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Background: Total neoadjuvant therapy (TNT) has been recommended by the National Comprehensive Cancer Network for treating locally advanced rectal cancer (LARC), but extremely rare studies have focused on establishing nomograms to predict the prognosis in these patients after TNT. We aimed to develop a nomogram to predict overall survival (OS) in rectal cancer patients who underwent TNT. Methods: In retrospective cohort study, we extract the data of the rectal cancer patients from the SEER database between 2010 and 2015, including demographic information and tumor characteristics. The cohort was divided into training set and validation set based on a ratio of 7:3. Univariate logistic regression analysis was utilized for the comparison of variables in training set. Candidate variables with P < 0.1 in training set was entered into the best subset selection, LASSO regression and Boruta feature selection. Finally, the selected variables significantly associated with the 3-year, 5-year, and 8-year OS were used to build a nomogram, followed by validation using receiver operating characteristic (ROC) curve, area under the curve (AUC), and calibration curve. Results: A total of 3265 rectal cancer patients (training set: 2285; test set: 980) were included in the present study. A nomogram was developed to predict the 3-year, 5-year, and 8-year OS based on age, household income, total number of in situ/malignant tumors, CEA, T stage, N stage and perineural invasion. The nomogram showed good efficiency in predicting the 3-year, 5-year and 8-year OS with good AUC for the training set and test set, respectively. Conclusion: We established a nomogram for predicting the 3-year, 5-year, and 8-year OS of the rectal cancer patients, which showed good prediction efficiency for the OS after TNT. [ABSTRACT FROM AUTHOR]

Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan–Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis. [ABSTRACT FROM AUTHOR]

Background: Circulating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseline (T0), after 2 months of therapy (T2) and, when feasible, at progression (TP), in 70 melanoma patients treated with BRAF and MEK inhibitors. The association of baseline cytokine levels with clinical response, progression-free survival (PFS) and overall survival (OS) was evaluated. Methods: Cytokine concentrations were measured using the xMAP technology. Their ability to discriminate between responding (Rs) and non-responding (NRs) patients was assessed by Receiver Operating Characteristics analysis. PFS and OS were estimated with the Kaplan–Meier method. The Cox proportional hazard model was used in the univariate and multivariate analyses to estimate crude and adjusted hazard ratios with 95% confidence intervals. Results: CCL4 and LIF were undetectable in the majority of samples. The median osteopontin concentration at T0 and T2 was significantly higher in NRs than in Rs. The median T0 and T2 values of IL-8 were also higher in NRs than in Rs, although the statistical significance was not reached. No differences were detected for BDNF. In 39 Rs with matched T0, T2, and TP samples, osteopontin and IL-8 significantly decreased from T0 to T2 and rose again at TP, while BDNF levels remained unchanged. In NRs, none of the cytokines showed a significant decrease at T2. Only osteopontin demonstrated a good ability to discriminate between Rs and NRs. A high IL-8 T0 level was associated with significantly shorter PFS and OS and higher risk of progression and mortality, and remained an independent negative prognostic factor for OS in multivariate analysis. An elevated osteopontin T0 concentration was also significantly associated with worse OS and increased risk of death. Patients with high IL-8 and high osteopontin showed the lowest PFS and OS, and in multivariate analysis this cytokine combination remained independently associated with a three- to six-fold increased risk of mortality. Conclusion: Circulating IL-8 and osteopontin appear useful biomarkers to refine prognosis evaluation of patients undergoing targeted therapy, and deserve attention as potential targets to improve its clinical efficacy. [ABSTRACT FROM AUTHOR]

Objectives: Pretreatment biomarkers are needed to identify patients with non‐small‐cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real‐world cohort of NSCLC patients who received ICIs. Materials and Methods: We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced‐stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil‐to‐lymphocyte ratio, C‐reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low‐ and high‐risk groups were defined using literature‐based cut‐offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. Results: Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low‐risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36–4.06) than CAR alone (aHR 2.22, 95% CI 1.79–2.76) or PNI alone (aHR 2.09, 95% CI 1.66–2.61). Conclusion: These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment. [ABSTRACT FROM AUTHOR]

Background: Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods: We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results: Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions: Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely. [ABSTRACT FROM AUTHOR]

Aim Patients and Methods Results Conclusion This study aims to identify the cut‐off drain amylase (DA) values on the first, third, and fifth post‐operative days (POD1‐DA, POD3‐DA, and POD5‐DA) that are correlated with clinically relevant post‐operative pancreatic fistula (CR‐POPF).All data were retrospectively collected from patients who underwent pancreatectomy at the Department of Surgery, Phramongkutklao Hospital, from January 2015 to December 2023. A total of 195 patients were included in the study.A total of 195 patients were analysed, including 35 patients with CR‐POPF, with a mean age of 60.84 years. There were no statistically significant differences in demographic data between patients with CR‐POPF and those without. In addition, no statistical differences were observed in pancreatic duct diameter (3 mm vs 2 mm), operative time (468.9 min vs 500.29 min), or blood loss (600 mL vs 600 mL) between the CR‐POPF and no CR‐POPF groups. Length of hospital stays was longer in the CR‐POPF group compared with the no CR‐POPF group (33 days vs 11 days, P = .001). In addition, the CR‐POPF group had significantly higher rates of post‐operative pancreatic haemorrhage (20% vs 2.5%), bile leakage (5.71% vs 0%), delayed gastric emptying (45.71% vs 3.13%), wound complications (34.29% vs 5%), and mortality (17.14% vs 1.88%) compared with the no CR‐POPF group. The optimal cut‐off values for CR‐POPF were 1313 U/L on day 1 (D1; area under the curve [AUC] 0.72, 95% confidence interval [CI] 0.65–0.84, sensitivity 91%, specificity 52%), 492 U/L on D3 (AUC 0.77, 95% CI 0.70–0.83, sensitivity 91%, specificity 64%), and 360 U/L on D5 (AUC 0.65, 95% CI 0.52–0.75, sensitivity 69%, specificity 61%). There were no significant perioperative factors associated with CR‐POPF in our study.DA levels of 1313, 492, and 360 U/L on post‐operative D1, D3, and D5, respectively, were associated with CR‐POPF. Drain removal can be safely performed without the risk of CR‐POPF when these levels are met. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)‐low‐expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Methods: Women aged ≤40 years with newly diagnosed early‐stage HER2‐negative BC (HER2‐0 and HER2‐low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi‐square test and Student t‐test were used to describe variable distribution between HER2‐0 and HER2‐low. Associations with HER2‐low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease‐free survival (DFS) and overall survival. Statistical significance was considered for p ≤.05. Results: Of 3547 included patients, 32.3% had HER2‐low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple‐negative (TN) tumors. HER2‐low vs. HER2‐0 BC were more often of grade 1/2 (p <.001), hormone receptor–positive (p <.001), and node‐positive (p =.003). BRCA2 PVs were more often associated with HER2‐low than BRCA1 PVs (p <.001). HER2‐low versus HER2‐0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76–0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64–0.95) and overall survival (HR, 0.65; 95% CI, 0.46–0.93) in the TN subgroup. Luminal A–like tumors in HER2‐low (p =.014) and TN and luminal A‐like in HER2‐0 (p =.019) showed the worst DFS. Conclusions: In young patients with HER2‐negative BC and germline BRCA1/2 PVs, HER2‐low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal‐like disease. HER2‐low status was associated with a modestly improved prognosis. Approximately 32% of human epidermal growth factor receptor 2 (HER2)‐negative breast cancer in an international multicenter cohort of 3547 women ≤40 years old with germline BRCA1/2 pathogenic variants was HER2‐low, and more frequently associated with hormone receptor–positive disease and BRCA2 variants than triple‐negative and BRCA1. HER2‐low status was associated with slightly better outcomes than HER2‐0, especially in triple‐negative tumors, without prognostic differences according to BRCA1 vs. BRCA2 variants, though within HER2‐low disease, luminal A–like tumors displayed worse disease‐free survival than luminal B–like and triple negative tumors. [ABSTRACT FROM AUTHOR]

