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Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma and is characterized by heterogeneity in biology and clinical behavior. Mutations in the myeloid differentiation primary response 88 (MYD88) are found in different lymphoproliferative disorders and are associated with variable clinical and prognostic impact. Aim: To investigate the frequency of MYD88 L265P mutation and its clinical impact in a cohort of Egyptian DLBCL patients. Methods: FFPE lymph node samples from 87 DLBCL patients (46 males / 41 females; median age, 58 years) were included and analyzed for MYD88 L265P by an allele-specific PCR. Results: MYD88 L265P mutations were found in 52 patients (59.8%) out of 87 DLBCL cases. Patients with L265 mutation were significantly younger than non-mutated patients (p = 0.022). None of the patients with the L265P mutation showed a significant association with the clinical parameters of DLBCL. Interestingly, MYD88 L265 mutated patients were found to be significantly correlated with HCV infection (p = 0.037). The median follow-up time across the entire cohort was 26 months. Univariate analysis showed that overall survival (OS) was affected by gender, LDH level, and CNS-IPI scoring (p = 0.048, 0.008, and 0.046, respectively), while disease-free survival (DFS) was affected by B symptoms and LDH level (p = < 0.000 and 0.02, respectively). However, the MYD88 mutation status and other prognostic factors showed no association with OS or DFS. Conclusions: Our findings indicate a high frequency of MYD88 L265P mutations in our study population and not associated with prognostic markers or the outcome of the disease. [ABSTRACT FROM AUTHOR]

Simple Summary: We present a case series of 16 patients with pancreatic acinar cell carcinoma treated at our institution for whom available molecular information was evaluated. Most of the patients had metastatic disease, and all patients tested for KRAS mutations were KRAS wild type. Five of 12 patients who underwent DNA damage repair gene testing had germline and/or somatic mutations. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. We also include two additional cases who underwent BostonGene testing, including genomic alterations, RNA expression, and tumor microenvironment (TME) features. One of the two cases was found to have NTRK1 fusion. These findings highlight the need for further investigation of acinar cell carcinoma using larger samples to refine treatment strategies for this rare pancreatic cancer. Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023–2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, one had borderline resectable disease, and one had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (one patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2− metastatic breast cancer. Methods: A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3–4 adverse events were summarized using the random-effects model of a single-arm meta-analysis. Results: This study included 44 arms from 48 publications, with a total sample size of 7881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and an ORR of 40%, whereas PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and an ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events. Conclusion: Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2− metastatic breast cancer in clinical guidelines. [ABSTRACT FROM AUTHOR]

Acute leukemia is a hematological malignancy affecting different organ systems including the eye and orbit through direct infiltration of tissues or secondary to hematological abnormalities. Ophthalmological manifestations in acute leukemia are variable ranging from asymptomatic presentation to serious manifestations that can alter the disease course and treatment. The purpose of this study is to detect the incidence of different ophthalmological manifestations in newly diagnosed acute leukemia patients and to assess the relationship between ocular findings and hematological characteristics and the sequel of these neoplasms. A cross-sectional study with analytical components was conducted on 222 newly diagnosed acute myeloid and acute lymphoblastic leukemia patients who presented at Oncology Center Mansoura University (OCMU) between January 2022 and February 2023. All patients underwent a complete ophthalmic evaluation at Mansoura Ophthalmology Center (MOC). The mean age was 43.45 ± 17.35 years (range, 17–85), and M/F was 137 (61.7%)/85 (38.3%). One-hundred and forty-four (64.9%) had acute myeloid leukemia (AML), and 78 (35.1%) had acute lymphoblastic leukemia (ALL). Ophthalmic manifestations were detected in 96 patients (43.2%). Among them, 4 (1.8%) had poor visual acuity. Retinal hemorrhage (19.8%) and Roth spots (17.1%) were the most common ocular manifestations. Other ophthalmological manifestations observed were orbital involvement (3.2%), ocular motility issues (1.4%), subconjunctival hemorrhage (5.9%), conjunctival chemosis (0.9%),lid swelling (4.1%), lid ecchymosis (3.2%), lagophthalmos (0.5%), lid ptosis (1.8%), retinal venous congestion & tortuosity (4.1%), preretinal hemorrhage (3.2%), vitreous hemorrhage (3.2%), macular affection (2.3%), retinal infiltration (1.8%), exudative retinal detachment (ERD) (1.8%), cotton-wool spots (0.9%), retinal vein occlusion (0.5%), papilledema (2.8%), optic disc infiltration (1.8%), disc pallor (1.8%).AML patients were significantly associated with a higher frequency of ocular affection, retinal hemorrhages, and Roth spots (P 0.028, 0.003, and 0.046, respectively) compared to ALL patients. Retinal hemorrhage was statistically significantly associated with anemia (P 0.021). Ophthalmological manifestations of acute leukemia are heterogeneous; they can be detected at initial presentations or relapse. Some manifestations are asymptomatic, others can affect visual acuity or even alter the disease course. Cooperation between ophthalmologists and haemato-oncologists is crucial for recognizing ocular involvement and disease management. [ABSTRACT FROM AUTHOR]

Mohs Micrographic Surgery (MMS) for treatment of melanoma offers several advantages over wide local excision (WLE), including complete histologic margin evaluation, same-day resection and closure, and sparing of healthy tissue in critical anatomic sites. Recently, a large volume of clinical data demonstrating efficacy in MMS treatment of melanoma was published, leading to emerging patient safety considerations of incurred treatment costs, risk of tumor upstaging, and failure of care coordination for sentinel lymph node biopsy (SLNB). MMS offers a safe, effective, and value-based treatment for both melanoma in situ (MIS) and invasive melanoma (IM), particularly with immunohistochemistry use on frozen sections. Compared to wide local excision, MMS treatment demonstrates similar or improved outcomes for local tumor recurrence, melanoma-specific survival, and overall survival at long-term follow-up. Tumor upstaging risk is low, and if present, alteration to clinical management is minimal. Discussion of SLNB for eligible head and neck IM cases should be done prior to MMS. Though challenging, successful multidisciplinary coordination of SLNB with MMS has been demonstrated. Herein, we provide a detailed clinical review of evidence for MMS treatment of cutaneous melanoma and offer recommendations to address current controversies surrounding the evolving paradigm of surgical management for both MIS and invasive melanoma (IM). [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the clinicopathological and prognostic significance of preoperative serum creatine kinase (CK) levels in colorectal cancer. Methods: This study analyzed 1169 patients with colorectal cancer at stages 0 (n = 35), I (n = 301), II (n = 456), III (n = 339), and IV (n = 38). The CK cut-off value was 52 U/L to predict recurrence based on receiver operative characteristics curve. Clinicopathological factors were compared between the low (< 52 U/L) and high CK groups (≥ 52 U/L). The multivariate analysis evaluated relapse-free survival (RFS) and overall survival (OS) following CK status. Results: The female sex, elderly age (≥ 75), deep tumor (pT4), and carcinoembryonic antigen (+) were independently associated with low CK status. The recurrent rate was significantly higher in the low CK group than in the high CK group (19.1% vs. 11.7%, p < 0.001). Elderly age, pT4, pN (+), preoperative carbohydrate antigen (CA) 19-9 (+), and low CK status were independent risk factors for RFS. Elderly age, pT4, pN (+), preoperative CA19-9 (+), and low CK status were independent risk factors for OS. Conclusion: Preoperative low CK status was associated with deep tumors and was a poor prognostic factor in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: After receiving neoadjuvant chemoradiation, the number of examined lymph nodes in resectable gastroesophageal cancer (GEC) will decrease, this may not accurately determine the N staging. So our study evaluates the clinical significance of a new staging model based on the logarithmic odds of positive lymph nodes (LODDS) in patients with GEC after receiving neoadjuvant chemoradiation. Methods: A total of 1 130 patients with pathologically diagnosed GEC who received neoadjuvant chemoradiation from 2004 to 2019 included in the National Cancer Institute Surveillance, Epidemiology, and Results (SEER) database were selected for analysis. Lymph nodes were staged according to the AJCC TNM staging system (eighth edition) and LODDS. Patient prognosis across the two systems were evaluated by the Kaplan–Meier method, differences in node staging were evaluated by the Akaike information criterion and Bayesian information criterion. In addition, 914 patients from our center were externally validated. Results: Compared to the traditional TNM staging system, the new TLODDSM staging system was comprised of stage I, stage II, stage IIIA, stage IIIB, and stage IVA, and decision curve analysis showed that the new staging system had higher benefits for different decision thresholds than the old staging system. The Akaike information criterion and Bayesian information criterion of the new staging system was lower than those of the old staging system, indicating the sensitivity of the TLODDSM staging system for predicting the prognosis of patients was higher. In addition, stage-IIIB or -IVA patients in the new staging system benefited from adjuvant chemotherapy. The externally validated data from our center supported this conclusion. Conclusions: Compared to the TNM staging system, the TLODDSM staging system has significant advantages in predicting prognosis of patients with GEC who have completed neoadjuvant chemoradiation, guiding the adjuvant chemotherapy for patients. [ABSTRACT FROM AUTHOR]

