Journal of Clinical Oncology, Vol 16, 2246-2252, Copyright © 1998 by American Society of Clinical Oncology

ARTICLES

Treatment of intrahepatic cancers with radiation doses based on a normal tissue complication probability model

CJ McGinn, RK Ten Haken, WD Ensminger, S Walker, S Wang and TS Lawrence
Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor 48109-0010, USA. mcginn@umich.edu

PURPOSE: To attempt to safely escalate the dose of radiation for patients with intrahepatic cancer, we designed a protocol in which each patient received the maximum possible dose while being subjected to a 10% risk of radiation-induced liver disease (RILD, or radiation hepatitis) based on a normal tissue complication probability (NTCP) model. We had two hypotheses: H1; with this approach, we could safely deliver higher doses of radiation than we would have prescribed based on our previous protocol, and H2; the model would predict the observed complication probability (10%). PATIENTS AND METHODS: Patients with either primary hepatobiliary cancer or colorectal cancer metastatic to the liver and normal liver function were eligible. We used an NTCP model with parameters calculated from our previous patient data to prescribe a dose that subjected each patient to a 10% complication risk within the model. Treatment was delivered with concurrent hepatic arterial fluorodeoxyuridine (HA FUdR). Patients were evaluated for RILD 2 and 4 months after the completion of treatment. RESULTS: Twenty-one patients completed treatment and were followed up for at least 3 months. The mean dose delivered by the current protocol was 56.6 +/- 2.31 Gy (range, 40.5 to 81 Gy). This dose was significantly greater than the dose that would have been prescribed by the previous protocol (46.0 +/- 1.65 Gy; range, 33 to 66 Gy; P < .01). These data are consistent with H1. One of 21 patients developed RILD. The complication rate of 4.8% (95% confidence interval, 0% to 23.8%) did not differ significantly from the predicted 8.8% NTCP (based on dose delivered) and excluded a 25% true incidence rate (P < .05). This finding supports H2. CONCLUSION: Our results suggest that an NTCP model can be used prospectively to safely deliver far greater doses of radiation for patients with intrahepatic cancer than with previous approaches. Although the observed complication probability is within the confidence intervals of our model, it is possible that this model overestimates the risk of complication and that further dose escalation will be possible. Additional follow-up and accrual will be required to determine if these higher doses produce further improvements in response and survival.
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