It remains uncertain whether smoking status can effect efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC). We performed a meta-analysis to address this issue. PubMed, Embase, Cochrane Library, Web of Science, and international meetings were searched until April 1, 2021, for phase 2 and 3 randomized controlled trials (RCTs) which compared ICIs with chemotherapy (CT) and reported overall survival (OS) and/or progression-free survival (PFS) data according to smoking status. This meta-analysis was registered in INPLASY platform (#INPLASY202140025). The random-effect model was used for statistical analysis. Twenty-eight articles from 24 RCTs including 13918 patients were eligible. ICIs significantly prolonged OS than CT in smokers (hazard ratio [HR] = 0.75, 95% confidence interval [CI]: 0.69-0.81), but not in never-smokers (HR = 0.87, 95% CI: 0.74-1.04); while there was no significant treatment-smoking interaction (P_interaction = 0.11). Significant heterogeneity was observed for both smokers (OS: I² = 60%, P = 0.0002; PFS: I² = 74%, P < 0.0001) and never smokers (PFS: I² = 69%, P < 0.0001). Subgroup analyses revealed that ICIs monotherapy significantly improved OS in smokers (HR = 0.76, 95% CI: 0.69-0.85) but not in never-smokers (HR = 0.93, 95% CI: 0.77-1.12, P_interaction = 0.07), and treatment-smoking interaction was significant in patients with PD-L1 ≥50% (HR, 0.61 vs 1.18; P_interaction = 0.005). ICIs plus CT achieved better OS either in smokers or never-smokers (HR, 0.76 vs 0.61; P_interaction = 0.39), while dual ICIs combination prolonged OS only in smokers but never-smokers (HR, 0.68 vs 1.02; P_interaction = 0.02). Either ICIs monotherapy or combination therapy was superior to CT in smokers. While ICIs monotherapy and dual ICIs combination were less effective in never-smokers, and ICIs plus CT might be the optimal selection. Nevertheless, given the limitation of the high heterogeneity of studies included, the findings need to be confirmed by future RCTs focusing on this subject. None.

The role of surgery in treating small cell lung cancer (SCLC) remains controversial. This meta-analysis aims to determine whether surgical-based treatment improves survival in comparison to radiotherapy, chemotherapy, and chemoradiotherapy for stage I to III SCLC. PubMed, PubMed Central, EMBASE, Web of Science, and Cochrane Library were searched for relevant articles. The main outcome were overall survival (OS), reported as hazard ratios (HRs), and 95% confidence intervals (CIs). Two randomized control trials (RCTs) and 13 retrospective studies that included a total of 41,483 patients were eligible. Surgical resection significantly improved OS when compared to non-surgical treatment in retrospective studies (HR = 0.56, 95% CI: 0.49–0.64, P < 0.001), but not in the 2 “older” RCTs (HR = 0.77, 95% CI: 0.32–1.84, P = 0.55). In the subgroup analysis for retrospective studies, surgical resection was associated with superior OS in stage I (HR = 0.56, 95% CI: 0.49–0.64, P < 0.001), stage II (HR = 0.75, 95% CI: 0.57–0.99, P = 0.04), and stage III diseases (HR = 0.70, 95% CI: 0.56–0.88, P = 0.002). Sublobar resection resulted in worse OS than a lobectomy (HR = 0.64, 95% CI: 0.56–0.74, P < 0.001) for patients undergoing surgical resection. Surgery-based multi-modality treatment appears to be associated with a favorable survival advantage in stage I and selected stage II to III SCLC. Lobectomy is likely to provide superior OS when compared to sublobar resection. Further prospective RCTs are needed to confirm these findings.

