Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in Patients With Brain Oligometastases: A...

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.

The whole brain plus 3-mm margin was defined as the planning target volume (PTV_wb), 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 (PTV_m). Radiation therapy was delivered in 10 daily fractions (2 weeks). Only the dose to PTV_m was progressively increased in the patient cohorts (35 Gy, 40 Gy, 45 Gy, 50 Gy), whereas the PTV_wb 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.

Thirty patients were enrolled in the study (dose PTV_m: 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.

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.