A real-world observation on thrombopoietic agents for patients with cancer treatment-induced thrombocytopenia in China: A multicenter, cross-sectional study.

BACKGROUND: Studies on various thrombopoietic agents for cancer treatment-induced thrombocytopenia (CTIT) in China are lacking. This study aimed to provide detailed clinical profiles to understand the outcomes and safety of different CTIT treatment regimens. METHODS: In this retrospective, cross-sectional study, 1664 questionnaires were collected from 33 hospitals between March 1 and July 1, 2021. Patients aged >18 years were enrolled who were diagnosed with CTIT and treated with recombinant interleukin 11 (rhIL-11), recombinant thrombopoietin (rhTPO), or a thrombopoietin receptor agonist (TPO-RA). The outcomes, compliance, and safety of different treatments were analyzed. RESULTS: Among the 1437 analyzable cases, most patients were treated with either rhTPO alone (49.3%) or rhIL-11 alone (27.0%). The most common combination regimen used was rhTPO and rhIL-11 (10.9%). Platelet transfusions were received by 117 cases (8.1%). In multivariate analysis, rhTPO was associated with a significantly lower proportion of platelet recovery, platelet transfusion, and hospitalization due to chemotherapy-induced thrombocytopenia (CIT) than rhIL-11 alone. No significant difference was observed in the time taken to achieve a platelet count of >100 × 109/L and chemotherapy dose reduction due to CIT among the different thrombopoietic agents. The outcomes of thrombocytopenia in 170 patients who received targeted therapy and/or immunotherapy are also summarized. The results show that the proportion of platelet recovery was similar among the different thrombopoietic agents. No new safety signals related to thrombopoietic agents were observed in this study. A higher proportion of physicians preferred to continue treatment with TPO-RA alone than with rhTPO and rhIL-11. CONCLUSIONS: This survey provides an overview of CTIT and the application of various thrombopoietic agents throughout China. Comparison of monotherapy with rhIL-11, rhTPO, and TPO-RA requires further randomized clinical trials. The appropriate application for thrombopoietic agents should depend on the pretreatment of platelets, treatment variables, and risk of bleeding. PLAIN LANGUAGE SUMMARY: To provide an overview of the outcome of cancer treatment-induced thrombocytopenia in China, our cross-sectional study analyzed 1437 cases treated with different thrombopoietic agents. Most of the patients were treated with recombinant interleukin 11 (rhIL-11) and recombinant thrombopoietin (rhTPO). rhTPO was associated with a significantly lower proportion of platelet recovery and platelet transfusion compared with rhIL-11.

Evidence of cure for extranodal nasal-type natural killer/T-cell lymphoma with current treatment: an analysis of the CLCG database.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.

Outcome and risk prediction of early progression in patients with extranodal natural killer/T cell lymphoma from the CLCG study.

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.

RIG-I Promotes Tumorigenesis and Confers Radioresistance of Esophageal Squamous Cell Carcinoma by Regulating DUSP6.

We investigated the expression and biological function of retinoic acid inducible gene I (RIG-I) in esophageal squamous cell carcinoma (ESCC). Materials and methods: An immunohistochemical analysis was performed on 86 pairs of tumor tissue and adjacent normal tissue samples of patients with ESCC. We generated RIG-I-overexpressing ESCC cell lines KYSE70 and KYSE450, and RIG-I- knockdown cell lines KYSE150 and KYSE510. Cell viability, migration and invasion, radioresistance, DNA damage, and cell cycle were evaluated using CCK-8, wound-healing and transwell assay, colony formation, immunofluorescence, and flow cytometry and Western blotting, respectively. RNA sequencing was performed to determine the differential gene expression between controls and RIG-I knockdown. Tumor growth and radioresistance were assessed in nude mice using xenograft models. RIG-I expression was higher in ESCC tissues compared with that in matched non-tumor tissues. RIG-I overexpressing cells had a higher proliferation rate than RIG-I knockdown cells. Moreover, the knockdown of RIG-I slowed migration and invasion rates, whereas the overexpression of RIG-I accelerated migration and invasion rates. RIG-I overexpression induced radioresistance and G2/M phase arrest and reduced DNA damage after exposure to ionizing radiations compared with controls; however, it silenced the RIG-I enhanced radiosensitivity and DNA damage, and reduced the G2/M phase arrest. RNA sequencing revealed that the downstream genes DUSP6 and RIG-I had the same biological function; silencing DUSP6 can reduce the radioresistance caused by the overexpression of RIG-I. RIG-I knockdown depleted tumor growth in vivo, and radiation exposure effectively delayed the growth of xenograft tumors compared with the control group. RIG-I enhances the progression and radioresistance of ESCC; therefore, it may be a new potential target for ESCC-targeted therapy.

