Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct;200(10):857-866.
doi: 10.1007/s00066-024-02199-6. Epub 2024 Jan 24.

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

Xiaoyan Lv  1 , Yajing Wu  1 , Qihui Li  1 , Chen Zheng  1 , Qiang Lin  2 , Qingsong Pang  3 , Min Zhao  4 , Jiandong Zhang  5   6 , Jun Wang  7   8
Affiliations

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

Xiaoyan Lv et al. Strahlenther Onkol. 2024 Oct.

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.

PubMed Disclaimer

Conflict of interest statement

X. Lv, Y. Wu, Q. Li, C. Zheng, Q. Lin, Q. Pang, M. Zhao, J. Zhang and J. Wang declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
ROC curve and the associated area for V5 as a predictor for grade 2 or higher treatment-related pneumonitis
Fig. 2
Fig. 2
Forest plots show factors associated with G2+ treatment-related pneumonitis in entire cohort
See this image and copyright information in PMC

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185countries. CA Cancer J Clin 68:394–424. 10.3322/caac.21492 - DOI - PubMed
    1. Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH et al (2020) Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer. J Clin Oncol 38(35):4138–4148. 10.1200/JCO.20.01888 - DOI - PubMed
    1. Pelosof L, Saung MT, Donoghue M, Casak S, Mushti S, Cheng J et al (2021) Benefit-risk summary of nivolumab for the treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior Fluoropyrimidine- and platinum-based chemotherapy. Oncologist 26(4):318–324. 10.1002/onco.13646 - DOI - PMC - PubMed
    1. Huang J, Xu J, Chen Y, Zhuang W, Zhang Y, Chen Z et al (2020) Camrelizumab versus investigator’s choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol 21(6):832–842. 10.1016/S1470-2045(20)30110-8 - DOI - PubMed
    1. Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T et al (2021) Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet 398(10302):759–771. 10.1016/S0140-6736(21)01234-4 - DOI - PubMed

MeSH terms

Substances

LinkOut - more resources