A high baseline NLR is associated with a poor prognosis of immunotherapy in patients with advanced HCC. As anti-tumour immune activation takes time, early dynamic changes in NLR may serve as a biomarker for predicting immunotherapy response. We conducted a retrospective study in which we enrolled 209 patients with aHCC who received ICIs (training cohort: N = 121, validation cohort: N = 88). In the training cohort, we categorized the patients based on the early changes in their NLR. Specifically, we defined patients as NLR Stable-Responder, NLR Responder and NLR Non-Responder. We compared the outcomes of these three patient groups using survival analysis. Additionally, we shortened the observation period to 6 weeks and validated the findings in the validation cohort. In the training cohort, early dynamic changes in NLR (HR 0.14, 95%CI 0.03–0.65, p = 0.012, HR 0.19, 95%CI 0.07–0.54, p = 0.002; HR 0.21, 95%CI 0.10–0.42, p < 0.001, HR 0.40, 95%CI 0.23–0.69, p = 0.001), PD-L1 < 1% (HR 5.36, 95%CI 1.12–25.66, p = 0.036; HR 2.98, 95%CI 1.51–5.91, p = 0.002) and MVI (HR 3.52, 95%CI 1.28–9.69, p = 0.015; HR 1.99, 95%CI 1.14–3.47, p = 0.015) were identified as independent predictors of OS and PFS. In the validation cohort, when the observation period was reduced to 6 weeks, early NLR changes still have predictive value. Early dynamic changes in NLR may be an easily defined, cost-effective, non-invasive biomarker to predict aHCC response to ICIs. [ABSTRACT FROM AUTHOR]

Introduction: Allogeneic hematopoietic cell transplantation (alloHCT) possessed direct cytotoxicity and graft-versus-multiple myeloma effect (GvMM). Growing trials have shown survival benefits of performing alloHCT in both newly diagnosed and relapsed MM. Methods: We aimed to provide a comprehensive analysis in the recent 10 years to verify the efficacy and survival outcome of alloHCT inMMpatients. A total of 61 studies which provide data between 14/04/2013 and 14/04/2023 and a total of 15,294 data from MM patients who had undergone alloSCT were included in our study. The best response rates (CR, VGPR, PR) and survival outcomes (1-, 2-, 3-,5-, and 10-year OS, PFS, NRM) were assessed. We further conducted metaanalysis in the NDMM/frontline setting and RRMM/salvage setting independently. Results: The pooled estimate CR, VGPR, and PR rates were 0.45, 0.21, and 0.24, respectively. The pooled estimates of 1-, 2-, 3-, 5-, and 10-year OS were 0.69, 0.57, 0.45, 0.45, and 0.36, respectively; the pooled estimates of 1-, 2-, 3-, 5-, and 10-year PFS were 0.47, 0.35, 0.24, 0.25, and 0.28, respectively; and the pooled estimates of 1-, 2-, 3-, 5-, and 10-year NRM were 0.16, 0.21, 0.16, 0.20, and 0.15, respectively. In the NDMM/upfront setting, the pooled estimate CR rate was 0.54, and those for 5-year OS, PFS, and NRM were 0.69, 0.40, and 0.11, respectively. In a relapsed setting, the pooled estimate CR rate was 0.31, and those for 5-year OS, PFS, and NRM were 0.24, 0.10, and 0.15, respectively. Discussion: Our results showed constant OS, PFS, and NRM from the third year onwards till the 10th year, suggesting that alloSCT has sustained survival benefits. Good response rate and promising survival outcome were observed in the NDMM/frontline setting. Conclusion: Although comparing with other treatments, alloSCT had a lower response rate and poorer short-term survival outcome, long-term follow-up could reveal survival benefits of alloSCT in MM patients. [ABSTRACT FROM AUTHOR]

Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role. Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammationrelated mediating variables in the causal relationship. Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-tohip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship. Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods: We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results: In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions: This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS. [ABSTRACT FROM AUTHOR]

Operator syndrome is a common and predictable constellation of interrelated medical and psychiatric conditions and social and functional impairments experienced by special operations forces. Nurses in all settings should be aware of this emerging trend among veterans they encounter in practice so they may identify and intervene using evidence-based approaches and effect a positive outcome. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the correlation between a novel integrated inflammatory marker: The inflammation-combined prognostic index (ICPI), combining NLR, PLR, and MLR, with the clinicopathological characteristics and overall survival (OS) of gastric cancer (GC). Patients and Methods: Data from 876 patients with GC were retrospectively analyzed from January 1, 2017, to April 30, 2023. PSM was employed to mitigate confounding factors between groups. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff value. Univariate, LASSO, and multivariate regression analyses were executed. Subsequently, a nomogram for predicting OS was developed and validated. Results: The cohort with a poor prognosis exhibited significantly elevated levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and ICPI (P< 0.001). Similarly, higher levels of NLR, PLR, MLR, and ICPI were associated with a poorer prognosis (P< 0.001). Following regression analysis, ICPI, T-stage, lymph node ratio (LNR), and primary site were identified as independent risk factors affecting OS. A nomogram was constructed based on these factors to predict 1-, 3-, and 5-year OS, yielding C-indexes of 0.8 and 0.743 for the training and validation sets, respectively. The calibration curves demonstrated close alignment between predicted and actual results, indicating high predictive accuracy. Moreover, the decision curve underscored the practical utility of the model. Conclusion: The new inflammatory parameter ICPI integrates NLR, PLR and MLR. The ICPI-based nomogram and web calculator accurately predict OS in patients with GC. [ABSTRACT FROM AUTHOR]

Abstract Background After receiving neoadjuvant chemoradiation, the number of examined lymph nodes in resectable gastroesophageal cancer (GEC) will decrease, this may not accurately determine the N staging. So our study evaluates the clinical significance of a new staging model based on the logarithmic odds of positive lymph nodes (LODDS) in patients with GEC after receiving neoadjuvant chemoradiation. Methods A total of 1 130 patients with pathologically diagnosed GEC who received neoadjuvant chemoradiation from 2004 to 2019 included in the National Cancer Institute Surveillance, Epidemiology, and Results (SEER) database were selected for analysis. Lymph nodes were staged according to the AJCC TNM staging system (eighth edition) and LODDS. Patient prognosis across the two systems were evaluated by the Kaplan–Meier method, differences in node staging were evaluated by the Akaike information criterion and Bayesian information criterion. In addition, 914 patients from our center were externally validated. Results Compared to the traditional TNM staging system, the new TLODDSM staging system was comprised of stage I, stage II, stage IIIA, stage IIIB, and stage IVA, and decision curve analysis showed that the new staging system had higher benefits for different decision thresholds than the old staging system. The Akaike information criterion and Bayesian information criterion of the new staging system was lower than those of the old staging system, indicating the sensitivity of the TLODDSM staging system for predicting the prognosis of patients was higher. In addition, stage-IIIB or -IVA patients in the new staging system benefited from adjuvant chemotherapy. The externally validated data from our center supported this conclusion. Conclusions Compared to the TNM staging system, the TLODDSM staging system has significant advantages in predicting prognosis of patients with GEC who have completed neoadjuvant chemoradiation, guiding the adjuvant chemotherapy for patients.

