BackgroundFirst-line immune checkpoint inhibitors (ICIs) have become the standard of care for advanced non-small cell lung cancer (NSCLC). However, whether tumor histology influences the efficacy of ICIs remains unclear.MethodsWe systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus for randomized controlled trials (RCTs) published up to February 28, 2026. Eligible studies compared ICIs with chemotherapy, or two ICI-based regimens, as first-line treatment for advanced squamous (SQ) or non-squamous (non-SQ) NSCLC. Trials that enrolled patients with NSCLC and reported outcomes stratified by histology were also eligible. The primary outcome was overall survival (OS), reported as hazard ratios (HRs) with 95% credible intervals. A fixed-effects consistency model was used for the statistical analysis.ResultsForty-one phase 3 RCTs comprising 23, 871 patients and 31 ICI-based regimens were included. The efficacy of individual ICI regimens varied by histological subtype. For example, toripalimab plus chemotherapy was associated with superior OS compared with most other ICI regimens (HR range: 0.42–0.65) and ranked as the best treatment in non-SQ-NSCLC (surface under the cumulative ranking curve [SUCRA] = 0.97). In contrast, the same regimen showed inferior OS relative to many comparators (HR range for comparators vs. toripalimab plus chemotherapy: 0.47–0.65) and had the lowest OS ranking in SQ-NSCLC (SUCRA = 0.09). In the PD-L1 < 1% subgroup, nivolumab plus ipilimumab demonstrated a trend toward better OS compared with pembrolizumab plus chemotherapy (HR = 0.59) and ranked as the best regimen for SQ-NSCLC (SUCRA = 0.83), whereas pembrolizumab plus chemotherapy provided the greatest OS benefit for non-SQ-NSCLC (SUCRA = 0.90). In the PD-L1 ≥ 50% subgroup, atezolizumab plus chemotherapy ranked second for OS benefit in SQ-NSCLC but was the least effective combination in non-SQ-NSCLC; conversely, cemiplimab plus chemotherapy was the least effective combination in SQ-NSCLC but ranked second in non-SQ-NSCLC.ConclusionsThe efficacy of individual first-line ICI regimens appear to vary by histological subtype across PD-L1 expression levels. These findings suggest that PD-L1 status alone might not be sufficient to guide treatment selection, and that histological subtype could be considered in clinical decision-making for advanced NSCLC.

Background:Immune checkpoint inhibitors (ICIs) are the preferred treatments for advanced non-small cell lung cancer (NSCLC) without targetable oncogene alterations. However, evidence in the elderly population (aged ≥ 65 years) remains limited. Methods:We searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases for eligible publications until September 30, 2024. The primary outcome of interest was overall survival (OS). A random-effects model was used for the statistical analysis. Findings:A total of 35 phase 3 randomized controlled trials (RCTs) involving 9788 patients and 64 real-world studies involving 37,111 patients were included. Results from phase 3 RCTs revealed that ICIs significantly improved OS (hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.74-0.82) and progression-free survival (PFS) (HR = 0.67, 95% CI: 0.60-0.75) compared to chemotherapy. The association between ICIs and improved OS was independent of patient characteristics (race and histological type) or treatment-related factors (ICI drug type, treatment mode, and treatment line). However, significantly prolonged OS was not observed in subgroups of aged ≥ 75 years and PD-L1 < 1%. In real-world studies, the pooled median OS of ICIs were 11.8 months (95% CI: 11.2-12.4); Eastern Cooperative Oncology Group (EOCG) score, histological type, PD-L1 status, with immune-related adverse events (irAEs), and treatment mode were predictive for OS; rates of irAEs and discontinuation were numerically higher for combination therapy vs. monotherapy. Interpretation:ICIs are associated with a significant improvement in OS and PFS compared to chemotherapy in elderly patients with advanced NSCLC. Nevertheless, some patient characteristics such as aged ≥ 75 years, ECOG score ≥ 2, and PD-L1 < 1% seem to have a negative impact on the efficacy of ICIs, while these findings require further validation in large RCTs. Funding:None.

