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Background: DNA damage response (DDR) pathways are essential to sustain genomic stability and play a critical role in cancer development and progression. Here, we investigated the profile of DDR gene mutations in early‐stage non‐small cell lung cancer (NSCLC) and their prognostic values. Methods: We first examined 74 DDR genes involved in seven DDR pathways and then focused on six specific genes: ATM, BRCA1, BRCA2, CHEK1, BARD1, and BRIP1. A total of 179 stage I and IIIa NSCLC patients who received curative resection in Peking Union Medical College Hospital and their corresponding samples were collected for DNA sequencing, immunohistochemistry and survival analysis. Results: A total of 167 eligible patients were finally analyzed. Mutation frequencies were 82% and 26.3% for the selected 74 genes and six genes, respectively. Mismatch repair (MMR) and nucleotide excision repair (NER) alterations were observed more frequently in lung squamous cell carcinoma (LUSC) and smokers were more likely to develop the selected six DDR gene mutations than those who never smoked. Deleterious mutations in the six genes were independent prognostic indicators of significantly longer disease‐free survival and overall survival. No association was found between DDR gene status and PD‐L1 expression, CD8 positive lymphocyte and tumor‐associated macrophage infiltration in tumor area. However, numbers of mutations were significantly increased among patients with DDR alterations. Conclusions: Deleterious mutations of these six genes were common in resected NSCLC and could serve as prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Background: The Controlling Nutritional Status (CONUT) score, regarded as the effective indicator of patient nutrition, has been demonstrated to be related to prognosis of numerous tumours. Nevertheless, the significance of CONUT for gastrointestinal stromal tumour (GIST) remains unclear. This study intended to clarify the association between CONUT and the prognosis of GISTs. Methods: Three hundred and fifty‐five patients with GISTs undergoing surgical resection at our center were retrospectively assessed. Receiver operating characteristic curve analysis was used to help determine the cut‐off value of CONUT score. Relapse‐free survival (RFS) and overall survival (OS) were assessed by Kaplan–Meier curve analysis. Prognostic factors for RFS and OS were examined by Cox proportional hazards models. Results: A total of 355 patients were enrolled in this study. Areas under the curve (AUC) were 0.638 for CONUT score, and the cut‐off value of CONUT was shown to be three. Kaplan–Meier curve analysis showed that high CONUT score was linked to poorer RFS and OS. Univariate and multivariate analyses ultimately revealed that CONUT was a risk factor for RFS and OS, independent of demographics and clinicopathological tumour characteristics. Conclusions: CONUT score was an effective and novel predictor for prognosis of GIST patients treated with surgery, indicating its potential as a prognostic marker in the overall management. [ABSTRACT FROM AUTHOR]

BACKGROUND: According to the eighth edition of the tumor node metastasis (TNM) staging system for esophageal cancer, it is recommended that extracapsular lymph node involvement (EC-LNI) is included as a registered independent variable for the disease. However, its role in the prognosis has not been clearly explained. OBJECTIVE: To study the value of EC-LNI in the prognosis of esophageal cancer and attempt to explore its molecular mechanism via an enrichment analysis. METHODS: A retrospective analysis was performed on 544 patients with esophageal squamous cell carcinoma (ESCC) who underwent radical surgery in the department of thoracic surgery of our hospital, focusing on the relationship between EC-LNI and clinicopathological characteristics and its effect on prognosis. Additionally, the mechanism of EC-LNI in esophageal cancer was explored. RESULTS: Among the 271 patients with lymph node metastasis, 125 were EC-LNI (+). The degrees of tumor differentiation, location, TNM stage, vascular tumor thrombus, and nerve invasion were related to the occurrence of EC-LNI. The stage of TNM was considered an independent risk factor for the development of EC-LNI. A significant difference was found in terms of overall survival (OS) and disease-free survival (DFS) between the EC-LNI (+) and EC-LNI (-) groups. A univariate analysis showed that the degrees of tumor differentiation, T stage, N stage, TNM stage, EC-LNI, EC-LNI number, and EC-LNI distance were significantly correlated with prognosis. A multivariate survival analysis showed that tumor differentiation, TNM stage, and EC-LNI were independent prognostic factors for OS, while TNM stage and EC-LNI were independent