Association between alcohol consumption and the risk of gastric cancer: a meta-analysis of prospective cohort studies Association between alcohol consumption and the risk of gastric cancer: a meta-analysis of prospective cohort studies

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. 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). 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. 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. None.

The Sineoculis homeobox homolog 1 (SIX1) protein has been found to be overexpressed in several human cancers. However, its expression pattern and biological roles in esophageal squamous cell carcinoma (ESCC) remain unexplored. This study examined the clinical significance of SIX1 in 119 ESCC tissues. It was found that SIX1 protein was upregulated in 36.9% (44/119) cases. SIX1 overexpression was an independent predictor for short survival of ESCC patients. siRNA knockdown and plasmid transfection were carried out in ESCC cell lines. SIX1 depletion inhibited cell growth, invasion, and colony formation, whereas its overexpression facilitated in vivo and in vitro cell growth, invasion, and colony formation. The apoptosis rate induced by X-ray irradiation was substantially increased by SIX1 knockdown in Eca-109 cells. Ectopic overexpression of SIX1 in TE-1 cells dramatically enhanced resistance to irradiation. Western blot analysis showed that SIX1 depletion downregulated cyclin E, matrix metalloproteinase-2 (MMP-2), Bcl-2 expression and upregulated Bim expression. SIX1 overexpression exhibited the opposite effect on these proteins. In addition, it was found that SIX1 could positively regulate extracellular signal-regulated kinase (ERK) and AKT signaling pathway. ERK inhibitor abolished the effect of SIX1 on MMP-2 expression. AKT inhibitor treatment blocked the role of SIX1 on anti-apoptotic protein Bcl-2. In conclusion, this study demonstrates that SIX1 overexpression predicts poor survival in ESCC patients and confers radioresistance through activation of AKT signaling pathways.

It remains unknown which is the most preferable regimen used concurrently with thoracic radiation for locally advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue. PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Overall survival (OS) data was the primary outcome of interest, and progression-free survival (PFS), and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs). 14 RCTs with a total of 2975 patients randomized to receive twelve categories of treatments were included in the meta-analysis. Direct comparison meta-analysis showed that etoposide-cisplatin (EP) was more effective than paclitaxel-cisplatin/carboplatin (PC) in terms of OS (HR = 0.85, 95% CI: 0.77–0.94) and PFS (HR = 0.66, 95% CI: 0.47–0.95). In network meta-analysis, all regimen comparisons did not produce statistically significant differences in survival. Based on treatment ranking of OS and the benefit-risk ratio, S-1-cisplatin (SP) was likely to be the most preferable regimen for its best efficacy and low risk of causing SAEs. Uracil/tegafur-cisplatin (UP) and pemetrexed-cisplatin/carboplatin (PP) were ranked the second and third respectively. Gemcitabine-cisplatin (GP) and PC + Cetuximab (PC-Cet) appeared to be the worst and second-worst regimens for their poor efficacy and poor tolerability. Based on efficacy and tolerability, SP is likely to be the most preferable regimen used concurrently with thoracic radiation for locally advanced NSCLC, followed by UP and PP. Further direct head-to-head studies are needed to confirm these findings.