IS TUMOR-CELL RADIATION-RESISTANCE CORRELATED WITH METASTATIC ABILITY

Patients who experience local failure following radiation treatment of epithelial malignancies exhibit a substantially higher rate of distan t metastasis than those patients who achieve permanent local control. This fact has raised concern that the local failure to control the pri mary/regional tumor may serve as a marker of a particularly malignant neoplasm, i.e., high metastatic activity and radiation resistance. If this were true, there would be no gains in survival by increasing the efficacy of treating the primary/regional disease because the new loca l controls would develop distant metastasis. To investigate this conce pt, the relationship between distant metastasis probability and tumor cell radiation resistance has been studied by examining laboratory and clinical data (in vitro and in vivo assays) from six collaborating ce nters. TCD50s (radiation dose which inactivates half of the irradiated tumors) and incidence of distant metastasis in mice with local contro l have been evaluated for 24 murine tumor systems. SF2s (surviving fra ction after 2 Gy) were determined in vitro for cell lines from 8 human , 13 mouse, and 15 rat tumors/tumor sublines and the metastatic activi ty assessed after injection of the cells into syngeneic murine hosts a nd xenogenic hosts for the human tumors. SF2s of cells from carcinomas of the head/neck, cervix, and endometrium which were controlled local ly by radiation +/- surgery from four centers were compared for those which did and those which did not metastasize. The total number of pat ients studied was 222. The cumulative distributions of SFs of locally controlled tumors which did and did not metastasize were not different in each of the data sets. Similarly, there was no demonstrable relati onship between TCD50s and metastatic frequency in local control mice. Furthermore, the SF2S of murine and human tumor cell lines did not tra ck with metastatic activity. Radiation sensitivity of clinical and lab oratory tumors did not correlate with metastatic activity in studies o f data from six centers.