Treatment-related pneumonitis after thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 monoclonal antibodies in advanced esophageal squamous cell carcinoma

Xiaoyan Lv; Yajing Wu; Qihui Li; Chen Zheng; Qiang Lin; Qingsong Pang; Min Zhao; Jiandong Zhang; Jun Wang

doi:10.1007/s00066-024-02199-6

Treatment-related pneumonitis after thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 monoclonal antibodies in advanced esophageal squamous cell carcinoma

Strahlenther Onkol. 2024 Jan 24. doi: 10.1007/s00066-024-02199-6. Online ahead of print.

Authors

Xiaoyan Lv¹, Yajing Wu¹, Qihui Li¹, Chen Zheng¹, Qiang Lin², Qingsong Pang³, Min Zhao⁴, Jiandong Zhang^{5

6}, Jun Wang^{7

8}

Affiliations

¹ Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China.
² Department of Oncology, North China Petroleum Bureau General Hospital, Hebei Medical University, Renqiu, China.
³ Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
⁴ Department of Oncology, the First Hospital of Hebei Medical University, Shijiazhuang, China.
⁵ Department of Oncology, The First Affiliated Hospital of Shandong First Medical University and Shandong Province Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, China.
⁶ Department of Oncology, Shandong First Medical University, Jinan, China.
⁷ Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Radiation Oncology, Shijiazhuang, China. wangjun0818@hebmu.edu.cn.
⁸ Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, 050011, Shijiazhuang, China. wangjun0818@hebmu.edu.cn.

PMID: 38267589
DOI: 10.1007/s00066-024-02199-6

Abstract

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.

Keywords: Anti-PD‑1 monoclonal antibodies; Dosimetric parameters; Esophageal squamous cell carcinoma; Pneumonitis; Thoracic radiotherapy.

Grants and funding

2057702D/Hebei Clinical Research Center for Radiation Oncology