目的:本研究旨在评估晚期食管鳞状细胞癌(ESCC)患者胸部放疗/放化疗联合抗PD-1单克隆抗体(mAb)后治疗相关性肺炎(TRP)的危险因素。
方法:我们回顾性分析了97例晚期ESCC患者接受胸部放疗/放化疗联合抗PD-1单克隆抗体治疗。其中,56例患者接受抗PD‑1mAb同步放疗,41例患者接受抗PD‑1mAb序贯放疗。规定的计划目标体积(PTV)的中位剂量为59.4Gy(范围为50.4至66Gy,1.8-2.2Gy/分数)。临床特征,分析了以5Gy递增量超过5-50Gy的肺容积百分比(分别为V5-V50)和平均肺剂量(MLD)作为TRP的潜在危险因素.
结果:46.4%(45/97),20.6%(20/97),20.6%(20/97),4.1%(4/97),1.0%(1/97)的患者出现任何级别的TRP,1级TRP,2级TRP,3级TRP,和致命的(5级)TRP,分别。与放疗同时施用的抗PD‑1单克隆抗体,V5,V10,V15,V25,V30,V35,V40和MLD与2级或更高TRP的发生有关。同时治疗(P=0.010,OR=3.990)和V5(P=0.001,OR=1.126)是2级及以上TRP的独立危险因素。根据接收机工作特性(ROC)曲线分析,预测2级或更高TRP的最佳V5阈值为55.7%.
结论:胸部放疗/放化疗联合抗PD‑1单克隆抗体显示出可耐受的肺安全性。虽然TRP的发病率很高,1-2级TRP占大多数。与放疗和肺V5同时施用的抗PD‑1mAb与2级或更高级别TRP的发生显着相关。因此,在临床上将V5控制在55%以下似乎更安全,特别是对于接受同步治疗的高危人群。
OBJECTIVE: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD‑1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC).
METHODS: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD‑1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD‑1 mAbs and 41 patients received sequential radiotherapy with anti-PD‑1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4 Gy (range from 50.4 to 66 Gy, 1.8-2.2 Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP.
RESULTS: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD‑1 mAbs administered concurrently with radiotherapy, V5, V10, V15, V25, V30, V35, V40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (P = 0.010, OR = 3.990) and V5 (P = 0.001, OR = 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V5 threshold for predicting grade 2 or higher TRP was 55.7%.
CONCLUSIONS: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD‑1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1-2 TRP accounted for the majority. Anti-PD‑1 mAbs administered concurrently with radiotherapy and the lung V5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy.