Studies on optimal dose of preoperative irradiation and time for surgery in the cure of a mouse lymphosarcoma.

Abstract

Interest in the clinical value of preoperative irradiation in the control of malignant tumors has mounted in the recent years. A number of animal experiments have demonstrated different cure rates with surgical excision, irradiation, or a combination of preoperative irradiation and surgical resection (1, 5, 6, 9, 20). Clinical studies on patients with carcinoma of the head and neck (7, 18, 23), breast (24), gastrointestinal tract (15), lung (4, 13), bladder (25), ovary (12), and colon and rectum (11) strongly suggest the value of lower dose preoperative irradiation in the improved control of the tumor and better survival rates of patients. The effect of preoperative fractionation has been studied experimentally by Feder et al. with a transplantable sarcoma in C3H mice (6). In the present experiments with a mouse lymphosarcoma we have investigated: 1. The effect of increasing doses of preoperative irradiation as measured by cure rate of surgical treatment in normal and immunologically incompetent mice. 2. The optimal period of delay for surgical excision after different doses of preoperative irradiation as manifested by: (a) frequency of inoperability; (b) rate of tumor control; (c) interference with wound healing. Materials and Methods Some of the experimental technics have been previously reported (20). Clinically palpable solid tumors were produced by implanting chunks of 6C3HED tumor (Gardner lymphosarcoma) into the intradermal tissue of the flank of C3H/Anf mice (Cumberland View Farms, Clinton, Tenn.). Experiment No. 1 A group of 400 normal mice and another of 260 mice rendered “immunologically incompetent” (300 rads whole-body irradiation and oral hydrocortisone2) were studied in a similar fashion. After the tumor became palpable (at least 3 mm in diameter, usually in three to five days) the animals were randomly placed into four groups. Those in one group received no irradiation, the mice in the other three groups were irradiated with a single dose of 500, 1,000, or 2,000 rads, respectively, to the tumor-bearing area. Surgical resection of the tumor with a wide skin flap was performed immediately after irradiation. The surgeon did not know to which group a given animal had been allocated. Both irradiation and surgery were performed under general anesthesia with intraperitoneal sodium pentobarbital.3 The incisions were closed with a continuous silk suture. The radiation was administered with a constant potential unit operated at 230 kV, 15 mA, 1.7 mm Cu h.v.l., 20 cm TSD, and a dose rate of 380 rads per minute. The animals were caged in groups of 10 and checked daily for tumor recurrence for at least six months or until death. Experiment No. 2 A series of 856 six- to eight-week-old normal C3H/Anf female mice were inoculated with chunks of Gardner lymphosarcoma, as described above. Radiation was administered to the tumor-bearing area in single doses of 500, 1,000, 2,000, 3,000, or 4,000 rads.