TBC1D10B promotes tumor progression in colon cancer via PAK4­mediated promotion of the PI3K/AKT/mTOR pathway.

This study aimed to explore the expression, function, and mechanisms of TBC1D10B in colon cancer, as well as its potential applications in the diagnosis and treatment of the disease.The expression levels of TBC1D10B in colon cancer were assessed by analyzing the TCGA and CCLE databases. Immunohistochemistry analysis was conducted using tumor and adjacent non-tumor tissues from 68 colon cancer patients. Lentiviral infection techniques were employed to silence and overexpress TBC1D10B in colon cancer cells. The effects on cell proliferation, migration, and invasion were evaluated using CCK-8, EDU, wound healing, and Transwell invasion assays. Additionally, GSEA enrichment analysis was used to explore the association of TBC1D10B with biological pathways related to colon cancer. TBC1D10B was significantly upregulated in colon cancer and closely associated with patient prognosis. Silencing of TBC1D10B notably inhibited proliferation, migration, and invasion of colon cancer cells and promoted apoptosis. Conversely, overexpression of TBC1D10B enhanced these cellular functions. GSEA analysis revealed that TBC1D10B is enriched in the AKT/PI3K/mTOR signaling pathway and highly correlated with PAK4. The high expression of TBC1D10B in colon cancer is associated with poor prognosis. It influences cancer progression by regulating the proliferation, migration, and invasion capabilities of colon cancer cells, potentially acting through the AKT/PI3K/mTOR signaling pathway. These findings provide new targets and therapeutic strategies for the treatment of colon cancer.

Analysis of the treatment and prognosis of 266 cases of extranodal natural killer/T-cell lymphoma, nasal type in a single medical center.

Objective: To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center. Methods and analysis: The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation. The Kaplan-Meier curves, univariate and multivariate Cox regression analyses were employed for survival and prognosis analysis. Statistical significance was set at P<0.05. Results: Following treatment, the post-intervention outcomes demonstrated a complete remission (CR) rate of 71.05% and a partial remission (PR) rate of 3.76%. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 70.4% and 70.9%, respectively. In addition, the PFS for patients in stage I/II was 79.8%, with an OS of 81.1%, whereas for those in stage III/IV, the PFS was 41.7% and the OS was 40.9%. Notably, the achievement of CR immediately after treatment was an independent prognostic factor (P<0.001). Patients in stage I/II depicted a favorable 5-year OS rate, while those in stage III/IV manifested a less favorable prognosis. Conclusion: Stages of the disease and whether CR was achieved following treatment are important factors determining the survival and prognosis of patients with ENKTL. Further researches focusing on disease onset and mechanisms of drug resistance will contribute to better management of ENKTL.

First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. METHODS: The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. FINDINGS: Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. INTERPRETATION: Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. FUNDING: National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.

Zebrafish Mbd5 binds to RNA m5C and regulates histone deubiquitylation and gene expression in development metabolism and behavior.

Complex biological processes are regulated by both genetic and epigenetic programs. One class of epigenetic modifications is methylation. Evolutionarily conserved methyl-CpG-binding domain (MBD)-containing proteins are known as readers of DNA methylation. MBD5 is linked to multiple human diseases but its mechanism of action remains unclear. Here we report that the zebrafish Mbd5 does not bind to methylated DNA; but rather, it directly binds to 5-methylcytosine (m5C)-modified mRNAs and regulates embryonic development, erythrocyte differentiation, iron metabolism, and behavior. We further show that Mbd5 facilitates removal of the monoubiquitin mark at histone H2A-K119 through an interaction with the Polycomb repressive deubiquitinase (PR-DUB) complex in vivo. The direct target genes of Mbd5 are enriched with both RNA m5C and H2A-K119 ubiquitylation signals. Together, we propose that zebrafish MBD5 is an RNA m5C reader that potentially links RNA methylation to histone modification and in turn transcription regulation in vivo.

Pan-cancer analysis of the prognostic significance and oncogenic role of GXYLT2.