Purpose: Aim of this study is to investigate the association between DM and oncological outcomes among patients with muscle-invasive (MI) or high-risk non-muscle invasive (NMI) bladder cancer (BC) who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion (RARC). Methods: An IRB approved multi-institutional BC database was queried, including patients underwent RARC between January 2013 and June 2023. Patients were divided into two groups according to DM status. Baseline, clinical, perioperative, pathologic data were compared. Chi-square and Student t tests were performed to compare categorical and continuous variables, respectively. Kaplan-Meier method and Cox regression analyses were performed to assess the association between DM and oncologic outcomes. Results: Out of 547 consecutive patients, 97 (17.7%) had DM. The two cohorts showed similar preoperative features, except for ASA score (p = 0.01) and Hypertension rates (p < 0.001). No differences were detected for perioperative complications, pT stage, pN stages and surgical margins status (all p > 0.12). DM patients displayed significantly lower 5-yr disease-free survival (DFS) (44.6% vs. 63.3%, p = 0.007), 5-yr cancer-specific survival (CSS) (45.1% vs. 70.1%, p = 0.001) and 5-yr Overall survival (OS) (39.9% vs. 63.8%, p = 0.001). At Multivariable Cox-regression analyses DM status was identified as independent predictor of worse cancer-specific survival (CSS) (HR 2.1; p = 0.001) and overall survival (OS) (HR 2.05; p < 0.001). Conclusion: Among BC patients who underwent RARC, DM patients showed worse oncologic outcomes than the non-DM patients, with DM status playing an independent negative predicting role in CSS and OS. Future prospective studies are awaited, stimulating basic and translational research to identify possible mechanisms of interaction between DM and BC. [ABSTRACT FROM AUTHOR]

Purpose: Single large hepatocellular carcinoma >5cm (SLHCC) traditionally requires a major liver resection. Minor resections are often performed with the goal to reduce morbidity and mortality. Aim of the study was to establish if a major resection should be considered the best treatment for SLHCC or a more limited resection should be preferred. Methods: A multicenter retrospective analysis of the HE.RC.O.LE.S. Group register was performed. All collected patients with surgically treated SLHCC were divided in 5 groups of treatment (major hepatectomy, sectorectomy, left lateral sectionectomy, segmentectomy, non-anatomical resection) and compared for baseline characteristics, short and long-term results. A propensity-score weighted analysis was performed. Results: 535 patients were enrolled in the study. Major resection was associated with significantly increased major complications compared to left lateral sectionanectomy, segmentectomy and non-anatomical resection (all p<0.05) and borderline significant increased major complications compared to sectorectomy (p=0.08). Left lateral sectionectomy showed better overall survival compared to major resection (p=0.02), while other groups of treatment resulted similar to major hepatectomy group for the same item. Absence of oncological benefit after major resection and similar outcomes among the 5 groups of treatment was confirmed even in the sub-population excluding patients with macrovascular invasion. Conclusion: Major resection was associated to increased major post-operative morbidity without long-term survival benefit; when technically feasible and oncologically adequate, minor resections should be preferred for the surgical treatment of SLHCC. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) is a pivotal treatment for lymphoma patients. The BeEAM regimen (Bendamustine, Etoposide, Cytarabine, Melphalan) traditionally relies on cryopreservation, whereas the CEM regimen (Carboplatin, Etoposide, Melphalan) has been optimized for short-duration administration without the need for cryopreservation. This study rigorously compares the clinical and safety profiles of the BeEAM and CEM regimens. Methods: A controlled, randomized clinical trial was conducted with 58 lymphoma patients undergoing ASCT at the International Medical Center (IMC) in Cairo, Egypt. Patients were randomly assigned to either the BeEAM (n = 29) or CEM (n = 29) regimen, with an 18-month follow-up period. Clinical and safety outcomes were meticulously compared, focusing on time to engraftment for neutrophils and platelets, side effects, length of hospitalization, transplant-related mortality (TRM), and survival rates. Results: The findings demonstrate a significant advantage for the CEM regimen. Neutrophil recovery was markedly faster in the CEM group, averaging 8.5 days compared to 14.5 days in the BeEAM group (p < 0.0001). Platelet recovery was similarly expedited, with 11 days in the CEM group versus 23 days in the BeEAM group (p < 0.0001). Hospitalization duration was substantially shorter for CEM patients, averaging 18.5 days compared to 30 days for those on BeEAM (p < 0.0001). Furthermore, overall survival (OS) was significantly higher in the CEM group at 96.55% (95% CI: 84.91–99.44%) compared to 79.31% (95% CI: 63.11–89.75%) in the BeEAM group (p = 0.049). Progression-free survival (PFS) was also notably superior in the CEM group, at 86.21% (95% CI: 86.14–86.28%) versus 62.07% (95% CI: 61.94–62.20%) in the BeEAM group (p = 0.036). Conclusion: The CEM regimen might demonstrate superiority over the BeEAM regimen, with faster neutrophil and platelet recovery, reduced hospitalization time, and significantly improved overall and progression-free survival rates. Future studies with longer duration and larger sample sizes are warranted. Trial registration: This study is registered on ClinicalTrials.gov under the registration number NCT05813132 (https://clinicaltrials.gov/ct2/show/NCT05813132). (The first submitted registration date: is March 16, 2023). [ABSTRACT FROM AUTHOR]

Background: Invasive micropapillary carcinoma (IMPC) was first proposed as an entity by Fisher et al. In the 2003 World Health Organization (WHO) guidelines for histologic classification of the breast tumors. IMPC was recognized as a distinct, rare histological subtype of breast cancer. IMPC is emerging as a surgical and oncological challenge due to its tendency to manifest as a palpable mass, larger in size and higher in grade than IDC with more rate of lymphovascular invasion (LVI) and lymph node (LN) involvement, which changes the surgical and adjuvant management plans to more aggressive, with comparative prognosis still being a point of ongoing debate. Aim of the study : In this study, we compared the clinicopathological characteristics, survival and surgical management of breast cancer patients having invasive micropapillary carcinoma pathological subtype in comparison to those having invasive duct carcinoma. Method: This is a comparative study on female patients presented to Baheya center for early detection and treatment of breast cancer, in the period from 2015 to 2022 diagnosed with breast cancer of IMPC subtype in one group compared with another group of invasive duct carcinoma. we analyzed 138 cases of IMPC and 500 cases of IDC. Results: The incidence of LVI in the IMPC group was 88.3% in comparison to 47.0% in the IDC group (p < 0.001). IMPC had a higher incidence of lymph node involvement than the IDC group (68.8% and 56% respectively). IMPC had a lower rate of breast conserving surgery (26% vs.37.8%) compared with IDC. The survival analysis indicated that IMPC patients had no significant difference in overall survival compared with IDC patients and no differences were noted in locoregional recurrence rate and distant metastasis rate comparing IMPCs with IDCs. Conclusion: The results from our PSM analysis suggested that there was no statistically significant difference in prognosis between IMPC and IDC patients after matching them with similar clinical characteristics. However, IMPC was found to be more aggressive, had larger tumor size, greater lymph node metastasis rate and an advanced tumor stage. [ABSTRACT FROM AUTHOR]

Introduction: Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease. Study design: Registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE Objectives: To improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern. Methods: Settings and participants: It is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. Variables: Full details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methods: The data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression. Results: The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC), the most prevalent form of oral cancer, poses significant challenges to the medical community due to its high recurrence rate and low survival rate. Mitochondrial Damage-Related Genes (MDGs) have been closely associated with the occurrence, metastasis, and progression of OSCC. Consequently, we constructed a prognostic model for OSCC based on MDGs and identified potential mitochondrial damage-related biomarkers. Gene expression profiles and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Differential analysis was conducted to identify MDGs associated with OSCC. COX analysis was employed to screen seven prognosis-related MDGs and build a prognostic prediction model for OSCC. Cases were categorized into low-risk or high-risk groups based on the optimal risk score threshold. Kaplan-Meier (KM) analysis revealed significant survival differences (P < 0.05). Additionally, the area under the ROC curve (AUC) for patient survival at 1 year, 3 years, and 5 years were 0.687, 0.704, and 0.70, respectively, indicating a high long-term predictive accuracy of the prognostic model. To enhance predictive accuracy, age, gender, risk score, and TN staging were incorporated into a nomogram and verified using calibration curves. Risk scoring based on MDGs was identified as a potential independent prognostic biomarker. Furthermore, BID and SLC25A20 were identified as two potential independent mitochondrial damage-related prognostic biomarkers, offering new therapeutic targets for OSCC. [ABSTRACT FROM AUTHOR]

