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Nasopharyngeal carcinoma (NPC) is an epithelial tumor located in the nasopharynx and is highly associated with Epstein-Barr virus (EBV) infection. Although radiotherapy alone can cure ~90% of patients with early-stage disease, >70% of patients with NPC have locoregionally advanced or metastatic disease at the first diagnosis due to the insidious and aggressive nature of NPC. After comprehensive radiochemotherapy, 20-30% of patients with advanced NPC still fail treatment, mainly due to recurrence and/or metastasis (R/M). Conventional salvage treatments, such as radiotherapy, chemotherapy and surgery, are suboptimal and frequently accompanied by severe adverse effects and limited efficacy. In recent years, immunotherapy has emerged as a promising treatment modality for R/M NPC. An increasing number of clinical studies have investigated the safety and efficacy of immunotherapy for advanced NPC and have shown considerable progress. In the present review, the rationale for the use of immunotherapy to treat NPC was summarized and the current status, progress and challenges of NPC clinical research on different immunotherapeutic approaches were highlighted, including immune checkpoint inhibitors, vaccines, immunomodulators, adoptive cell transfer and EBV-specific monoclonal antibodies. The comprehensive overview of immunotherapy in NPC may provide insight for clinical practice and future investigation.

Chimeric antigen receptor T-cell (CAR-T) therapy has significantly improved overall survival (OS) in relapsed or refractory large B-cell lymphomas (R/R LBCL). However, factors associated with outcomes of CAR-T cell therapy in patients with R/R LBCL have not been fully elucidated. And limited evidence supports the use of early endpoints to evaluate the efficacy and long-term survival. Progression-free survival (PFS) at 6 months (PFS6) was defined as being alive and free of relapse or progression within 6 months of CAR-T cell infusion. We aimed to assessed OS stratified by PFS6 by analyzing data from 71 R/R LBCL patients treated with CAR-T therapy across 2 hospitals. Subsequent OS was defined from the time of PFS6 or progression within 6 months to death. Among them, 58% reached PFS6. Compared with patients failed to achieve PFS6, 1-year OS was 91.3% vs. 40.2% and 2-year OS was 91.3% vs. 32.1%, respectively. Patients achieving PFS6 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. Key predictors of PFS failure included older age (> 60) ( P  = 0.040, OR:3.40, 95%CI:1.06–10.93), lower pretransfusion hemoglobin level ( P  = 0.019 OR:0.27, 95%CI:0.09–0.81), and higher IFN-ʏ level ( P  = 0.022, OR:2.00, 95% CI:1.66–4.08). This insight could aid in risk stratification and support the use of PFS6 as a surrogate endpoint in clinical trials.

Osimertinib showed encouraging efficacy in patients with advanced EGFR T790M-positive NSCLC in previous randomized controlled trials. This real-world study aimed to evaluate the effectiveness and safety of osimertinib in a real-world setting. This observational study (NCT03133234) included 74 patients with metastatic EGFR T790M-positive NSCLC who progressed on prior EGFR TKI therapy and received osimertinib between May 2016 and April 2018 at the Kiang Wu Hospital in Macau. Response rate (RR) and other endpoints (progression-free survival [PFS], overall survival [OS], disease control rate [DCR], stable disease rate, and adverse events) were assessed. Survival data were estimated using the Kaplan-Meier method. All patients had stage IV lung adenocarcinoma and 25.6% had brain metastases; median age was 58 years (range 28-84 years) and 83.8% of patients had received at least three prior lines of treatment. The median duration of osimertinib treatment was 8 months (range, 1-25 months). RR and DCR were 67.5% (95% CI 56.9-78.1) and 79.8% (95% CI 70.7-88.9), respectively, while 12.1% had stable disease. The median PFS was 9.0 months (95% CI 6.7-11.2 months), and the median OS was 12.0 months (95% CI 8.8-15.1 months). Nausea (25.8%) and decreased appetite (20.2%) were the most common adverse events associated with osimertinib treatment. Even though most patients had at least three lines of prior treatment, real-world RR and PFS with osimertinib in this study were consistent with those from randomized controlled trials; no new safety signals were observed.

