A Phase I Trial of Stereotactic Body Proton Therapy (SBPT) for Liver Metastases

Abstract

Purpose/Objective(s): To determine the maximum tolerated dose (MTD) of stereotactic body proton therapy (SBPT) for liver metastases in anticipation of a subsequent phase II study. Although phase I studies have shown safety with photon based treatments, similar clinical safety profile and tolerability with proton based therapy has not been reported. Materials/Methods: An IRB approved phase I clinical trial was conducted. Eligible patients had 1-3 liver metastases measuring less than 5cm, and no CNS metastases, tense ascites requiring frequent paracentesis or metastases location within 2cm of the GI tract. The initial cohort received 36 GyE to the planning target volume (PTV) in 3 fractions. Subsequent cohorts received 48 GyE in 3 fractions and finally 60 GyE in 3 fractions, the final chosen maximum dose. At least 700mL of normal liver had to receive <15 GyE. Dose-limiting toxicity (DLT) included acute grade 3 liver, intestinal or spinal cord toxicity or any grade 4 toxicity. The MTD is defined as the dose level below that which results in DLT in 2 or more of the 6 patients in the highest dose level cohort. Results: Nine patients were enrolled (6 male, 3 female): median age 64 years (range, 33-77 years); median gross tumor volume 11.1 ml (range, 2.14-89.3 ml); most common primary site, colorectal (5 patients). Four patients had multiple tumors. No patient experienced a DLT and dose was escalated to 60 GyE in 3 fractions without reaching MTD. The only toxicity within 90 days of completion of treatment was one patient with a grade 1 skin hyperpigmentation without tenderness or desquamation. Two patients in the first cohort had local recurrence and repeat SBPT was done to previously treated lesions without any reported toxicities. Conclusion: Biologically ablative SBPT doses are well tolerated in patients with limited liver metastases with no patients experiencing any grade 2+ acute toxicity. Results from this trial provide the grounds for an ongoing phase II SBPT study of 60 GyE over 3 fractions for liver metastases.