Purpose To construct a prediction model for radiation pneumonitis (RP) in lung cancer patients based on clinical information, medical text, and 2.5D deep learning (DL) features. Methods and Materials A total of 356 patients with lung cancer from the Heping Campus of the First Hospital of China Medical University were randomly divided at a 7:3 ratio into training and validation cohorts, and 238 patients from 3 other centers were included in the testing cohort for assessing model generalizability. We used the term frequency-inverse document frequency method to generate numerical vectors from computed tomography (CT) report texts. The CT and radiation therapy dose slices demonstrating the largest lung region of interest across the coronal and transverse planes were considered as the central slice; moreover, 3 slices above and below the central slice were selected to create comprehensive 2.5D data. We extracted DL features via DenseNet121, DenseNet201, and Twins-SVT and integrated them via multi-instance learning (MIL) fusion. The performances of the 2D and 3D DL models were also compared with the performance of the 2.5D MIL model. Finally, RP prediction models based on clinical information, medical text, and 2.5D DL features were constructed, validated, and tested. Results The 2.5D MIL model based on CT was significantly better than the 2D and 3D DL models in the training, validation, and test cohorts. The 2.5D MIL model based on radiation therapy dose was considered to be the optimal model in the test1 cohort, whereas the 2D model was considered to be the optimal model in the training, validation, and test3 cohorts, with the 3D model being the optimal model in the test2 cohort. A combined model achieved Area Under Curve values of 0.964, 0.877, 0.868, 0.884, and 0.849 in the training, validation, test1, test2, and test3 cohorts, respectively. Conclusion We propose an RP prediction model that integrates clinical information, medical text, and 2.5D MIL features, which provides new ideas for predicting the side effects of radiation therapy.

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery remains a standard of care for resectable esophageal cancer (EC), and definitive chemoradiotherapy (dCRT) is an alternative for unresectable diseases. However, it is controversial for the use of the two aggressive regimens in elderly patients. We systematically searched multiple databases for studies comparing overall survival (OS) and/or progression-free survival (PFS) between dCRT and surgery (nCRT + surgery or surgery alone) or between dCRT and radiotherapy (RT) alone in elderly patients (age ≥ 65 years) until March 28, 2024. Statistical analysis was performed using random-effects model. Fourty-five studies with 33,729 patients were included. dCRT significantly prolonged OS (hazard ratio [HR] = 0.64, 95

PURPOSE:Chemoradiotherapy (CRT) combined with immune checkpoint inhibitors (ICIs) is the standard of care for patients with unresectable and locally advanced non-small cell lung cancer. This study aimed to determine whether the addition of ICIs to CRT is associated with an increased risk of pneumonitis. METHODS AND MATERIALS:The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible studies published between January 1, 2015, and July 31, 2023. The outcome of interest was the incidence rate of pneumonitis. A random-effects model was used for statistical analysis. RESULTS:A total of 185 studies with 24,527 patients were included. The pooled rate of grade ≥2 pneumonitis for CRT plus ICIs was significantly higher than that for CRT alone (29.6%; 95% CI, 25.7%-33.6% vs 20.2%; 95% CI, 17.7%-22.8%; P < .0001) but not that of grade ≥3 (5.7%; 95% CI, 4.8%-6.6% vs 5.6%; 95% CI, 4.7%-6.5%; P = .64) or grade 5 (0.1%; 95% CI, 0.0%-0.2% vs 0.3%; 95% CI, 0.1%-0.4%; P = .68). The results from the subgroup analyses of prospective studies, retrospective studies, Asian and non-Asian studies, concurrent CRT (cCRT), and durvalumab consolidation were comparable to the overall results. However, CRT or cCRT plus PD-1 inhibitors not only significantly increased the incidence of grade ≥2 but also that of grade ≥3 pneumonitis compared to CRT alone or cCRT plus PD-L1 inhibitors. CONCLUSIONS:Compared with CRT alone, durvalumab consolidation after CRT appears to be associated with a higher incidence of moderate pneumonitis and CRT plus PD-1 inhibitors with an increased risk of severe pneumonitis. Nevertheless, these findings are based on observational studies and need to be validated in future large head-to-head studies.

