Incidence and risk factors of pneumonitis in ALK-rearranged non-small cell lung cancer patients treated with alectinib and thoracic radiotherapy.

Background: Alectinib and thoracic radiotherapy (TRT) are important modalities in the management of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), both of which can cause treatment-related pneumonitis (TRP), a serious adverse effect. We therefore aimed to assess the incidence and risk factors of TRP, when these two treatments were combined and to guide the medical decisions.

Methods: Patients with ALK-rearranged NSCLC, receiving alectinib and TRT from January 2018 to December 2023 were reviewed, and the clinical and dosimetric data were collected. Logistic regression analyses were performed to evaluate risk factors associated with TRP. The prediction ability of dosimetric parameters for TRP was examined by receiver-operating characteristic (ROC) curve analyses.

Results: Of the 62 enrolled patients, 39 (62.9%) developed TRP, and 22 (35.5%) developed grade 2 or higher TRP. Logistic regression analyses revealed age [odds ratio (OR) =1.103, 95% confidence interval (CI): 1.027-1.185, P=0.007], tumor location (OR =0.170, 95% CI: 0.035-0.816, P=0.03), duration of alectinib use (OR =1.006, 95% CI: 1.002-1.011, P=0.006), and total lung V30 (OR =1.149, 95% CI: 1.040-1.269, P=0.006) to be risk factors for TRP. After developing TRP, 35 patients recovered or improved, but one patient died due to respiratory failure.

Conclusions: The combined use of alectinib and TRT significantly increased the risk of TRP. Clinicians should consider the elevated risks and related dosimetric factors when deciding on combination treatment for ALK-rearranged NSCLC patients.