Session Item

November 28
10:30 - 11:30
Clinical Stream 2
Proffered papers 4: CNS
Proffered Papers
10:30 - 10:40
SIB accelerated RT and concomitant TMZ in GBM patients: results of a phase I study (ISIDE BT-2)


SIB accelerated RT and concomitant TMZ in GBM patients: results of a phase I study (ISIDE BT-2)
Authors: Ferro|, Marica(1);Ianiro|, Anna(2);Re|, Alessia(1);Macchia|, Gabriella(1)*;Cilla|, Savino(2);Picardi|, Vincenzo(1);Boccardi|, Mariangela(1);Ferro|, Milena(1)[];Cammelli|, Silvia(3);Romano|, Carmela(2);Bisello|, Silvia(3);Buwenge|, Milly(3);Mignogna|, Samantha(4);Giglio|, Gianfranco(5);Cucci|, Eleonora(6);Valentini|, Vincenzo(7);Morganti|, Alessio Giuseppe(3);Deodato|, Francesco(1);
(1)Università Cattolica del Sacro Cuore, Radiation Oncology Department- Fondazione di Ricerca e Cura "Giovanni Paolo II", Campobasso, Italy;(2)Università Cattolica del Sacro Cuore, Medical Physics Unit- Fondazione di Ricerca e Cura "Giovanni Paolo II", Campobasso, Italy;(3)University of Bologna- S. Orsola-Malpighi Hospital, Radiation Oncology Center- Dept. of Experimental- Diagnostic and Specialty Medicine – DIMES, Bologna, Italy;(4)Università Cattolica del Sacro Cuore, Oncology Department- Fondazione di Ricerca e Cura "Giovanni Paolo II", Campobasso, Italy;(5)‘A. Cardarelli’ Hospital, Oncology Department, Campobasso, Italy;(6)Università Cattolica del Sacro Cuore, Radiology Department- Fondazione di Ricerca e Cura "Giovanni Paolo II", Campobasso, Italy;(7)Università Cattolica del Sacro Cuore- Policlinico Universitario “A. Gemelli”, Radiotherapy- Radiology and Hematology Department – Gemelli ART Advanced Radiation Therapy, Roma, Italy;
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Purpose or Objective

To determine the maximum tolerated dose (MTD) of Volumetric Modulated Arc Therapy (VMAT) with standard concurrent and sequential dose temozolomide (TMZ) in patients with resected glioblastoma multiforme.

Material and Methods

A Phase I clinical trial was performed. Patients with histological proven glioblastoma underwent VMAT dose escalation. VMAT was delivered over 5 weeks with the simultaneous integrated boost (SIB) technique to the two planning target volumes (PTVs) defined by adding 5-mm margin to the respective clinical target volumes (CTVs). CTV1 was the tumor bed + MR enhancing residual lesion with a 10-mm margin; CTV2 was CTV1 plus 20-mm isotropic margin.

VMAT was delivered in 25 fractions. Only the dose for PTV1 was escalated while maintaining the same dose for PTV2 (45 Gy/1.8 Gy). Four PTV1 dose levels were planned: Level 1 (77.5/3.1 Gy), Level 2 (80/3.2 Gy), Level 3 (82.5/3.3 Gy) and Level 4 (85/3.4 Gy). 

Patients were treated in cohorts of between three and six per group using a Phase I study design. The recommended dose was exceeded if one of the three patients in a cohort experienced dose-limiting toxicity within 3 months from treatment. Concurrent and sequential TMZ chemotherapy was administered according to Stupp’s protocol. Two arc techniques were used to cover at least 95% of the target volume with the 95% isodose line. Dose-limiting toxicity (DLT) were defined as any treatment-related non-haematological adverse effects rated as Grade > 3 or any haematological toxicity rated as > 4 by Radiation Therapy Oncology Group (RTOG) criteria.

Twenty-one consecutive glioblastoma patients (male/female: 14/7; median age: 66 years) were treated. Dose to the PTV1: 10 patients 77.5 Gy; 9 patients, 80 Gy; 2 patients, 82.5 Gy,; 0 patients, 85 Gy. Median follow-up time was 10 months (range: 1-23.3 months). Grade 1-2 treatment-related neurological and cutaneous toxicities were registered (6 and 16 patients, respectively). Two patients experienced DLT to dose of 82.5 Gy (1 neurological toxicity grade 3, 1 haematological grade 4).


DMT was reached at the dose level of 82.5 Gy. Volumetric Modulated Arc Therapy in patients with resected glioblastoma multiforme to a dose of 80 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg/mq.