The value of CT radiomics features to predict visceral pleural invasion in ≤3 cm peripheral type early non-small cell lung cancer.

OBJECTIVE: To investigate predictive value of CT-based radiomics features on visceral pleural invasion (VPI) in ≤3.0 cm peripheral type early non-small cell lung cancer (NSCLC). METHODS: A total of 221 NSCLC cases were collected. Among them, 115 are VPI-positive and 106 are VPI-negative. Using a stratified random sampling method, 70% cases were assigned to training dataset (n = 155) and 30% cases (n = 66) were assigned to validation dataset. First, CT findings, imaging features, clinical data and pathological findings were retrospectively analyzed, the size, location and density characteristics of nodules and lymph node status, the relationship between lesions and pleura (RAP) were assessed, and their mean CT value and the shortest distance between lesions and pleura (DLP) were measured. Next, the minimum redundancy-maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) features were extracted from the imaging features. Then, CT imaging prediction model, texture feature prediction model and joint prediction model were built using multifactorial logistic regression analysis method, and the area under the ROC curve (AUC) was applied to evaluate model performance in predicting VPI. RESULTS: Mean diameter, density, fractal relationship with pleura, and presence of lymph node metastasis were all independent predictors of VPI. When applying to the validation dataset, the CT imaging model, texture feature model, and joint prediction model yielded AUC = 0.882, 0.824 and 0.894, respectively, indicating that AUC of the joint prediction model was the highest (p < 0.05). CONCLUSION: The study demonstrates that the joint prediction model containing CT morphological features and texture features enables to predict the presence of VPI in early NSCLC preoperatively at the highest level.

MRI-based radiomics and ADC values are related to recurrence of endometrial carcinoma: a preliminary analysis.

BACKGROUND: To identify predictive value of apparent diffusion coefficient (ADC) values and magnetic resonance imaging (MRI)-based radiomics for all recurrences in patients with endometrial carcinoma (EC). METHODS: One hundred and seventy-four EC patients who were treated with operation and followed up in our institution were retrospectively reviewed, and the patients were divided into training and test group. Baseline clinicopathological features and mean ADC (ADCmean), minimum ADC (ADCmin), and maximum ADC (ADCmax) were analyzed. Radiomic parameters were extracted on T2 weighted images and screened by logistic regression, and then a radiomics signature was developed to calculate the radiomic score (radscore). In training group, Kaplan-Meier analysis was performed and a Cox regression model was used to evaluate the correlation between clinicopathological features, ADC values and radscore with recurrence, and verified in the test group. RESULTS: ADCmean showed inverse correlation with recurrence, while radscore was positively associated with recurrence. In univariate analyses, FIGO stage, pathological types, myometrial invasion, ADCmean, ADCmin and radscore were associated with recurrence. In the training group, multivariate Cox analysis showed that pathological types, ADCmean and radscore were independent risk factors for recurrence, which were verified in the test group. CONCLUSIONS: ADCmean value and radscore were independent predictors of recurrence of EC, which can supplement prognostic information in addition to clinicopathological information and provide basis for individualized treatment and follow-up plan.

