Aim: The present study aimed to evaluate the combined value of locoregional extension patterns (LEPs) and circulating cell-free Epstein–Barr virus (cf EBV) DNA for risk stratification of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) to better guide therapeutic strategies. Methods: A total of 7227 cases of LA-NPC were reviewed retrospectively and classified into six groups according to their LEP (ascending, descending, or mixed type) and pre-treatment cf EBV-DNA load (⩾ versus <4000 copy/ml). Using a supervised statistical clustering approach, patients in the six groups were clustered into low, intermediate, and high-risk clusters. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan–Meier method and differences were compared using the log-rank test. Results: Survival curves for the low, intermediate, and high-risk clusters were significantly different for all endpoints. The 5-year survival rate for the low, intermediate, and high-risk clusters, respectively, were: PFS (83.5%, 73.2%, 62.6%, p < 0.001), OS (91.0%, 82.7%, 73.2%, p < 0.001), DMFS (92.3%, 83.0%, 73.4%, p < 0.001), and LRRFS (91.0%, 88.0%, 83.3%, p < 0.001). The risk clusters acted as independent prognostic factors for all endpoints. Among the patients in the high-risk cluster, neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (CCRT) significantly improved the patients 5-year PFS (66.4% versus 57.9%, p = 0.014), OS (77.6% versus 68.6%; p < 0.002), and DMFS (76.6% versus 70.6%; p = 0.028) compared with those treated with CCRT. Conclusion: Our results could facilitate the development of risk-stratification and risk-adapted therapeutic strategies for patients with LA-NPC.

ObjectiveTo investigate the clinical implications of sleep quality, anxiety and depression in patients with advanced lung cancer (LC) and their family caregivers (FCs).MethodsA total of 98 patients with advanced LC and their FCs (n=98) were recruited from the Oncology Department in Nanfang Hospital. The Pittsburgh Sleep Quality Index (PSQI), consisting of seven components that evaluate subjective sleep quality, sleep latency, duration of sleep, sleep efficiency, sleep disturbances, sleep medication usage and daytime dysfunction, was used to assess sleep quality. Using the tool of Zung Self-rating Anxiety Scale (SAS) and Zung Self-rating Depression Scale (SDS), we tested the patients’ status of anxiety and depression, respectively.ResultsThe prevalences of poor sleep quality, anxiety and depression in patients were 56.1%, 48.9% and 56.1%, respectively, while those in FCs were 16.3%, 32.6% and 25.5%, respectively. Patients had higher PSQI, SAS and SDS scores than did FCs (p<0.05). Significant correlations were found between the patients’ and FCs’ scores of PSQI/SAS/SDS (p<0.05). Multivariate Cox regression analyses indicated that sleep disturbances in patients (HR 0.413, 95% CI 0.21 to 0.80, p=0.01) and the global PSQI score of FCs (HR 0.31, 95% CI 0.14 to 0.71, p=0.00) were independent risk factors for patients’ first-line progression-free survival (PFS). Moreover, patients’ sleep latency (HR 2.329, 95% CI 1.36 to 3.96, p=0.00) and epidermal growth factor receptor mutations (HR 1.953, 95% CI 1.12 to 3.38, p=0.01) were significant prognostic factors for their overall survival (OS).ConclusionsWe demonstrated that presence of sleep disturbances in patients with advanced LC and the global PSQI Score of their FCs may be risk predictors for patients’ poor first-line PFS. Patients’ sleep latency was a potential risk factor for their OS.

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Background: Genetic factors play an important role in colorectal cancer (CRC) risk, yet the prevalence and spectrum of germline cancer susceptibility gene mutations among unselected Chinese CRC patients is largely undetermined. Methods: We performed next-generation sequencing with a 73-genes panel and analyzed the prevalence and spectrum of germline mutations in 618 unselected Chinese CRC patients. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations. Clinical characteristics were assessed by age and mutation status. Protein expressions and interactions of MLH1 missense variants were evaluated by western blot and co- immunoprecipitation. Results: Overall, 112 (18.1%) of 618 unselected Chinese CRC patients were found to carry at least one pathogenic or likely pathogenic variant (totaling 97 variants), including 70 (11.3%) Lynch syndrome (LS) mutation carriers and 42 (6.8%) non-LS mutation carriers. LS mutation carriers were significantly younger at CRC diagnosis and were more likely to have right-sided, poorly differentiated, early stage, high-frequency microsatellite instability (MSI-H) or dMMR CRC and a family history of cancer compared with noncarriers. Non-LS mutation carriers were more likely to be proficient mismatch repair (pMMR) than noncarriers ( p =0.039). We found four clinical variables (gender, tumor histological stage, cancer stage and mutation status) that showed significant differences between patients younger and older than 50 years old. Higher mutation rates were found in patients under 50 years old ( p =0.017). Thirty-three novel variants were discovered and evaluated as pathogenic mutations by our study. Conclusion: Given the high frequency and wide spectrum of mutations, genetic testing with a multigene panel should be considered for all Chinese CRC patients under 50 years old and is also needed to determine whether a gene is associated with CRC susceptibility and to promote clinical translation.

Stimuli‐Responsive Smart Membranes In article number 2211983, Yanxin Wang, Jianguo Tang, Linjun Huang, Jun Chen, and co‐workers review the recent development in stimuli‐responsive smart membranes for nanofiltration. The stimuli include pH, temperature, light, and electricity, which are introduced by size sieving, electrostatic repulsion, and wettability switching. This review also provides a critical analysis of the current advances in smart membranes and insights into remaining challenges and future directions.

Aim: To compare and evaluate the prognostic value of various pretreatment combinations of inflammatory factors in patients with lung cancer (LC). Materials & methods: This study enrolled 1005 patients with LC and categorized into a discovery cohort and a validation cohort. Results: A combination of lymphocyte to C-reactive protein levels (LCR) demonstrated the highest correlation with poor first-line progression-free survival (PFS) and overall survival (OS) (p < 0.05), but not disease-free survival (p > 0.05) compared with other parameters in LC patients. Decreased preoperative LCR was an independent prognostic factor for first-line PFS and OS (p < 0.05), but not disease-free survival (p > 0.05) in patients. Conclusion: Pretreatment LCR is a promising biomarker for first-line PFS and OS in patients with LC.

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Background This study aimed to explore the prognostic value of tumor mutational burden (TMB) combined with smoking status in advanced non‐small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitor therapy (anti PD‐1/PD‐L1 therapy) combined with chemotherapy or anti‐angiogenesis therapy. Methods We conducted a retrospective analysis of NSCLC patients who underwent next‐generation sequencing test (either 295‐gene panel NGS or 1021‐gene panel NGS) from September 2017 to November 2020. The relationship between TMB and smoking status was investigated. Kaplan–Meier survival analysis was used to compare progression‐free survival (PFS) of the NSCLC patients who received combination immunotherapy grouped by TMB value and smoking status. Results We enrolled 323 cases and 388 cases of NSCLC patients in the 295‐gene panel cohort and 1021‐gene panel cohort, respectively. Positive correlation between TMB and smoking status was found in lung adenocarcinoma, but not in lung squamous cell carcinoma. Participants with both high TMB and smoking status who received immune checkpoint therapy combined with chemotherapy or anti‐angiogenesis therapy had longer PFS than other participants (p < 0.05). Conclusions The combination of TMB with smoking status might be a potential predictor for the efficacy of combination immunotherapy in advanced NSCLC.