Phase I Dose-Escalation Study of Stereotactic Body Radiotherapy in Patients With Hepatic Metastases

To identify a tolerable and effective dose for 5-fraction stereotactic body radiotherapy for hepatic metastases. Patients were enrolled onto three dose-escalation cohorts: 30 Gy in 3 fractions, 50 Gy in 5 fractions, and 60 Gy in 5 fractions. Eligible patients had one to five hepatic metastases, ability to spare a critical hepatic volume (volume receiving < 21 Gy) of 700 ml, adequate baseline hepatic function, no concurrent antineoplastic therapy, and a Karnofsky performance score of a parts per thousand yen60. Dose-limiting toxicity included treatment-related grade 3 toxicity in the gastrointestinal, hepatobiliary/pancreas, and metabolic/laboratory categories. Any grade 4 or 5 event attributable to therapy was defined as a dose-limiting toxicity. Local control (LC) and complete plus partial response rates were assessed. Twenty-seven patients, 9 in each cohort, with 37 lesions were enrolled and treated: 17 men and 11 women; median age 62 (range 48-86) years; most common site of primary disease, colorectal (44.4%). Median follow-up was 20 (range 4-53) months. There was no grade 4 or 5 toxicity or treatment-related grade 3 toxicity. Actuarial 24-month LC rates for the 30-, 50-, and 60-Gy cohorts were 56%, 89%, and 100%, respectively. There was a statistically significant difference for LC between the 60- and 30-Gy cohorts (P = 0.009) but not between the 60- and 50-Gy cohorts (P = 0.56) or the 50- and 30-Gy cohorts (P = 0.091). The maximum tolerated dose was not reached. A dose of 60 Gy in 5 fractions can be safely delivered to selected patients with hepatic metastases as long as the critical liver volume is respected. A dose of 60 Gy in 5 fractions yields an excellent level of LC.