The rate of radiation pneumonitis (RP) for patients receiving chemoradiotherapy has been various across studies. Whether it is related to different chemotherapy schedules used in combination with radiation therapy were evaluated in this study. New factors associated with RP were also investigated. A total of 369 consecutive patients with Stage III non small cell lung cancer treated with chemoradiotherapy were followed after radiotherapy (RT). Among them 262 patients received concurrent chemoradiotherapy followed by consolidation chemotherapy and 107 patients received only sequential chemotherapy after RT. RP was graded according to Common Terminology Criteria for Adverse Events version 4.0. The rate of grade ≥ 2 were 39.7%, 31% and 33.6% in the concurrent DP (docetaxel/cisplatin), concurrent NP (vinorelbine/cisplatin) and sequential group, and grade ≥ 3 RP were 18.4%, 9.5%, and 11.2% respectively. The rate of grade ≥ 3 RP was significantly higher in concurrent DP group than that in concurrent NP group (p = 0.04). RP occurred earlier in concurrent DP group than that in the other two groups. There were no significant differences in response rate among the three groups. In the multivariate analysis, age (OR = 1.99, p = 0.038 and OR = 8.90, p < 0.001), chemotherapy schedule (OR = 1.45, p = 0.041 and OR = 1.98, p = 0.013), mean lung dose(OR = 1.42, p < 0.001 and OR = 1.64, p < 0.001), and planning target volume(OR = 1.004, p = 0.001 and OR = 1.005, p = 0.021) were predictors for both grade ≥ 2 and grade ≥ 3 RP. Response to treatment was a new predictor for grade ≥ 3 RP only (OR = 4.39, p = 0.034). Response to treatment was found to be a new predictor for grade ≥ 3 RP. Compared to concurrent NP schedule, concurrent DP schedule achieved similar response to treatment but resulted in a higher risk of grade ≥ 3 RP.

Thoracic reirradiation (re-RT) is increasingly administered. However, radiation pneumonitis (RP) remains to be the most common side effect from retreatment. This study aimed to determine the risk and predictors for severe RP in patients receiving thoracic re-RT. Sixty seven patients with lung cancer received thoracic re-RT for recurrent or metastatic disease. Three-dimensional conformal radiotherapy (3D-CRT)/intensity modulated radiotherapy (IMRT) was used for 60 patients, and stereotactic body radiation therapy (SBRT) was used in 7 patients. Deformable image registration (DIR) was performed to create a composite plan. Severe (grade ≥ 3) RP was graded according to Common Terminology Criteria for Adverse Events version 4.0. Eighteen patients (26.9%) developed grade ≥ 3 RP (17 of grade 3, and 1 of grade 4). In univariate analyses, V5 and mean lung dose (MLD) of initial RT or re-RT plans, V5 and V20 of composite plans, and the overlap between V5 of initial RT and V5 of re-RT plans/V5 of re-RT plans (overlap-V5/re-V5) were significantly associated with grade ≥ 3 RP (P < 0.05 for each comparison). Multivariate analysis revealed that MLD of the initial RT plans (HR = 14.515, 95%CI:1.778–118.494, P = 0.013), V5 of the composite plans (HR = 7.398, 95%CI:1.319–41.495, P = 0.023), and overlap-V5/re-V5 (P = 0.041) were independent predictors for grade ≥ 3 RP. Out-of-field failures with medium overlap-V5/re-V5 of 0.4–0.8 was associated with higher risk of grade ≥ 3 RP compared with in-field failures (18.3% vs. 50%, P = 0.014). The risk of grade ≥ 3 RP could be predicted not only by dose-volume variables from re-RT plan, but also by some from initial-RT and composite plans. Out-of-field failures was associated with higher risk of severe RP compared with in-field failures in some cases.

Grade ≥ 3 radiation pneumonitis (RP) is generally severe and life-threatening. Predictors of grade ≥ 2 are usually used for grade ≥ 3 RP prediction, but it is unclear whether these predictors are appropriate. In this study, predictors of grade ≥ 2 and grade ≥ 3 RP were investigated separately. The increased risk of severe RP in elderly patients compared with younger patients was also evaluated. A total of 176 consecutive patients with locally advanced non-small cell lung cancer were followed up prospectively after three-dimensional conformal radiotherapy. RP was graded according to Common Terminology Criteria for Adverse Events version 3.0. Mean lung dose (MLD), mean heart dose, ratio of planning target volume to total lung volume (PTV/Lung), and dose-volume histogram comprehensive value of both heart and lung were associated with both grade ≥ 2 and grade ≥ 3 RP in univariate analysis. In multivariate logistic regression analysis, age and MLD were predictors of both grade ≥ 2 RP and grade ≥ 3 RP; receipt of chemotherapy predicted grade ≥ 3 RP only; and sex and PTV/Lung predicted grade ≥ 2 RP only. Among patients who developed high-grade RP, MLD and PTV/Lung were significantly lower in patients aged ≥ 70 years than in younger patients (p < 0.05 for both comparisons). The predictors were not completely consistent between grade ≥ 2 RP and grade ≥ 3 RP. Elderly patients had a higher risk of severe RP than younger patients did, possibly due to lower tolerance of radiation to the lung.