Reactive oxygen species (ROS) are widely regarded as signaling molecules and play essential roles in various cellular processes, but when present in excess, they can lead to oxidative stress (OS). Growing evidence suggests that the OS plays a critical role in the pathogenesis of HIV infection and is associated with several comorbidities in HIV-infected individuals. ROS, generated both naturally during mitochondrial oxidative metabolism and as a response to various cellular processes, can trigger host antiviral responses but can also promote viral replication. While the multifaceted roles of ROS in HIV pathophysiology clearly need more investigation, this review paper unravels the mechanisms of OS generation in the context of HIV infections, offering insights into HIV viral protein-mediated and antiretroviral therapy-generated OS. Though the viral protein Tat is significantly attributed to the endogenous cellular increase in ROS post HIV infection, this paper sums up the contribution of other viral proteins in HIV-mediated elicitation of ROS. Given the investigations recognizing the significant role of ROS in the onset and progression of diverse pathologies, the paper also explores the critical function of ROS in the mediation of an of array of pathologies associated with HIV infection and retroviral therapy. HIV patients are observed with disruption to the antioxidant defense system, the antioxidant therapy is gaining focus as a potential therapeutic intervention and is well discussed. While ROS play a significant role in the HIV scenario, further exploratory studies are imperative to identifying alternative therapeutic strategies that could mitigate the toxicities and pathologies associated with ART-induced OS.

Abstract A high baseline NLR is associated with a poor prognosis of immunotherapy in patients with advanced HCC. As anti-tumour immune activation takes time, early dynamic changes in NLR may serve as a biomarker for predicting immunotherapy response. We conducted a retrospective study in which we enrolled 209 patients with aHCC who received ICIs (training cohort: N = 121, validation cohort: N = 88). In the training cohort, we categorized the patients based on the early changes in their NLR. Specifically, we defined patients as NLR Stable-Responder, NLR Responder and NLR Non-Responder. We compared the outcomes of these three patient groups using survival analysis. Additionally, we shortened the observation period to 6 weeks and validated the findings in the validation cohort. In the training cohort, early dynamic changes in NLR (HR 0.14, 95%CI 0.03–0.65, p = 0.012, HR 0.19, 95%CI 0.07–0.54, p = 0.002; HR 0.21, 95%CI 0.10–0.42, p

Abstract Background Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle. Materials and methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS). Results: A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery. Conclusions: ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.

Abstract Background The molecular mechanisms of osteosarcoma (OS) are complex. In this study, we focused on the functions of melanoma cell adhesion molecule (MCAM), methyltransferase 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in OS development. Methods qRT-PCR assay and western blot assay were performed to determine mRNA and protein expression of MCAM, METTL3, IGF2BP1 and YY1. MTT assay and colony formation assay were conducted to assess cell proliferation. Cell apoptosis, invasion and migration were evaluated by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Methylated RNA Immunoprecipitation (MeRIP), dual-luciferase reporter, Co-IP, RIP and ChIP assays were performed to analyze the relationships of MCAM, METTL3, IGF2BP1 and YY1. The functions of METTL3 and MCAM in tumor growth were explored through in vivo experiments. Results MCAM was upregulated in OS, and MCAM overexpression promoted OS cell growth, invasion and migration and inhibited apoptosis. METTL3 and IGF2BP1 were demonstrated to mediate the m6A methylation of MCAM. Functionally, METTL3 or IGF2BP1 silencing inhibited OS cell progression, while MCAM overexpression ameliorated the effects. Transcription factor YY1 promoted the transcription level of METTL3 and regulated METTL3 expression in OS cells. Additionally, METTL3 deficiency suppressed tumor growth in vivo, while MCAM overexpression abated the effect. Conclusion YY1/METTL3/IGF2BP1/MCAM axis aggravated OS development, which might provide novel therapy targets for OS.

Background: Retinoblastoma (RB) is a rare primary malignant tumor primarily affecting children. Our study aims to compare the overall survival (OS) between pediatric and adult RB patients and establish a predictive model for adult RB patients' OS to assist clinical decision-making. Methods: This study retrospectively analyzed data from 1938 RB patients in the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2000 to 2015. Propensity score matching (PSM) ensured balanced characteristics between pediatric and adult groups. A Cox proportional hazards regression model was used to assess prognostic factors, and selected variables were utilized to construct a predictive survival model. The Nomogram model's performance was evaluated through the C-index, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). Results: Following PSM, adult RB patients had lower OS compared to pediatric RB patients. Independent prognostic factors for adult RB OS included age, gender, disease stage, radiation therapy, income, and diagnosis confirmation. In the training cohort, the Nomogram achieved a C-index for OS of 0.686 and accurately predicted 2-year, 3-year, and 5-year OS with AUC values of 0.672, 0.680, and 0.660, respectively. The C-index, time-dependent ROC curves, calibration curves, and DCA in both training and validation cohorts confirmed the Nomogram's excellent performance. Conclusion: In this study, adult RB patients have worse OS than pediatric RB patients. Consequently, we constructed a Nomogram to predict the risk for adult RB patients. The Nomogram demonstrated good accuracy and reliability, making it suitable for widespread application in clinical practice to assist healthcare professionals in assessing patients’ prognoses.

Simple Summary: Y-90 Selective Internal Radiotherapy (SIRT) uses injectable radioactive microspheres to treat inoperable liver metastases. It is poorly understood how the effective local control of small-volume metastatic disease with Y-90 SIRT may improve patient survival. Here, we demonstrate that failure to locally control liver metastases with ytrritum-90 (Y-90) SIRT is associated with worse 1-year overall survival for patients with ≤5 metastases, emphasizing the importance of disease control in those with early metastatic disease. Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients. [ABSTRACT FROM AUTHOR]

Background: The molecular mechanisms of osteosarcoma (OS) are complex. In this study, we focused on the functions of melanoma cell adhesion molecule (MCAM), methyltransferase 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) in OS development. Methods: qRT-PCR assay and western blot assay were performed to determine mRNA and protein expression of MCAM, METTL3, IGF2BP1 and YY1. MTT assay and colony formation assay were conducted to assess cell proliferation. Cell apoptosis, invasion and migration were evaluated by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Methylated RNA Immunoprecipitation (MeRIP), dual-luciferase reporter, Co-IP, RIP and ChIP assays were performed to analyze the relationships of MCAM, METTL3, IGF2BP1 and YY1. The functions of METTL3 and MCAM in tumor growth were explored through in vivo experiments. Results: MCAM was upregulated in OS, and MCAM overexpression promoted OS cell growth, invasion and migration and inhibited apoptosis. METTL3 and IGF2BP1 were demonstrated to mediate the m6A methylation of MCAM. Functionally, METTL3 or IGF2BP1 silencing inhibited OS cell progression, while MCAM overexpression ameliorated the effects. Transcription factor YY1 promoted the transcription level of METTL3 and regulated METTL3 expression in OS cells. Additionally, METTL3 deficiency suppressed tumor growth in vivo, while MCAM overexpression abated the effect. Conclusion: YY1/METTL3/IGF2BP1/MCAM axis aggravated OS development, which might provide novel therapy targets for OS. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures. A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, p < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, p < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities. Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication. [ABSTRACT FROM AUTHOR]

