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Abstract Background Combination of chidamide and anti‐PD‐L1 inhibitor produce synergistic anti‐tumor effect in advanced NSCLC patients resistant to anti‐PD‐1 treatment. However, the effect of chidamide plus envafolimab has not been reported. Aims This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti‐PD‐1 treatment. Materials and Methods Eligible advanced NSCLC patients after resistant to anti‐PD‐1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression‐free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD‐L1, and blood TMB (bTMB) was also analyzed. Results After a median follow‐up of 8.1 (range: 7.6–9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9–5.5) months. Biomarker analysis revealed that patients with high‐level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD‐L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low‐level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable. Discussion High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD‐L1 and low‐level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion. Conclusion Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

Abstract Background Currently, no biomarkers can accurately predict survival outcomes in patients with SCLC undergoing treatment. Tumor growth rate (TGR; percent size change per month [%/m]) is suggested as an imaging predictor of response to anti‐cancer treatment. We aimed to evaluate the predictive role of the maximum TGR (TGRmax) for outcomes of small‐cell lung cancer (SCLC) patients undergoing first‐line chemotherapy plus immune‐checkpoint inhibitor (ICI) treatment. Methods Patients with SCLC receiving first‐line chemotherapy plus immunotherapy were analyzed within this retrospective study. The X‐tile program was used to identify the cut‐off value of TGRmax based on maximum progression‐free survival (PFS) stratification. The Kaplan–Meier methods and Cox regression models were used to evaluate the effect of the presence of TGRmax on PFS and overall survival (OS). Results In total, 104 patients were evaluated. Median (range) TGRmax was −33.9 (−65.2 to 21.6) %/m and the optimal cut‐off value of TGRmax was −34.3%/m. Multivariate Cox regression analysis revealed that patients with TGRmax > −34.3%/m was associated with shorter PFS (hazard ratio [HR], 2.81; 95% CI, 1.71–4.63; p −34.3%/m had worse PFS and OS in first‐line ICI plus platin‐based chemotherapy. TGRmax could independently serve as an early biomarker to predict the benefit from chemoimmunotherapy.

Abstract Background There has been no study systematically assessing the causal effects of putative modifiable risk factors on lung cancer. In this study, we aimed to construct a modifiable risk factors atlas of lung cancer by using the two‐sample Mendelian randomization framework. Methods We included 46 modifiable risk factors identified in previous studies. Traits with p‐value smaller than 0.05 were considered as suggestive risk factors. While the Bonferroni corrected p‐value for significant risk factors was set to be 8.33 × 10−4. Results In this two‐sample Mendelian randomization analysis, we found that higher socioeconomic status was significantly correlated with lower risk of lung cancer, including years of schooling, college or university degree, and household income. While cigarettes smoked per day, time spent watching TV, polyunsaturated fatty acids, docosapentaenoic acid, eicosapentaenoic acid, and arachidonic acid in blood were significantly associated with higher risk of lung cancer. Suggestive risk factors for lung cancer were found to be serum vitamin A1, copper in blood, docosahexaenoic acid in blood, and body fat percentage. Conclusions This study provided the first Mendelian randomization assessment of the causality between previously reported risk factors and lung cancer risk. Several modifiable targets, concerning socioeconomic status, lifestyle, dietary, and obesity, should be taken into consideration for the development of primary prevention strategies for lung cancer.

