X-IRRADIATION OF THE TUMOR BED. I. A STUDY OF THE INDIRECT ACTIONS OF RADIATION ON TRANSPLANTABLE TUMORS.

Abstract

The effects of ionizing radiation on living organisms are the complex summation of numerous factors. In higher animals one is concerned not only with cellular effects, but also with tissue, organ, and systemic responses. All of these must be considered in the use of radiation in the treatment of malignant neoplasms. In addition to acting directly on the tumor cells to cause their death, radiation affects the environment of the tumor (i.e., the host), reducing proliferation of the malignant cells. It is of importance to determine the relative significance of these factors in order to establish a more rational basis for radiation therapy. Numerous studies of the effects of ionizing radiation on tumor growth, metabolism, and genetic composition have been reported (8, 38, 46, 56). The common consideration of the great majority of these studies is the effect of radiation on the tumor itself. Several studies have, however, been concerned with the importance of the condition of the host tissue to the subsequent growth of a tumor (24, 29, 45, 46). It is the purpose of this paper to present experimental work that further clarifies the mode of action of radiation on the tumor bed (the tumor bed effect, TBE), in so far as this action modifies tumor growth. Survey of Literature The early literature related to the effect of irradiation on the tumor bed has been previously reviewed (45, 52, 53). Murphy et al. (30) concluded that the essential mechanism was the induction of a lymphocytic inflammation. Ewing (8) stated that local lymphoid reaction and degeneration of the blood supply which in turn led to anemic infarction were important events in the action of radiation on malignant tissue. In 1928 Wood (59) reported that the growth of a transplantable carcinoma was dependent on the surrounding blood supply, and that radiation produced vascular effects that might lead to a decrease in the nonnal blood supply to a given area. Wood thus implicated vascular damage as one type of indirect action. This point of view was supported by Ewing (9) in a review on radiosensitivity of tumors. The effect of irradiation on host-tumor relationship was studied by Oughterson et al. (34). They believed that irradiation augmented the “natural resistance” of the F1 animals to a grafted tumor of a parent strain genotype and emphasized the importance of the environment to which a tumor was subjected. Glucksmann (10) felt that late degeneration of cells and breakup of tumor cell “nests” were indicative of indirect action (mediated by host-tissue effects), while mitotic inhibition and early degeneration were evidence of direct action (cytocidal effects on tumor cells).