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Summary: Anti‐PD‐1 antibody has shown certain effects in patients with newly diagnosed extranodal NK/T‐cell lymphoma (ENKTL). Here, we evaluated the clinical efficacy and safety of first‐line anti‐PD‐1 antibody for the treatment of patients with ENKTL and explored biomarkers for treatment response. The clinical data of 107 patients with newly diagnosed ENKTL were retrospectively analysed. Patients received either first‐line anti‐PD‐1 antibody induction treatment or anti‐PD‐1 antibody combined with asparaginase‐based chemotherapy (immunochemotherapy). We found that immunochemotherapy was an independent prognostic factor for longer PFS (p < 0.001). The overall response rate and complete remission rate of immunochemotherapy group was higher than immunotherapy induction group (86.11% vs. 62.86% and 72.22% vs. 52.29%, respectively, p = 0.013). We also observed pretreatment CD4/CD8 ratio >0.83 was significant associated with better response and longer PFS in ENKTL patients received first‐line anti‐PD1‐antibody. Plasma copy number of EBV decreased more significantly in patients with CD4/CD8 ratio >0.83 after treatment. PD‐L1 expression was associated with better response and PFS, while elevated plasma IL‐6, IL‐10 and IFN‐γ were associated with poor prognosis. Anti‐PD‐1 antibody treatment showed promising results in newly diagnosed ENKTL patients. The assessment of pretreatment CD4/CD8 ratio in ENKTL seems feasible for identifying responders to anti‐PD‐1 antibody treatment. [ABSTRACT FROM AUTHOR]

The prognosis of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. The efficacy of salvage therapy with ICE (ifosfamide, carboplatin, and etoposide) is limited. DLBCL can evade immune surveillance by upregulating programmed cell death ligand 1 (PD-L1). The purpose of this study was to explore the efficacy and safety of programmed cell death 1 (PD-1) blockade combined with ICE regimen (P-ICE) in the treatment of R/R DLBCL patients. In this study, we retrospectively explored efficacy and toxicity in R/R DLBCL patients treated with P-ICE. Prognostic biomarkers, including clinical features and molecular markers related to efficacy, were explored. From February 2019 to May 2020, a total of 67 patients treated with the P-ICE regimen were analyzed. The median follow-up time was 24.7 months (range: 1.4–39.6 months), with an objective response rate (ORR) of 62.7% and a complete response rate (CRR) of 43.3%. The 2-year progression-free survival (PFS) and overall survival (OS) rates were 41.1% (95% CI: 35.0–47.2%) and 65.6% (95% CI: 59.5–71.7%), respectively. Age, Ann Arbor stage, international prognostic index (IPI) score, and response to first-line chemotherapy were correlated with the ORR. Grade 3 and 4 adverse events (AEs) related to the P-ICE regimen were reported in 21.5% of patients. The most common AE was thrombocytopenia (9.0%). No treatment-related deaths occurred. In patients with R/R DLBCL, the P-ICE regimen has promising efficacy and mild toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Anti-PD-1 antibody (anti-PD-1 mAb) showed favorable outcomes in some patients with relapsed/refractory (r/r) extranodal NK/T-cell lymphoma (ENKTL). However, the role of anti-PD-1 antibody in NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (NK/T-LAHS) remains unclear. Here, we evaluated the efficacy and toxicity of anti-PD-1 antibody-based treatment in NK/T-LAHS patients. Methods: The clinical data of 98 patients diagnosed with NK/T-LAHS at Sun Yat-sen University Cancer Center and the First Affiliated Hospital of Guangdong Pharmaceutical University from May 2014 to November 2021 were retrospectively analyzed. All patients received anti-HLH [HLH-2004 (etoposide, dexamethasone, cyclosporine A) or DEP-based (liposomal doxorubicin, etoposide, methylprednisolone)] regimen and sequential anti-ENKTL chemotherapy (ChT) combined with anti-PD-1 antibody or not. Results: The overall response rate (ORR) of the anti-PD-1 mAb plus ChT regimens was higher than that of the ChT regimens (73.3% vs. 45.5%, P = 0.041). The toxicity of the anti-PD-1 mAb plus ChT regimens was tolerable. Except for higher rate of neutropenia, no significant difference in adverse events (AEs) was observed between the two groups. When the optimal response to anti-ENKTL was achieved, the median EBV DNA levels in patients who received anti-PD-1 mAb plus ChT were significantly lower than patients who received ChT only (878 copies/mL vs. 18,600 copies/mL, P = 0.001). With a median follow-up of 26.6 months (range 0–65.9 months), the median overall survival (mOS) was 3.5 months (95% CI：2.3–4.7 months). Patients treated with anti-PD-1 mAb plus ChT experienced a longer mOS than those who received ChT only [5.2 months (95% CI: 2.5–7.8 months) vs. 1.5 months (95% CI: 0.5–2.6 months), P = 0.002]. Cox multivariate analysis found that anti-PD-1 mAb was an independent prognostic factor for all NK/T-LAHS patients. Conclusion: In conclusion, anti-PD-1 mAb combined with ChT regimens seemed to be associated with prolonged survival in NK/T-LAHS patients and may represent a potentially promising treatment strategy for this population. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent type of lymphoma that is potentially curable by chemotherapy. Immunogenic cell death (ICD) is regarded as an essential process for the clearance of residual tumor cells. However, the impact of ICD on DLBCL remains unknown. Here, we tried to explore the prognostic role of ICD in DLBCL. Methods: A gene expression microarray of DLBCL was downloaded from the Gene Expression Omnibus (GEO). The genes involved in ICD were obtained via literature reviews. Then, based on univariate, multivariate, and LASSO Cox regression analysis, the ICD-related gene signature was identified. The effect of the ICD-related gene signature on DLBCL was explored. The chi-square test was used to compare complete response rate (CRR) and recurrence rate between high- and low-risk groups. Results: The signature based on 12 ICD-related genes could independently predict the overall survival of DLBCL. Furthermore, high risk was linked to lower CRR and higher recurrence rate. Then, a nomogram based on the ICD-related gene signature was established. The area under the curve of the prediction model reached 0.820 in the training set and 0.780 in the validation set. Conclusions: This study suggested that the ICD-related gene signature could be a novel prognostic indicator for DLCBL. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most prevalent cancer in men worldwide, presenting a significant global public health challenge that necessitates early detection and personalized treatment. Recently, non-invasive liquid biopsy methods have emerged as promising tools to provide insights into the genetic landscape of PCa and monitor disease progression, aiding decision-making at all stages. Research efforts have concentrated on identifying liquid biopsy biomarkers to improve PCa diagnosis, prognosis, and treatment prediction. This article reviews recent research advances over the last five years utilizing extracellular vesicles (EVs) as a natural biomarker library for PCa, and discusses the clinical translation of EV biomarkers, including ongoing trials and key implementation challenges. The findings underscore the transformative role of liquid biopsy, particularly EV-based biomarkers, in revolutionizing PCa diagnosis, prediction, and treatment. • EVs provide non-invasive, reliable biomarkers for PCa liquid biopsy. • Beyond mRNAs, miRNAs, and proteins, Other EV molecules exhibit promising biomarker potential for PCa. • Well-designed multicentre trials are crucial to comfirm the effectiveness of EV-based liquid biopsies for PCa management. [ABSTRACT FROM AUTHOR]

