Tumor and normal tissue tolerance for fractionated low-dose-rate radiotherapy

Radiobiological evidence suggests that an improved therapeutic ratio might be achieved through the use of smaller than conventional dose fractions. The ultimate in small dose fractions for external beam radiotherapy would be fractionated low-dose-rate (LDR) irradiation, and clinical trials of fractionated external beam LDR therapy are already in progress. Using the BA1112 rat sarcoma, we have determined the 50% tumor control dose for LDR and for conventional-dose-rate (CDR) fractionated radiotherapy. These tumor control doses were compared to normal tissue tolerance doses for hemi-body irradiation in similar CDR and LDR schedules. Animals were treated 3 times per week without anesthesia using 10-19 fractions. LDR radiotherapy was done with 60Co at dose rates of 0.028-0.033 Gy/min; CDR radiotherapy was done with 250 kVp X rays at dose rates of 0.54-2.1 Gy/min. The tumor control dose modification factor (DMF) for LDR compared to CDR irradiation was 1.3 (1.0-1.5). For LDR and CDR hemi-body irradiation, the dose modification factor for 7 day lethality (gastrointestinal damage) was 1.7 (1.5-1.9), for 100 day morbidity was 1.8 (1.6-2.2), and for radiation nephritis at 90 days was 1.9 (1.7-2.3). The therapeutic gain factor for fractionated low-dose-rate irradiation compared to conventional-dose-rate fractionated radiotherapy was therefore 1.8/1.3 = 1.4 (1.2-1.8). The study shows that there is an experimental as well as a theoretical basis for anticipating a therapeutic benefit from the use of external beam fractionated LDR radiotherapy, and implies that the recognized therapeutic efficacy of brachytherapy is not due solely to the high localized dose.