Background: Tumor-associated macrophages (TAMs) constitute a plastic and heterogeneous cell population of the tumor microenvironment (TME) that can regulate tumor proliferation and support resistance to therapy, constituting promising targets for the development of novel anticancer agents. Our previous results suggest that SHP2 plays a crucial role in reprogramming the phenotype of TAMs. Thus, we hypothesized that SHP2+ TAM may predict the treatment efficacy of non-small cell lung cancer NSCLC patients as a biomarker. Methods: We analyzed cancer tissue samples from 79 NSCLC patients using multiplex fluorescence (mIF) staining to visualize various SHP-2+ TAM subpopulations (CD68+SHP2+, CD68+ CD86+, CD68 + 206+, CD68+ CD86+SHP2+, CD68+ CD206+SHP2+) and T cells (CD8+ Granzyme B +) of immune cells. The immune cells proportions were quantified in the tumor regions (Tumor) and stromal regions (Stroma), as well as in the overall tumor microenvironment (Tumor and Stroma, TME). The analysis endpoint was overall survival (OS), correlating them with levels of cell infiltration or effective density. Cox regression was used to evaluate the associations between immune cell subsets infiltration and OS. Correlations between different immune cell subsets were examined by Spearman's tests. Results: In NSCLC, the distribution of different macrophage subsets within the TME, tumor regions, and stroma regions exhibited inconsistency. The proportions of CD68+ SHP2+ TAMs (P < 0.05) were higher in tumor than in stroma. And the high infiltration of CD68+SHP2+ TAMs in tumor areas correlated with poor OS (P < 0.05). We found that the expression level of SHP2 was higher in M2-like macrophages than in M1-like macrophages. The CD68+SHP2+ subset proportion was positively correlated with the CD68+CD206+ subset within TME (P < 0.0001), tumor (P < 0.0001) and stroma (P < 0.0001). Conclusions: The high infiltration of CD68+SHP2+ TAMs predict poor OS in NSCLC. Targeting SHP2 is a potentially effective strategy to inhibit M2-phenotype polarization. And it provides a new thought for SHP2 targeted cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the prognostic outcomes in mRCC patients receiving second‐line TKI following first‐line IO combination therapy. Methods: This study retrospectively included 243 mRCC patients receiving second‐line TKI after first‐line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO–IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO–TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients. Results: In the IO–IO and IO–TKI groups, the objective response rates to second‐line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second‐line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non‐CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c‐indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively. Conclusions: There were no significant differences in the prognostic outcomes after introducing second‐line TKI between the IO–IO and IO–TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second‐line TKI, irrespective of first‐line IO combination therapies. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB) is a rare primary malignant tumor primarily affecting children. Our study aims to compare the overall survival (OS) between pediatric and adult RB patients and establish a predictive model for adult RB patients' OS to assist clinical decision-making. This study retrospectively analyzed data from 1938 RB patients in the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2000 to 2015. Propensity score matching (PSM) ensured balanced characteristics between pediatric and adult groups. A Cox proportional hazards regression model was used to assess prognostic factors, and selected variables were utilized to construct a predictive survival model. The Nomogram model's performance was evaluated through the C-index, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). Following PSM, adult RB patients had lower OS compared to pediatric RB patients. Independent prognostic factors for adult RB OS included age, gender, disease stage, radiation therapy, income, and diagnosis confirmation. In the training cohort, the Nomogram achieved a C-index for OS of 0.686 and accurately predicted 2-year, 3-year, and 5-year OS with AUC values of 0.672, 0.680, and 0.660, respectively. The C-index, time-dependent ROC curves, calibration curves, and DCA in both training and validation cohorts confirmed the Nomogram's excellent performance. In this study, adult RB patients have worse OS than pediatric RB patients. Consequently, we constructed a Nomogram to predict the risk for adult RB patients. The Nomogram demonstrated good accuracy and reliability, making it suitable for widespread application in clinical practice to assist healthcare professionals in assessing patients' prognoses. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a common primary bone tumor in children and adolescents. Circular RNA (circRNA)-IARS acts as an oncogene in multiple human tumors. However, the circ-IARS function in OS is unclear. This research aimed to elucidate the roles and mechanisms of circ-IARS in OS. In this study, circ-IARS expressions were raised in OS tissues and cells. circ-IARS expressions were closely related to clinical stage and distant metastasis. Furthermore, overall survival rates were reduced in OS patients with high circ-IARS levels. Also, silencing circ-IARS weakened OS cell proliferation and invasion, yet enhanced cell ferroptosis. Mechanistically, circ-IARS targeted miR-188-5p to regulate RAB14 expressions in OS cells. Moreover, circ-IARS knockdown repressed OS cell proliferation, invasion, and induced ferroptosis, yet these impacts were abolished by co-transfection with anti-miR-188-5p or pcDNA-RAB14. Meanwhile, interference with circ-IARS reduced OS cell proliferation, and decreased RAB14 (a member of the RAS oncogene family), GPX4, and xCT (crucial ferroptosis regulators) expressions in vivo. In conclusion, circ-IARS facilitated OS progression via miR-188-5p/RAB14. [ABSTRACT FROM AUTHOR]

Osteosarcoma stands as the most prevalent bone tumor, characterized by a heightened tendency for local recurrence and distant metastasis, resulting in a bleak prognosis. Presently, there exists a shortage of novel markers to effectively determine the prognosis of osteosarcoma patients. Recent research indicates that hematological markers partially mirror an individual’s microenvironment, offering potential insights into predicting patient prognosis. However, prior studies predominantly focused on the prognostic significance of singular hematological indices, failing to comprehensively represent the tumor microenvironment of patients. In our investigation, we meticulously gathered data on 22 hematological and electrolyte markers, utilizing LASSO Cox regression analysis to devise an Electrolyte Prognostic Scoring System (EPSS). The EPSS encompasses various indicators, including immunity, inflammation, coagulation, and electrolyte levels. Our findings indicate that the EPSS stands as an independent prognostic factor for overall survival among osteosarcoma patients. It serves as a valuable addition to clinical characteristics, adept at discerning high-risk patients from those deemed clinically low-risk. Furthermore, EPSS-based nomograms demonstrate commendable predictive capabilities.