Abstract Background Platinum‐based chemotherapy is the standard of care as first‐line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM‐NPC); however, the prognosis of patients with RM‐NPC remains poor. The aim of this study was to evaluate the role of anti‐epidermal growth factor receptor (anti‐EGFR) antibody plus chemotherapy for RM‐NPC. Methods RM‐NPC patients who received first‐line chemotherapy plus an anti‐EGFR antibody were recruited from Sun Yat‐Sen University Cancer Center between July 2007 and November 2017. Survival analyses were performed using the Kaplan‐Meier method with a log‐rank test. A Cox proportional hazards model was used for the multivariate analyses. Results A total of 203 patients were enrolled in the present study. The median follow‐up time was 34.3 months (interquartile range: 19.7‐66.5 months). The median progression‐free survival (PFS) was 8.9 months (95% CI: 7.7‐10.0 months) and the median overall survival (OS) was 29.1 months (95% CI: 23.5‐34.6 months). The 1‐, 3‐, and 5‐year PFS and OS rates were 35.5% and 79.6%, 15.2% and 42.5%, and 11.6% and 23.6%, respectively. The objective response rate (ORR) was 67.5% and the disease control rate (DCR) was 91.1%. The multivariate analysis identified the following prognostic factors for PFS: anti‐EGFR agent (P = .010), recurrence/metastasis sequence (P = .016), KPS (P = .017), and combined chemotherapy regimen (P = .015). Independent risk factors for OS included age >43 years (P = .002), Karnofsky performance score ≤80 (P

Abstract Background Observational studies have shown that excessive dietary fat may be associated with lung carcinogenesis. However, findings from previous studies are inconsistent and it remains unclear whether docosapentaenoic acid (DPA), a kind of polyunsaturated fatty acid, is linked to the risk of lung cancer. The aim of this study is to investigate the causal effect of DPA on lung cancer with Mendelian randomization (MR) method. Methods With a two‐sample MR approach, we analyzed the summary data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, 8866 individuals of European ancestry) Consortium and International Lung Cancer Consortium (ILCCO, 11 348 lung cancer cases and 15 861 controls; European ancestry) to assess the possible causal relationship of DPA on the risk of lung cancer. Results Our results indicated that genetically predicted higher DPA level has a positive association with lung cancer, where 1% higher DPA was associated with a 2.01‐fold risk of lung cancer (odds ratio [OR]: 2.01, 95% CI = 1.34‐3.01; P = 7.40 × 10−4). Additionally, lung cancer was not a causal factor for DPA. The results of MR‐Egger regression analysis showed that there was no evidence for the presence of directional horizontal pleiotropy. Conclusions Genetically elevated DPA is positively associated with risk of lung cancer, and more work is needed to investigate the potential mechanisms.

Abstract Concurrent chemoradiotherapy (CRT) has been recommended and applied widely as the standard treatment for limited‐stage small cell lung cancer (LS‐SCLC). However, controversies remain regarding the optimal timing and treatment duration of thoracic radiotherapy (TRT), and their effects on patient survival. To evaluate prognostic values of TRT timing and duration on progression‐free survival (PFS) in LS‐SCLC and their dependence on TRT fractionation and clinicopathological characteristics, we retrospectively analyzed 197 LS‐SCLC patients receiving CRT from 2000 to 2016 at Sun Yat‐sen University Cancer Center. Based on the optimal cut‐off values of TRT timing and duration generated by Cutoff Finder, patients were divided into early TRT/late TRT group and short TRT/long TRT group respectively. Univariate and multivariate Cox analysis were performed to assess correlations of TRT timing, duration, fractionation, and clinicopathological characteristics with PFS. Univariate analysis revealed that early‐initiated TRT (P = 2.54 × 10−4) and short TRT (P = .001) significantly correlated with longer PFS. Their PFS benefits persisted in patients receiving hyperfractionated TRT and etoposide‐cisplatin (EP) chemotherapy, but were less prominent in those receiving once‐daily TRT and non‐EP chemotherapy. Multivariate analysis further identified early initiated TRT (P = .004) and short TRT (P = .017) as independent prognostic factors for longer PFS in LS‐SCLC. Our study confirmed that early‐initiated TRT and short TRT had positive prognostic roles in LS‐SCLC, especially in patients receiving hyperfractionated TRT and etoposide‐cisplatin chemotherapy. TRT fractionation was not an independent prognostic factor in LS‐SCLC.