Andrew McPartlin1, Anand Swaminath1, Ri Wang2, Melania Pintilie2, James Brierley1, John Kim1, Jolie Ringash1, Rebecca Wong1, Rob Dinniwell1, Tim Craig3, Laura A Dawson4. 1. Radiation Medicine Program, Princess Margaret Cancer Centre, and Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. 2. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. 3. Department of Medical Physics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. 4. Radiation Medicine Program, Princess Margaret Cancer Centre, and Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada. Electronic address: Laura.dawson@rmp.uhn.on.ca.
Abstract
PURPOSE: To report mature outcomes of prospective phase 1 and 2 studies of stereotactic body radiation therapy (SBRT) for the treatment of colorectal liver metastases (CLMs). METHODS AND MATERIALS: Patients with histologically confirmed CLMs unsuitable for resection or standard therapies were eligible for sequential phase 1 and 2 studies conducted from 2003 to 2012. RESULTS: Of 60 patients treated, 82% had received previous chemotherapy, 23% had undergone previous focal liver treatment, and 38% had extrahepatic disease at the time of SBRT. The median number of gross tumor volume (GTV) targets per patient was 1 (range, 1-6), with a median total target volume of 117.7 cm3 (range, 6.7-3115.4 cm3). The median minimum dose to the GTV was 37.6 Gy (range, 22.7-62.1 Gy) in 6 fractions over a period of 2 weeks. Other than 1 case of grade 3 nausea, there were no acute toxicities greater than grade 2. With a median follow-up period of 28.1 months for survivors, no gastrointestinal bleed or biliary or liver toxicity was seen. The local control rate per lesion at 1 and 4 years was 49.8% and 26.2%, respectively. Increasing minimum dose to the GTV was associated with improved local control (P=.003). Median overall survival was 16.0 months (95% confidence interval, 11.9-20.5 months). On multivariate analysis, improved survival was associated with smaller total GTV (P=.017), performance status of 0 or 1 (P=.007), no extrahepatic disease at the time of treatment (P=.005), and local control of targeted liver disease (P=.001). Two long-term survivors remain disease free at 49 and 125 months. CONCLUSIONS: Six-fraction SBRT for CLM is safe and may be associated with long-term cure. Local control was significantly associated with delivered dose and was lower than seen in other studies using a higher SBRT dose. Survival was associated with smaller tumor volume, absence of extrahepatic disease, performance status of 0 or 1, and local control of treated liver lesions.
PURPOSE: To report mature outcomes of prospective phase 1 and 2 studies of stereotactic body radiation therapy (SBRT) for the treatment of colorectal liver metastases (CLMs). METHODS AND MATERIALS: Patients with histologically confirmed CLMs unsuitable for resection or standard therapies were eligible for sequential phase 1 and 2 studies conducted from 2003 to 2012. RESULTS: Of 60 patients treated, 82% had received previous chemotherapy, 23% had undergone previous focal liver treatment, and 38% had extrahepatic disease at the time of SBRT. The median number of gross tumor volume (GTV) targets per patient was 1 (range, 1-6), with a median total target volume of 117.7 cm3 (range, 6.7-3115.4 cm3). The median minimum dose to the GTV was 37.6 Gy (range, 22.7-62.1 Gy) in 6 fractions over a period of 2 weeks. Other than 1 case of grade 3 nausea, there were no acute toxicities greater than grade 2. With a median follow-up period of 28.1 months for survivors, no gastrointestinal bleed or biliary or liver toxicity was seen. The local control rate per lesion at 1 and 4 years was 49.8% and 26.2%, respectively. Increasing minimum dose to the GTV was associated with improved local control (P=.003). Median overall survival was 16.0 months (95% confidence interval, 11.9-20.5 months). On multivariate analysis, improved survival was associated with smaller total GTV (P=.017), performance status of 0 or 1 (P=.007), no extrahepatic disease at the time of treatment (P=.005), and local control of targeted liver disease (P=.001). Two long-term survivors remain disease free at 49 and 125 months. CONCLUSIONS: Six-fraction SBRT for CLM is safe and may be associated with long-term cure. Local control was significantly associated with delivered dose and was lower than seen in other studies using a higher SBRT dose. Survival was associated with smaller tumor volume, absence of extrahepatic disease, performance status of 0 or 1, and local control of treated liver lesions.
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