prognostic factors for DFS. The enrichment analysis identified the molecular targets and signaling pathways that can regulate cell proliferation, differentiation, and apoptosis. CONCLUSION: Extracapsular LNI has a high prognostic value in patients with esophageal cancer and is closely related to the stage of tumors. Our preliminary molecular mechanism research indicated that the molecular targets of EC-LNI are expected to become a new direction for the treatment of esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: To evaluate the immune checkpoint inhibitors (CPI) for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC). Materials and methods: A meta‐analysis was conducted, and the efficacy and safety of CPI were assessed. Results: A total of 13 studies with 980 patients were included. The pooled objective response rate (ORR) and disease control rate were 47.2% and 64.4%, separately. In addition, patients with primary tumor located in head and neck (odds ratio [OR]: 0.374, 95% confidence interval [CI]: 0.219–0.640, p < 0.001) and positive expression of programmed death ligand 1 (OR: 0.364, 95% CI: 0.158–0.842, P = 0.018) had superior ORR during CPI treatment. The incidence of progression free survival at 6 and 12 months was 59.3% and 52.8%, and 80.6% and 76.4% for overall survival. As for safety, the overall incidence of adverse events with all grades and 3–4 grade was 76.9% and 20.2%. Conclusions: Our systematic review confirmed the satisfying efficacy and acceptable toxicity of CPI for advanced CSCC. [ABSTRACT FROM AUTHOR]

Background: To use ddPCR to quantify plasma exosomal class III β‐tubulin (βIII‐tubulin, TUBB3, encoded by the TUBB3 gene) mRNA expression in metastatic castration‐resistant prostate cancer (mCRPC) patients, and study the association of this expression with abiraterone efficacy. Methods: Blood samples were prospectively collected from 52 mCRPC patients using abiraterone as first‐line therapy to measure plasma exosomal TUBB3 mRNA expression value before the initiation of abiraterone. Study endpoints were PSA response rate, PSA‐progression‐free survival (PSA‐PFS), and overall survival (OS, from CRPC to death). Results: Patients with positive exosomal TUBB3 expression showed shorter PSA‐PFS (negative TUBB3 vs. positive TUBB3: 11.0 vs. 7.9 months; p = 0.014). Further analysis demonstrated that patients with strongly positive exosomal TUBB3 (>20 copies/20 µl) was associated with even shorter PSA‐PFS (negative TUBB3 vs. positive TUBB3 [<20 copies/20 µl] vs. strongly positive TUBB3 [>20 copies/20 µl]: 11.0 vs. 8.3 vs. 3.6 months, p = 0.005). In multivariate analyzes, TUBB3 (+) (HR: 2.114, p = 0.033) and ECOG score >2 (HR: 3.039, p = 0.006) were independent prognosticators of poor PSA‐PFS. PSA response and OS did not present significant differences. Conclusion: The exosomal TUBB3 mRNA expression level is associated with poor PSA‐PFS of abiraterone in mCRPC patients. The detection of exosomal TUBB3 can be valuable in their management. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the survival benefit and safety of individualized schedules for sunitinib in patients with metastatic renal cell carcinoma (mRCC) through plasma concentration monitoring. Methods: A total of 105 patients with mRCC were enrolled. The schedule was adjusted in two ways: therapeutic drug monitoring (TDM) and toxicity-adjusted schedule (TAS). One group of patients were without any schedule adjustment (maintained schedule, MAS). Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were compared. The relationship between AEs and steady-state concentration or consecutive monitoring curves was explored. Further monitoring of individualized schedules was also conducted. Results: Based on the plasma concentration, the schedules of 18 patients were adjusted in the TDM group. The schedules were adjusted in 37 patients due to severe AEs in the TAS group, while 50 patients were without any schedule adjustment. The median PFS and OS were better in the TDM group than the other two groups (p = 0.001 and p = 0.004, respectively). Univariate and multivariate analyses indicated that TDM could decrease the risk of death independently (p = 0.026). Moreover, the incidence of grades 3/4 AEs decreased from 88.9% to 33.3% in the TDM group (p = 0.001). Sunitinib concentration in  150– 200ng/mL was regarded as a "transitional zone" due to severe AEs mainly happened when concentration elevated over it. After TDM, further plasma concentration monitoring indicated that individualized schedules enabled sunitinib concentration to fluctuate in a much safer range. Conclusion: Treatment-related toxicities could be minimized through plasma concentration monitoring. Patients with adjusted schedules by therapeutic drug monitoring could achieve better survival benefits. [ABSTRACT FROM AUTHOR]