Purpose: Brain metastases (BM) often leave residual tumors despite having visible margins, which increases the risk of local tumor recurrence and can impact overall patient survival rates. Fluorescence-guided surgery (FGS) utilizing sodium fluorescein (FL) has been reported as an effective technique in recent studies. This study aimed to evaluate the efficacy of FL FGS in improving the extent of resection of brain metastases and its impact on overall survival. Methods: We conducted a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Our primary focus was on gross total resection (GTR). Additionally, we extracted survival data and evaluated the risk of bias using a modified version of the Joanna Briggs Institute critical appraisal tool. Results: The study comprised 970 patients with brain metastases through eight different studies. The study found that patients who underwent FL-guided resection had a significantly higher rate of GTR (OR: 2.02, 95% CI: 1.14–3.56, p = 0.0156, I2 = 41.5%). Additionally, the study concluded that FL-guided resection is associated with better overall survival rates (HR: 0.61, 95%CI: 0.47 0.80, p = 0.0003, I2 = 41.5%). Conclusion: Our research suggests that the use of FL is associated with a higher rate of GTR and improved overall patient survival. None of the studies we reviewed reported significant complications associated with the use of FL in patients. [ABSTRACT FROM AUTHOR]

Mucinous adenocarcinoma (MAC) is a distinct subtype of colorectal cancer. Previous studies have confirmed the poor prognosis of rectal or left-sided colon MAC, while the prognosis and response to chemotherapy in proximal colon MAC remains controversial. The aim of this study was to investigate the clinicopathological characteristics, prognosis, response to chemotherapy, and risk prediction factors of proximal colon MAC. Patients with proximal colon MAC and non-mucinous adenocarcinoma (NMAC) were retrospectively analyzed in this study. The analyzed variables included gender, age, smoking, drinking, chemotherapy, metastasis, pathological stage, and tumor size. Overall survival (OS) was the primary outcome. Kaplan–Meier analysis was used to assess the impact of mucinous subtype and chemotherapy on OS. We conducted univariate and multivariate Cox regression analyses to determine prognosis factors for proximal colon MAC and NMAC. A total of 284 cases of proximal colon MAC and 1384 cases of NMAC were included in the study. Compared to NMAC, proximal colon MAC was diagnosed at a younger age. The proportion of synchronous and metachronous metastasis was also higher, as well as the pathological stage and tumor size. Proximal colon MAC had a worse prognosis than NMAC, especially in stage 3. Moreover, the prognosis of proximal colon NMAC improved after chemotherapy, while MAC showed no improvement in prognosis after chemotherapy. Advanced age, N1 and N2 stage were independent prognostic factors for adverse outcomes in MAC. For proximal colon adenocarcinoma, the independent predictors of adverse outcomes included mucinous subtype, order age, N1 and N2 stages, and pathological stage 4. Proximal colon MAC had a worse prognosis compared to NMAC. Chemotherapy did not improve the prognosis of proximal colon mucinous adenocarcinoma. [ABSTRACT FROM AUTHOR]

To examine the potential correlation between chemotherapy and the risk of individual of second primary endometrial cancer (SEC) in patients with rectal cancer (RC) and assess survival outcomes. The study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, it encompasses a substantial cohort of patients diagnosed with RC between 1975 and 2018. This study involved a total of 30,847 individuals diagnosed with RC, of whom 168 individuals (5.45‰) experienced SEC. Among them, 107 patients (3.47‰) received chemotherapy treatment, while 61 patients (1.98‰) did not receive chemotherapy. The analysis of the overall occurrence of SEC revealed a significant association between SEC and chemotherapy treatment. Univariate and multivariate analyses confirmed a significant association between chemotherapy treatment and an increased risk of developing SEC in RC patients. Upon implementation of a dynamic analysis on the variables of relative risk and standardized incidence ratios, the results revealed that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC after receiving and not receiving chemotherapy revealed no substantial disparities in the 10-year overall survival (OS) and (cancer-specific survival) CSS rates. The results were the same after propensity score matching. Nevertheless, a notable discrepancy emerged when comparing the OS and CSS rates at 10 years between patients afflicted with SEC subsequent to chemotherapy and those afflicted with primary endometrial cancer, and the result was the same situation in the no-chemotherapy group. The use of chemotherapy in RC patients has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing chemotherapy-related SEC occurrences and improving the prognosis of affected individuals. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion Currently, the primary treatment modality for patients with colorectal adenocarcinoma (CRA) is radical surgery combined with postoperative adjuvant chemotherapy (PAC). However, many elderly patients decline PAC due to concerns about their underlying physiological condition, and the impact of PAC on the prognosis of elderly patients remains uncertain.We extracted data from the SEER database for CRA patients aged 75 and above between 2010 and 2019. Utilizing propensity score matching (PSM), we stratified the patients into a PAC group and a non‐PAC group, enabling us to compare the differences in Kaplan–Meier survival curves between these two groups. Furthermore, through univariate and multivariate Cox regression analyses, we identified the clinical factors that influence the survival of elderly CRA patients and compared the prognostic disparities between the two patient groups within specific subgroups of these clinical factors.Following PSM, a total of 3668 patients were included and divided into the PAC group and the non‐PAC group, with no statistically significant differences observed in crucial clinical characteristics between the two groups. Kaplan–Meier analysis revealed a significantly better prognosis for patients in the PAC group compared with those in the non‐PAC group. In addition, age, chemotherapy, TNM staging, gender, and preoperative CEA levels were all identified as important factors affecting patient prognosis. Moreover, PAC provided survival benefits across the majority of levels within the aforementioned subgroups. However, in specific subgroups (age > 90, Grade IV stage, median household income < $40 000), PAC did not confer any survival benefits.PAC can significantly improve the prognosis of elderly CRA patients. Nonetheless, in certain population subsets characterized by specific clinical features, PAC does not provide any survival benefits. [ABSTRACT FROM AUTHOR]

ABSTRACT Phosphorylated signal transducer and activator of transcription 3 (pSTAT3), which is related to anti‐apoptosis, cellular proliferation, invasion and migration of tumours, has prognostic significance in malignant tumours in humans as well as in canine melanoma. However, the significance of pSTAT3 in canine liver tissues has not yet been evaluated. This study's objective was to compare its expression in canine normal, non‐neoplastic hepatic disease and hepatocellular carcinoma (HCC) tissues by immunohistochemical analysis. Furthermore, the association between pSTAT3 immunostaining and clinicopathological factors was investigated. Overall, 68 canine liver tissues, including 10 normal liver tissues, 30 non‐neoplastic hepatic disease tissues and 28 HCC tissues were examined, revealing distinct differences in pSTAT3 immunostaining among the groups. (p < 0.001). Additionally, high pSTAT3 immunostaining was significantly associated with increased tumour size (5 > cm) (p = 0.041), and metastasis (p = 0.046). Furthermore, Kaplan–Meier survival curve analysis revealed a correlation between high pSTAT3 immunostaining and poor disease‐free survival (p = 0.013) and overall survival (p = 0.011). These findings suggest that overactivation of STAT3 is associated with poor prognosis in canine HCC. Therefore, pSTAT3 is considered a potential prognostic marker and therapeutic target for canine HCC. [ABSTRACT FROM AUTHOR]

Introduction Materials and Methods Results Conclusion Elderly acute myeloid leukemia (AML) patients with poor‐risk cytogenetics have a poor outcome with intensive chemotherapy (IC). While Venetoclax (VEN) has changed the outcomes of elderly unfit patients treatment, it is unknown whether it could be effective in poor‐risk cytogenetics 60–75 years old patients.We included 60–75‐year‐old AML patients eligible to allogenic stem cell transplantation (allo‐SCT) treated with VEN (combined with azacitidine or with Cladribin and Aracytine) at Institut Paoli Calmettes, between 2020 and 2023 and compared this cohort with patients treated by IC between 2010 and 2019.Twenty six patients were treated with VEN (17 in combination with azacitidine and 9 with Cladribin and Aracytine) and 90 were treated with IC. Thirteen patients (50%) had a TP53 mutation. The median time for leucocyte and platelet counts recovery was 26 days (range 0–103) and 26 days (range, 0–63). The median duration of the first hospitalization was 32 days (ranges, 7–79). The composite response rate was 69% (CR = 50%, CRi = 4%, MLFS = 15%). Allo‐SCT could be performed in 42% of cases. Median overall survival (OS) was 7.9 months (20.9 months in the group of patients who transitioned to allo‐SCT). We found no difference with the historical cohort of patients treated with IC except a trend toward less lower and upper tract gastro‐intestinal (GI) tract infections in the VEN group (respectively 8% vs 26%, p = .06; and 0% vs. 13% p = .06).VEN‐based treatment was found to be effective in high risk AML can be considered as an alternative to IC in patients aged 60–75 with adverse cytogenetics. [ABSTRACT FROM AUTHOR]

