Marica Ferro1, Silvia Chiesa2, Gabriella Macchia3, Savino Cilla4, Federica Bertini5, Giovanni Frezza6, Andrea Farioli7, Silvia Cammelli5, Mario Balducci2, Anna Ianiro4, Anna Lisa Angelini8, Gaetano Compagnone8, Vincenzo Valentini2, Francesco Deodato1, Alessio G Morganti5. 1. Radiotherapy Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II," Catholic University of Sacred Heart, Campobasso, Italy. 2. Department of Radiotherapy, Fondazione Policlinico Universitario "A. Gemelli," Catholic University of Sacred Heart, Rome, Italy. 3. Radiotherapy Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II," Catholic University of Sacred Heart, Campobasso, Italy. Electronic address: gmacchia@rm.unicatt.it. 4. Medical Physics Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II," Catholic University of Sacred Heart, Campobasso, Italy. 5. Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 6. Radiotherapy Department, Ospedale Bellaria, Bologna, Italy. 7. Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 8. Medical Physics Unit, S. Orsola-Malpighi Hospital, Bologna, Italy.
Abstract
PURPOSE: To investigate the maximum tolerated dose of intensity modulated radiation therapy simultaneous integrated boost whole-brain radiation therapy for palliative treatment of patients with <5 brain metastases using a standard linear accelerator. MATERIALS AND METHODS: The whole brain plus 3-mm margin was defined as the planning target volume (PTVwb), whereas each brain metastasis, defined as the contrast-enhancing tumor on MRI T1 scans, plus a 3-mm isotropic margin, was defined as metastases PTV (PTVm). Radiation therapy was delivered in 10 daily fractions (2 weeks). Only the dose to PTVm was progressively increased in the patient cohorts (35 Gy, 40 Gy, 45 Gy, 50 Gy), whereas the PTVwb was always treated with 30 Gy (3 Gy per fraction) in all patients. The dose-limiting toxicity 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 dose-limiting toxicity: 1 patient at dose level 2 presented grade 3 (G3) skin toxicity; 1 patient at dose level 4 presented G3 neurologic toxicity; and 1 patient at the same level showed brain hemorrhage. Most patients showed G1 to 2 acute toxicity, in most cases skin (n=19) or neurologic (n=10). Twenty-seven were evaluable for response: 6 (22%) stable disease, 18 (67%) partial response, and 3 (11%) complete response. Median survival and 1-year overall survival were 12 months and 53%, respectively. No patient showed late toxicity. CONCLUSIONS: In this first prospective trial on the use of intensity modulated radiation therapy simultaneous integrated boost delivered with a standard linear accelerator in patients with brain oligometastases, a boost dose up to 50 Gy in 10 fractions was tolerable according to the study design.
PURPOSE: To investigate the maximum tolerated dose of intensity modulated radiation therapy simultaneous integrated boost whole-brain radiation therapy for palliative treatment of patients with <5 brain metastases using a standard linear accelerator. MATERIALS AND METHODS: The whole brain plus 3-mm margin was defined as the planning target volume (PTVwb), whereas each brain metastasis, defined as the contrast-enhancing tumor on MRI T1 scans, plus a 3-mm isotropic margin, was defined as metastases PTV (PTVm). Radiation therapy was delivered in 10 daily fractions (2 weeks). Only the dose to PTVm was progressively increased in the patient cohorts (35 Gy, 40 Gy, 45 Gy, 50 Gy), whereas the PTVwb was always treated with 30 Gy (3 Gy per fraction) in all patients. The dose-limiting toxicity 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 dose-limiting toxicity: 1 patient at dose level 2 presented grade 3 (G3) skin toxicity; 1 patient at dose level 4 presented G3 neurologic toxicity; and 1 patient at the same level showed brain hemorrhage. Most patients showed G1 to 2 acute toxicity, in most cases skin (n=19) or neurologic (n=10). Twenty-seven were evaluable for response: 6 (22%) stable disease, 18 (67%) partial response, and 3 (11%) complete response. Median survival and 1-year overall survival were 12 months and 53%, respectively. No patient showed late toxicity. CONCLUSIONS: In this first prospective trial on the use of intensity modulated radiation therapy simultaneous integrated boost delivered with a standard linear accelerator in patients with brain oligometastases, a boost dose up to 50 Gy in 10 fractions was tolerable according to the study design.