Growing evidence supports an oncogenic role for glucoside xylosyltransferase 2 (GXYLT2) in a number of malignancies. To evaluate the prognostic value and oncogenic function of GXYLT2 in diverse cancer types, we analyzed sequencing data from public databases on 33 tumor tissues and their corresponding normal tissues. We found that GXYLT2 was overexpressed in a number of tumors, and that its expression was positively correlated with disease progression and mortality in several major cancer types including stomach adenocarcinoma (STAD). GXYLT2 was also linked to tumor size, grade, and the immune and molecular subtypes of STAD. GO and KEGG pathway analyses of GXYLT2 co-expressed genes in STAD suggested that GXYLT2 possibly plays a role in epithelial-mesenchymal transition, extracellular matrix production and degradation, angiogenesis, apoptosis, as well as in tumor inflammation, such as cytokine production and T cell activation. Finally, prognostic nomograms were created and validated for predicting 1, 3, and 5-year survival of patients with STAD. Our findings indicate that GXYLT2 may play a role in tumorigenesis and tumor immunity, and it may serve as a prognostic marker and potential immunotherapeutic target for STAD and some other types of cancer.

Significance of platelet adhesion-related genes in colon cancer based on non-negative matrix factorization-based clustering algorithm.

Background: Although surgical methods are the most effective treatments for colon adenocarcinoma (COAD), the cure rates remain low, and recurrence rates remain high. Furthermore, platelet adhesion-related genes are gaining attention as potential regulators of tumorigenesis. Therefore, identifying the mechanisms responsible for the regulation of these genes in patients with COAD has become important. The present study aims to investigate the underlying mechanisms of platelet adhesion-related genes in COAD patients. Methods: The present study was an experimental study. Initially, the effects of platelet number and related genomic alteration on survival were explored using real-world data and the cBioPortal database, respectively. Then, the differentially expressed platelet adhesion-related genes of COAD were analyzed using the TCGA database, and patients were further classified by employing the non-negative matrix factorization (NMF) analysis method. Afterward, some of the clinical and expression characteristics were analyzed between clusters. Finally, least absolute shrinkage and selection operator regression analysis was used to establish the prognostic nomogram. All data analyses were performed using the R package. Results: High platelet counts are associated with worse survival in real-world patients, and alternations to platelet adhesion-related genes have resulted in poorer prognoses, based on online data. Based on platelet adhesion-related genes, patients with COAD were classified into two clusters by NMF-based clustering analysis. Cluster2 had a better overall survival, when compared to Cluster1. The gene copy number and enrichment analysis results revealed that two pathways were differentially enriched. In addition, the differentially expressed genes between these two clusters were enriched for POU6F1 in the transcription factor signaling pathway, and for MATN3 in the ceRNA network. Finally, a prognostic nomogram, which included the ALOX12 and ACTG1 genes, was established based on the platelet adhesion-related genes, with a concordance (C) index of 0.879 (0.848-0.910). Conclusion: The mRNA expression-based NMF was used to reveal the potential role of platelet adhesion-related genes in COAD. The series of experiments revealed the feasibility of targeting platelet adhesion-associated gene therapy.

A common thalamic hub for general and defensive arousal control.

The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATmVGluT2+) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATmVGluT2+ population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATmVGluT2+ neurons or multiple downstream pathways. In awake mice, ATmVGluT2+ activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.

TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

A novel prognostic model based on ferritin and nomogram-revised risk index could better stratify patients with extranodal natural killer/T-cell lymphoma.

BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is an aggressive lymphoma with marked heterogeneity, resulting in a distinct prognosis even in patients with the same disease stage. The nomogram-revised risk index (NRI) has been proposed to stratify patients with ENKTCL. Numerous reports have revealed the prognostic role of serum ferritin in various cancers. PURPOSE: We aimed to evaluate the role of NRI in our single cohort of patients with ENKTCL treated uniformly, explore the prognostic value of ferritin, and establish a new prognostic model to better stratify patients with ENKTCL. METHODS: We included 326 patients with ENKTCL with detailed data regarding clinical characteristics and survival outcomes. All patients were treated with asparaginase-based chemotherapy with or without radiotherapy. Multiple R packages were used to analyze the prognostic factors and derive a novel prognostic model. RESULTS: In the training cohort comprising 236 patients with ENKTCL, NRI significantly correlated with progression-free survival (PFS) and overall survival (p < 0.0001). Using a ferritin level of 400 µg/L as the cutoff value, patients with high ferritin levels had significantly inferior PFS (p = 0.00028). Integrating the NRI score and four easily accessible clinical parameters, namely ferritin, hemoglobin, albumin, and D-dimer, a new prognostic model was constructed, stratifying patients with ENKTCL into three risk groups. This new prognostic model was independent of disease stage and NRI and performed better than NRI. Furthermore, this model helped to stratify patients within the same NRI risk groups. Finally, the role of this novel prognostic model was validated in the external validation cohort comprising 90 patients with ENKTCL. CONCLUSIONS: Serum ferritin level could be a novel prognostic factor in patients with ENKTCL. The new prognostic model combining NRI and clinical parameters could better predict the prognosis of ENKTCL, thereby warranting further validation and potentially guiding individualized treatment in future prospective clinical trials.

