PMID- 33692944 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220421 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 10 DP - 2020 TI - Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2). PG - 626400 LID - 10.3389/fonc.2020.626400 [doi] LID - 626400 AB - BACKGROUND: 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. METHODS: 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(1) was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV(2) was the CTV(1) plus 20-mm margin. Only PTV(1) dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV(2) 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). RESULTS: 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. CONCLUSIONS: 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. CI - Copyright (c) 2021 Ferro, Ferro, Macchia, Cilla, Buwenge, Re, Romano, Boccardi, Picardi, Cammelli, Cucci, Mignogna, Di Lullo, Valentini, Morganti and Deodato. FAU - Ferro, Marica AU - Ferro M AD - Radiation Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Ferro, Milena AU - Ferro M AD - Radiation Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Macchia, Gabriella AU - Macchia G AD - Radiation Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Cilla, Savino AU - Cilla S AD - Medical Physics Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Buwenge, Milly AU - Buwenge M AD - Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. AD - DIMES, Alma Mater Studiorum Bologna University, Bologna, Italy. FAU - Re, Alessia AU - Re A AD - Radiation Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Romano, Carmela AU - Romano C AD - Medical Physics Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Boccardi, Mariangela AU - Boccardi M AD - Radiation Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Picardi, Vincenzo AU - Picardi V AD - Radiation Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Cammelli, Silvia AU - Cammelli S AD - Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. AD - DIMES, Alma Mater Studiorum Bologna University, Bologna, Italy. FAU - Cucci, Eleonora AU - Cucci E AD - Radiology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Mignogna, Samantha AU - Mignogna S AD - Medical Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Di Lullo, Liberato AU - Di Lullo L AD - Medical Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. FAU - Valentini, Vincenzo AU - Valentini V AD - Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche, Roma, Italy. AD - Istituto di Radiologia, Universita Cattolica del Sacro Cuore, Roma, Italy. FAU - Morganti, Alessio Giuseppe AU - Morganti AG AD - Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. AD - DIMES, Alma Mater Studiorum Bologna University, Bologna, Italy. FAU - Deodato, Francesco AU - Deodato F AD - Radiation Oncology Unit, Gemelli Molise Hospital - Universita Cattolica del Sacro Cuore, Campobasso, Italy. AD - Istituto di Radiologia, Universita Cattolica del Sacro Cuore, Roma, Italy. LA - eng PT - Journal Article DEP - 20210222 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC7937791 OTO - NOTNLM OT - adjuvant treatment OT - glioblastoma multiforme OT - simultaneous integrated boost OT - temozolomide OT - volumetric modulated arc therapy COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/03/12 06:00 MHDA- 2021/03/12 06:01 PMCR- 2020/01/01 CRDT- 2021/03/11 06:37 PHST- 2020/11/05 00:00 [received] PHST- 2020/12/31 00:00 [accepted] PHST- 2021/03/11 06:37 [entrez] PHST- 2021/03/12 06:00 [pubmed] PHST- 2021/03/12 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2020.626400 [doi] PST - epublish SO - Front Oncol. 2021 Feb 22;10:626400. doi: 10.3389/fonc.2020.626400. eCollection 2020.