BACKGROUND:The role of postoperative radiotherapy (PORT) after complete tumor resection in patients with thymoma or thymic carcinoma remains controversial. We performed a meta-analysis to identify groups that would benefit from PORT. METHODS:Multiple scientific databases were systematically searched for studies comparing overall survival (OS) and/or disease-free survival (DFS) between PORT and surgery alone in patients with completely resected thymomas or thymic carcinomas until April 10, 2024. A random-effects model was used for the statistical analysis. RESULTS:A total of 31 studies with 10543 patients were included (17 studies involving 4763 patients with thymoma, seven studies involving 1045 patients with thymic carcinoma, and seven studies involving 4735 patients with mixed histological types). Notably, PORT significantly prolonged OS (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.59-0.91) and DFS (HR = 0.62, 95% CI: 0.43-0.89). Similar results were also observed when the multivariate-adjusted HRs were used as the measure of effect (OS: HR = 0.60, 95% CI: 0.43-0.83; DFS: HR = 0.48, 95% CI: 0.29-0.79). In subgroup analyses, PORT was associated with a longer OS and DFS for thymoma (HR = 0.73, 95% CI: 0.56-0.96 and HR = 0.65, 95% CI: 0.46-0.93), thymic carcinoma (HR = 0.72, 95% CI: 0.49-1.07 and HR = 0.38, 95% CI: 0.19-0.77), and stage 3-4 disease (HR = 0.50, 95% CI: 0.34-0.74 and HR = 0.44, 95% CI: 0.27-0.70), but not for stage 2 disease (HR = 0.81, 95% CI: 0.55-1.19 and HR = 0.97, 95% CI: 0.51-1.83). CONCLUSIONS:PORT is likely to improve OS and DFS in patients with completely resected stage 3-4 thymoma or thymic carcinoma; however, the value of PORT for stage 2 disease requires further evaluation in large-scale studies.

Objectives: It remains unclear whether hypofractionated (Hypo) thoracic radiotherapy (TRT) is superior to hyperfrac-tionated or conventionally fractionated (Con) TRT in limited-stage small-cell lung cancer.Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for eligible studies until April 30, 2023. The outcomes of interest were overall survival (OS), and grade >= 3 esophagitis and pneumonitis, reported as hazard ratios (HRs) or odds ratios (ORs) with their 95% confidence intervals (CIs).Results: A total of 23 studies with 7987 patients were identified. Hypo-TRT showed similar OS compared to Hyper-TRT (HR = 1.22, 95% CI: 0.80-1.86 in randomized controlled trials [RCTs] and HR = 1.12, 95% CI: 0.99-1.28 in retrospective studies) and better OS compared to Con-TRT (HR =0.83, 95% CI: 0.70-0.97). Hyper-TRT achieved longer OS compared to Con-TRT in retrospective studies (HR = 0.91, 95% CI: 0.84-0.99), but not in RCTs (HR = 0.90, 95% CI: 0.80-1.01). There were no significant differences in incidence of grade >= 3 esophagitis or pneumonitis between the three schedules.Conclusion: Hyper-TRT (45 Gy) or Con-TRT (60-70 Gy) remains a standard schedule. Hypo-TRT (40-45 Gy) is likely to be an alternative regimen. Nevertheless, these findings need to be validated in large phase 3 RCTs.