Body Composition Changes in Hepatocellular Carcinoma: Prediction of Survival to Transcatheter Arterial Chemoembolization in Combination With Clinical Prognostic Factors.

Treatment-related toxicities and decreased levels of patient performance during cancer therapy might contribute to body composition changes (BCC) and thereby impact outcomes. This study investigated the association between BCC during transcatheter arterial chemoembolization (TACE) and outcome in patients with hepatocellular carcinoma (HCC), and developed a nomogram for predicting survival in combination with clinical prognostic factors (CPF). Pretreatment and posttreatment computed tomography (CT) images of 75 patients with HCC who were treated between 2015 and 2018 were analyzed. The bone mineral density (BMD), cross-sectional area of paraspinal muscles (CSAmuscle), subcutaneous fat area (SFA), and visceral fat area (VFA) were measured from two sets of CT images. Count the changes in body composition during treatment and sort out the CPF of patients. Using cox regression models, CSAmuscle change, SFA change, VFA change, child-push class, and portal vein thrombosis were independent prognostic factors for overall survival (OS) (HR=5.932, 2.384, 3.140, 1.744, 1.794, respectively. P < 0.05). Receiver operating characteristic curves (ROCs) showed the prediction model combination of BCC and CPF exhibited the highest predictive performance (AUC=0.937). Independent prognostic factors were all contained into the prognostic nomogram, the concordance index (C-index) of prognostic nomogram was 0.787 (95% CI, 0.675-0.887). Decision curve analysis (DCA) demonstrated that the prognostic nomogram was clinically useful. Nomogram-based risk classification systems were also constructed to facilitate risk stratification in HCC for optimization of clinical management. In conclusion, we identified CSAmuscle change, SFA change, VFA change, Child-Pugh class, and portal vein thrombosis were independent prognostic factors for HCC. The prognostic nomogram with a combination of BCC and CPF that can be applied in the individualized prediction of survival in patients with HCC after TACE.

EphA5 knockdown enhances the invasion and migration ability of esophageal squamous cell carcinoma via epithelial-mesenchymal transition through activating Wnt/ß-catenin pathway.

BACKGROUND: The erythropoietin-producing hepatocellular (Eph) receptor A5 (EphA5) has been found to be overexpressed in some malignant tumors and is associated with disease prognosis. However, the role of EphA5 in esophageal squamous cell carcinoma (ESCC) is not clear. METHODS: In the present study, we measured the expression of EphA5 in ESCC tissues and cell lines including KYSE150 and KYSE450 cells. siRNA transfection was used to interfere with EphA5 expression in ESCC cell lines. Cell viability, colony formation, scratch and invasion assays were performed to explore the roles of EphA5 in ESCC cell lines. Flow cytometry analysis was performed to investigate whether EphA5 could affect the cell apoptosis and cycle. The biomarkers related to epithelial-mesenchymal transition (EMT) and molecules associated with Wnt/ß­catenin signaling were also measured by western blot and immunofluorescence. RESULTS: The protein and mRNA expression of EphA5 were significantly higher in fresh ESCC tissues and cell lines compared with normal control groups and human normal esophageal epithelial cells (HEEC). The cell viability assay and colony formation assay revealed that EphA5 knockdown enhanced the proliferation of KYSE150 and KYSE450 cells in vitro. The invasion and migration of ESCC cells were accelerated after EphA5 knockdown. The expression of EMT biomarkers was altered in ESCC cells transfected with siRNA targeting EphA5. Moreover, EphA5 downregulation enhanced the protein levels of ß­catenin and p-GSK-3ßSer9, which play a key role in the Wnt/ß­catenin pathway. CONCLUSIONS: EphA5 knockdown promotes the proliferation of esophageal squamous cell carcinoma,enhances invasion and migration ability via epithelial-mesenchymal transition through activating Wnt/ß­catenin pathway.

Risk-based, response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study.

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.

Risk-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma: analysis from a multicenter study.

