Low dose hyper-radiosensitivity in metastatic tumors

Abstract

Introduction: The laboratory phenomenon of low dose hyper-radiosensitivity (LDHRS) describes excess cell kill at doses below 1 Gy relative to that predicted by the linear quadratic model. These data have stimulated the investigation of whether LDHRS can be exploited clinically.

Methods: Patients with metastatic tumor nodules to skin were recruited. The nodules were measured in three dimensions, consecutively numbered according to volume, and randomized, in matched pairs, to receive either conventionally fractionated radiotherapy (1.5 Gy/day) or ultrafractionated radiotherapy (0.5 Gy TDS: 4-h gap). Both groups were treated for 12 days. Measurements were taken Days 0, 5, 8, 12, and 26 and monthly until regrowth occurred. Tumor volumes were normalized to those on Day 0 and plotted against time from the start of treatment. Time to regrowth to original volume was calculated and compared between groups using the Wilcoxon signed rank test.

Results: Eight patients with a total of 40 paired nodules were analyzed; 36 nodules have regrown and are therefore evaluable. Analysis of the whole data set demonstrates a two-tailed p-value of 0.14 in favor of the "ultrafractionated" treatment. Analysis of the tumors generally accepted as being radioresistant and known to show LDHRS in vitro demonstrates a two-tailed p value of 0.009.

Conclusions: LDHRS can be demonstrated in tumors clinically. An "ultrafractionated" radiotherapy regime produces significantly increased growth delay in radioresistant malignant tumors.