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution.

BACKGROUND: To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution. METHODS: This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS). RESULTS: During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P  = 0.025 and P  = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups. CONCLUSION: Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.

Effects of Mechanical Stress on Insulation Structure and Performance of HV Cable.

Mechanical stresses generated during manufacturing and laying process of high voltage cables can result in degradation of insulation properties, affecting the stable operation of the transmission system. Traditional test methods for testing the effect of mechanical stress on the insulation properties of polyethylene still have some shortcomings to be explored and it is able to explain the changes of the insulation properties of polyethylene under mechanical stress from a microscopic perspective. In order to further study the effect of stress on the insulation properties of polyethylene, microstructural changes, the breakdown field strength, conductivity and charge distribution of polyethylene at different elongation rates are investigated by a combination of experimental and molecular dynamics simulations. The results show that the increase in stress leads to a decrease in crystallinity and microcrystalline size of the material decrease. The untwisting and orientation of the polyethylene molecular chains during the stretching process can create cavities, resulting in an uneven sample distribution and thickness reduction, leading to a reduction in the breakdown field strength. Meanwhile, some crystal regions are transformed into amorphous regions. The loose amorphous regions facilitate the directional migration of carriers, resulting in the increase of conductivity. When the elongation ratio is smaller, the distance between the molecular chains increases and the trap depth of the specimen becomes shallower. This facilitates the migration of ions and electrons and increases the rate of decay of the surface potential. When the stretch is further increased, new traps are created by broken molecular chains to limit the movement of charges, decreasing the decay rate of the surface potential and reducing the insulation properties of the polyethylene. Meanwhile, the molecular dynamics model of semi-crystalline polyethylene was developed to observe the microstructure and energy changes during the stretching process. The conclusions in terms of tensile tests were verified from a microscopic perspective.

Case Report: Balanced Reciprocal Translocation t (17; 22) (p11.2; q11.2) and 10q23.31 Microduplication in an Infertile Male Patient Suffering From Teratozoospermia.

Two chromosomal abnormalities are described in an infertile man suffering from teratozoospermia: balanced reciprocal translocation t (17; 22) (p11.2; q11.2) and a microduplication in the region 10q23.31. Twenty genes located on the breakpoints of translocation (e.g., ALKBH5, TOP3A, SPECC1L, and CDC45) are selected due to their high expression in testicular tissues and might be influenced by chromosome translocation. Four genes located on the breakpoints of microduplication including FLJ37201, KIF20B, LINC00865, and PANK1 result in an increased dosage of genes, representing an imbalance in the genome. These genes have been reported to be associated with developmental disorders/retardation and might be risk factors affecting spermatogenesis. Bioinformatics analysis is carried out on these key genes, intending to find the pathogenic process of reproduction in the context of the translocation and microduplication encountered in the male patient. The combination of the two chromosomal abnormalities carries additional risks for gametogenesis and genomic instability and is apparently harmful to male fertility. Overall, our findings could contribute to the knowledge of male infertility caused by genetic factors.

CD56-Negative Extranodal Natural Killer/T-Cell Lymphoma: A Retrospective Study in 443 Patients Treated by Chemotherapy With or Without Asparaginase.

