Influence of time interval between surgery and radiotherapy on tumor regrowth

In order to evaluate the influence of time intervals between tumor cell injection and radiotherapy on tumor control and regrowth after surgery, we performed two kinds of experiments on C3D2F1 mice bearing a mammary carcinoma inoculated in the foot or leg. 1 s t experiment: tumor in foot. End point: Tumor Control Probability (TCP). Single dose radiation treatments (RT) were administered at different period times from injection time of tumor cells (day 1). 1 s t group: unirradiated control, 2 n d group: RT on day 2 (TCP50 29′2.1 Gy), 3 r d group: RT on day 7 (TCP 52.5 ′ 2.9 Gy), 4 t h group: RT on day 12 (TCP50 61.9 ′ 2.4 Gy). 2 n d experiment: tumor in leg. End point: percentage of tumor regrowth. Mice were randomly assigned to three groups: 1st control group (tumor growth in all mice), 2 n d surgical excision of macroscopically evident tumor on day 7-9 from injection (tumor regrowth in 85% of mice), 3 r d as the previous group plus 30 Gy radiation treatment within 24 hours from excision (tumor regrowth in 33% of cases). The radiation dose was selected on the basis of TCP50 observed in the 1 s t experiment for mice with sub-clinical disease. These data indicate that the radiation dose able to control 50% of tumors increases with the time interval between tumor cells injection and RT. A short time interval between surgery and RT should increase the probability of local control, supporting the rationale of intraoperative radiation therapy (IORT) as adjuvant therapy after surgical resection, when subclinical residual cells are suspected.