Radiation sensitivity in vitro of primary tumors and metastatic lesions of malignant melanoma.

The radiation sensitivity of cells isolated directly from surgical specimens of the primary tumor and one to three distant metastases in ten different melanoma patients was measured in vitro using the Courtenay soft agar colony assay. Dose-response curves were fitted to the cell survival data by the method of least squares using the multitarget-single hit and the linear-quadratic models. The ten patients could be divided into three distinct groups. Group I consisted of four patients with radioresistant primary tumors (D0s from 1.38 +/- 0.06 Gy to 1.69 +/- 0.08 Gy). The radiation sensitivity of the metastases (D0s from 1.33 +/- 0.10 Gy to 1.73 +/- 0.06 Gy) was not significantly different from that of the primary tumor in this group; i.e., no heterogeneity was observed. Group II consisted of three patients with radiosensitive primary tumors (D0s from 0.84 +/- 0.06 Gy to 0.91 +/- 0.05 Gy). Heterogeneity was not observed in this group either; i.e., all metastases were radiosensitive (D0s from 0.85 +/- 0.05 Gy to 1.00 +/- 0.06 Gy). Group III consisted of three patients with a heterogeneous disease. The primary tumor of all patients in this group was radiosensitive (D0s from 0.85 +/- 0.05 Gy to 1.03 +/- 0.05 Gy). The most radioresistant metastasis in each patient was significantly (P much less than 0.05) more resistant (D0s from 1.46 +/- 0.06 Gy to 1.56 +/- 0.07 Gy) than the primary tumor. None of the metastases were significantly more radiosensitive than the primary tumor in any patient. These observations suggest that the progression of tumors to increased levels of malignancy includes the increased ability to become radioresistant, and it may be speculated that similar genomic alterations are responsible for the development of the metastatic and the radioresistant tumor cell phenotype. If so, this may have severe implications for the treatment of metastatic malignant melanoma with low linear energy transfer ionizing radiation as well as for the development of predictive assays for tumor treatment sensitivity.