图像引导放射治疗时代晚期放射毒性的遗传标记:较低的毒性率降低了接受盆腔放射治疗的患者中γ-H2AX病灶衰减比的预测价值。
Genetic markers of late radiation toxicity in the era of image-guided radiotherapy: lower toxicity rates reduce the predictive value of γ-H2AX foci decay ratio in patients undergoing pelvic radiotherapy.
发表日期:2024 Sep 02
作者:
Anna C Nuijens, Arlene L Oei, Lisa Koster, Ron A Hoebe, Nicolaas A P Franken, Coen R N Rasch, Lukas J A Stalpers
来源:
MOLECULAR & CELLULAR PROTEOMICS
摘要:
晚期放射毒性的预测测定将允许更加个性化的治疗计划,减少更敏感的少数人的毒性负担,并提高大多数人的治疗指数。在之前针对前列腺癌患者的一项研究中,γ-H2AX 病灶衰减比 (γ-FDR) 是晚期放射毒性的最强预测因子。目前的研究旨在在更多不同的盆腔癌患者群体中验证这一发现。此外,还调查了 γ-FDR 与患者报告的结果之间的潜在相关性。当前的分析包括随访时间≥24 个月的前列腺癌和妇科癌症患者。毒性由医生(CTCAE 第 4 版)和患者(EORTC 问卷)进行评估。 γ-FDR 在离体照射的淋巴细胞中测定。使用线性和逻辑回归分析评估 γ-FDR 和毒性之间的相关性。使用随访期间记录的最高毒性等级。通过比较 γ-FDR < 或≥ 3.41(先前设定的阈值)患者的生活质量随时间的变化,测试了总体生活质量与 γ-FDR 之间的关联。纳入了 88 名患者。医生评估和患者报告的累积≥2级毒性分别为25%和29%;这比之前的队列低得多(即 51% CTCAE 等级 ≥ 2)。具有毒性的患者表现出不太有利的剂量体积参数。在男性中,这些参数与之前的队列相比显示出显着改善。 γ-FDR低的患者比例随着毒性的严重程度而增加,但这种趋势并不具有统计学意义。此外,γ-FDR < 3.41 与中度至重度毒性的发生无关。治疗后总体生活质量下降很小,对于 γ-FDR < 或 ≥ 3.41 的患者而言,治疗后的下降程度相似。在本研究中,γ-H2AX 病灶衰减比无法被验证为患者晚期放射毒性的预测因子患有盆腔癌。改进的放射治疗技术以及较小的受照射膀胱和肠道体积可能会减少毒性。未来对毒性遗传标记的研究应该以这些较低的发生率为基础。我们进一步建议除了严重性之外,还要考虑持久性。© 2024。作者。
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.© 2024. The Author(s).