Background: Glioblastoma (GBM) is a very common primary malignant tumor of the central nervous system (CNS). Aging, macrophage, autophagy, and methylation related genes are hypothesized to be crucial to its pathogenesis. In this study, we aimed to explore the role of these genes in the prognosis of GBM. Methods: The RNA sequence (RNA-seq) and clinical information were downloaded from The Cancer Genome Atlas database (TCGA) and the Chinese Glioma Genome Atlas database (CGGA). We performed univariate and least absolute shrinkage and selection operator (LASSO) multivariate Cox regression analysis to identify risk signatures related to overall survival (OS). We further developed a nomogram to predict individual outcomes. In addition, the immune microenvironment was analyzed by CIBERSORT. Results: 256 differentially expressed genes (DEGs) were obtained based on aging, macrophage, autophagy, and methylation related genes between GBM samples and normal tissues in TCGA-GBM cohort. We identified five optimal risk signatures with prognostic values in TCGA-GBM cohort and established a prognostic risk score model. The validity of the model was verified in the CGGA cohort and Huanhu cohort. Finally, we constructed a nomogram for clinical application by combining age, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and risk score. Activated NK cells and resting mast cells were highly expressed and memory B cells, plasma cells, resting NK cells, M1 macrophages, and neutrophils exhibited low expression in the high-risk score group. GBM patients with a low-risk score had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score. The risk score of hot tumors was higher than that of the cold tumors. Additionally, 29 genes involved in glucose and lipid metabolism were highly expressed with a high-risk score. 31 metabolism-related pathways were significantly different between high-risk and low-risk groups. Conclusions: We constructed and validated a novel prognostic model for GBM. Aging, macrophage, autophagy, and methylation related genes may serve as prognostic and therapeutic biomarkers. The model developed may assist in guiding treatment for GBM patients. Our research had great significance in accurately predicting the prognosis of GBM and may offer reference for immunotherapy decision for GBM patients.

Background: Doublet platin-chemotherapy was the old standard treatment for different histology types of advanced and metastatic lung cancer (LC) and is still an option for patients who are not eligible for immune checkpoint inhibitors. However, in low- and middle-income countries, chemotherapy, either in monotherapy or in combination with platinum, is still the only accessible option in public institutions. The efficacy of different platin-based chemotherapy in patients with LC who are treatment-naïve is unknown. Methods: In this retrospective study, we selected patients with advanced and metastatic (IIIB-IVB) non-squamous non-small cell LC (NSCLC), squamous NSCLC, and lung neuroendocrine tumours (small cell LC (SCLC), large cell neuroendocrine, and atypical carcinoid) aged beyond 18 years who received first-line chemotherapy (docetaxel, gemcitabine, etoposide, paclitaxel, pemetrexed, and vinorelbine) combined with platinum between January 1, 2013, and December 31, 2022. Within the population with non-squamous NSCLC, squamous NSCLC, and neuroendocrine tumours, progression-free survival (PFS) and overall survival (OS) were the primary assessed endpoints. Hematologic safety was the secondary endpoint. Results: Overall, 611 patients were included. In the group of patients with non-squamous NSCLC (n = 390), there was no statistical difference between subgroups of patients who received first-line platin-chemotherapy. The median PFS was 182 (95 % confidence interval [CI], 167–208) days (hazard ratio for progression: NR [Not Reached]; p = 0.37), and the median OS was 446 (95 % CI, 405–559) days (hazard ratio for death: 1.31; 95 % CI, 0.94 - 1.82; p = 0.1). In the group of patients with squamous NSCLC (n = 149), we note the absence of statistical significance between subgroups of patients who received platin-based chemotherapy. The median PFS was 195 (95 % CI, 142–238; hazard ratio for progression: 1.21, 95 % CI, 0.29–5.02; p = 0.27), while the median OS was 428 (95 % CI, 324–940) days (hazard ratio for death: 1.76; 95 % CI, 0.93 to 3.3; p = 0.32). The absence of significance has been noticed in the neuroendocrine subgroup of patients who received first etoposide-platinum, vinorelbine-platinum, or paclitaxel-platinum (n = 72). The median PFS was 216 (95 % CI, 193–277) days; hazard ratio for progression: 1.74, 95 % CI, 0.41–7.27; p = 0.69, while the median OS was 273 (95 % CI, 241–459) days (hazard ratio for death: 2.95; 95 % CI, 0.4–21.7; p = 0.51). Grade 3–4 neutropenia grade was the predominant adverse event associated with chemotherapy in almost 11 % of patients. Conclusion: Moving forward, treatment strategies must be refined for patients, with an emphasis on increasing the number of patients who can benefit from emergent approaches in order to guarantee a wider, deeper, and longer-lasting outcome.

Increased oxidative stress (OS) and systemic inflammation are key players in the pathophysiology of chronic obstructive pulmonary disease (COPD). We aimed to clarify the effects of synthetic glutathione (GSH) analogue peptides UPF1 and UPF17 on the mRNA levels of enzymes involved in systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs) from patients with acute exacerbation of COPD (AE-COPD) and stable COPD along with non-obstructive smokers and non-smokers. UPF1 and UPF17 increased the expression of enzymes involved in the formation of the antioxidant capacity: superoxide dismutase 1 (SOD1) and the catalytic subunit of glutamyl-cysteine ligase (GCLC) in patients with AE-COPD and stable COPD, but also in non-obstructive smokers and non-smokers. Similarly, both UPF1 and UPF17 increased the expression of inflammatory enzymes poly(ADP-ribose) polymerase-1 (PARP-1), dipeptidyl peptidase 4 (DPP4), and cyclooxygenase-2 (COX-2). Both UPF analogues acted in a gender-dependent manner by increasing the expression of certain anti-inflammatory (histone deacetylase 2 (HDAC2)) and GSH metabolism pathway (SOD1 and GSH reductase (GSR))-related enzymes in females and decreasing them in males. UPF1 and UPF17 are able to increase the expression of the enzymes involved in GSH metabolism and could serve as a lead for designing potential COPD therapies against excessive OS.

Wenying Qiao,1– 5,&ast; Shugui Sheng,1– 3,&ast; Junnan Li,1– 3,&ast; Ronghua Jin,1– 4 Caixia Hu5 1Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Changping Laboratory, Beijing, People’s Republic of China; 5Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghua Jin, Beijing Key Laboratory of Emerging Infectious Diseases, BeijingDitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email ronghuajin@ccmu.edu.cn Caixia Hu, Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China, Email hucaixia1217@126.comPurpose: The aim of the study is to identify and evaluate multifaceted factors impacting the survival of elderly cirrhotic HCC patients following ablation therapy, with the goal of constructing a nomogram to predict their 3-, 5-, and 8-year overall survival (OS).Patients and Methods: A retrospective analysis was conducted on 736 elderly cirrhotic HCC patients who underwent ablation therapy between 2014 and 2022. LASSO regression, random survival forest (RSF), and multivariate Cox analyses were employed to identify independent prognostic factors for OS, followed by the development and validation of a predictive nomogram. Harrell’s concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to assess the performance of the nomogram. The nomogram was finally utilized to stratify patients into low-, intermediate-, and high-risk groups, aiming to assess its efficacy in precisely discerning individuals with diverse overall survival outcomes.Results: Alcohol drinking, tumor number, globulin (Glob) and prealbumin (Palb) were identified and integrated to establish a novel prognostic nomogram. The nomogram exhibited strong discriminative ability with C-indices of 0.723 (training cohort) and 0.693 (validation cohort), along with significant Area Under the Curve (AUC) values for 3-year, 5-year, and 8-year OS in both cohorts (0.758, 0.770, and 0.811 for training cohort; 0.744, 0.699 and 0.737 for validation cohort). Calibration plots substantiated its consistency, while DCA curves corroborated its clinical utility. The nomogram further demonstrated exceptional effectiveness in discerning distinct risk populations, highlighting its robust applicability for prognostic stratification.Conclusion: Our study successfully developed and validated a robust nomogram model based on four key clinical parameters for predicting 3-, 5- and 8-year OS among elderly cirrhotic HCC patients following ablation therapy. The nomogram exhibited a remarkable capability in identifying high-risk patients, furnishing clinicians with invaluable insights for postoperative surveillance and tailored therapeutic interventions.Keywords: hepatocellular carcinoma, HCC, nomogram, LASSO regression, random survival forest, RSF, overall survival, OS

Background: Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. Methods: The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. Results: A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Conclusion: Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop riskadapted therapy for RPLS patients. [ABSTRACT FROM AUTHOR]

