Clinical Outcomes for Frameless Image-Guided Stereotactic Radiation Therapy to Intact Brain Metastases in Five Daily Hypofractionated Treatments

Abstract

Image-guided multi-lead collimator (MLC) linac-based hypofractionated stereotactic radiation (FSRT) is increasingly practiced for brain metastases. We report our outcomes for 5-fraction FSRT including the rate of radiation necrosis. 113 patients with 184 brain metastases who were treated with FSRT from Oct 2009-Dec 2014 were retrospectively reviewed. Overall Survival (OS) and progression free survival (PFS) rates were calculated using the Kaplan-Meier method. Local control rates were determined with Fine and Gray’s competing risk method with death as the competing risk. Predictive factors were identified using Cox regression multivariable analysis. All patients were treated in a thermoplastic mask using a cone-beam CT image-guided linac equipped with a MLC and six-degrees-of-freedom treatment couch. All patients were treated with a 5 daily fraction dose scheme to the gross tumor volume (GTV) with a 2 mm planning target volume (PTV). 30 Gy in 5 fractions was the most common prescription. The median follow-up was 11 months. Non-small cell lung cancer the most frequently treated histology (46%) followed by breast cancer (21%) and melanoma (9%). FSRT was given for a single brain metastasis in 67 (59%) patients and for multiple metastases in 46 patients (41%). 77 patients (68%) were treated as upfront and 36 (32%) as salvage following whole brain radiation. 50 patients (44%) had treated lesions >2 cm in maximum diameter. 43 targets (23%) received 25-27.5Gy, 111 (60%) received 30 Gy, and 30 (16%) received >30 Gy in 5 fractions. The PFS rates at 6 months, 12 months and 24 months were 65%, 38%, and 15%, respectively (median, 9.0 months). The OS rates at 6 months, 12 months and 24 months were 69% 47% and 20%, respectively (median OS, 11.8 months). The local failure rates at 6 months, 12 months and 24 months were 8.2%, 22% and 35%, respectively (median, 11.43 months). With regards to other patterns of failure, cumulative incidence rates of leptomeningeal disease at 6 months, 12 months and 24 months were 9.8%, 14% and 17% respectively (median, 4.4 months). 28 targets in 25 patients (15%) developed radiation necrosis, of which 17 were symptomatic (9%). Post-treatment necrosis was a positive prognostic factor (HR 2.1, p=0.003) for OS. Upfront therapy as opposed to salvage (HR 0.54, p=0.02) and those treated with doses > 30Gy (HR 0.55, p=0.03) were predictive for local control. Frameless image-guided MLC-based linac FSRT for intact brain metastasis results in long-term local control with an acceptable rate of RN.