PurposeTo compare the lesion characteristics and radiotherapy efficacy of patients with single and multiple esophageal squamous cell carcinoma (ESCC), to evaluate the effect of multiple lesions on ESCC, and establish a nomogram survival prediction model for patients with synchronous multiple primary esophageal squamous cell carcinoma (SMPESCC) who received definitive radiotherapy.Materials and methods:The study enrolled 1,034 patients with ESCC who underwent definitive radiotherapy between 2010 and 2020. The efficacy of radiotherapy was compared between 101 patients with SMPESCC and 933 patients with single ESCC. Propensity score matching was used to control for potential confounders. For patients with SMPESCC, a nomogram prediction model was established based on the Cox regression model.ResultsThe median OS was 30.00 (95% CI = 25.08-34.92) months for the single lesion group and 19.00 (95% CI = 15.51-22.48) months for the multiple cancer group respectively. Multivariate COX regression analysis showed that multiple cancer was an independent prognostic factor for ESCC patients (HR=1.89, 95%CI=1.49-2.38, P<0.001). Cox multivariate analysis of SMPESCC patients showed that T stage (P =0.002), chemotherapy (P =0.006), and lesion spacing (P =0.004) were independent prognostic factors associated with OS. The nomogram was established by combining T stage, chemotherapy, and lesion spacing, and Harrell’s C index was 0.711 after internal cross-validation. The calibration curve and decision curve analysis confirmed that the nomogram survival prediction model had a good predictive value for individual survival.ConclusionsThe survival rate of single esophageal cancer is significantly better than that of multiple lesions. Patients with SMPESCC exhibit worse survival than patients with single ESCC. Multiple lesions have a significant impact on the survival of patients with ESCC. The nomogram model established for SMPESCC patients can well predict the individual survival of patients.

Background Pneumonitis is a common complication for patients with locally advanced non-small cell lung cancer undergoing definitive chemoradiotherapy (CRT). It remains unclear whether there is ethnic difference in the incidence of post-CRT pneumonitis.Methods PubMed, Embase, Cochrane Library, and Web of Science were searched for eligible studies from January 1, 2000 to April 30, 2023. The outcomes of interest were incidence rates of pneumonitis. The random-effect model was used for statistical analysis. This meta-analysis was registered with PROSPERO (CRD42023416490).Findings A total of 248 studies involving 28,267 patients were included. Among studies of CRT without immunotherapy, the pooled rates of pneumonitis for Asian patients were significantly higher than that for non -Asian patients (all grade: 66.8%, 95% CI: 59.2%-73.9% vs. 28.1%, 95% CI: 20.4%-36.4%; P < 0.0001; grade >= 2: 25.1%, 95% CI: 22.9%-27.3% vs. 14.9%, 95% CI: 12.0%-18.0%; P < 0.0001; grade >= 3: 6.5%, 95% CI: 5.6%-7.3% vs. 4.6%, 95% CI: 3.4%-5.9%; P = 0.015; grade 5: 0.6%, 95% CI: 0.3%-0.9% vs. 0.1%, 95% CI: 0.0%-0.2%; P < 0.0001). Regarding studies of CRT plus immunotherapy, Asian patients had higher rates of all-grade (74.8%, 95% CI: 63.7%-84 .5% vs. 34.3%, 95% CI: 28.7%-40.2%; P < 0.0001) and grade >= 2 (34.0%, 95% CI: 30.7%-37.3% vs. 24.6%, 95% CI: 19.9%-29.3%; P = 0.001) pneumonitis than non-Asian patients, but with no significant differences in the rates of grade >= 3 and grade 5 pneumonitis. Results from subgroup analyses were generally similar to that from the all studies. In addition, the pooled median/mean of lung volume receiving >= 20 Gy and mean lung dose were relatively low in Asian studies compared to that in non-Asian studies.Interpretation Asian patients are likely to have a higher incidence of pneumonitis than non-Asian patients, which appears to be due to the poor tolerance of lung to radiation. Nevertheless, these findings are based on observational studies and with significant heterogeneity, and need to be validated in future large prospective studies focusing on the subject.

Review question / Objective: It remains uncertain whether first-line treatment with upfront brain radiotherapy (RT) in combination with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is superior to EGFR-TKIs alone in EGFR-mutated non-small-cell lung cancer with newly diagnosed brain metastases (BMs). We performed a meta-analysis to address this issue. Condition being studied: Brain radiotherapy (RT) has been shown to damage the blood-brain barrier (BBB) and improve the concentration of EGFR-TKIs in the CSF. Additionally, RT can result in a reduction of EGFR-TKIs resistance. Therefore, EGFR-TKIs in combination with brain RT should be more effective than EGFR-TKIs alone theoretically. However, results from retrospective studies are inconsistent. There is the possibility that patients characteristics or brain RT technique affect the efficacy of treatments. To date, there is still no randomized controlled trials (RCTs) comparing the two treatment strategies.