Introduction KRAS mutation is observed in up to 30% of non-small-cell lung cancer (NSCLC) cases and is corelated with a poor prognosis. In the cases with KRAS p.G12C mutation and first-line chemotherapy (± immunotherapy) resistance, a targeted drug option is available. Objectives Our study aimed to examine the correlation between first-line chemotherapy agents and treatment response in patients with KRAS-mutated metastatic NSCLC. Materials and Methods Retrospective database searches were performed on cases diagnosed with metastatic NSCLC at our center between January 2019 and December 2021 that were found to be KRAS mutation positive using the next-generation sequencing (NGS) approach. The cases were classified into five subgroups based on the chemotherapy regimens (platinum + gemcitabine, platinum + taxane, platinum + pemetrexed, platinum + vinorelbine, and others). The clinical and demographic data of 41 cases were analyzed retrospectively, and survival analyses were performed using the Kaplan–Meier method. Results Thirty-seven of 41 patients (90.2%) were males, and 27 (65.9%) had adenocarcinoma histology. The most prevalent mutation was KRAS G12C, with 12 cases (29.2%), followed by KRAS G12V, with 9 cases (21.9%). Other mutations were as follows: KRAS G12D 4 (9%), KRAS G13C 3 (7.3%), KRAS G12A 2 (4.8%), KRAS G12R 2 (4.8%), KRAS Q61H 2 (4.8%), KRAS Q61L 2 (4.8%), KRAS V14I 2 (4.8%), KRAS A146T 1 (2.4%), KRAS G13G 1 (2.4%), and KRAS G1C 1 (2.4%). The median progression-free survival (mPFS) for all groups was 4.6 months (95% confidence interval [CI]: 2.7-6.5), and there were no statistically significant differences between the groups (p = 0.121). The median overall survival (mOS) for all groups was 9.3 months (95% CI: 3.8–14.5), and there were no statistically significant differences between the groups (p = 0.805). Conclusions OS and PFS analyses showed no differences between platinum + taxane, platin + pemetrexed, platinum + gemcitabine, and platin + vinorelbine used in first-line treatments for KRAS mutant NSCLC cases. We believe that patient-specific characteristics may be a determining factor in selecting chemotherapy for this patient population. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a complex clonal malignancy that is impacted by both environmental variables and chromosomal anomalies. High tumour load and a poor prognosis are pathologically indicated by elevated white blood cell (WBC) count and lactate dehydrogenase (LDH) values. Objective: This study aimed to assess the clinical significance and prognostic value of serum LDH levels in AML patients. Patients and methods: At the Hematology Unit, Oncology Center, Mansoura University, we performed a retrospective analysis with 40 AML patients (19 males and 21 females) with a mean age of 44.3 ± 15.1 years. Hemoglobin was 8.5 g/dL, platelet count was 32.2 x 109/L, and median WBC was 31.5 x 109/L. Median serum LDH was 731.5 IU/L. The eligible patients had intermediate dose Cytarabine consolidation after receiving standard-intensity induction chemotherapy. Results: AML patients exhibited significantly higher LDH levels compared to healthy controls (215 IU/L; range 107-330) (P<0.001). Higher LDH levels correlated positively with WBC count and were notably associated with age over 60 and WBC > 50x109/L (P < 0.05). Patients whose LDH was higher than the median had an OS of two months, which was significantly shorter (range 1-6 months) versus 6 months (range 1-9 months) for those below the median (P=0.035). Univariable and multivariable analyses confirmed elevated LDH as a poor prognostic indicator for OS (P=0.036; HR=1.007, 95% CI, 1.005-1.011). Conclusion: High serum LDH level at diagnosis is an inexpensive, predictive marker of poor survival outcomes in patients with recently diagnosed AML, underscoring its importance in prognostic assessments. [ABSTRACT FROM AUTHOR]

Introduction: Anlotinib, a novel multi-kinase inhibitor, was found to improve progression-free survival (PFS) in brain metastases. Methods: This paper retrospectively analyzed 26 newly diagnosed or recurrent high-grade gliomas from 2017 to 2022, and the patients received oral anlotinib during concurrent postoperative chemoradiotherapy or after recurrence. Efficacy was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria, and the main study endpoints were PFS at 6 months and overall survival (OS) at 1 year. Results: After the follow-up, until May 2022, 13 patients survived and 13 patients died, with a median follow-up time of 25.6 months. The disease control rate (DCR) was 96.2% (25/26), and the overall response rate (ORR) rate was 73.1% (19/26). The median PFS after oral anlotinib was 8.9 months (0.8--15.1), and the PFS at 6 months was 72.5%. The median OS after oral anlotinib was 12 months (1.6--24.4), and the OS at 12 months was 42.6%. Anlotinib-related toxicities were observed in 11 patients, mostly grades 1--2. In the multivariate analysis, patients with Karnofsky Performance Scale (KPS) above 80 had a highermedian PFS of 9.9months (p = 0.02), and their sex, age, IDH mutation, MGMTmethylation, and whether anlotinib was combined with chemoradiotherapy or maintenance treatment had no effect on PFS. Conclusion: We found that anlotinib combined with chemoradiotherapy in treating high-grade central nervous system (CNS) tumors can prolong PFS and OS and that it was safe. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance has been proven to be associated with renal cell carcinoma (RCC). However, the prognostic value of the triglyceride-glucose (TyG) index, as a marker for insulin resistance (IR), is still unclear. Therefore, we conducted research to explore the prognostic value and the predictive performance of the TyG index in postoperative RCC patients. Methods: A total of 651 postoperative RCC patients from January 2016 to June 2018 were enrolled in the final study. Their clinical and laboratory parameters were collected from medical records and through follow-up by phone. The triglyceride-glucose (TyG) index was calculated as follows: TyG = Ln[TG (mg/dl) × FBG (mg/dL)/2]. The overall survival (OS) and disease-free survival (DFS) were identified as the main outcomes. Results: The TyG index is an independent prognostic factor for OS (HR = 2.340, 95% CI = 1.506 to 3.64, P < 0.001) and DFS (HR = 2.027, 95% CI = 1.347 to 3.051, P < 0.001) in postoperative RCC patients. Kaplan-Meier survival curves of the different TyG index levels showed statistically significant differences in terms of OS and DFS (log-rank test, P < 0.0001). Furthermore, the TyG index was significantly associated with RCC risk factors. Conclusion: The TyG index is significantly associated with RCC survival. The mechanisms responsible for these results may contribute toward the improvement of RCC prognosis and immunotherapy efficacy and the development of new immunotherapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction: Anlotinib, a novel multi-kinase inhibitor, was found to improve progression-free survival (PFS) in brain metastases. Methods: This paper retrospectively analyzed 26 newly diagnosed or recurrent high-grade gliomas from 2017 to 2022, and the patients received oral anlotinib during concurrent postoperative chemoradiotherapy or after recurrence. Efficacy was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria, and the main study endpoints were PFS at 6 months and overall survival (OS) at 1 year. Results: After the follow-up, until May 2022, 13 patients survived and 13 patients died, with a median follow-up time of 25.6 months. The disease control rate (DCR) was 96.2% (25/26), and the overall response rate (ORR) rate was 73.1% (19/26). The median PFS after oral anlotinib was 8.9 months (0.8-15.1), and the PFS at 6 months was 72.5%. The median OS after oral anlotinib was 12 months (1.6-24.4), and the OS at 12 months was 42.6%. Anlotinib-related toxicities were observed in 11 patients, mostly grades 1-2. In the multivariate analysis, patients with Karnofsky Performance Scale (KPS) above 80 had a highermedian PFS of 9.9months (p = 0.02), and their sex, age, IDH mutation, MGMTmethylation, and whether anlotinib was combined with chemoradiotherapy or maintenance treatment had no effect on PFS. Conclusion: We found that anlotinib combined with chemoradiotherapy in treating high-grade central nervous system (CNS) tumors can prolong PFS and OS and that it was safe. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to identify and evaluate multifaceted factors impacting the survival of elderly cirrhotic HCC patients following ablation therapy, with the goal of constructing a nomogram to predict their 3-, 5-, and 8-year overall survival (OS). Patients and Methods: A retrospective analysis was conducted on 736 elderly cirrhotic HCC patients who underwent ablation therapy between 2014 and 2022. LASSO regression, random survival forest (RSF), and multivariate Cox analyses were employed to identify independent prognostic factors for OS, followed by the development and validation of a predictive nomogram. Harrell's concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to assess the performance of the nomogram. The nomogram was finally utilized to stratify patients into low-, intermediate-, and high-risk groups, aiming to assess its efficacy in precisely discerning individuals with diverse overall survival outcomes. Results: Alcohol drinking, tumor number, globulin (Glob) and prealbumin (Palb) were identified and integrated to establish a novel prognostic nomogram. The nomogram exhibited strong discriminative ability with C-indices of 0.723 (training cohort) and 0.693 (validation cohort), along with significant Area Under the Curve (AUC) values for 3-year, 5-year, and 8-year OS in both cohorts (0.758, 0.770, and 0.811 for training cohort; 0.744, 0.699 and 0.737 for validation cohort). Calibration plots substantiated its consistency, while DCA curves corroborated its clinical utility. The nomogram further demonstrated exceptional effectiveness in discerning distinct risk populations, highlighting its robust applicability for prognostic stratification. Conclusion: Our study successfully developed and validated a robust nomogram model based on four key clinical parameters for predicting 3-, 5- and 8-year OS among elderly cirrhotic HCC patients following ablation therapy. The nomogram exhibited a remarkable capability in identifying high-risk patients, furnishing clinicians with invaluable insights for postoperative surveillance and tailored therapeutic interventions. [ABSTRACT FROM AUTHOR]

