Individual Radiosensitivity and Correlation with Tumoral Regression

Abstract

On the one hand, higher individual radiosensitivity increases the risk for side effects of radiotherapy, on the other hand it could also lead to improved tumor response after neoadjuvant chemoradiation. Our point of interest was the correlation of individual radiosensitivity (γH2AX as a reliable factor of radiosensitivity) and regression of the rectal cancer. We investigated a total of 22 patients (19 male, 3 female, all in stage T3 N0/N + M0) with locally advanced rectal adenocarcinoma. All patients received neoadjuvant chemoradiation (RCT) followed by resection. Before treatment, 2ml of blood was collected, lymphocytes were isolated and irradiated with 2 Gy. After 24 hours, lymphocytes were stained with γH2AX antibodies. We compared our results with untreated lymphocytes of the same patient. At least 500 lymphocytes (and the included γH2AX -foci) were microscopically analyzed per patient. Subsequently, we statistically evaluated the correlation of the number of γH2AX foci (γH2AX as a sign for unrepaired DNA DSB), and tumor regression (RG) by Dworak et al. (RG 0 to 4; RG 0: no regression, RG 4: complete regression). Five of 22 (23%) had a complete (RG 4), and 11 (50%) patients an almost complete tumoral regression (RG 3); However, 6 patients showed only a minor regression (RG1-2). In the untreated lymphocytes an average of 0.36 (± 0.21) foci was counted; after irradiation with 2 Gy and a 24 hour delay 2.25 Foci were still present. Tumoral regression (RG 3 + 4 vs. RG 0-2) correlated positively (p = 0.05) with the number of γH2AX-foci. However, regression did not correlate with other parameters such as age, weight, tumor size, dose and volume. In patients with adenocarcinoma of the rectum there is an obvious positive correlation of remaining γH2AX foci in peripheral lymphocytes and histopathological regression of primary tumor. These findings could be an indication that patients of rectal cancer with increased radiosensitivity benefit of better response to neoadjuvant RCT.