), 9 patients (80 Gy), 2 patients (82.5 Gy), and 0 patients (85 Gy). Eleven patients (29.7%) had G1-2 acute neurological toxicity, while 3 patients (8.1%) showed G ≥ 3 acute neurological toxicities at 77.5 Gy, 80 Gy, and 82.5 Gy levels, respectively. Since two DLTs (G3 neurological: 1 patient and G5 hematological toxicity: 1 patient) were observed at 82.5 Gy level, the trial was closed and the 80 Gy dose-level was defined as the MTD. Two asymptomatic histologically proven radionecrosis were recorded. According to the results of this Phase I trial, 80 Gy in 25 fractions accelerated hypofractionated RT is the MTD using VMAT-SIB plus standard dose TMZ in resected GBM.