Numerous clinical trials have demonstrated a significant improvement in recurrence‐free survival among melanoma patients receiving high‐dose interferon‐α, immune checkpoint inhibitors (pembrolizumab, nivolumab), and BRAF/MEK inhibitors (dabrafenib‐trametinib). This study aimed to investigate whether these findings hold true in real‐world conditions for patients with stage III and IV melanoma. In particular, the study explores the efficacy and side effects of adjuvant therapies, focusing on anti‐PD‐1 antibodies and BRAF/MEK inhibitors. While clinical trials have shown comparable efficacy, differences in side‐effect profiles, especially the persistence of immune‐related adverse events with anti‐PD‐1 antibodies, highlight the need for careful consideration in adjuvant settings. In the absence of established biomarkers for guiding adjuvant therapy decisions, it becomes imperative to transparently communicate the advantages and disadvantages of drug administration to patients. The study also delved into the impact of melanoma subtype and BRAF mutation status on the effectiveness of adjuvant therapy, emphasizing the need for further investigation. [ABSTRACT FROM AUTHOR]

Background: The role of microsatellite instability (MSI) and prognosis for stage II-III colorectal cancer (CRC) has been described, but the role of MSI in stage I and IV CRC is controversial. Methods: A total of 2,540 CRC patients were collected from Huzhou Central Hospital, China, from January 2006 to 2016, and 783 cases were excluded. This retrospective study illustrates the correlation between MMR status and prognosis for 1,757 CRC patients as well as the correlation between MSI and prognosis for CRC patients. Two groups were classified as MSI-H and MSI-L&MSS. If the expression of one or more mismatch repair (MMR) proteins was negative, it was considered as microsatellite instability high expression (MSI-H), whereas positive expression was considered as microsatellite instability low expression and microsatellite stability (MSI-L&MSS), as assessed by correlation analyses. Overall and disease-free survival were analyzed using the Kaplan-Meier method. Univariable and multivariable analyses were conducted using Cox regression. Results: Preoperative serum S-CEA, positive lymph, tumor size, pathologic tumor (Pt) status, node (N) stage, differentiation, chemotherapy, and the 8th Edition of the American Joint Committee on Cancer (AJCC-8) were significantly correlated with MSI (P=0.028, 0.037, 0.019, 0.007, 0.002, <0.001, <0.001, and <0.001, respectively), whereas tumor location was not associated with MSI. Univariable and multivariable analyses showed that MSI was an independent factor for CRC. The 5-year overall survival (OS) and 5-year disease-free survival (DFS, P<0.001) rates differed significantly between the two groups in stages II, III, and IV, whereas stage I did not show a significant difference (P>0.05). Conclusion: MSI-H was associated with a good prognosis for stages II to IV, whereas stage I did not show any significant correlation. Moreover, MSI expression was an independent prognostic factor. [ABSTRACT FROM AUTHOR]

Abstract Objective Mucinous breast cancer (MBC) is a kind of breast cancer (BC), which is rare in clinic, mainly for women, because of the low incidence rate, so there is no unified standard treatment protocol. Elderly patients have a poor prognosis due to their combined comorbidities. This study aims to investigate the effect of surgery and chemoradiotherapy on the prognosis of elderly female MBC patients and construct nomograms for predicting the OS and CSS in elderly female MBC patients. Methods Data for female MBC patients over 65 years are obtained from the Surveillance, Epidemiology and End Results (SEER) database, patients were divided into two groups: the training set and the validation set. External validation data of the prediction model were provided by Kunming Hospital of Traditional Chinese Medicine. We used Cox regression modeling, which was used to identify independent risk factors affecting patient prognosis. After avoiding confounding bias according to the multifactorial Cox regression model, we used these screened statistically significant results to construct column‐line plots. The performance of the model was tested using the consistency index (c‐index), the calibration curve, and the area under the operating characteristic curve of the receiver (AUC). Subsequently, we used decision curve analysis (DCA) to examine the potential clinical value of our nomograms. Results A total of 8103 elderly MBC female patients were extracted from the database SEER and were assigned to the training and validation set, randomly. A total of 83 patients from Kunming Hospital of Traditional Chinese Medicine were used in the external verification set. After multifactorial Cox regression analysis, we found that age, race, T‐stage, M‐stage, surgical approach, radiotherapy, and tumor size were independent risk factors for OS in elderly MBC patients. Similarly, independent risk factors of CSS included age, marital status, N stage, M stage, surgical approach, chemotherapy, and tumor size. The C‐index for the OS training, validation, and external verification set were 0.731 (95%CI 0.715–0.747), 0.738 (95%CI 0.724–0.752), and 0.809 (95%CI 0.731–0.8874). The C‐index of the training set, the validation set, and external verification set for CSS were 0.786 (95%CI 0.747–0.825), 0.776 (95%CI 0.737–0.815), and 0.84 (95%CI0.754–0.926), respectively. The AUC, calibration curves and DCA also showed good accuracy. Conclusions In this study, we construct a new nomogram to predict the prognosis of elderly patients with MBC. The nomograms have undergone internal and external validation and have been confirmed to have good clinical applicability. At the same time, we found that for elderly female MBC patients, surgery and radiotherapy significantly benefit their survival, but chemotherapy is not conducive to patient survival.