Background: Zinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated. Methods: In this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients. Results: The pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects. Conclusions: ZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC. [ABSTRACT FROM AUTHOR]

Background: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). Methods: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. Results: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). Conclusions: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications. [ABSTRACT FROM AUTHOR]

AbstractBackgroundAimMaterials and MethodsResultsConclusions and SignificanceLactate dehydrogenase (LDH) is involved in the Warburg effect. Elevated serum LDH is a prognostic marker for metastatic solid cancer.To investigate the prognostic impact of serum LDH in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors (ICIs).This retrospective study included 129 patients treated with ICIs between 2017 and 2023. The effects of pretreatment LDH, LDH at 3 months, and change in LDH during the first 3 months (ΔLDH) on overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan–Meier method and Cox regression model.The 1-year PFS and OS rates for high and low groups were 6.0% and 30.1% for pretreatment LDH (p = 0.044), 25.7% and 38.3% for on-treatment LDH (p = 0.079), and 14.3% and 38.7% for ΔLDH (p = 0.008), as well as 42.1% and 60.9% for pretreatment LDH (p = 0.109), 56.0% and 80.5% (p < 0.001) for on-treatment LDH, and 31.0% and 81.0% for ΔLDH (p < 0.001), respectively. ΔLDH was an independent prognostic factor for both PFS and OS.ΔLDH can be used to predict ICI treatment outcomes and as a marker in deciding to continue ICI therapy. [ABSTRACT FROM AUTHOR]

Background: Tumor burden score (TBS) based on maximum tumor diameter and number has been shown to correlate with prognosis in patients with hepatocellular carcinoma (HCC). Nevertheless, the results are conflicting. Hence, we conducted a meta-analysis to analyze the association between TBS and survival outcomes of HCC patients. Methods: A comprehensively search of the databases including PubMed, Embase and Web of Science was performed to retrieve studies satisfying the inclusion criteria until August 31, 2023. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All the data analyses were carried out by STATA 12.0. Results: 10 retrospective studies containing 25073 patients were incorporated in the study. The results demonstrated that high TBS was markedly association with poor overall survival (OS) (HR: 1.79, 95% CI: 1.45–2.23) and relapse-free survival / progression-free survival(RFS/PFS) (HR: 1.71; 95% CI: 1.42–2.07). Subgroup analysis showed that the prognostic value of TBS in HCC was not affected by any subgroup. Conclusions: TBS may be an efficient prognostic index in HCC patients. [ABSTRACT FROM AUTHOR]

The Gasdermin E gene (GSDME) plays roles in deafness and cancers. However, the roles and mechanisms in cancers are complex, and the same gene exhibits different mechanisms and actions in different types of cancers. Online databases, such as GEPIA2, cBioPortal, and DNMIVD, were used to comprehensively analyze GSDME profiles, DNA methylations, mutations, diagnosis, and prognosis in patients with tumor tissues and matched healthy tissues. Western blotting and RT-PCR were used to monitor the regulation of GSDME by Cordycepin (CD) in cancer cell lines. We revealed that GSDME expression is significantly upregulated in eight cancers (ACC, DLBC, GBM, HNSC, LGG, PAAD, SKCM, and THYM) and significantly downregulated in seven cancers (COAD, KICH, LAML, OV, READ, UCES, and UCS). The overall survival was longer only in ACC, but shorter in four cancers, including COAD, KIRC, LIHC, and STAD, when GSDME was highly expressed in cancers compared with the corresponding normal tissues. Moreover, the high expression of GSDME was negatively correlated with the poor prognosis of ACC, while the low expression of GSDME was negatively correlated with the poor prognosis of COAD, suggesting that GSDME might serve as a good prognostic factor in these two cancer types. Accordingly, results indicated that the DNA methylations of those 7 CpG sites constitute a potentially effective signature to distinguish different tumors from adjacent healthy tissues. Gene mutations for GSDME were frequently observed in a variety of tumors, with UCES having the highest frequency. Moreover, CD treatment inhibited GSDME expression in different cancer cell lines, while overexpression of GSDME promoted cell migration and invasion. Thus, we have systematically and successfully clarified the GSDME expression profiles, diagnostic values, and prognostic values in pan-cancers. Targeting GSDME with CD implies therapeutic significance and a mechanism for antitumor roles in some types of cancers via increasing the sensitivity of chemotherapy. Altogether, our study may provide a strategy and biomarker for clinical diagnosis, prognostics, and treatment of cancers by targeting GSDME. [ABSTRACT FROM AUTHOR]

Introduction: The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. Methods: Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan–Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. Results: In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P =.007), DFS (HR 1.129, P =.015), LRFS (HR 1.211, P =.002), and DMFS (HR 1.131, P =.057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. Conclusions: EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning. [ABSTRACT FROM AUTHOR]

Nucleophosmin‐1 (NPM1)‐mutated AML is a molecularly defined subtype typically associated with favorable treatment response and prognosis; however, its prognostic significance in AML evolving from an antecedent chronic myeloid malignancy is unknown. This study's primary objective was to determine the impact of mutated NPM1 on the prognosis of AML evolving from an antecedent chronic myeloid malignancy. We conducted a retrospective chart review including patients with NPM1‐mutated de novo and sAML. sAML was defined as those with a preceding chronic‐phase myeloid malignancy before diagnosis of AML. Of 575 NPM1‐mutated patients eligible for inclusion in our study, 51 (8.9%) patients were considered to have sAML. The median time from diagnosis of NPM1‐mutated chronic myeloid malignancy to sAML evolution was 3.6 months (0.5–79.3 months). No significant differences in leukemia‐free (2‐year LKFS 52.0% vs. 51.2%, p = .9922) or overall survival (2‐year OS 56.3% vs. 49.4%, p = .4246) were observed between patients with NPM1‐mutated de novo versus sAML. Our study suggests that evolution from a preceding myeloid malignancy is not a significant predictor of poor prognosis in the setting of an NPM1 mutation. Our study demonstrated a short time to progression to sAML in most patients, which further supports the consideration of NPM1 as an AML‐defining mutation. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to identify the risk factors that influence metastasis and prognosis in patients with nodular melanoma (NM), as well as to develop and validate a prognostic model using artificial intelligence (AI) algorithms. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for 4,727 patients with NM based on the inclusion/exclusion criteria. Their clinicopathological characteristics were retrospectively reviewed, and logistic regression analysis was utilized to identify risk factors for metastasis. This was followed by employing Multilayer Perceptron (MLP), Adaptive Boosting (AB), Bagging (BAG), logistic regression (LR), Gradient Boosting Machine (GBM), and eXtreme Gradient Boosting (XGB) algorithms to develop metastasis models. The performance of the six models was evaluated and compared, leading to the selection and visualization of the optimal model. Through integrating the prognostic factors of Cox regression analysis with the optimal models, the prognostic prediction model was constructed, validated, and assessed. Results: Logistic regression analyses identified that marital status, gender, primary site, surgery, radiation, chemotherapy, system management, and N stage were all independent risk factors for NM metastasis. MLP emerged as the optimal model among the six models (AUC = 0.932, F1 = 0.855, Accuracy = 0.856, Sensitivity = 0.878), and the corresponding network calculator (https://shimunana-nm-distant-m-nm-m-distant-8z8k54.streamlit.app/) was developed. The following were examined as independent prognostic factors: MLP, age, marital status, sequence number, laterality, surgery, radiation, chemotherapy, system management, T stage, and N stage. System management and surgery emerged as protective factors (HR < 1). To predict 1-, 3-, and 5-year overall survival (OS), a nomogram was created. The validation results demonstrated that the model exhibited good discrimination and consistency, as well as high clinical usefulness. Conclusion: The developed prediction model more effectively reflects the prognosis of patients with NM and differentiates between the risk level of patients, serving as a useful supplement to the classical American Joint Committee on Cancer (AJCC) staging system and offering a reference for clinically stratified individualized treatment and prognosis prediction. Furthermore, the model enables clinicians to quantify the risk of metastasis in NM patients, assess patient survival, and administer precise treatments. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that m6A modification is related to the occurrence and development of papillary thyroid carcinoma (PTC). The disorder of succinic acid metabolism is associated with the occurrence and development of various tumors. However, there are few studies based on m6A and succinate metabolism-related genes (SMRGs) in PTC. Methods: The TCGA-Thyroid carcinoma (THCA), GSE33630, 1159 SMRGs, and 23 m6A regulatory factors were collected from the online databases. Subsequently, the differentially expressed genes (DEGs) were selected between PTC (Tumor) and Normal samples. The overlapping genes among the DEGs, m6A, and SMRGs were applied to screen the biomarkers. Using the 3 machine-learning algorithms, the biomarkers were determined based on the overlapping genes. Next, the biomarkers were evaluated by the ROC curve and expression analysis in TCGA-THCA and GSE33630. Then, the overall survival (OS) differences were compared between the high-and low-expression biomarkers. Finally, immune infiltration analysis, molecular regulatory network, and drug prediction were performed based on the biomarkers. Results: In TCGA-THCA, there were 2800 DEGs between and Normal samples, and then 7 overlapping genes were obtained. Importantly, ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ were determined as biomarkers with excellent diagnostic efficiency (AUC > 0.7). In PTC samples, ADK and TNFRSF10B were high-expressed while CYP7B1, FGFR2, and CPQ were low-expressed. Especially, the high-expression groups of ADK had a better prognosis, while the high-expression groups of CYP7B1, FGFR2, and CPQ had a worse prognosis. Afterward, immune infiltration analysis found that 16 immune cells had infiltration differences between the Tumor and Normal samples. Finally, transcription factor SP1 could regulate CYP7B1 and TNFRSF10B. Moreover, Navitoclax was a potential drug for PTC patients. Conclusion: Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC), one of the most fatal urologic tumors, accounts for approximately 3% of all adult cancers and exhibits a high metastatic index at diagnosis and a high rate of relapse. Radical or partial nephrectomy is a curative option for nonmetastatic RCCs. Targeted therapy has been shown to improve the survival of patients with metastatic RCCs. However, the underlying cellular and molecular events associated with RCC pathogenesis are not well known. Methods: To investigate the clinical role of the transcription factor activator protein (AP)-2α in RCC, methylated CpG island recovery assays and microarray analysis were employed. COBRA and RT‒qPCR assays were performed to assess AP-2α expression in RCC. Results: A negative correlation was noted between AP-2α mRNA expression levels and methylation status. Multivariate analyses showed that AP-2α mRNA was a major risk factor not only for overall and disease-free survival in RCC but also for disease-free survival in clear cell RCC. Conclusions: Our results indicated that AP-2α expression was deregulated in RCC and associated with overall patient survival and disease-free survival. Such findings suggest that AP-2α might play an important role in the pathogenesis of RCC. [ABSTRACT FROM AUTHOR]