Prognostic factors and role with chemotherapy (CT) and radiotherapy (RT) remain unclear for patients of pulmonary carcinoid (PC) with positive lymph node after surgery. PC patients who underwent surgery and with positive lymph node between 2000 and 2016 were identified from the SEER database. Univariate and multivariate cox regression analysis were used to identify independent risk factors for overall survival (OS). A total of 552 patients were identified. Multivariate analysis indicated that age (≤ 70/ > 70) (HR = 0.32, 95

Background It remains uncertain whether neoadjuvant immune checkpoint inhibitor (nICI) is superior to neoadjuvant chemotherapy (nCT) in resectable non-small cell lung cancer. In addition, there are outstanding questions for nICI such as the ideal treatment mode and predictors. Methods PubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible single-arm or multi-arm trials until 31 December 2021. The primary outcomes of interest were major pathological response (MPR) and pathological complete response (pCR). The random-effect model was used for statistical analysis. Results Twenty-four trials of nICI (n = 1,043) and 29 trials of nCT (n = 2,337) were identified. nICI combination therapy was associated with higher MPR (63.2%, 95% CI: 54.2%–72.1%) and pCR (35.3%, 95% CI: 27.4%–43.3%) rates compared to nCT (16.2%, 95% CI: 7.5%–25.0%, P < 0.001 and 5.5%, 95% CI: 3.5%–7.5%, P < 0.001) and nICI monotherapy (23.3%, 95% CI: 12.7%–33.8%, P < 0.001, and 6.5%, 95% CI: 1.7%–11.2%, P < 0.001). As for safety, nICI monotherapy had the best tolerability; nICI combination showed a similar surgical resection rate and higher R0 resection rate compared to nCT. PD-1 inhibitor and high PD-L1 expression (≥1% or ≥50%) were correlated with higher MPR and pCR rates compared to PD-L1 inhibitor and PD-L1 expression <1%. Conclusions nICI combination therapy is associated with higher MPR and pCR rates compared to nCT and nICI monotherapy. PD-1 inhibitor seems to be superior to PD-L1 inhibitor. PD-L1 status appears to be predictive of MPR and pCR for patients receiving nICI. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=278661, CRD42021278661.

Background Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy (nICT) or chemoradiotherapy (nICRT) has been tested in resectable esophageal cancer. Nevertheless, efficacy and safety for this new strategy have not been clearly demonstrated. Patients and methods PubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible trials until June 30, 2022. The primary outcome of interest was pathological complete response (pCR). The random-effect model was used for statistical analysis. Results Twenty-seven trials with 809 patients were identified. The estimated rates of pCR for nICRT and nICT were comparable (32.7%, 95% CI: 20.3%-45.1% vs 26.3%, 95% CI: 19.8%-32.8%; P = 0.37). As for safety, surgical resection rate, R0 resection rate, surgical delay rate, and surgical mortality rate were similar between nICRT and nICT, while more grade ≥3 treatment-related adverse events were observed for nICRT (52.6%, 95% CI: 30.7%-74.5% vs 19.9%, 95% CI: 8.8%-31.0%; P = 0.01). In subgroup analysis, nICRT achieved higher pCR rate compared to nICT (56.2%, 95% CI: 41.0%-71.3% vs 27.2%, 95% CI: 20.2%-34.1%; P < 0.001) for squamous cell carcinoma (SCC) but adenocarcinoma. In patients receiving nICT, PD-L1 expression CPS ≥1 showed higher pCR rate compared to CPS <1 (51.3%, 95% CI: 41.4%-61.2% vs 26.6%, 95% CI: 8.6%-44.5%; P = 0.02); regimen of paclitaxel plus carboplatin/cisplatin (PC/TP) and 3-4 cycles of nICT did not lead to an significantly improved pCR rate compared to other chemotherapy regimens and 2 cycles of nICT, respectively, despite without increased toxicity. Conclusion Both nICT and nICRT achieved promising pCR rates with acceptable tolerability, and nICRT was likely to have more antitumor efficacy compared to nICT for patients with SCC. PD-L1 status seemed to be predictive of pCR in patients receiving nICT; pCR rate did not appear to be greatly affected by CT regimen and increasing cycles of nICT.

