Tumor induction following intraoperative radiotherapy: late results of the National Cancer Institute canine trials.

Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a "collision" tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months (median 40 months). The IORT dose range associated with tumor development was 20-35 Gy (median 30 Gy). The carcinogenesis capability of single fraction, high dose radiation in animals is discussed, as are the implications of these data for continued research and clinical usage of IORT in the treatment of humans.

Patterns of failure in patients with stage I, grade 3 carcinoma of the endometrium.

Patients with high grade, early stage endometrial carcinoma are reported to have worse survival and local control rates than those with low grade carcinomas. To define failure patterns further in patients with FIGO Stage I, grade 3 endometrial carcinomas, the patients from three institutions who received adjuvant or definitive radiation (RT) were analyzed. Of 119 patients meeting the criteria of Stage I, grade 3 endometrial carcinoma, 57 patients received preoperative radiation, 49 patients received postoperative radiation, and 10 patients received definitive radiation with 5-year actuarial survival rates of 64%, 73%, and 65%, respectively. Three additional patients received both preoperative and postoperative treatment. The overall local control rate was 88% with a median follow-up of 70 months. Of 36 patients who failed, 14 had a component of local failure, and 31 had a component of distant failure. Eighteen of 31 distant failures involved metastatic spread to the abdominal cavity. Recurrence patterns by method of treatment are documented. Patients with high grade tumors do have a propensity for distant metastasis. Clinical investigation into the value of systemic therapy is necessary.