Objective: Localized Upper Urinary Tract Urothelial Carcinoma (UTUC) is an uncommon cancer typically detected at an advanced stage. Currently, radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for high-risk UTUC. This meta-analysis aims to evaluate the 5-year overall and cancer-specific survival and bladder recurrence rates in studies comparing endoscopic kidney-sparing surgeries (E-KSS) with RNU in localized UTUC. Evidence acquisition: We performed a literature search on 20th April 2023 through PubMed, Web of Science, and Scopus. The PICOS model was used for study inclusion: P: adult patients with localized UTUC; I: E-KSS. C: RNU; O: primary: overall survival (OS); secondary: cancer-specific survival (CSS), bladder recurrence rate, and metastasis-free survival (MFS). S: retrospective, prospective, and randomized studies. Evidence synthesis: Overall, 11 studies involving 2284 patients were eligible for this meta-analysis, 737 in the E-KSS group and 1547 in the RNU group. E-KSS showed a similar overall 5-year OS between E-KSS and RNU, and for low-grade tumors, while 5-year OS favored RNU for high-grade tumors (RR 1.84, 95% CI 1.26–2.69, p = 0.002). No difference emerged for 5-year CSS between the two groups, even when the results were stratified for low- and high grade tumors. Bladder recurrence rate and 5-year MFS were also similar between the two groups. Conclusions: Our review showed that E-KSS is a viable option for patients with localized UTUC with non-inferior oncological outcomes as compared with RNU, except for 5-year OS in high-grade tumors which favoured RNU. [ABSTRACT FROM AUTHOR]

An increasing number of studies have reported the close relation of the hemoglobin glycation index (HGI) with metabolism, inflammation, and disease prognosis. However, the prognostic relationship between the HGI and patients with sepsis remains unclear. Thus, this study aimed to analyze the association between the HGI and all-cause mortality in patients with sepsis using data from the MIMIC-IV database. In this study, 2605 patients with sepsis were retrospectively analyzed. The linear regression equation was established by incorporating glycated hemoglobin (HbA1c) and fasting plasma glucose levels. Subsequently, the HGI was calculated based on the difference between the predicted and observed HbA1c levels. Furthermore, the HGI was divided into the following three groups using X-tile software: Q1 (HGI ≤ − 0.50%), Q2 (− 0.49% ≤ HGI ≤ 1.18%), and Q3 (HGI ≥ 1.19%). Kaplan–Meier survival curves were further plotted to analyze the differences in 28-day and 365-day mortality among patients with sepsis patients in these HGI groups. Multivariate corrected Cox proportional risk model and restricted cubic spline (RCS) were used. Lastly, mediation analysis was performed to assess the factors through which HGI affects sepsis prognosis. This study included 2605 patients with sepsis, and the 28-day and 365-day mortality rates were 19.7% and 38.9%, respectively. The Q3 group had the highest mortality risk at 28 days (HR = 2.55, 95% CI: 1.89–3.44, p < 0.001) and 365 days (HR = 1.59, 95% CI: 1.29–1.97, p < 0.001). In the fully adjusted multivariate Cox proportional hazards model, patients in the Q3 group still displayed the highest mortality rates at 28 days (HR = 2.02, 95% CI: 1.45–2.80, p < 0.001) and 365 days (HR = 1.28, 95% CI: 1.08–1.56, p < 0.001). The RCS analysis revealed that HGI was positively associated with adverse clinical outcomes. Finally, the mediation effect analysis demonstrated that the HGI might influence patient survival prognosis via multiple indicators related to the SOFA and SAPS II scores. There was a significant association between HGI and all-cause mortality in patients with sepsis, and patients with higher HGI values had a higher risk of death. Therefore, HGI can be used as a potential indicator to assess the prognostic risk of death in patients with sepsis. [ABSTRACT FROM AUTHOR]

Introduction and purpose of the study: Small bowel obstruction (SBO) accounts for a substantial proportion of emergency surgical admissions. Malignancy is a common cause of obstruction, either due to a primary tumour or intra-abdominal metastases. However, little is known regarding the current treatment or outcomes of patients with malignant SBO. This study aimed to characterise the treatment of malignant SBO and identify areas for potential improvement and compare overall survival of patients with malignant SBO to patients with non-malignant SBO. Materials and methods: This was a subgroup analysis of a multicentre observational study of patients admitted with SBO. Details regarding these patients' diagnoses, treatments, and outcomes up to 1-year after admission were recorded. The primary outcome was overall survival in patients with malignant SBO. Results: A total of 316 patients with small bowel obstruction were included, of whom 33 (10.4%) had malignant SBO. Out of the 33 patients with malignant SBO, 20 patients (60.6%) were treated with palliative intent although only 7 patients were seen by a palliative team during admission. Nutritional assessments were performed on 12 patients, and 11 of these patients received parenteral nutrition. 23 patients underwent surgery, with the most common surgical interventions being loop ileostomies (9 patients) and gastrointestinal bypasses (9 patients). 4 patients underwent right hemicolectomies, with a primary anastomosis formed and 1 patient had a right hemicolectomy with a terminal ileostomy. Median survival was 114 days, and no difference was seen in survival between patients treated with or without palliative intent. Conclusion: Malignant SBO is associated with significant risks of short-term complications and a poor prognosis. Consideration should be given to the early involvement of senior decision-makers upon patient admission is essential for optimal management and setting expectation for a realistic outcome. [ABSTRACT FROM AUTHOR]

