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Abstract Background This study aimed to propose a new user-friendly, cost effective and robust risk model to facilitate risk stratification for diffuse large B-cell lymphoma (DLBCL) treated with frontline R-CHOP regimens. Methods Data on 998 patients with de novo DLBCL diagnosed between Jan 1st, 2005 and Dec 31st, 2018 at our center, who received frontline R-CHOP or R-CHOP-like regimens, were retrospectively collected. Patients were randomly divided into the training cohort (n = 701) and the validation cohort (n = 297). A new prognostic model for overall survival (OS) was built based on the training cohort. The performance of the new model was compared with International prognostic index (IPI), revised IPI (R-IPI) and National Comprehensive Cancer Network (NCCN)-IPI (NCCN-IPI). The new model was validated in the validation cohort. Results The multivariate analysis of the training cohort showed that the IPI, β2-microglobulin, platelet count and red blood cell distribution width were independent factors for OS, which were incorporated into the new prognostic model. Patients were stratified into low risk, low-intermediate risk, high-intermediate risk, high risk and very high risk groups, with distinct survival outcomes. The new model achieved good C-indexes for 5-year OS prediction of 0.750 (95%CI 0.719–0.781) and 0.733 (95%CI 0.682–0.784) in the training and validation cohorts, respectively, and displayed well-fitted calibration curves. The C-index and the time-dependent ROC analysis demonstrated better performance of the new model than the IPI, R-IPI and NCCN-IPI in both training and validation cohorts. The integrated Brier score for predicting 5-year OS of the new model was lower than that of the IPI, R-IPI and NCCN-IPI in both cohorts, and decision curve analysis also showed a higher net benefit, indicating the superiority of the new model over the conventional models. Conclusion The new prognostic model might be a useful predictive tool for DLBCL treated with R-CHOP regimens. Further external validation is warranted.

Abstract Background This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. Method RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.

Abstract Introduction Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response. Materials and Methods We performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations. Results We found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C>G and C>A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such as EGFR(L858R), KRAS (p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy. Conclusions Collectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.

Abstract The difference in clinical features and treatment outcomes between localized sinonasal diffuse large B cell lymphoma (SN-DLBCL) and sinonasal extranodal NK/T cell lymphoma (SN-ENKTL) is unclear. Therefore, we analyzed a total of 47 patients with localized SN-DLBCL and 211 patients with localized SN-ENKTL. The age distribution for these two subtypes is very distinct and the B symptoms were more common in SN-ENKTL. However, both SN-DLBCL and SN-ENKTL patients could achieve high overall response rate (ORR) and favorable prognoses. The 3-year overall survival (OS) rates for patients with SN-DLBCL and SN-ENKTL were 79.7 and 83.6% (p = 0.707), and the 3-year progression-free survival (PFS) rates were 61.4 and 70.1% (p = 0.294), respectively. For SN-DLBCL patients, chemotherapy followed by involved-field radiotherapy (IFRT) resulted in higher OS (83.7 vs 62.5%) and PFS (63.9 vs 50.0%) compared with chemotherapy alone, but the difference was not significant. No significant difference was found in the OS or PFS between radiotherapy alone and radiotherapy combined with chemotherapy for all patients with SN-ENKTL. But in extensive stage I and stage II SN-ENKTL patients, radiotherapy combined with chemotherapy could significantly improve the PFS (73.8 vs 50.0%) compared with radiotherapy alone. These results indicate that remarkable clinical disparities exist between localized SN-DLBCL and SN-ENKTL. However, different treatment strategies for them can result in similarly favorable prognoses.