ABSTRACT: To report on the outcomes of a phase I study of stereotactic body radiotherapy (SBRT) for treatment of liver metastases.
Patients with liver metastases that were inoperable or medically unsuitable for resection, and who were not candidates for standard therapies, were eligible for this phase I study of individualized SBRT. Individualized radiation doses were chosen to maintain the same nominal risk of radiation-induced liver disease (RILD) for three estimated risk levels (5%, 10%, and 20%). Additional patients were treated at the maximal study dose (MSD) in an expanded cohort. Median SBRT dose was 41.8 Gy (range, 27.7 to 60 Gy) in six fractions over 2 weeks.
Sixty-eight patients with inoperable colorectal (n = 40), breast (n = 12), or other (n = 16) liver metastases were treated. Median tumor volume was 75.2 mL (range, 1.19 to 3,090 mL). The highest RILD risk level investigated was safe, with no dose-limiting toxicity. Two grade 3 liver enzyme changes occurred, but no RILD or other grade 3 to 5 liver toxicity was seen, for a low estimated risk of serious liver toxicity (95% CI, 0 to 5.3%). Six (9%) acute grade 3 toxicities (two gastritis, two nausea, lethargy, and thrombocytopenia) and one (1%) grade 4 toxicity (thrombocytopenia) were seen. The 1-year local control rate was 71% (95 CI, 58% to 85%). The median overall survival was 17.6 months (95% CI, 10.4 to 38.1 months).
Individualized six-fraction liver metastases SBRT is safe, with sustained local control observed in the majority of patients.
Journal of Clinical Oncology 05/2009; 27(10):1585-91. · 18.37 Impact Factor
ABSTRACT: Pancreatic cancer is associated with a poor prognosis. While surgical resection is the only treatment that holds the potential of cure, a minority of patients are surgical candidates. Despite surgery, the overall survival rates remain low. Neoadjuvant treatment has been investigated both in the setting of resectable disease at diagnosis, or in an attempt to downstage locally advanced disease for resection. Single institution studies of neoadjuvant chemoradiation have demonstrated favourable outcomes, compared to similar series of patients treated with surgery with or without adjuvant therapy. For unresectable disease, partial or complete responses have been observed which have allowed some patients to subsequently undergo resection. The reports of neoadjuvant therapy for pancreatic cancer are heterogeneous with regards to patient population, treatment methods and modalities, making comparisons of different regimens inherently flawed. To date, no randomized controlled trials of neoadjuvant therapy have been conducted, however given the positive outcomes of single institutional series of neoadjuvant therapy this approach is worthy of further study.
Critical Reviews in Oncology/Hematology 04/2008; 65(3):263-74. · 4.41 Impact Factor
ABSTRACT: To report outcomes of a phase I study of individualized stereotactic body radiotherapy treatment (SBRT) for unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC).
Patients with unresectable HCC or IHC, and who are not suitable for standard therapies, were eligible for six-fraction SBRT during 2 weeks. Radiation dose was dependent on the volume of liver irradiated and the estimated risk of liver toxicity based on a normal tissue complication model. Toxicity risk was escalated from 5% to 10% and 20%, within three liver volume-irradiated strata, provided at least three patients were without toxicity at 3 months after SBRT.
Forty-one patients with unresectable Child-Pugh A HCC (n = 31) or IHC (n = 10) completed six-fraction SBRT. Five patients (12%) had grade 3 liver enzymes at baseline. The median tumor size was 173 mL (9 to 1,913 mL). The median dose was 36.0 Gy (24.0 to 54.0 Gy). No radiation-induced liver disease or treatment-related grade 4/5 toxicity was seen within 3 months after SBRT. Grade 3 liver enzymes were seen in five patients (12%). Two patients (5%) with IHC developed transient biliary obstruction after the first few fractions. Seven patients (five HCC, two IHC) had decline in liver function from Child-Pugh class A to B within 3 months after SBRT. Median survival of HCC and IHC patients was 11.7 months (95% CI, 9.2 to 21.6 months) and 15.0 months (95% CI, 6.5 to 29.0 months), respectively.
Individualized six-fraction SBRT is a safe treatment for unresectable HCC and IHC.
Journal of Clinical Oncology 03/2008; 26(4):657-64. · 18.37 Impact Factor