The optimal combination and sequence of radiotherapy (RT) and chemotherapy (CT) for extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) are not well-defined. The aim of this study was to create a risk-adapted therapeutic strategy for early-stage NKTCL. A total of 1273 early-stage patients from 10 institutions were reviewed. Patients received CT alone (n = 170), RT alone (n = 253), RT followed by CT (n = 209), or CT followed by RT (n = 641). A comprehensive comparative study was performed using multivariable and propensity score-matched analyses. Early-stage NKTCL was classified as low risk or high risk based on 5 independent prognostic factors (stage, age, performance status, lactate dehydrogenase, primary tumor invasion). RT alone and RT with or without CT were more effective than CT alone (5-year overall survival [OS], 69.6% and 67.7% vs 33.9%, P < .001). For low-risk patients, RT alone achieved a favorable OS (88.8%); incorporation of induction or consolidation CT did not provide additional benefit (86.9% and 86.3%). For high-risk patients, RT followed by CT resulted in superior OS (72.2%) compared with induction CT and RT (58.3%, P = .004) or RT alone (59.6%, P = .017). After adjustment, similar significant differences in OS were still observed between treatment groups. New CT regimens provided limited benefit in early-stage NKTCL. Risk-adapted therapy involving RT alone for low-risk patients and RT consolidated by CT for high-risk patients is a viable, effective strategy for early-stage NKTCL.

The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer.

Chemoresistance prevents the curative cancer therapy, our understanding of which remains inadequate. Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the γ-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.

miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway.

BACKGROUND: Chemoresistance is a major obstacle to the curative cancer chemotherapy and presents one of the most formidable challenges in both research and management of cancer. RESULTS: From the detailed studies of a multi-chemosensitive (5637) versus a chemoresistant (H-bc) bladder cancer cell lines, we showed that miR-193a-3p [GenBank: NR_029710.1] promotes the multi-chemoresistance of bladder cancer cells. We further demonstrated that lysyl oxidase-like 4 (LOXL4) gene [GenBank: NM_032211.6] is a direct target of miR-193a-3p and executes the former's impact on bladder cancer chemoresistance. The Oxidative Stress pathway activity is drastically affected by a forced reversal of miR-193a-3p or LOXL4 levels in cell and may act at the downstream of LOXL4 gene to relay the miR-193a-3p's impact on the multi-chemoresistance in both cultured cells and the tumor xenografts in nude mice. CONCLUSIONS: In addition to a new mechanistic insight, our results provide a set of the essential genes in this newly identified miR-193a-3p/LOXL4/Oxidative Stress axis as the diagnostic targets for a guided anti-bladder cancer chemotherapy.

Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel.

Background: Lung cancer, most of which is non-small cell lung cancer (NSCLC), is the most common tumor in the world, and drug resistance, as a major problem in clinical treatment, has attracted extensive attention. However, the role and mechanism of Targeting protein for Xenopus kinesin-like protein 2 (TPX2), which is highly expressed in NSCLC, is still unclear. Methods: Bioinformatics analysis was used to analyze the relationship between TPX2 and the clinicopathological features of NSCLC. Stable TPX2 overexpression cell lines with were constructed by lentivirus infection, and the effect of TPX2 on proliferation, migration, invasion and chemoresistance to docetaxel was characterized by the CCK8, wound healing, transwell, colony formation assay and FACS. An in vivo lung homing mouse model was used to further confirmed the role of TPX2 on metastasis. Exosomes were extracted by differential centrifugation from the culture supernatant, and their functions were investigated by co-culture with tumor cells. Gene expression was detected via Western blot and real time PCR (RT-qPCR). Results: Overexpression of TPX2 was related to the poor prognosis of NSCLC. Promoted migration, invasion and metastasis, and reduced the sensitivity of NSCLC cells to docetaxel. The abundance of TPX2 can be packaged in vesicles and transported to other cells. In addition, overexpression of TPX2 induced the accumulation of ß-catenin and C-myc. Conclusion: Our findings indicated that intercellular transfer of exosomal TPX2 triggered metastasis and resistance against to docetaxel in lung cancer cells, through activating downstream WNT/ß-catenin signaling pathway.

