Tumor radiocurability: relationship to intrinsic tumor heterogeneity and to the tumor bed effect.
Recent in vitro clonogenic assays of cells from human head and neck carcinomas recurring after fractionated irradiation showed that the mean radiation resistance was significantly greater than that of cells from unirradiated head and neck cancers. Analysis of these data using the linear-quadratic formalism of radiation inactivation indicates that such increased resistance was associated with a large decrease in the parameter describing cell killing by one-hit processes, while the parameter describing cell inactivation by two-hit processes was unchanged. These data suggest that head and neck carcinomas contained intrinsically radioresistant tumor subpopulations that were selected for during the fractionated radiation therapy. Consequently, we have generated a model of how the phenomenon of clonal intraneoplastic diversity might be related to the selection of radioresistant sub-populations. There is, however, an additional major modulating factor which may impact upon the proposed selection process, known as the tumor bed effect. This effect refers to the fact that solid tumors grow at slower rates and to decreased carrying capacities in radiation-damaged normal tissue stroma. We hypothesize that the tumor bed effect is a reflection of an altered, hostile microenvironment within which competition among neoplastic subpopulations for limited resources is increased. This then produces a situation leading to extinction of minority subpopulations within heterogeneous neoplasms, regardless of whether such populations are radioresistant. The final result of these selection/extinction processes will be dependent upon total dose, dose per fraction, overall time, and the initial partial volume percentages of radioresistant subpopulations.
Leith
J T
JT
Department of Radiation Medicine, Brown University, Providence, R.I.
Michelson
S
S
D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D009364:Neoplasm Recurrence, Local; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000009:adverse effects; D016019:Survival Analysis