Department of Radiation Oncology, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
Radiat Oncol. 2024 Sep 2;19(1):116. doi: 10.1186/s13014-024-02501-x.
A predictive assay for late radiation toxicity would allow more personalized treatment planning, reducing the burden of toxicity for the more sensitive minority, and improving the therapeutic index for the majority. In a previous study in prostate cancer patients, the γ-H2AX foci decay ratio (γ-FDR) was the strongest predictor of late radiation toxicity. The current study aimed to validate this finding in a more varied group of patients with pelvic cancer. Additionally, the potential correlation between the γ-FDR and patient-reported outcomes was investigated.
Prostate and gynecological cancer patients with ≥ 24 months of follow-up were included in the current analysis. Toxicity was evaluated by physician (CTCAE version 4) and patient (EORTC questionnaires). γ-FDRs were determined in ex vivo irradiated lymphocytes. Correlation between γ-FDR and toxicity was assessed using both linear and logistic regression analyses. The highest toxicity grade recorded during follow-up was used. The association between global quality of life and γ-FDR was tested by comparing the change in quality of life over time in patients with γ-FDR < or ≥ 3.41, a previously established threshold.
Eighty-eight patients were included. Physician-assessed and patient-reported cumulative grade ≥ 2 toxicity was 25% and 29%, respectively; which is much lower than in the previous cohort (i.e., 51% CTCAE grade ≥ 2). Patients with toxicity exhibited less favorable dose-volume parameters. In men, these parameters showed significant improvement compared to the previous cohort. The proportion of patients with a low γ-FDR increased with severity of toxicity, but this trend was not statistically significant. In addition, a γ-FDR < 3.41 was not correlated with the development of moderate to severe toxicity. Post-treatment decline in global quality of life was minimal, and similar for patients with γ-FDR < or ≥ 3.41.
In the present study, the γ-H2AX foci decay ratio could not be validated as a predictor of late radiation toxicity in patients with pelvic cancer. Improved radiotherapy techniques with smaller irradiated bladder and bowel volumes have probably resulted in less toxicities. Future studies on genetic markers of toxicity should be powered on these lower incidences. We further recommend taking persistency, next to severity, into consideration.
预测晚期放射性毒性的检测方法将有助于制定更加个体化的治疗方案，减少少数对毒性更为敏感患者的负担，并提高大多数患者的治疗效果。在之前的前列腺癌患者研究中，γ-H2AX 焦点衰减比（γ-FDR）是晚期放射性毒性的最强预测因子。本研究旨在验证这种方法在更广泛的盆腔癌患者群体中的适用性，并进一步探究 γ-FDR 与患者报告结局之间的潜在相关性。
本研究纳入了至少随访 24 个月的前列腺癌和妇科癌症患者。毒性评估由医生（CTCAE 第 4 版）和患者（EORTC 问卷）进行。在离体照射的淋巴细胞中测定 γ-FDR。使用线性和逻辑回归分析评估 γ-FDR 与毒性之间的相关性。使用随访期间记录的最高毒性等级。通过比较 γ-FDR<或≥3.41 的患者在时间上的生活质量变化，测试 γ-FDR 与整体生活质量之间的关联，γ-FDR 为之前建立的一个阈值。
本研究共纳入 88 例患者。医生评估和患者报告的累积 2 级及以上毒性发生率分别为 25%和 29%，远低于之前的队列（即 51%的 CTCAE 分级≥2）。有毒性的患者表现出较差的剂量-体积参数。男性的这些参数与之前的队列相比有显著改善。具有低 γ-FDR 的患者比例随毒性严重程度的增加而增加，但这种趋势无统计学意义。此外，γ-FDR<3.41 与中重度毒性的发生无关。治疗后整体生活质量的下降很小，且对于 γ-FDR<或≥3.41 的患者来说相似。
在本研究中，γ-H2AX 焦点衰减比不能作为盆腔癌患者晚期放射性毒性的预测因子。具有较小膀胱和肠道照射体积的改良放疗技术可能导致毒性降低。未来关于毒性遗传标志物的研究应考虑到这些较低的发生率。我们还建议不仅要考虑严重程度，还要考虑持久性。