Purpose: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are rare, aggressive thyroid cancers with poor prognosis. At present, there are a limited number of research reports on PDTC and ATC. The study aimed to analysis the predictive value of hematologic parameters and clinicopathological features of PDTC and ATC. Methods: This study retrospectively analyzed 67 patients at Tianjin Medical University Cancer Hospital from 2007 to 2019. We analyzed the clinicopathological features and survival outcomes of PDTC and ATC. Results: This study showed that positive D-dimer, a high NLR, and a high PLR were more common in death patients. At the end of follow-up, 22 (32.8%) patients were alive at the time of study and 45 (67.2%) patients died from thyroid carcinoma. Disease-related death rates were 93.8% in ATC and 42.9% in the PDTC group. The median overall survival (OS) was 2.5 (0.3–84) months for patients with ATC, and 56 (3-113) months of PDTC patients. Univariate analysis showed that age at diagnosis and surgery were associations with OS in ATC patients, what's more, age at diagnosis, a high NLR, a high PLR, and positive D-dimer were associations with OS in PDTC patients. Multivariate analysis revealed that age at diagnosis was an independent association with OS in ATC patients. Conclusions: The hematologic parameters and clinicopathological features may provide predictive value of prognosis for patients with PTDC and ATC. [ABSTRACT FROM AUTHOR]

Purpose: The value of upfront primary tumor resection (PTR) for asymptomatic unresectable metastatic colorectal cancer (mCRC) patients remains contentious. This meta-analysis aimed to assess the prognostic significance of upfront PTR for asymptomatic unresectable mCRC. Methods: A systematic literature search was performed on June 21st, 2024. To minimize the bias and ensure robust evidence, only randomized controlled trials (RCTs) and case-matched studies (CMS) that compared PTR followed by chemotherapy to chemotherapy alone were included. The primary outcome was overall survival (OS), while cancer-specific survival (CSS) served as the secondary outcome. Results: Eight studies (three RCTs and five CMS) involving 1221 patients were included. Compared to chemotherapy alone, upfront PTR followed by chemotherapy did not improve OS (hazard ratios [HR] 0.91, 95% confidence interval [CI] 0.79–1.04, P = 0.17), but was associated with slightly better CSS (HR 0.59, 95% CI 0.40–0.88, P = 0.009). Conclusions: The current limited evidence indicates that upfront PTR does not improve OS but may enhance CSS in asymptomatic unresectable mCRC patients. Ongoing trials are expected to provide more reliable evidence on this issue. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC), although patient survival is still unsatisfactory. Accurate predictive markers capable of personalizing the treatment of patients with NSCLC are still lacking. Circulating extracellular vesicles involved in cell-to-cell communications through miRNAs (EV-miRs) transfer are promising markers. Plasma from 245 patients with advanced NSCLC who received nivolumab as second-line therapy was collected and analyzed. EV-miRnome was profiled on 174/245 patients by microarray platform, and selected EV-miRs were validated by qPCR. A prognostic model combining EV-miR and clinical variables was built using stepwise Cox regression analysis and tested on an independent patient cohort (71/245). EV-PD-L1 gene copy number was assessed by digital PCR. For 54 patients with disease control, EV-miR changes at best response versus baseline were investigated by microarray and validated by qPCR. EV-miRNome profiling at baseline identified two EV-miRs (miR-181a-5p and miR-574-5p) that, combined with performance status, are capable of discriminating patients unlikely from those that are likely to benefit from immunotherapy (median overall survival of 4 months or higher than 9 months, respectively). EV-PD-L1 digital evaluation reported higher baseline copy number in patients at increased risk of mortality, without improving the prognostic score. Best response EV-miRNome profiling selected six deregulated EV-miRs (miR19a-3p, miR-20a-5p, miR-142-3p, miR-1260a, miR-1260b, and miR-5100) in responding patients. Their longitudinal monitoring highlighted a significant downmodulation already in the first treatment cycles, which lasted more than 6 months. Our results demonstrate that EV-miRs are promising prognostic markers for NSCLC patients treated with nivolumab. [ABSTRACT FROM AUTHOR]

Summary Background Methods Results Conclusions The benefits of HCV eradication on distinct recurrence patterns and long‐term hepatic outcomes in patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) remain uncertain. This study aims to assess the impact of HCV eradication on HCC recurrence patterns and long‐term hepatic outcomes after RFA and to identify predictors of recurrence in patients achieving sustained virological response (SVR).We retrospectively enrolled 274 patients receiving RFA for HCV‐related HCC, including 73 and 88 patients treated with interferon‐based (IFN) and direct‐acting antivirals (DAA) therapy, respectively. We analysed factors associated with local tumour progression (LTP), distant recurrence, overall survival, and hepatic decompensation.SVR was achieved in 49.3% of patients undergoing IFN therapy and 93.2% of patients undergoing DAA therapy. HCV eradication was not associated with LTP but significantly correlated with reduced risk of distant recurrence (by DAA: hazard ratio (HR) = 0.449, p = 0.006), overall survival (by IFN: HR = 0.242, p < 0.001; by DAA: HR = 0.274, p < 0.001) and hepatic decompensation (by IFN: HR = 0.313, p = 0.004; by DAA: HR = 0.281, p < 0.001). The benefits of achieving SVR in terms of overall survival and hepatic decompensation remained significant in subgroups of patients with and without recurrence. Patients with SVR showed a significant decline in FIB‐4 score and a higher proportion of ALBI grade improvement. Among SVR patients, the IMbrave050 criteria predicted LTP but not distant recurrence, whereas the FIB‐4 score after SVR, rather than the baseline FIB‐4, predicted distant recurrence.HCV eradication was associated with a significant reduction in distant recurrence, mortality and hepatic decompensation following RFA in patients with HCV‐related HCC. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation. Results: A total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03–3.19). Conclusions: Increased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a hematologic malignancy characterized by abnormal plasma cell proliferation in the bone marrow. Recent advancements in anti-CD38 monoclonal antibody therapies, such as daratumumab and isatuximab, have significantly improved MM patient survival. However, the lack of predictive factors of response to these therapies remains a challenge. Notably, anti-CD38 antibodies can interfere with laboratory tests, complicating response assessment. We conducted a retrospective study to evaluate the association between the appearance of positive IgGk (therapeutic antibody) on immunofixation/immunosubtraction (IF) and clinical parameters in 87 non-IgGk MM patients treated with anti-CD38 therapy. Positive IgGk IF was observed in 42 patients after a median of three treatment courses. Patients with positive IgGk IF had higher rates of complete/very good partial responses (p = 0.03) and improved progression-free survival (median not reached vs. 21.83 months, p < 0.01). High BMI (p = 0.03), higher hemoglobin (p = 0.02), lower CRP (p = 0.04), and lower monoclonal protein levels (p = 0.03) were associated with positive IgGk IF. Our findings suggest that monitoring therapeutic antibody appearance on IF may predict and optimize anti-CD38 therapy in MM. Potential explanations include the impact of patient factors (e.g. BMI) on drug pharmacokinetics, the relationship between antibody levels and immune response, and the influence of tumor biology. Further research is needed to elucidate the underlying mechanisms and clinical utility of this biomarker. Nonetheless, our results highlight the importance of considering therapeutic antibody detection when interpreting laboratory tests and managing MM patients receiving anti-CD38 therapies. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Design Setting Participants Main Outcome Measures Results Conclusions Laryngeal squamous cell carcinoma (SCC) is a predominantly male illness. Although the rate of female patients increased, a knowledge gap exists in the medical literature regarding gender‐based differences.Retrospective cohort study.Adult patients treated for laryngeal SCC in a tertiary medical centre between 2006 and 2020. Data were collected on demographics, clinical presentation, treatment modalities, disease recurrence and survival status.Two hundred ninety‐one patients with laryngeal SCC, 50 (17.2%) females and 241 (82.8%) males.Disease‐specific survival (DSS), overall survival (OS) and disease‐free survival (DFS), as well as differences in disease characteristics and treatment modalities.Tumour subsites differed significantly between females and males (36% vs. 19.5% supraglottic, 62% vs. 80.5% glottic and 2% vs. 0% subglottic, respectively; p = 0.006). Females were diagnosed at younger ages (61.7 ± 10.58 vs. 65.87 ± 11.11 years, p = 0.016) and advanced‐stage disease (58% vs. 39.4%, p = 0.018). Females were treated with combined modalities at higher rates (36% vs. 54.8% for single modality, p = 0.031). DSS rates did not differ between genders (log‐rank p = 0.12). Despite being diagnosed at more advanced disease stages, females demonstrated prolonged median OS compared to males (130.17 vs. 106.17 months, log‐rank p = 0.017). No significant differences in DFS were observed (log‐rank p = 0.32). In a multivariate Cox proportional hazards model, male gender remained an independent negative OS predictor (HR = 2.08; CI, 1.10–3.96; p = 0.025), along with increasing age (HR = 1.06; CI, 1.04–1.09; p < 0.001) and advanced disease stage (HR = 1.7; CI, 1.08–2.67; p = 0.023).Our findings suggest the importance of considering gender‐specific factors in the management of laryngeal SCC. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Plain Language Summary Particulate matter consisting of fine particles measuring 2.5 microns or less in diameter (PM2.5), a component of air pollution, has been linked to adverse health outcomes. The objective of this study was to assess the association between ambient PM2.5 exposure and survival in children with cancer in the United States.Individuals aged birth to 19 years who were diagnosed with cancer between January 1, 2004, and December 31, 2019, were selected from the National Cancer Database. The association between the annual PM2.5 level at the patient's zip code of residence at the time of diagnosis and overall survival was evaluated using time‐varying Cox proportional hazards models (crude and adjusted for diagnosis year and age). To address concerns that exposure to air pollution is correlated with other social determinants of health, the authors tested the association between PM2.5 levels and survival among sociodemographic subgroups.Of the 172,550 patients included, 27,456 (15.9%) resided in areas with annual PM2.5 concentrations above the US Environmental Protection Agency (EPA) annual PM2.5 standard of 12 μg/m3. Residing in these high‐pollution areas was associated with worse overall survival (adjusted hazard ratio [aHR], 1.06; 95% confidence interval [CI], 1.012–1.10). Similarly, when PM2.5 was evaluated as a linear measure, each unit increase in PM2.5 exposure was associated with worse survival (aHR, 1.011; CI, 1.005–1.017). Exposure to PM2.5 at levels above the EPA standards was also significantly associated with worse overall survival among sociodemographic subgroups.Exposure to PM2.5 was significantly associated with worse overall survival among children with cancer, even at levels below EPA air quality standards. These results underscore the importance of setting appropriate air quality standards to protect the health of this sensitive population. The authors investigated how living in areas with high air pollution (defined as particulate matter consisting of fine particles measuring 2.5 microns or less in diameter; PM2.5) affects the overall survival of children with cancer in the United States. The results indicated that children living in areas with higher PM2.5 levels, and even at levels below prior and current US Environmental Protection Agency standards, had lower survival rates than children living in areas with lower levels of PM2.5. This finding emphasizes the need for stricter air quality standards to better protect children, particularly those with serious health conditions like childhood cancer. The authors investigated how living in areas with high air pollution (defined as particulate matter consisting of fine particles measuring 2.5 microns or less in diameter; PM2.5) affects the overall survival of children with cancer in the United States.The results indicated that children living in areas with higher PM2.5 levels, and even at levels below prior and current US Environmental Protection Agency standards, had lower survival rates than children living in areas with lower levels of PM2.5.This finding emphasizes the need for stricter air quality standards to better protect children, particularly those with serious health conditions like childhood cancer. [ABSTRACT FROM AUTHOR]