Objective: Extranodal natural killer/T cell lymphoma (NKTCL) is an aggressive EBV-related lymphoma, originating from NK cells or T cells. Previous study demonstrated that CD56 negative NKTCL should be recognized as a distinct subtype. In this study, the value of CD56 in NKTCL is validated in the era of asparaginase, and genomic analysis was done to dissect the differences between CD56-negative and positive NKTCL. Methods: 443 patients with newly diagnosed NKTCL were enrolled in this retrospective study, and correlation between CD56 positivity and survival outcomes was analyzed. The gene sequencing data was downloaded (http://www.biosino.org/node/project/detail/OEP000498), and bioinformatics analysis was done to delineate the tumor microenvironment and differentially expressed genes. Results: CD56 was expressed in 337 patients (76.1%). Within a median follow-up time of 51 months, the 5-year overall survival (OS) and progression free survival (PFS) rates were 63.8% and 51.9%, respectively. For the whole cohort, patients who were CD56-positive had superior OS (5-year OS, 86.2% vs. 51.9%, p=0.019) and PFS (5-year PFS, 55.9% vs. 40.1%, p=0.016). For patients in early stage disease, CD56 positivity was associated with superior OS and PFS (p=0.008 and 0.005, respectively). In patients who received non-asparaginase-based chemotherapy, CD56-negative was associated with shorter OS and PFS (p<0.001), and in patients who received asparaginase-based chemotherapy, CD56-negative was not related to inferior OS and PFS (p=0.093 and p=0.829, respectively). The genomic analysis demonstrated that CD56 positive NKTCL probably originated from NK cells and CD56 negative NKTCL originated from T cells. CD56 positive NKTCL had significantly higher proportion of resting NK cells, activated NK cells, and activated CD8+ and CD4+ T cells in the tumor microenvironment. Conclusions: CD56 negative NKTCL differs from CD56 positive NKTCL in both the tumor microenvironment and survival outcomes, and asparaginase-based treatment may overcome the poor prognosis brought by CD56 negativity.

LncRNA BCYRN1-induced autophagy enhances asparaginase resistance in extranodal NK/T-cell lymphoma.

Background: Asparaginase (ASP) is the cornerstone drug in the treatment of extranodal NK/T-cell lymphoma (ENKTCL), and the mechanisms of resistance to ASP remain largely unknown. Long non-coding RNAs play important roles in chemotherapy resistance in various cancers. However, the expression of BCYRN1 and its role in ENKTCL still remain unidentified. Methods: Lentivirus-mediated BCYRN1 overexpression and knockdown were performed in SNK-6 cells. Cell autophagy was analyzed by adenovirus expressing GFP-LC3B fusion protein. RNA pull-down and RNA Binding Protein Immunoprecipitation Assay were performed to investigate the relationship between BCYRN1 and p53. Western blot analysis was performed to assess the effect of BCYRN1 on different autophagy pathways. Finally, in vivo xenograft tumor model was constructed to analyze the effect of BCYRN1 on tumor growth and ASP resistance. Results: BCYRN1 was overexpressed in ENKTCL than normal NK cells, and patients with higher expression had significantly inferior progression-free survival (PFS). The IC50 value of ASP was significantly increased in BCYRN1-overexpressed SNK-6 cells and BCYRN1 overexpression could resist the inhibitory effect of ASP on proliferation. ASP could induce concurrent apoptosis and autophagy in ENKTCL, and the latter process was enhanced by overexpression of BCYRN1, mainly through affecting both PI3K/AKT/mTOR and p53/mTOR pathways. BCYRN1 could induce the degradation of p53 via ubiquitination, thus resulting in enhancement of autophagy and ASP resistance, which could be reversed by drug-induced autophagy inhibition. The effect of BCYRN1 on tumor growth and autophagy were confirmed in vivo xenograft model. Conclusions: It was found that BCYRN1 was a valuable prognostic biomarker in ENKTCL. BCYRN1 could promote resistance to ASP by inducing autophagy, which could be reversed by inhibition of autophagy. Our findings highlight the feasibility of combining autophagy inhibition and ASP in the treatment of ENKTCL.

Using etoposide + dexamethasone-based regimens to treat nasal type extranodal natural killer/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis.

