Purpose

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%.

Conclusion

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.

中文翻译：

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晚期食管鳞癌胸部放疗/放化疗联合抗PD-1单克隆抗体后治疗相关性肺炎

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）后发生治疗相关性肺炎（TRP）的危险因素。

方法

我们回顾性分析了 97 例接受胸部放疗/放化疗联合抗 PD-1 mAb 治疗的晚期 ESCC 患者。其中，56名患者接受抗PD-1单克隆抗体同步放疗，41名患者接受抗PD-1单克隆抗体序贯放疗。中位规定计划靶体积 (PTV) 剂量为 59.4 Gy（范围为 50.4 至 66 Gy，1.8–2.2 Gy/分次）。_{临床特征、接受超过 5-50 Gy 以 5 Gy 增量（分别为 V 5} –V ₅₀ ）的肺体积百分比和平均肺剂量 (MLD) 被分析为 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) 和 1.0% (1/97) 的患者出现任何级别的 TRP、分别为 1 级 TRP、2 级 TRP、3 级 TRP 和致命（5 级）TRP。抗 PD-1 mAb 与放射治疗同时使用，V ₅、V ₁₀、V ₁₅、V ₂₅、V ₃₀、V ₃₅、V ₄₀和 MLD 与 2 级或更高级别 TRP 的发生相关。同步治疗 ( P  = 0.010, OR = 3.990) 和 V ₅ ( P  = 0.001, OR = 1.126) 是 2 级或以上 TRP 的独立危险因素。根据受试者工作特征（ROC）曲线分析，预测2级或更高TRP的最佳V ₅阈值为55.7%。

结论

胸部放疗/放化疗与抗 PD-1 mAb 的组合显示出可耐受的肺部安全性。尽管TRP的发生率较高，但1~2级TRP占大多数。_{与放疗和肺 V 5}同时施用的抗 PD-1 mAb 与2 级或更高级别 TRP 的发生显着相关。_{因此，临床上将V 5}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。