Nomograms Combining Clinical and Imaging Parameters to Predict Recurrence and Disease-free Survival After Concurrent Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer.

PURPOSES: To investigate the value of nomograms based on clinical prognostic factors (CPF), intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and MRI-derived radiomics in predicting recurrence and disease-free survival (DFS) after concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). METHODS: Retrospective analysis of data from 115 patients with ⅠB-ⅣA cervical cancer who underwent CCRT and had been followed up consistently. All patients were randomized 2:1 into training and validation groups. Pre-treatment IVIM-DWI parameters (ADC-value, D-value, D*-value and f-value) and pre- and post-treatment three-dimensional radiomics parameters (from axial T2WI) of primary lesions were measured. The LASSO algorithm and Logistic regression analysis were used to filter texture features and calculate radiomics score (Rad-score). Multivariate Logistic and Cox regression analysis was used to construct nomograms to predict recurrence and DFS for patients with LACC after CCRT respectively, with internal and external validation. RESULTS: External beam radiotherapy dose, f-value, pre-treatment and post-treatment Rad-score were independent prognostic factors for recurrence and DFS in patients with cervical cancer, forming Model1 and Model2, with OR values of 0.480, 1.318, 3.071, 3.200 and HR values of 0.322, 3.372, 5.138, 7.204. The area under the curve (AUC) of Model1 for predicting recurrence of cervical cancer was 0.977, with internal and external validation C-indexes of 0.977 and 0.962. The AUC for Model2 predicting disease-free survival (DFS) at 1, 3, and 5 years was 0.895, 0.888 and 0.916 respectively, with internal and external C-indexes of 0.860 and 0.892. The decision curves analysis and clinical impact curves further indicate the high predictive efficiency and stability of nomograms. CONCLUSION: The nomograms based on clinical, IVIM-DWI and radiomics parameters have high clinical value in predicting recurrence and DFS of patients with LACC after CCRT and can provide a reference for prognostic assessment and individualized treatment of cervical cancer patients.

LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia.

BACKGROUND: Cancer cachexia is a deadly wasting syndrome that accompanies various diseases (including ~ 50% of cancers). Clinical studies have established that cachexia is not a nutritional deficiency and is linked to expression of certain proteins (e.g., interleukin-6 and C-reactive protein), but much remains unknown about this often fatal syndrome. METHODS: First, cachexia was created in experimental mouse models of lung cancer. Samples of human lung cancer were used to identify the association between the serum lipocalin 2 (LCN2) level and cachexia progression. Then, mouse models with LCN2 blockade or LCN2 overexpression were used to ascertain the role of LCN2 upon ferroptosis and cachexia. Furthermore, antibody depletion of tissue-infiltrating neutrophils (TI-Neu), as well as myeloid-specific-knockout of Lcn2, were undertaken to reveal if LCN2 secreted by TI-Neu caused cachexia. Finally, chemical inhibition of ferroptosis was conducted to illustrate the effect of ferroptosis upon tissue wasting. RESULTS: Protein expression of LCN2 was higher in the wasting adipose tissue and muscle tissues of experimental mouse models of lung cancer cachexia. Moreover, evaluation of lung cancer patients revealed an association between the serum LCN2 level and cachexia progression. Inhibition of LCN2 expression reduced cachexia symptoms significantly and inhibited tissue wasting in vivo. Strikingly, we discovered a significant increase in the number of TI-Neu in wasting tissues, and that these innate immune cells secreted high levels of LCN2. Antibody depletion of TI-Neu, as well as myeloid-specific-knockout of Lcn2, prevented ferroptosis and tissue wasting in experimental models of lung cancer cachexia. Chemical inhibition of ferroptosis alleviated tissue wasting significantly and also prolonged the survival of cachectic mice. CONCLUSIONS: Our study provides new insights into how LCN2-induced ferroptosis functionally impacts tissue wasting. We identified LCN2 as a potential target in the treatment of cancer cachexia.