BackgroundTo assess the effect of asymptomatic and/or treated brain metastases (BMs) on the efficacy of immune checkpoint inhibitors (ICIs) in metastatic non-small cell lung cancer (NSCLC).Patients and MethodsPubMed, Embase, Cochrane Library, Web of Science, and recent meetings were searched for randomized controlled trials (RCTs). The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS).ResultsSeventeen articles reporting 15 RCTs with 10,358 patients (1,199 with and 9,159 without BMs) were eligible. ICIs were associated with longer OS and PFS than those in chemotherapy either in patients with (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.51–0.82 and HR, 0.60; 95% CI, 0.45–0.79) or without BMs (HR, 0.74; 95% CI, 0.70–0.78 and HR, 0.70; 95% CI, 0.57–0.86); no significant difference in the pooled HRs for OS (Pinteraction = 0.29) and PFS (Pinteraction = 0.37) was observed between the two patient populations. Subgroup analyses revealed that either ICI monotherapy or combination therapy significantly improved OS and PFS compared with those in chemotherapy both for patients with and without BMs. Superior OS benefit from ICI combination therapy than that in monotherapy was observed in patients with BMs (HR, 0.49 vs. 0.81, Pinteraction = 0.005) but not in patients without BMs (HR, 0.71 vs. 0.76, Pinteraction = 0.27).ConclusionThere was no compelling statistical evidence that the efficacy of ICIs in metastatic NSCLC was modified by the presence of asymptomatic and/or treated BMs. Patients with BMs were likely to obtain more OS benefit from ICI combination therapy than that from monotherapy.

Aim: We assessed the efficiency of immune checkpoint inhibitors relative to other systemic therapies in previously treated recurrent/metastatic head and neck cancer. Materials & methods: Relative treatment effects were assessed from eligible randomized controlled trials using Bayesian network meta-analyses. Results: Among 15 trials evaluating 14 treatments, nivolumab achieved the best overall survival (OS) benefit; zalutumumab and buparlisib + paclitaxel provided the best progression-free survival benefit and objective response rate. Buparlisib + paclitaxel and zalutumumab were associated with the best OS rate at 6 and 12 months, respectively; nivolumab yielded the best OS rate at 18-24 months. Conclusion: Nivolumab was the most favorable treatment. Zalutumumab and buparlisib + paclitaxel had better efficiency, and might be a better selection for patients with programmed death-ligand 1-low/negative tumors than other treatments.

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 (Pinteraction = 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, Pinteraction = 0.07), and treatment-smoking interaction was significant in patients with PD-L1 ≥50% (HR, 0.61 vs 1.18; Pinteraction = 0.005). ICIs plus CT achieved better OS either in smokers or never-smokers (HR, 0.76 vs 0.61; Pinteraction = 0.39), while dual ICIs combination prolonged OS only in smokers but never-smokers (HR, 0.68 vs 1.02; Pinteraction = 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.

Background: 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.Patients and methods: 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.Findings: 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: I-2 = 60%, P = 0.0002; PFS: I-2 = 74%, P < 0.0001) and never smokers (PFS: I-2 = 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).Interpretation: 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. (C) 2021 The Authors. Published by Elsevier Ltd.

目的 探讨Raf激酶抑制蛋白(RKIP)在非小细胞肺癌(NSCLC)中的表达及其与NSCLC放射敏感性的关系.方法 应用免疫组化方法检测106例放射治疗前NSCLC组织中RKIP蛋白的表达.应用logistic回归分析NSCLC放射敏感性相关因素.结果 RKIP表达与NSCLC临床分期及淋巴结转移相关(P<0.05).临床分期及RKIP表达水平与NSCLC的放射敏感性具有相关性(P<0.05),临床分期早、RKIP表达水平高的患者放射敏感性高.RKIP表达是NSCLC放射敏感性的独立相关因素.结论 RKIP是评价NSCLC放射敏感性的关键指标.