Objectives: Extranodal natural/killer T-cell lymphoma (ENKTL) is a rare subtype of T cell non-Hodgkin's lymphoma. Current clinical prognostic models for ENKTL still have their limitations. Validated prognostic models for ENKTL have not yet been established. Methods: Tumor microenvironment IL-6 was measured by immunohistochemistry in 78 ENKTL patients. Results: Patients with negative IL-6 expression in the tumor microenvironment have a longer PFS (56.0 months vs. 25.6 months, p < 0.001) and OS (96.0 months vs. 43.3 months, p < 0.001). In the multivariate analysis, tumor microenvironment IL-6 [p = 0.048, HR = 1.76(1.00-3.08)] and extranodal involvement [p = 0.001, HR = 2.69(1.50-4.82)] were independent prognostic factors for PFS. Tumor microenvironment IL-6 [p = 0.033, HR = 2.69 (1.08-6.67)], Ann Arbor stage [p = 0.002, HR = 2.77 (1.47-5.23)] and B symptom [p = 0.027, HR = 2.02 (1.08-3.78)] were independent prognostic factors for OS. Expert opinion: A high IL-6 expression was related to poor survival, which may be a valuable biomarker for prognostic evaluation at baseline in ENKTL. These results showed that anti-IL-6R may be a potential targeted therapy for the treatment of advanced or relapsed ENKTL. [ABSTRACT FROM AUTHOR]

