THE IMPACT OF RADIATION-DOSE IN COMBINED EXTERNAL-BEAM AND INTRALUMINAL IR-192 BRACHYTHERAPY FOR BILE-DUCT CANCER

Purpose: To examine the impact of radiation dose on both survival and morbidity in combined modality treatment of bile duct cancer. Methods and Materials: Forty-eight patients with cancer of the extrahepatic bile ducts were treated at Thomas Jefferson University Hospital from 1984-1990. Twenty-four patients received radiation as part of a combined modality approach using external beam radiation, brachytherapy implant and chemotherapy. Twenty-four patients received no radiation in the course of their treatment. Radiation was delivered via high energy photons at standard fractionation, 5 days/week, for an average of 46 Gy. The implant used Ir-192 ribbon sources (average activity was 29 mCi, active length was 6 cm) for a mean dose of 25 Gy at 1 cm. Chemotherapy consisted of 5-FU alone or combined with adriamycin or mitomycin-C. Results: Two-year survival for all 48 patients was 18% (median 9 months). Patients treated with radiation had a 2-year survival of 30% (median 12 months) vs. the no-radiation group, 17% (5.5 months, median), p = 0.0 1. Those treated to > 55 Gy experienced an extended 2-year survival of 48% (24 months, median), vs. those receiving < 55 Gy, 0% (6 months, median), p = 0.0003. This benefit was also seen when patients were stratified by T-stage. A dose response is further suggested by a lengthening of the median survival with increasing radiation dose (4.5 months, 9 months, 18 months and 25 months for < 45 Gy, 45-55, 55-65, 66-70 Gy, respectively). Neither surgical resection nor chemotherapy produced statistically significant benefits as independent variables. Complications due to radiation occurred in only one patient. Conclusion: A dose response is shown with more than double the 2-year and median survival for doses > 55 Gy. A brachytherapy dose of 25 Gy, plus 44-46 Gy external beam is well tolerated. High dose combined brachytherapy and external beam radiation (60-75 Gy) appears to be the most effective modality for extrahepatic bile duct cancer.