The risk of carcinogenesis and optimization in radiotherapy

J.J. Broerse MD PhD, C.F. Hollander, J.T.M. Jansen, J. Zoetelief

Dept. Clinical Oncology, Leiden University Medical Center, Leiden and Interfaculty Reactor Institute, Delft, The Netherlands

.AIMS. Assessment of a carcinogenic risk from studies in long-term surviving monkeys after high dose total body irradiation (TBI). Calculation of effective doses in radiotherapy procedures in man and optimization of irradiation geometry . METHODS. Rhesus monkeys exposed to average doses of 6.8 Gy X-rays or 3.4 Gy fission neutrons, and a control group, were screened during thirty years for the occurrence of neoplasms. For treatment of benign diseases in man the carcinogenic risk was assessed on the basis of tissue weighting factors and organ doses derived from radiation transport codes . RESULTS At post irradiation intervals of 4 to 21 years an appreciable number of tumours was observed in the monkeys. Tumours in the control group appeared at much older age compared with those in the irradiated cohorts. Effective doses calculated for radiotherapy of endocrine orbitopathy, hidradenitis suppurativa, heterotopic ossification, omarthritis and gonarthrosis range from 13 to 420 mSv. Employing a risk factor of 10 percent per Sv for induction of fatal cancers, the attributable life time risks vary between 0.1 and 4 percent. CONCLUSION. When corrected for competing risks, the carcinogenic risk of TBI in Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a factor of 8, observed in the monkeys, indicates that patients are likely to develop malignancies more frequently and earlier in life after TBI than non-exposed individuals. This finding underlines the necessity of regular screening of long-term surviving patients subjected to TBI and bone marrow transplantation. The calculation of effective doses for radiotherapy of benign diseases offers the possibility to optimize the irradiation procedure. For treatment of Graves orbitopathy in two geometries the effective dose could be reduced from 65 to 34 mSv. When irradiations are performed at older age, the risk factor will be reduced by an approximate factor of three

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Risk Assessment, Part 2.