The role of neoadjuvant chemotherapy and its benefits in patients with triple-negative breast cancer (TNBC) and small tumors are unclear. This study aims to compare survival differences between clinical T1 TNBC receiving neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC). Data for patients with clinical T1 TNBC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized according to whether they received chemotherapy before or after surgery. Propensity Score Matching (PSM) was used to minimize the influence of confounding factors. OS and BCSS were compared between the two treatment sequences using Kaplan–Meier and univariate and multivariable Cox proportional hazards regression analyses. The study included 6249 women with T1 TNBC. In multivariate analysis, compared with that in the AC group, the hazard ratio for death in the NAC group was 1.54 (95% confidence interval 1.26–1.89, p < 0.001). NAC offers no additional benefits in any age group or T, N subgroups. Our findings suggest that NAC does not provide additional benefit to patients with clinical T1 TNBC, even in the presence of lymph node metastasis, or T1c. [ABSTRACT FROM AUTHOR]

Background: Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. Objective: This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival. Materials and methods: This is a retrospective study of histologically confirmed fusion-positive ARMS patients over 18 years of age, who were treated at MD Anderson Cancer Center (MDACC) from 2004 to 2021 and received systemic chemotherapy. Descriptive clinical statistics were performed, including staging, front-line chemotherapy, multimodal therapy usage, response rates, and survival analyses. Results: 49 ARMS patients who received upfront chemotherapy were identified. Locoregional treatments included radiotherapy (RT) alone (29%, n = 14), surgery alone (10%, n = 5), or both (45%, n = 22). Median overall survival (OS) for the entire cohort was 3.6 years, and the overall response rate to systemic therapy was 89%. No chemotherapy regimen showed OS benefit, specifically analyzing the pediatric-based vincristine, actinomycin-D, cyclophosphamide (VAC) or adult-based vincristine, doxorubicin, ifosfamide (VDI) regimens, even when controlled for other clinical risk factors. Conclusion: In this single-center contemporary series, adult ARMS patient outcomes remain poor. There was no statistically significant OS difference in patients who did or did not receive adult or pediatric based ARMS regimens, although a high overall response rate to chemotherapy was seen across the entire cohort. Based on these observations, further randomized prospective studies are necessary to delineate which frontline chemotherapy regimen is most beneficial in this rare adult cancer. [ABSTRACT FROM AUTHOR]

Lung Squamous Cell Carcinoma is characterised by significant alterations in RNA expression patterns, and a lack of early symptoms and diagnosis results in poor survival rates. Our study aimed to identify the hub genes involved in LUSC by differential expression analysis and their influence on overall survival rates in patients. Thus, identifying genes with the potential to serve as biomarkers and therapeutic targets. RNA sequence data for LUSC was obtained from TCGA and analysed using R Studio. Survival analysis was performed on DE genes. PPI network and hub gene analysis was performed on survival-relevant genes. Enrichment analysis was conducted on the PPI network to elucidate the functional roles of hub genes. Our analysis identified 2774 DEGs in LUSC patient datasets. Survival analysis revealed 511 genes with a significant impact on patient survival. Among these, 20 hub genes—FN1, ACTB, HGF, PDGFRB, PTEN, SNAI1, TGFBR1, ESR1, SERPINE1, THBS1, PDGFRA, VWF, BMP2, LEP, VTN, PXN, ABL1, ITGA3 and ANXA5—were found to have lower expression levels associated with better patient survival, whereas high expression of SOX2 correlated with longer survival. Enrichment analysis indicated that these hub genes are involved in critical cellular and cancer-related pathways. Our study has identified six key hub genes that are differentially expressed and exhibit significant influence over LUSC patient survival outcomes. Further, in vitro and in vivo studies must be conducted on the key genes for their utilisation as therapeutic targets and biomarkers in LUSC. [ABSTRACT FROM AUTHOR]

PURPOSE: Early-onset biliary tract cancer (eoBTC) is among the fast-growing subset of early-onset cancers, yet little is known about its biology. We sought to identify novel molecular characteristics of eoBTC in relation to average-onset BTC (aoBTC) using a real-world multiomics data set. METHODS: The study comprised patients with BTC whose tumors underwent molecular analyses at Caris Life Sciences and were categorized by age (<50 years for eoBTC, ≥50 years for aoBTC). P values were adjusted for multiple testing and considered significant at Q < 0.05 (molecular comparisons) or Q < 0.25 (Gene Set Enrichment Analysis [GSEA]). Insurance claims data were used for survival analysis. RESULTS: The study included 5,587 patients with BTC (453 eoBTC, median age = 44 years and 5,134 aoBTC, median age = 68 years). FGFR2 fusion (15.7% in eoBTC v 5.9% in aoBTC) and NIPBL fusion (1.1% v 0%) were significantly more prevalent in eoBTC (both Q < 0.001). The interferon gamma-IFG score (fold change [FC], 1.1; Q = 0.01) and T-cell inflammation score (FC, 17.3; Q = 0.03) were significantly higher in aoBTC. On GSEA, angiogenesis was enriched in eoBTC (normalized enrichment score [NES] = 1.51; Q = 0.16), whereas IFG (NES = –1.58; Q = 0.06) and inflammatory response (NES = –1.46; Q = 0.18) were enriched in aoBTC. The median overall survival (OS) was 16.5 (eoBTC) versus 13.3 months (aoBTC), hazard ratio = 0.86, P =.004. The median OS by FGFR2 fusion (with fusion v without) was 21.7 versus 15.0 months (P =.47) for eoBTC and 18.6 versus 12.2 months (P <.001) for aoBTC. CONCLUSION: We identified crucial differences including higher prevalence of FGFR2 fusions in eoBTC and variations in immunotherapy-related markers. Better outcomes in eoBTC were affected by the FGFR2 fusion status. Our findings underscore the need for ensuring access to next-generation sequencing testing, including prompt identification of actionable targets. Multiomic analysis shows higher FGFR2 fusions and #immunotherapy marker variations in early-onset biliary cancer [ABSTRACT FROM AUTHOR]

