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. 2021 Dec;10(23):8518-8529.
doi: 10.1002/cam4.4363. Epub 2021 Oct 19.

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer

Yu Chen  1   2 , Xinchao Liu  1   2 , Zhaoqin Huang  3 , Kaikai Zhao  4 , Yao Wang  2 , Fei Ren  2 , Jinming Yu  1   2 , Xiangjiao Meng  1   2
Affiliations
Free PMC article

Safety of thoracic radiotherapy after PD-(L)1 inhibitor treatment in patients with lung cancer

Yu Chen et al. Cancer Med. 2021 Dec.
Free PMC article

Abstract

Background: The safety of thoracic radiotherapy (TRT) after programmed death 1/programmed death ligand 1 (PD-(L)1) inhibitor treatment in patients with lung cancer was scarcely reported. This retrospective study was conducted to evaluate the incidence, severity, and risk factors of symptomatic treatment-related pneumonitis in patients with lung cancer who received this sequential combination.

Methods: We conducted a retrospective study of a cohort of patients with lung cancer who received TRT after at least two cycles of PD-(L)1 inhibitor treatment between January 2018 and August 2020. Treatment-related pneumonitis was evaluated and analyzed to illustrate the safety profile of this sequential combination. Potential risk factors were explored by univariate and multivariate logistic regression analyses.

Results: Among the 828 patients with prior PD-(L)1 inhibitor treatment, 96 patients receiving subsequent TRT were included in the analysis. Of these, 49 patients (51%) received radical TRT while 47 patients (49%) received palliative TRT. The median total dose was 52 Gy (IQR 50-60 Gy). The median time from the initiation of PD-(L)1 inhibitor treatment to TRT was 4.8 months (1.6-14.1 months) with most of the patients (74%) administering no less than four cycles of PD-(L)1 inhibitor. During follow-up, 47 patients (48.96%) developed symptomatic treatment-related pneumonitis (grade 2 n = 28, grade ≥3 n = 19) while six patients (6.25%) suffered from fatal toxicity. The median time of pneumonitis onset after completion of TRT was 35 days (0-177 days) with six patients developing during TRT. Pulmonary emphysema and lung V20 were demonstrated to be independent risk factors of symptomatic pneumonitis (OR: 5.67, 95% CI: 1.66-19.37, p = 0.006; OR: 3.49, 95% CI: 1.41-8.66, p = 0.007, respectively).

Conclusion: TRT after PD-(L)1 inhibitor treatment resulted in significantly increased incidence and severity of treatment-related pneumonitis in patients with lung cancer. Intensive attention should be emphasized to the safety of this sequential combination in clinical practice.

Keywords: PD-(L)1 inhibitor; lung cancer; pneumonitis; safety; thoracic radiotherapy (TRT).

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

FIGURE 1
FIGURE 1
Cumulative incidence of treatment‐related pneumonitis by grade
FIGURE 2
FIGURE 2
Representative CT images of four patients with symptomatic pneumonitis. (A) Radiation planning imaging with target volume and dose distribution of TRT (B) CT images before TRT; (C) CT images at time of diagnosis of symptomatic pneumonitis
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