Corbeau Anouk, Heemsbergen Wilma D, Kuipers Sander C, Godart Jeremy, Creutzberg Carien L, Nout Remi A, de Boer Stephanie M
Department of Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Int J Radiat Oncol Biol Phys. 2024 May 1;119(1):127-142. doi: 10.1016/j.ijrobp.2023.11.010. Epub 2023 Nov 17.
Women with locally advanced cervical cancer (LACC) undergoing primary platinum-based chemoradiotherapy and brachytherapy often experience toxicities. Normal-tissue complication probability (NTCP) models quantify toxicity risk and aid in optimizing radiation therapy to minimize side effects. However, it is unclear which predictors to include in an NTCP model. The aim of this systematic review was to provide an overview of the identified predictors contributing to gastrointestinal (GI), genitourinary (GU), and vaginal toxicities and insufficiency fractures for LACC.
A systematic search was performed and articles evaluating the relationship between predictors and toxicities in women with LACC treated with primary chemoradiation were included. The Quality In Prognosis Studies tool was used to assess risk of bias, with high-risk studies being excluded from further analysis. Relationships between dose-volume parameters, patient and treatment characteristics, and toxicity endpoints were analyzed.
Seventy-three studies were identified. Twenty-six had a low or moderate risk of bias and were therefore included. Brachytherapy-related dose-volume parameters of the GI tract, including rectum and bowel equivalent dose in 2 Gy fractions (EQD2) D2 cm, were frequently related to toxicities, unlike GU dose-volume parameters. Furthermore, (recto)vaginal point doses predicted toxicities. Few studies evaluated external beam radiation therapy dose-volume parameters and identified rectum EQD2 V30 Gy, V40 Gy, and V55 Gy, bowel and bladder EQD2 V40 Gy as toxicity predictors. Also, total reference air kerma and vaginal reference length were associated with toxicities. Relationships between patient characteristics and GI toxicity were inconsistent. The extent of vaginal involvement at diagnosis, baseline symptoms, and obesity predicted GU or vaginal toxicities. Only 1 study evaluated insufficiency fractures and demonstrated lower pretreatment bone densities to be associated.
This review detected multiple candidate predictors of toxicity. Larger studies should consider insufficiency fractures, assess dose levels from external beam radiation therapy, and quantify the relationship between the predictors and treatment-related toxicities in women with LACC to further facilitate NTCP model development for clinical use.
接受以铂类为基础的同步放化疗和近距离放疗的局部晚期宫颈癌（LACC）患者常出现毒性反应。正常组织并发症概率（NTCP）模型可量化毒性风险，并有助于优化放射治疗以尽量减少副作用。然而，尚不清楚在NTCP模型中应纳入哪些预测因素。本系统评价的目的是概述已确定的与LACC患者胃肠道（GI）、泌尿生殖系统（GU）、阴道毒性及不全骨折相关的预测因素。
进行了系统检索，纳入评估接受初始放化疗的LACC女性患者预测因素与毒性反应之间关系的文章。使用预后研究质量工具评估偏倚风险，高风险研究被排除在进一步分析之外。分析了剂量体积参数、患者和治疗特征与毒性终点之间的关系。
共识别出73项研究。其中26项偏倚风险低或中等，因此被纳入。与近距离放疗相关的胃肠道剂量体积参数，包括直肠和肠道2 Gy分次等效剂量（EQD2）D2 cm，与毒性反应的相关性较为常见，这与GU剂量体积参数不同。此外，（直肠）阴道点剂量可预测毒性反应。很少有研究评估外照射放疗剂量体积参数，并确定直肠EQD2 V30 Gy、V40 Gy和V55 Gy、肠道和膀胱EQD2 V40 Gy为毒性预测因素。此外，总参考空气比释动能和阴道参考长度也与毒性反应相关。患者特征与GI毒性之间的关系并不一致。诊断时阴道受累程度、基线症状和肥胖可预测GU或阴道毒性。仅有1项研究评估了不全骨折，并表明较低的治疗前骨密度与之相关。
本综述发现了多个毒性反应的候选预测因素。规模更大的研究应考虑不全骨折，评估外照射放疗的剂量水平，并量化LACC女性患者预测因素与治疗相关毒性之间的关系，以进一步推动用于临床的NTCP模型的开发。