Clinical characteristics, treatment, and survival of 30 patients with gastrointestinal natural killer/T-cell lymphoma.

BACKGROUND: The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI-ENKTL). METHODS: The clinical data of GI-ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively. RESULTS: A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty-nine patients received chemotherapy, of whom 15 patients received asparaginase-based (ASP-based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP-based regimens, and 50.0% and 25.0% for those treated with non-ASP-based regimens, respectively. The median follow-up was 12.9 months and the 1-year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP-based regimens resulted in a superior 1-year progression-free survival rate compared to non-ASP-based regimens (100.0% vs. 36.0%, p = .07). However, ASP-based regimens did not improve survival in patients at an advanced stage. CONCLUSION: GI-ENKTL still has a poor prognosis, even in the era of modern asparaginase-based treatment strategies.

Characteristics and prognosis of distant metastasis after primary treatment for early-stage extranodal nasal-type natural killer/T-cell lymphoma from the China Lymphoma Collaborative Group database.

This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early-stage extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM-free survival (DMFS) and overall survival (OS). The 5-year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis - distant LN, SST, extracutaneous site, and lymphoma-associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late-onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early-stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

IVIM-DWI and MRI-based radiomics in cervical cancer: Prediction of concurrent chemoradiotherapy sensitivity in combination with clinical prognostic factors.

PURPOSE: To identify the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and magnetic resonance imaging (MRI)-based radiomics combined with clinical prognostic factors (CPF) in predicting concurrent chemoradiotherapy (CCRT) sensitivity of locally advanced cervical cancer (LACC). METHODS: A retrospective analysis of 163 patients (assigned to training or test groups) who underwent conventional MRI and IVIM-DWI before CCRT were divided into sensitive and resistant groups according to their efficacy at 6 months after CCRT. Per-treatment IVIM-DWI parameters (ADC, D, D⁎ and f value), 3D texture features (from axial T2WI) and CPF were measured, analyzed and screened. The prediction model and its nomogram were developed by combining screened parameters and then validated internally and externally. RESULTS: Clinical stage, f value, D value, InverseVariance, SizeZoneNonUniformity, and Minimum were selected to construct prediction model. All parameters except D value showed independent diagnostic value in multivariate Logistic regression analysis and composed prediction model, with AUCs of 0.987 and 0.984 for training and test groups, respectively. The calibration curve (Brier score of 0.042, C-index of 0.987), decision curve and clinical impact curve further demonstrated the reliability and clinical value of prediction model. CONCLUSION: IVIM-DWI, MRI-based radiomics and CPF showed high clinical value in predicting CCRT sensitivity for LACC with better predictive performance when combined.

Corrigendum: Analysis of Anxiety and Depression Status in Patients Undergoing Radiotherapy During the COVID-19 Epidemic.

[This corrects the article DOI: 10.3389/fpsyt.2021.771621.].

Constructing novel molecular subtypes and an 11-gene signature based on pyroptosis signaling for lung adenocarcinoma.

Pyroptosis plays important roles in various cancers. In this study, we focused on lung adenocarcinoma (LUAD) and aimed to develop new molecular subtypes based on pyroptosis signaling. Pyroptosis-related genes were used as a basis to classify molecular subtypes through unsupervised consensus clustering. Gene set enrichment analysis was performed to characterize tumor microenvironment (TME) and functional pathways. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify prognostic genes for establishing a prognostic model. Three molecular subtypes were established with distinct overall survival, TME and enriched pathways. C3 subtype had the longest survival and the highest immune infiltration. 11 prognostic genes were screened to build a prognostic signature for predicting LUAD prognosis. This study emphasized the important role of pyroptosis in LUAD development. Pyroptosis was considered to play critical roles in regulating TME. Moreover, the 11-gene signature could serve as an indicator for predicting LUAD prognosis, and was potential targets for developing targeted drugs.