Preliminary results of a phase I study of stereotactic radiotherapy for unresectable primary and metastatic liver cancer

Abstract

4127 Purpose: To report initial toxicity and response data from a phase I study of stereotactic radiotherapy (SRT) for unresectable liver cancer. Methods: Eligible patients have unresectable or medically inoperable primary or metastatic liver cancer, Childs score A and KPS ≥ 60. Standard treatment options have been explored. Patients are stratified based on diagnosis (metastases vs. primary cancer) and volume of uninvolved liver treated (< 20%, 20–50%, 50–80%). SRT is delivered in 6 fractions/2 weeks to maximize patient convenience, resource utilization and therapeutic gain. Dose is individualized to maintain the same estimated risk of liver toxicity for patients at each level (level I - 5% risk, level II - 10% risk, level III - 20%, max. dose 60 Gy in 6 fractions). Escalation to level II and III occurs once at least 3 patients have been followed for >3 months without dose limiting toxicity for each stratum at the previous level. Patients are treated during breath hold to reduce organ motion, with daily imaging and repositioning to reduce setup error. Acute toxicity scored using CTC v3.0. Results: From Aug 2003 to Dec 2004, 36 patients completed SRT at levels I and II (14 hepatocellular carcinoma, 6 cholangiocarcinoma, 16 metastases). The median tumor volume was 213.9 cm3 (range 9.2 to 3088cm3). The average SRT dose to tumor was 35.7 Gy (range: 24 to 56.3 Gy). Median follow-up was 5.5 months (1.4 to 14.9 months). No grade 4/5 related toxicity was seen. At 1 month, 4 patients with HCC had a decline in liver function to Child B. No radiation-induced liver disease (RILD) was observed. Toxicity within 3 months included: grade 3 fatigue (1), vomiting (1); grade 2: thrombocytopenia (2), gastritis (4), pruritis (2), vomiting (2), nausea (6), anorexia (2) fatigue (8), hepatic pain (2). One gastrointestinal bleed occurred 6.4 months following SRT in a patient with tumor extension to the stomach on endoscopy. In 28 evaluable patients, in-field response assessed using CT at 3 months was: CR (1), PR (9), MR/SD (14), PD (4) Conclusion: This approach of individualized dose SRT appears safe, with no severe liver toxicity observed to date. More patients and longer follow up are required for a further assessment of late toxicity and efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ASCO CDA, Canadian Institutes of Health Research, NIH (US)/ NCI, NIH (US)/ Ontario portion/year, Ontario Cancer Research Network, Lustgarten Foundation for Pancreatic Cancer Research