Background: Intestinal-type gastric adenocarcinoma, representing 95 % of gastric malignancies, originates from the malignant transformation of gastric gland cells. Despite its prevalence, existing methods for prognosis evaluation of this cancer subtype are inadequate. This study aims to enhance patient-specific prognosis evaluation by analyzing the clinicopathological characteristics and prognostic risk factors of intestinal-type gastric adenocarcinoma patients using data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Methods: We extracted clinical data for patients diagnosed with intestinal-type gastric adenocarcinoma between 2010 and 2015 from the SEER database, selecting 257 cases based on predefined inclusion and exclusion criteria. Independent risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified using a Cox regression model. A nomogram model for predicting OS or CSS was developed from the Cox risk regression analysis and validated through the consistency index (C-index), ROC curve, and calibration curve. Results: Age, primary tumor resection, chemotherapy, lymph node metastasis, and tumor size were identified as independent prognostic factors for OS and CSS (P

BackgroundTumor-associated macrophages (TAMs) constitute a plastic and heterogeneous cell population of the tumor microenvironment (TME) that can regulate tumor proliferation and support resistance to therapy, constituting promising targets for the development of novel anticancer agents. Our previous results suggest that SHP2 plays a crucial role in reprogramming the phenotype of TAMs. Thus, we hypothesized that SHP2+ TAM may predict the treatment efficacy of non-small cell lung cancer NSCLC patients as a biomarker.MethodsWe analyzed cancer tissue samples from 79 NSCLC patients using multiplex fluorescence (mIF) staining to visualize various SHP-2+ TAM subpopulations (CD68+SHP2+, CD68+CD86+, CD68 + 206+, CD68+ CD86+SHP2+, CD68+ CD206+SHP2+) and T cells (CD8+ Granzyme B +) of immune cells. The immune cells proportions were quantified in the tumor regions (Tumor) and stromal regions (Stroma), as well as in the overall tumor microenvironment (Tumor and Stroma, TME). The analysis endpoint was overall survival (OS), correlating them with levels of cell infiltration or effective density. Cox regression was used to evaluate the associations between immune cell subsets infiltration and OS. Correlations between different immune cell subsets were examined by Spearman’s tests.ResultsIn NSCLC, the distribution of different macrophage subsets within the TME, tumor regions, and stroma regions exhibited inconsistency. The proportions of CD68+ SHP2+ TAMs (P < 0.05) were higher in tumor than in stroma. And the high infiltration of CD68+SHP2+ TAMs in tumor areas correlated with poor OS (P < 0.05). We found that the expression level of SHP2 was higher in M2-like macrophages than in M1-like macrophages. The CD68+SHP2+ subset proportion was positively correlated with the CD68+CD206+ subset within TME (P < 0.0001), tumor (P < 0.0001) and stroma (P < 0.0001).ConclusionsThe high infiltration of CD68+SHP2+ TAMs predict poor OS in NSCLC. Targeting SHP2 is a potentially effective strategy to inhibit M2-phenotype polarization. And it provides a new thought for SHP2 targeted cancer immunotherapy.

Abstract Chimeric antigen receptor T-cell therapy (CAR-T) has been successful in treating relapsed/refractory B-cell lymphomas. However, its role in the treatment of diseases involving the central nervous system (CNS) is not well studied. We performed a multicenter retrospective cohort study to evaluate the outcomes of patients with secondary CNS lymphoma (SCNSL) who received CAR-T. Eligibility required active CNSL at the time of apheresis. The objectives included evaluation of overall survival (OS), progression-free survival (PFS), identification of predictors of complete response (CR) post-CAR-T, and assessment of risk factors for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Sixty-one patients were included in the analysis. The overall response rate was 68% with a CR rate of 57%. In the multivariable analysis, patients who experienced any grade CRS had higher odds of achieving CR (OR = 3.9, 95% CI = 1.01–15.39, p = 0.047). The median PFS was 3.3 months (95% CI = 2.6–6.0 months) with 6- and 12-month PFS rates of 35% and 16%, respectively. The median OS was 7.6 months (95% CI = 5.0–13.5 months) with 6- and 12-month OS rates of 59% and 41%, respectively. Any grade CRS and ICANS were 70% (n = 43) and 57% (n = 34), respectively with grade ≥ 3 CRS and ICANS rates of 16% and 44%. Factors associated with increased risk of CRS and ICANS included receiving axi-cel or having leptomeningeal ± parenchymal + CNS involvement, respectively. Despite achieving high response rates, most patients experience early relapse or death following CAR-T in SCNSL. The current study provides a benchmark for future trials exploring novel therapeutic options in SCNSL.

Abstract Background The aim of this study was to investigate the expression of PTK6 in different groups of triple negative breast cancer and its impact on prognosis. Methods Retrospective study of a total of 209 surgical specimens of breast cancer were identified by IHC or FISH methods as triple negative,and divided into a lymph node metastasis positive (LNM +)group (n = 102) and a lymph node metastasis negative(LNM-) group (n = 107) according to the lymph node status of the surgical specimen. PTK6 expression was detected by IHC technique in all surgical specimens. PTK6 expression and clinicopathological features was explored by Chi-square test. The prognosis of different groups of patients was analyzed by Kaplan–Meier survival analysis and COX analysis. Results The incidence of PTK6 expression in the LNM + group (78.4%) was significantly higher than in the LNM- group (28%). Clinicopathological analysis showed that PTK6 expression in the LNM + group was negatively correlated with the 5-year survival of patients. Kaplan–Meier analysis showed that only PTK6 expression in the LNM + group was negatively correlated with OS and DFS. COX analysis also showed that PTK6 expression and N stage were independent prognostic factors for DFS in the LNM + group. No correlation was observed between HER2 and PTK6 expression in any of the groups. Conclusions This study suggests that PTK6 promotes tumor development and was associated with poor prognosis in the LNM + group of triple negative breast cancer. Inhibition of PTK6 may be a new approach for the treatment of triple negative breast cancer patients, especially those with metastasis.

Objective: Prostate cancer (PC) is a significant disease affecting men's health worldwide. More than 60% of patients over 65 years old and more than 80% are diagnosed with localized PC. The current choice of treatment modalities for localized PC and whether overtreatment is controversial. Therefore, we wanted to construct a nomogram to predict the risk factors associated with cancer-specific survival (CSS) and overall survival (OS) in elderly patients with localized PC while assessing the survival differences in surgery and radiotherapy for elderly patients with localized PC. Methods: Data of patients with localized PC over 65 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models were used to determine independent risk factors for CSS and OS. Nomograms predicting CSS and OS were built using multivariate Cox regression models. The consistency index (C-index), the area under the subject operating characteristic curve (AUC), and the calibration curve were used to test the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to test the potential clinical value of this model. Results: A total of 90,434 patients over 65 years and diagnosed with localized PC from 2010 to 2018 were included in the study. All patients were randomly assigned to the training set (n = 63,328) and the validation set (n = 27,106). Univariate and multivariate Cox regression model analysis showed that age, race, marriage, T stage, surgical, radiotherapy, prostate-specific antigen (PSA), and Gleason score (GS) were independent risk factors for predicting CSS in elderly patients with localized PC. Age, race, marriage, surgery, radiotherapy, PSA, and GS were independent risk factors for predicting OS in elderly patients with localized PC. The c-index of the training and validation sets for the predicted CSS is 0.802(95%CI:0.788–0.816) and 0.798(95%CI:0.776–0.820, respectively). The c-index of the training and validation sets for predicting OS is 0.712(95%:0.704–0.720) and 0.724(95%:0.714–0.734). It shows that the nomograms have excellent discriminatory ability. The AUC and the calibration curves also show good accuracy and discriminability. Conclusion: We have developed new nomograms to predict CSS and OS in elderly patients with localized PC. After internal validation and external temporal validation with reasonable accuracy, reliability and potential clinical value, the model can be used for clinically assisted decision-making. [ABSTRACT FROM AUTHOR]