Efficacy and safety of immunoradiotherapy for advanced non-small cell lung cancer: a retrospective comparative cohort study

Abstract

Background Treatment of radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) may remarkably improve the prognosis in patients with metastatic non-small cell lung cancer (NSCLC). However, the treatment time of RT, irradiated lesion and the optimum combined scheme, have not been fully determined. Methods Data regarding overall survival (OS), progression-free survival (PFS), treatment response, and adverse events of 357 patients with advanced NSCLC treated with ICI alone or in combination with RT prior to/during ICI treatment were retrospectively collected. Additionally, subgroup analyses for radiation dose, time interval between RT and immunotherapy, and number of irradiated lesions were performed. Results Median PFS of the ICI alone and ICI + RT groups was 6 and 12 months, respectively (P<0.0001). The objective response rate (ORR) and disease control rate (DCR) were significantly higher in the ICI + RT group than in the ICI alone group (P=0.014; P=0.015, respectively). However, OS, the distant response rate (DRR), and the distant control rate (DCRt) did not differ significantly between the groups. Out-of-field DRR and DCRt were defined in unirradiated lesions only. Compared with RT application prior to ICI, its application concomitant with ICI led to higher DRR (P=0.018) and DCRt (P=0.002). Subgroup analyses revealed that single-site, high biologically effective dose (BED) (≥72 Gy), planning target volume (PTV) size (<213.7 mL) RT groups had better PFS. In multivariate analysis, PTV volume [≥213.7 vs . <213.7 mL: hazard ratio (HR), 1.89; 95% confidence interval (CI): 1.04–3.42; P=0.035] was an independent predictor of immunotherapy PFS. Additionally, radio-immunotherapy increased the incidence rate of grade 1–2 immune-related pneumonitis compared with ICI alone. Conclusions Combination therapy using ICIs and radiation may improve PFS and tumor response rates in advanced NSCLC patients regardless of programmed cell death 1 ligand 1 (PD-L1) level or previous treatments. However, it may increase the incidence of immune-related pneumonitis.

PD‐L1 expression in patients with non‐small‐cell lung cancer is associated with sex and genetic alterations: A retrospective study within the Caucasian population

“…44 This mechanism might explain the significant clinical benefit achieved with the platinum-pemetrexed and pembrolizumab combination even in the subgroup of metastatic NSCLC patients with PD-L1 negative tumors, 45 and the higher objective response rate and disease control rate in patients receiving radiotherapy and immunotherapy in comparison to immune-monotherapy. 45,46 Contradictory to this hypothesis, some clinical trials described a downregulation of the PD-L1 expression on tumor cells after a cisplatin-gemcitabine combination, paclitaxel-based regimen, or TKIbased therapy. 47,48 The primary limitation of our study lies in its retrospective single-center design and the relatively limited number of included patients.…”

The Efficacy and Safety of Immunotherapy Followed by Thoracic Radiation in Advanced Non-small Cell Lung Cancer: A Retrospective Analysis

“…The study ndings demonstrated that the combination of ICIs and radiation therapy resulted in improved long-term outcomes and tumor remission in patients with advanced NSCLC. In the study, out of the total 202 cases, 160 cases (79.2%) underwent radiotherapy prior to receiving immunotherapy, while 42 cases (20.8%) received concurrent radiotherapy and immunotherapy [25]. There is a lack of research examining the e cacy of advanced NSCLC immunotherapy followed by thoracic radiotherapy.…”

“…In Gao's study, the incidence of pneumonitis was found to be signi cantly different between the two groups (P = 0.007). The immunotherapy combined with radiotherapy group had 36 cases (17.8%), while the immunotherapy alone group had 12 cases (7.7%) [25]. A retrospective analysis was conducted on patients who had previously encountered side effects related to immunotherapy.…”