Background It remains unclear which treatment is the most effective for previously treated patients with advanced esophageal and esophagogastric junction (EGJ) cancer. We conducted a network meta-analysis to address this important issue. Methods PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant phase II and III randomized controlled trials (RCTs). Overall survival (OS) was the primary outcome of interest, which was reported as hazard ratio (HR) and 95% confidence intervals (CIs). Results Sixteen RCTs involving 3372 patients and evaluating 15 treatments were included in this network meta-analysis. Ramucirumab+chemotherapy (CT) (HR = 0.52, 95% CI: 0.35-0.77) and use of programmed death receptor 1 (PD-1) inhibitors, including camrelizumab (HR = 0.71, 95% CI: 0.57-0.88), sintilimab (HR = 0.70, 95% CI: 0.50-0.98), nivolumab (HR = 0.76, 95% CI: 0.62-0.94), and pembrolizumab (HR = 0.84, 95% CI: 0.72-0.98), conferred better OS than CT; however, this OS benefit was not observed for PD-L1 inhibitor (avelumab) and other target agents (trastuzumab, everolimus, gefitinib, and anlotinib). In subgroup analysis, ramucirumab+CT and pembrolizumab showed significant improvement in OS, when compared to CT, in esophageal/EGJ adenocarcinoma (AC) cases; moreover, all PD-1 inhibitors had significant OS advantage over CT in treating esophageal squamous cell carcinoma (SCC). Based on treatment ranking in terms of OS, ramucirumab+CT and camrelizumab were ranked the best treatments for patients with AC and SCC, respectively. Conclusions Ramucirumab+CT and PD-1 inhibitors were superior to CT for previously treated cases of advanced esophageal/EGJ cancer. Ramucirumab+CT seemed to be the most effective treatment in patients with esophageal/EGJ AC, while use of PD-1 inhibitors, especially camrelizumab, was likely to be the optimal treatment in patients with esophageal SCC.

Although a large number of influential studies that have been conducted worldwide on locally advanced esophageal cancer (EC) have employed the treatment modality of three-dimensional conformal radiotherapy (3D-CRT), an advanced as well as highly conformal technology known as intensity-modulated radiotherapy (IMRT) has attracted increasing attention from the radiotherapy research community. This is because of the clear advantages of IMRT, including decrease in radiation dose that reaches critical cardiopulmonary organs. These two treatment modalities need to be investigated with regard to their effect on local control rate and patient survival. In addition, related clinical factors also need to be explored. Data from a total of 431 patients with locally advanced EC, who underwent radiation therapy between January 1, 2010 and December 31, 2013, were included in the present study. Two hundred and ninety-three patients received 3D-CRT, while 138 patients received IMRT. We constructed propensity score matches to make the two groups be comparable (136 patients in 3D-CRT group and 138 patients in IMRT group. Kaplan–Meier analysis was conducted to evaluate the endpoint of overall survival (OS). A Cox proportional hazards model was employed to analyze the relationship between the associated factors and the outcomes via univariate and multivariate approaches. The mean follow-up period was 36.2 months, and the median follow-up period was 23 months. For the IMRT group, the median OS was 31 months, and the 1-, 3-, and 5-year OS rates were 70.3%, 50.0%, and 42.8%, respectively, while for the 3D-CRT group, the median OS was 22 months, and the 1-, 3-, and 5-year OS rates were 63.2%, 41.0%, and 35.4%, respectively (p<0.05). The univariate analysis revealed that quit drinking, chemotherapy, and concurrent chemotherapy were significant risk factors for the prognosis of EC (p<0.05), as well as the radiation therapy technique used (p=0.052). The multivariate analysis indicated that chemotherapy and quit drinking were independent predictive factors for OS. OS is found to be significantly better in the IMRT group, compared with that of the 3D-CRT group. Even though these outcomes need further validation, IMRT should be considered preferentially as a therapeutic option for EC, in combination with chemotherapy and persuading patients to quit drinking.