Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost in Patients With Brain Oligometastases : A Phase I Study (ISIDE-BM-1)
Mené sur 30 patients atteints d'un cancer et présentant moins de 5 oligométastases cérébrales (âge : 18 à 85 ans), cet essai de phase I évalue la dose maximale tolérée de rayonnements ionisants dans le cadre d'un traitement comportant simultanément une radiothérapie de l'ensemble du cerveau et une radiothérapie avec modulation d'intensité de type "boost"
Purpose : To investigate the maximum tolerated dose (MTD) of IMRT-SIB-WBRT for palliative treatment of patients with < 5 brain metastases (BM) using a standard linear accelerator (LINAC). Patients and Methods : The whole brain plus 3 mm margin was defined as Planning Target Volume (PTVwb), while each BM, defined as the contrast enhancing tumor on MRI T1 scans, plus a 3 mm isotropic margin, was defined as metastases PTV (PTVm). Radiotherapy was delivered in 10 daily fractions (2 weeks). Only the dose to PTVm was progressively increased in the patients cohorts (35 Gy, 40 Gy, 45 Gy, 50 Gy), while the PTVwb was always treated with 30 Gy (3 Gy/fraction) in all patients. The dose limiting toxicity (DLT) was evaluated providing that 3 months of follow-up had occurred after the treatment of a 6-patient cohort. Results : Thirty patients were enrolled in the study (dose PTVm: 35 Gy, 8 patients; 40 Gy, 6 patients; 45 Gy, 6 patients; 50 Gy, 10 patients). The number of treated brain metastases was 1 in 18 patients, 2 in 5 patients, 3 in 6 patients, and 4 in 1 patient. Three patients experienced DLT: 1 patient at dose level II presented G3 skin toxicity; 1 patient at dose level IV presented G3 neurological toxicity and 1 patient at the same level showed brain hemorrhage. Most patients showed G1-2 acute toxicity, in most cases skin (19) or neurological (10). Twenty-seven were evaluable for response: 6 (22%) SD, 18 (67%) PR, and 3 (11%) CR. Median survival and 1-year overall survival (OS) were 12 months and 53%, respectively. No patient showed late toxicity. Conclusions : In this first prospective trial on the use of IMRT-SIB delivered with a standard LINAC in patients with brain oligometastases, a boost dose up to 50 Gy in 10 fractions was tolerable according to the study design.