Tumor volume and local control probability: Clinical data and radiobiological interpretations

Purpose: It is well established for certain human tumor histologies that increasing tumor volume leads to a decreasing probability of tumor control, The simplest explanation for these findings is that the number of tumor clonogens that must be sterilized to control a tumor increases with tumor volume, In this investigation we consider whether clinical evidence favors a further hypothesis, namely, that clonogen number increases in direct proportion to tumor volume. Methods and Materials: Previously published data on the volume-cure relationship for breast tumors, neck nodes, malignant melanoma, and squamous cell carcinomas of the oropharynx and the uterine cervix were analyzed. Results: We found in all these data sets evidence that the effect of tumor volume on tumor control probability was less than what would be expected under the assumption of proportionality between number of clonogens and volume, We describe good reasons to believe that this is the result of patient-to-patient variability in radiocurability, and possibly other factors as well. Conclusions: Clinical data do provide evidence for a highly significant reduction of tumor control probability with increasing tumor volume, However, because of heterogeneity in patient and tumor characteristics, the volume effect is less pronounced than would be expected from a simple proportionality between number of clonogens and volume, In principle this simple proportionality does hold in individual patients, so that standard approaches for treatment plan optimization in individuals may still be valid.