Esophageal cancer is one of the most common types of malignant tumors located within the digestive system, with >50% of esophageal cancer cases worldwide occurring in China. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer; however, few lncRNAs have been characterized in esophageal squamous cell carcinoma (ESCC). In the present study, a novel lncRNA, SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1) was exhibited in ESCC. Expression levels of SBF2-AS1 in ESCC and adjacent non-cancerous tissues were detected using the reverse transcription-quantitative polymerase chain reaction. SBF2-AS1 was knocked down, and proliferation, migration, invasion, apoptosis and the cell cycle were examined in ESCC cells. Results identified that SBF2-AS1 was significantly upregulated in ESCC compared with adjacent non-cancerous tissues (fold increase, 8.82; P=0.023). The SBF2-AS1 expression level was significantly increased in patients who had a smoking (9.927 vs. 4.507; P=0.030) and/or drinking (10.938 vs. 4.232; P=0.032) history. Patients with a large tumor size exhibited increased SBF2-AS1 expression (=4 vs. <4 cm, 14.898 vs. 5.435; P=0.018). Patients with advanced ESCC exhibited increased upregulation of SBF2-AS1 [tumor-node-metastasis (TNM) I-II vs. TNM III-IV, 1.302 vs. 15.475; P<0.01]. SBF2-AS1 was also silenced using small interfering RNA. Cell proliferative and invasive ability were significantly inhibited (P<0.05) following SBF2-AS1 silencing, the cell cycle was arrested in the G2 phase; however, there was no significant difference in the proportion of apoptotic cells. Gene Set Enrichment Analysis revealed that genes associated with cell cycle biological processes, including the cancer suppressor gene cyclin-dependent kinase 1A (CDKN1A), were significantly associated with SBF2-AS1 in ESCC tissues. Further validation confirmed that CDKN1A expression levels were increased in ECA-109 cells following SBF2-AS1 silencing. The results of the present study demonstrate that SBF2-AS1 is significantly upregulated in ESCC, and that silencing of SBF2-AS1 inhibits the proliferative and invasive ability of ESCC cells. SBF2-AS1 may be a novel biomarker and therefore a potential therapeutic target for ESCC. [ABSTRACT FROM AUTHOR]

Lymphoplasmacytic lymphoma secreting IgG or IgA (non-IgM LPL) is rarely seen. Systematic studies of the clinical features and treatment outcomes are lacking in these patients. This study evaluated 17 patients with non-IgM LPL. The paraprotein secreted by these tumors was IgA (n = 8; 47%) and IgG (n = 9; 53%). The median serum level of paraprotein was 2,475 mg/dl (range = 747–5260) for IgA and 2580 mg/dl (range = 1900–7100) for IgG. The IgA-LPL group was more likely to present with B symptoms, a high beta2-microglobulin level and extramedullary involvement. Compared with patients with Waldenström macroglobulinemia (WM), patients with non-IgM LPL showed similar clinical and pathologic features, but a higher mortality within the first year after diagnosis (p < 0.001) and worse overall survival (p = 0.024), with no difference in progression-free survival and disease-specific survival. Rituximab alone or rituximab-based therapy was used frequently and was effective as either first-line or salvage therapy. [ABSTRACT FROM PUBLISHER]

• We developed a radiomic nomogram to predict early recurrence in patients with AGC. • The nomogram incorporated radiomic signature, Borrmann type, CEA, CA 199 and cN stage. • Both hand-crafted features and deep learning features had prognostic values. • The radiomic nomogram had a better performance than the clinical factor-based model. • Radiomic nomogram provided incremental value to the diagnostic management of AGC. In the clinical management of advanced gastric cancer (AGC), preoperative identification of early recurrence after curative resection is essential. Thus, we aimed to create a CT-based radiomic model to predict early recurrence in AGC patients preoperatively. We enrolled 669 consecutive patients (302 in the training set, 219 in the internal test set and 148 in the external test set) with clinicopathologically confirmed AGC from two centers. Radiomic features were extracted from preoperative diagnostic CT images. Machine learning methods were applied to shrink feature size and build a predictive radiomic signature. We incorporated the radiomic signature and clinical risk factors into a nomogram using multivariable logistic regression analysis. The area under the curve (AUC) of operating characteristics (ROC), accuracy, and calibration curves were assessed to evaluate the nomogram's performance in discriminating early recurrence. A radiomic signature, including three hand crafted features and six deep learning features, was significantly associated with early recurrence (p -value <0.0001 for all sets). In addition, clinical N stage, carbohydrate antigen 199 levels, carcinoembryonic antigen levels, and Borrmann type were considered useful predictors for early recurrence. The nomogram, combining all these predictors, showed powerful prognostic ability in the training set and two test sets with AUCs of 0.831 (95% CI, 0.786–0.876), 0.826 (0.772–0.880) and 0.806 (0.732–0.881), respectively. The predicted risk yielded good agreement with the observed recurrence probability. By incorporating a radiomic signature and clinical risk factors, we created a radiomic nomogram to predict early recurrence in patients with AGC, preoperatively, which may serve as a potential tool to guide personalized treatment. [ABSTRACT FROM AUTHOR]