Background and purpose: In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC). Methods: This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI. Results: 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group. Conclusion: The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: Growth differentiation factor-15 (GDF-15), a member of the TGF-β superfamily, is overexpressed in various cancers and facilitates immune evasion by inhibiting T-cell activation. GDFATHER-TRIAL's phase 2a results demonstrated promising outcomes when combining the GDF-15 neutralizing antibody visugromab (CTL002) with nivolumab, enhancing the response to immunotherapy. This study evaluated the prognostic significance of GDF-15 expression in non-small cell lung cancer (NSCLC) tumor tissues in terms of immunotherapy response. Methods: This retrospective study included 50 patients with metastatic NSCLC treated with nivolumab at Gazi University Hospital between January 2021 and July 2023. GDF-15 expression was evaluated using immunochemistry staining and categorized based on the intensity of cytoplasmic or membranous staining. Samples were divided into a low expression group (scores 0 and 1) and a high expression group (scores 2 and 3). The primary outcomes were progression-free survival (PFS) and overall survival (OS), which were analyzed using Kaplan‒Meier and Cox proportional hazards models. Objective response rates were assessed in secondary outcomes. Results: Of the 50 patients, 43 were men (86%), with a median age of 63.9 years. Half of the patients exhibited low GDF-15 expression. High GDF-15 expression correlated with shorter PFS and OS. The median PFS was 7.8 months for the low-expression group versus 4.4 months for the high-expression group (HR, 0.41; 95% CI, 0.20–0.83; p = 0.013). The median OS was 18.1 months for the low-expression group compared to 11.8 months for the high-expression group (HR, 0.36; 95% CI, 0.16–0.78; p = 0.007). The objective response rate was significantly greater in the low GDF-15 group (52%) than in the high GDF-15 group (24%) (p = 0.040). Conclusion: Elevated GDF-15 expression in NSCLC tumor tissues is associated with poorer response to nivolumab, suggesting that GDF-15 is a potential prognostic biomarker for immunotherapy efficacy. These findings warrant further validation through prospective studies to optimize treatment strategies for NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Limited data exists on the efficacy of immune checkpoint inhibitor (ICI) combinations in non-small-cell lung cancer (NSCLC) with uncommon driver alterations in genes such as ERBB2, BRAF, RET, and MET. This study retrospectively assessed ICI-combination therapy outcomes in this molecular subset of NSCLC. Methods: We retrospectively analyzed patients with advanced NSCLC confirmed with driver alterations in genes including ERBB2, BRAF, RET or MET, and received ICI combined with chemotherapy (ICI + chemo) and/or targeted therapy (ICI + chemo/TT) as first-line (1L) or second- or third-line (≥ 2L) treatment at Hunan Cancer Hospital between January 2018 and May 2024. Results: Of the 181 patients included in the study, 131 patients received 1L-ICI + chemo (ERBB2, n = 64; BRAF, n = 34; RET, n = 23; and MET, n = 10), and 50 patients received ≥ 2L-ICI + chemo/TT (ERBB2, n = 16; BRAF, n = 7; RET, n = 14; MET, n = 13). The full cohort had an overall response rate (ORR) of 45.9% and disease control rate of 84.0%. Among patients who received 1L-ICI + chemo, ORR ranged between 51.6% and 60.0%, with the median progression-free survival (mPFS) and overall survival (mOS) of 8.2 and 21.0 months for those with ERBB2-altered tumors, 10.0 and 15.0 months for BRAF-altered tumors, 12.1 months and OS not reached for RET-altered tumors, and 6.2 and 28.0 months for MET-altered tumors, respectively. Additionally, ORR ranged between 14.3% and 30.8% for ≥ 2L-ICI + chemo/TT; mPFS and mOS were 5.4 and 16.2 months for patients with ERBB2-altered tumors, 2.7 and 5.0 months for BRAF-altered tumors, 6.2 and 14.3 months for RET-altered tumors, and 5.7 and 11.5 months for MET-altered tumors, respectively. Conclusion: ICI-based combination therapies, regardless of treatment line, were effective in treating patients with advanced NSCLC harboring driver alterations in ERBB2, BRAF, RET, or MET. This suggests their potential as alternative treatment options in this patient population. [ABSTRACT FROM AUTHOR]

Summary The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high‐dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high‐dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end‐point was a 2‐year progression‐free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60–81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty‐six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow‐up duration of 36.0 months, the 2‐year PFS rate was 58.7%. Treatment was generally well‐tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment‐related mortality was reported. The 2‐year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high‐dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab. [ABSTRACT FROM AUTHOR]

Summary Background Objective Methods Results Conclusion High‐dose post‐transplant cyclophosphamide allows safe and effective use of allografts from haploidentical relatives (siblings, parents and children) in patients undergoing allogeneic blood or marrow transplant (alloBMT). More recently, second‐ and third‐degree relatives have also been shown to be safe allograft donors. An increasing number of older patients undergoing alloBMT have been receiving allografts from haploidentical donors. However, older patients are more likely to have older siblings and children, and older donor age is associated with worse outcomes.In the current study, we report the safety and utility of grandchildren as haploidentical donors and compared with children as donors in patients undergoing alloBMT.We compared characteristics and outcomes of alloBMT patients aged 55 years and older with children older than 30 years as donors (C group; n = 276) and those with grandchildren as donors (GC group; n = 40). Because many important baseline characteristics predict outcomes after alloBMT, we performed propensity score matched analysis based on recipient age, alloBMT year, disease, graft source and haematopoietic cell transplantation comorbidity index (HCT‐CI).The median age of recipients was 67 years (range 55–79) in the C group and 73 years (range 57–78) in the GC group. More than 70% of recipients in the GC group were older than 70 years, compared with 27% in the C group. The median donor age was 37 years (range 31–52) in the C group and 20 years (range 14–34) in the GC group. More patients in the GC group had HCT‐CI scores ≥3 than in the C group (32.5% vs. 23%, p = 0.27).Two‐year overall survival did not differ between the two groups (GC 62% vs. C 60%, hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.53–1.75, p = 0.90) despite recipients of allografts from grandchildren being older. The 2‐year RFS was 55% in the C group compared with 50% in the GC group (HR 1.05, 95% CI 0.62–1.77, p = 0.85). Non‐relapse mortality subdistribution [SD] (SDHR 1.36, 95% 0.70–2.63, p = 0.36), relapse (SDHR 0.72, 95% CI 0.33–1.58, p = 0.42) or relapse‐free survival (HR 1.05, 95% CI 0.62–1.77, p = 0.85). Propensity score matching analysis showed no significant differences in 2‐year overall survival (GC 64% vs. C 53%; HR 0.77, 95% CI 0.42–1.42, p = 0.40), non‐relapse mortality (SDHR 1.26, 95% 0.66–2.41, p = 0.48), relapse (SDHR 0.57, 95% CI 0.21–1.52, p = 0.26) or relapse‐free survival (HR 0.94, 95% CI 0.57–1.54, p = 0.81).Our results indicate that outcomes of alloBMT patients with grandchild donors are similar to those with child donors, despite recipients' older age and higher comorbidities in the GC group. Grandchildren should be considered when selecting a donor for older alloBMT recipients. [ABSTRACT FROM AUTHOR]

The landscape of the management of renal cell carcinoma has evolved substantially in the last decade, leading to improved survival in localised and advanced disease. We review the epidemiology, pathology, and diagnosis of renal cell carcinoma and discuss the evidence for current management strategies from localised to metastatic disease. Developments in adjuvant therapies are discussed, including use of pembrolizumab—the first therapy to achieve overall survival benefit in the adjuvant setting. The treatment of advanced disease, including landmark trials that have established immune checkpoint inhibition as a standard of care, are also reviewed. We also discuss the current controversies that exist surrounding the management of metastatic renal cell carcinoma, including the use of risk assessment models for disease stratification and treatment selection for frontline therapy. Management of non-clear cell renal cell carcinoma subtypes is also reviewed. Future directions of research, including a discussion of ongoing clinical trials and the need for reliable biomarkers to guide treatment in kidney cancer, are also highlighted. [ABSTRACT FROM AUTHOR]