Table_10_Radiation-induced lung injury after breast cancer treatment: incidence in the CANTO-RT cohort and associated clinical and dosimetric risk factors.docx

PurposeRadiation-induced lung injury (RILI) is strongly associated with various clinical conditions and dosimetric parameters. Former studies have led to reducing radiotherapy (RT) doses to the lung and have favored the discontinuation of tamoxifen during RT. However, the monocentric design and variability of dosimetric parameters chosen have limited further improvement. The aim of our study was to assess the incidence of RILI in current practice and to determine clinical and dosimetric risk factors associated with RILI occurrence.
Material and methodsData from 3 out of the 10 top recruiting centers in CANTO-RT, a subset of the CANTO prospective longitudinal cohort (NCT01993498), were retrospectively analyzed for RILI occurrence. This cohort, which recruited invasive cT0-3 cN0-3 M0 breast cancer patients from 2012 to 2018, prospectively recorded the occurrence of adverse events by questionnaires and medical visits at the end of, and up to 60 months after treatment. RILI adverse events were defined in all patients by the association of clinical symptoms and compatible medical imaging.
ResultsRILI was found in 38/1565 (2.4%) patients. Grade II RILI represented 15/38 events (39%) and grade III or IV 2/38 events (6%). There were no grade V events. The most frequently used technique for treatment was 3D conformational RT (96%). In univariable analyses, we confirmed the association of RILI occurrence with pulmonary medical history, absence of cardiovascular disease medical history, high pT and pN, chemotherapy use, nodal RT. All dosimetric parameters were highly correlated and had close predictive value. In the multivariable analysis adjusted for chemotherapy use and nodal involvement, pulmonary medical history (OR=3.05, p<0.01) and high V30 Gy (OR=1.06, p=0.04) remained statistically significant risk factors for RILI occurrence. V30 Gy >15% was significantly associated with RILI occurrence in a multivariable analysis (OR=3.07, p=0.03).
ConclusionOur study confirms the pulmonary safety of breast 3D RT in CANTO-RT. Further analyses with modern radiation therapy techniques such as IMRT are needed. Our results argue in favor of a dose constraint to the ipsilateral lung using V30 Gy not exceeding 15%, especially in patients presenting pulmonary medical history. Pulmonary disease records should be taken into account for RT planning.

研究目的：辐射性肺损伤（Radiation-induced lung injury, RILI）与多种临床病症及剂量学参数密切相关。既往研究已提出降低肺部放疗（radiotherapy, RT）剂量，并倾向于在放疗期间停用他莫昔芬。然而，单中心设计及所选剂量学参数的异质性限制了研究结果的进一步优化与推广。本研究旨在评估当前临床实践中RILI的发生率，并明确与RILI发生相关的临床及剂量学危险因素。

材料与方法：本研究回顾性分析了CANTO-RT队列（CANTO前瞻性纵向队列研究（NCT01993498）的子队列）中10家核心招募中心里的3家中心的相关数据，以评估RILI的发生情况。该队列于2012年至2018年间招募了侵袭性cT0-3 cN0-3 M0乳腺癌患者，通过治疗结束时及治疗后长达60个月的问卷随访与门诊就诊记录，前瞻性收集不良事件发生情况。所有患者的RILI不良事件均通过临床症状与匹配的医学影像检查结果联合定义。

研究结果：本研究共纳入1565例患者，其中38例（2.4%）发生RILI。38例RILI事件中，Ⅱ级损伤占15例（39%），Ⅲ级或Ⅳ级损伤占2例（6%），无Ⅴ级损伤病例。最常用的放疗技术为三维适形放疗（3D conformational RT），占比达96%。单因素分析显示，RILI发生与肺部病史、无心血管疾病病史、较高的pT及pN分期、化疗使用情况、淋巴结放疗存在显著关联。所有剂量学参数均具有较高相关性，且预测价值相近。在校正化疗使用情况及淋巴结受累情况的多因素分析中，肺部病史（OR=3.05, p<0.01）及高V30Gy剂量参数（OR=1.06, p=0.04）仍为RILI发生的独立统计学显著危险因素。多因素分析显示，V30Gy>15%与RILI发生显著相关（OR=3.07, p=0.03）。

研究结论：本研究证实了CANTO-RT队列中乳腺癌三维适形放疗的肺部安全性。未来仍需针对调强放疗（IMRT）等现代放疗技术开展进一步分析。本研究结果支持在放疗计划中对患侧肺部施加V30Gy不超过15%的剂量约束，尤其针对存在肺部病史的患者。放疗计划制定时应充分考虑患者的肺部疾病史。