This study aimed to identify key prognostic factors for Natural killer/T-cell lymphoma (NKTCL) in the context of L-asparaginase/pegaspargase-based therapy and to develop a simplified yet accurate prognostic model for risk stratification. Data from 854 NKTCL patients at the Sun Yat-sen University Cancer Center were divided into a training cohort (n = 598) and an internal validation cohort (n = 256). A further 222 patients from Sichuan Cancer Hospital & Institute were used to create an external validation cohort. Least absolute shrinkage and selection operator (LASSO) and Cox regression were used to identify independent risk factors for overall survival (OS). A nomogram (Nomogram-CA) was constructed and evaluated using the consistency index (C-index), calibration curves, time-dependent ROC (tdROC) and decision curve analysis (DCA). Kaplan–Meier survival curves were generated to show the difference in OS between groups. Age, CA stage, B symptoms and hemoglobin (Hb) level were all identified as independent risk factors for OS. Nomogram-CA was constructed based on multivariate analysis results. The DCA curves demonstrated that Nomogram-CA provided more net benefit to patients in the training, internal validation and external validation cohorts. Furthermore, analysis of the Kaplan–Meier survival curve revealed a significantly lower survival rate among patients identified as high-risk by Nomogram-CA when compared to those classified as low-risk ( P  <  0.05 ). Nomogram-CA constructed based on independent prognostic factors has better predictive ability compared to the traditional staging system, which can assist clinical doctors in evaluating patient prognosis.

Background Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored. Methods Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels. Results Our study not only confirmed previously reported common NKTCL mutational targets like STAT3 , TP53 , and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9 , DST , and RBMX . In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0–C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole. Conclusions The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.

Background Survival prediction accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in extra-nodal natural killer/T-cell lymphoma (ENKTL) is controversial. This study aimed to evaluate the prognostic value of 18 F-FDG PET/CT parameters including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), and to develop a new prognostic model for ENKTL. Methods We analyzed 390 ENKTL patients with comprehensive clinical and survival data. All patients received asparaginase-based chemotherapy with or without radiotherapy, or radiotherapy alone. Metabolic tumor volume (MTV) was calculated using a 41% SUVmax threshold, and TLG was computed as MTV multiplied by the average SUV. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier curves and compared with log-rank tests. Optimal cut-off values were determined using the Youden’ index. Cox regression analysis identified significant prognostic factors. A nomogram predicting 1-, 3-, and 5-year survival was developed and validated using the C-index and calibration curves. Statistical significance was set at p  < 0.05. Results Of the 390 patients, 262 (67.2%) were included in the training set and 128 (32.8%) in the validation set. 18 F-FDG PET-CT parameters with cutoff values of SUVmax > 12.8, TMTV > 16.4 cm 3 , and TLG > 137.0, were significantly associated with poorer OS ( p  = 0.009) and PFS ( p  = 0.003). Multivariable Cox regression identified the following as independent predictors of worse OS: age > 60 years (HR = 1.923, 95% CI: 1.001—3.693), presence of B symptoms (HR = 1.861, 1.132—3.059), ECOG score ≥ 2 (HR = 2.076, 1.165—3.699), extranodal involvement ≥ 2 sites (HR = 2.349, 1.384—3.988), bone marrow involvement (HR = 4.884, 2.137—11.163), SUVmax > 12.8 (HR = 2.226, 1.260—3.930), and TMTV > 16.4 cm 3 (HR = 1.854, 1.093—3.147). The new prognostic model achieved a C-index of 0.772 for OS and 0.750 for PFS in the training set, and 0.777 for OS and 0.696 for PFS in the validation set. Area under the curve (AUC) values for 1-, 3-, and 5-year OS were 0.841, 0.804, and 0.767 in the training set, and 0.718, 0.786, and 0.893 in the validation set. Risk stratification divided patients into four groups with significant differences in survival ( p  < 0.001). Conclusion SUVmax, TMTV, and TLG are independent prognostic factors in ENKTL. Our new model, which integrates 18 F-FDG PET/CT metrics with clinical data, enhances survival prediction and may support personalized treatment strategies, though further validation is required.

Background The prognostic value of programmed death-ligand 1 (PD-L1) and BRAF expression in nasopharyngeal carcinoma (NPC) is not well-defined. In this study we investigated alterations in PD-L1, BRAF and EGFR by using immunohistochemistry analysis in a cohort of consecutively enrolled NPC patients. Methods A retrospective review of 154 NPC patients form our previous study (BMC Cancer. 2013; 13:226) were conducted. Survival and prognostic impacts were analyzed based on PD-L1, BRAF and EGFR expression levels. Results One hundred fifty four patients were included in this study. PD-L1 expression was detected in 87.7% of patients; 14.3% had 1–5% PD-L1 expression, 47.4% had 5–49% expression while 26% had ≥50% expression Higher PD-L1 expression was significantly associated with shorter PFS and OS. The median PFS was 25 months (95% CI 15.7–34.3 months) and OS was 35 months (95% CI 22.60–47.4 months) for patients with PD-L1 expression ≥50%; both median PFS and OS were not yet reached for patients with PD-L1 expression < 50%. PFS was significantly higher in BRAF mutation positive patients (5-year PFS: 55.1% vs. 30.8%, P  = 0.044). Conclusion Tumor PD-L1 expression and BRAF mutation are associated with poor outcomes in patients with NPC. This study was retrospectively registered in ClinicalTrials.gov (NCT03989297) on 2019-6-18.