Selective boosting of tumor subvolumes

Purpose and background: It is no longer considered mandatory to deliver a uniform dose to the tumor volume in radiotherapy. Non-uniform doses are unavoidable in brachytherapy and in stereotactic radiosurgery, with often good results. Deliberately non-uniform doses may increase tumor control probability (TCP) and enable steeper dose gradients outside the treated volume to be achieved. New methods of tumor imaging might show regions of specific activity or hypoxia which could be selectively targeted. This paper investigates by modeling the effect of boosting, by dose ratios up to 2, for a range of tumor subvolumes. Methods and Materials: A standard linear-quadratic algorithm was used to define the dose-response curve for tumors of various volumes (numbers of clonogenic cells), radiosensitivity (SF₂), assumed slope (γ₅₀) and dose for 50% tumor control (TCD₅₀). Curves of tumor control probability (TCP) were constructed to show the increase of TCP, as a function of the ratio of boost dose to the TCD₅₀, above the baseline 50% TCP, for a set of different proportions of tumor volume boosted. Results: Calculated values of TCP increased rapidly with both boost dose ratio and with proportion of volume boosted. The increase in TCP reached a plateau after boost dose ratios of 1.2-1.3, as has been noted before, except where very large proportions of tumor volume exceeding 90% were boosted. Quite large increases of TCP, to about 75%, could be achieved if the γ₅₀ slope was steep, and especially in small tumors (having fewer cells). Radiosensitivity was not an independent factor because radiosensitive tumors had a low TCD₅₀ and this was the baseline dose considered as unity. Conclusion: There were few situations where a boost dose ratio exceeding 1.3 appeared to be worthwhile or necessary. Significant increases of TCP, up from 50% to 75%, might therefore be achieved for a small increase in risk of necrosis, where a substantial proportion of tumor volume (60-80%) could be boosted.