PURPOSE: Nasal type extranodal natural killer/T-cell lymphoma (ENKTL) can be associated with hemophagocytic lymphohistiocytosis (NK/T-LAHLH), which is a rare and fatal disease with no effective therapy. We evaluated whether etoposide + dexamethasone-based chemotherapy regimens might be useful for treating NK/T-LAHLH. METHODS: This retrospective single-center study evaluated clinical data from 37 patients with NK/T-LAHLH who were treated between May 2008 and January 2020. RESULTS: Among 363 patients with ENKTL, the cumulative incidence of HLH was 11.9%. Among 43 patients with NK/T-LAHLH, 37 patients received etoposide + dexamethasone-based chemotherapy regimens, with an overall response rate of 45.9% for the HLH. The overall response rate was substantially higher for newly diagnosed NK/T-LAHLH than it was for relapsed or refractory NK/T-LAHLH (66.7% vs. 18.8%). The median overall follow-up time was 4 months, with overall survival rates of 81.1% at 1 month, 62.2% at 2 months, 56.8% at 3 months, and 34.4% at 6 months. Significantly better overall survival (all P < 0.05) was observed for patients with newly diagnosed NK/T-LAHLH (vs. relapsed/refractory disease), stage I/II disease (vs. stage III/IV disease), and nasal disease (vs. non-nasal disease). Patients who responded to the ENKTL treatment also experienced response in their HLH; 8 patients experienced continued complete response for both HLH and ENKTL. Multivariate analysis revealed that a poor prognosis among patients with NK/T-LAHLH was independently related to relapsed/refractory ENKTL and non-nasal disease. CONCLUSION: Although patients with NK/T-LAHLH generally experienced poor outcomes, etoposide + dexamethasone-based chemotherapy regimens were associated with good outcomes among select patients with newly diagnosed or stage I/II NK/T-LAHLH.

Outcomes of patients treated with SVILE vs. P-GemOx for extranodal natural killer/T-cell lymphoma, nasal type: a prospective, randomized controlled study.

Objective: To compare the efficacy and safety of the novel SVILE regimen with the P-GemOx regimen in patients with newly diagnosed extranodal natural killer/T-cell lymphoma, nasal type (ND-ENKTL). Methods: From April 2015 to July 2018, 103 patients with ND-ENKTL were randomly assigned to SVILE (experimental group) or P-GemOx (control group) chemotherapy followed by radiotherapy and consolidation chemotherapy. The primary endpoint was the overall response rate after 3 cycles of chemotherapy, and secondary study endpoints were complete response (CR), progression-free survival (PFS), and overall survival (OS). Safety was also evaluated. Results: There were no significant differences in baseline characteristics in the experimental vs. control groups. In experimental and control groups, respectively, the overall response rates were 91.7% vs. 97.0% for stage I/II and 75.0% vs. 72.2% for stage III/IV. The CR rates were 83.4% vs. 97.0% for stage I/II and 68.8% vs. 61.1% for stage III/IV. None of those differences were significant. There was no significant difference in PFS and OS between groups and between patients in stage I/II and stage III/IV. The 3-year PFS and OS in stage I/II were 88.3% vs. 93.3% and 88.8% vs. 97.0%, respectively. The 3-year PFS and OS in stage III/IV were 46.2% vs. 65.7% and 68.8% vs. 72.2%, respectively. The common adverse events were hematological toxicity, hepatotoxicity, and coagulation abnormalities, which were found to be reversible with supportive therapy. Conclusions: The novel SVILE regimen has comparable effects to those of P-GemOx in patients with ND-ENKTL and is well tolerated. SVILE is a therapeutic option for ND-ENKTL.

SVILE regimen, a combination of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide, for treating relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type.

OBJECTIVE: To explore the effectiveness and safety of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide combination (SVILE regimen) in the treatment of relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (R/R-ENKTL). METHODS: This descriptive, retrospective medical chart review assessed data from 20 R/R-ENKTL patients treated with the SVILE regimen between November 2014 and August 2019. Complete response (CR) rate, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) since SVILE treatment were analysed. RESULTS: After receiving 1-5 SVILE regimen chemotherapy cycles (median 2 cycles), patients had ORR and CR rates of 70.0 % and 45.0 %, respectively. Stage Ⅰ/Ⅱ patients had CR rate of 100.0 % and stage Ⅲ/Ⅳ patients had ORR and CR rates of 60.0 % and 26.7 %, respectively. Three-year PFS and OS rates of the 20 patients were 43.8 % and 54.2 %, respectively. Three-year PFS and OS rates of stage Ⅰ/Ⅱ patients and stage Ⅲ/Ⅳ patients were 100.0 % vs. 26.7 % and 100.0 % vs. 40.0 % (P ＜ 0.05), respectively. The PFS and OS of patients who achieved CR after SVILE chemotherapy were significantly better than those of non-CR patients. The main adverse events were reversible haematological toxicity. CONCLUSIONS: The SVILE regimen is a new treatment option that is effective and safe for R/R-ENKTL patients.