Survival Outcomes In Patients Research Articles

Impact of radiological follow-up frequency on resected lung cancer: a propensity score matching analysis.

Despite advances in lung cancer treatment and the subsequent improvement in oncological outcomes, the optimal frequency of radiological follow-up remains unclear. Current recommendations lack consensus and do not consider individual patient characteristics and tumor factors. This study aimed to examine the impact of radiological follow-up frequency on oncological outcomes following lung cancer resection. A prospective multicenter study, involving patients who underwent anatomical lung resection in the GEVATS database between December 2016 and March 2018. The relationship between surveillance frequency and oncological outcomes was evaluated. Two groups were established based on follow-up frequency: low frequency (LF) and high frequency (HF). Subgroup analyses were performed based on tumor stage, histology, lymphadenectomy, and adjuvant therapy. Propensity score matching (PSM) was applied to balance the groups. A total of 1,916 patients were included in the study, LF 444 (23.17%), HF 1,472 (76.83%). Factors associated with HF surveillance included higher stage, adjuvant chemotherapy and adjuvant radiotherapy. Subanalyses were performed after PSM for various factors, revealing significant differences between LF and HF groups in cancer-specific survival among who received adjuvant therapy {LF 53.021 months [95% confidence interval (CI): 48.622-57.421] vs. HF 58.836 months (95% CI: 55.343-62.330); HR 0.453, 95% CI: 0.242-0.849; P=0.013}, as well as overall survival for patients with squamous cell carcinoma [LF 54.394 months (95% CI: 51.424-57.364) vs. HF 61.578 months (95% CI: 59.091-64.065); HR 0.491, 95% CI: 0.299-0.806; P=0.005] and those who received adjuvant therapy LF 50.176 months [95% CI: 45.609-54.742) vs. HF 57.189 months (95% CI: 53.599-60.778); HR 0.503, 95% CI: 0.293-0.865; P=0.013]. Findings suggest that high-frequency surveillance only improves survival outcomes in lung cancer patients who received adjuvant treatment or had squamous cell carcinoma. Therefore, future guidelines for lung cancer follow-up should consider individualizing the frequency of radiological surveillance based on patients' risk profiles.

Treatment patterns and outcomes in patients with nonmetastatic castration-resistant prostate cancer in the United States.

Aim: Androgen receptor pathway inhibitors (ARPIs) prolong metastasis-free survival and overall survival in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). This study aimed to evaluate real-world treatment patterns, utilization and survival outcomes in patients with nmCRPC. Patients & methods: This retrospective cohort study used Optum database electronic health records of patients with nmCRPC from 1 January 2007 to 31 December 2020 in the US. Results: Of 1955 patients, >80% received androgen-deprivation therapy (ADT) alone or ADT+first-generation nonsteroidal antiandrogen (NSAA) as first-line treatment, while only 8.24% received ADT+ARPI. ADT+ARPI remained underutilized even among those with high-risk nmCRPC. Further, ADT+NSAA had no survival benefit compared with ADT alone. Conclusion: Practice-improvement strategies are needed for treatment intensification with ARPIs for patients with nmCRPC.

Establishment of nomogram to predict overall survival and cancer-specific survival of local tumor resection in patients with colorectal cancer liver metastasis with unresectable metastases: a large population-based analysis

Background and PurposeThe tumour-node metastasis (TNM) classification is a common model for evaluating the prognostic value of tumour patients. However, few models have been used to predict the survival outcomes of patients with colorectal cancer liver metastasis (CRLM) with unresectable metastases who received the primary local surgery. Thus, we utilized the Surveillance, Epidemiology, and End Results (SEER) database to establish novel nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of these patients.MethodsExtracted primary data on CRLM patients by local surgery from SEER database. All prognostic factors of OS and CSS were determined by Cox regression analysis. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were used to further evaluate the accuracy and discrimination of these nomograms. Decision curve analysis (DCA) was executed to evaluate the nomograms for the clinical net benefit. Risk stratification analysis (RSA) was used to evaluate the reliability of them in clinical.Results3622 eligible patients were screened and assigned to training cohort (1812) or validation cohort (1810). The age, chemotherapy, tumour grade, primary tumour site, tumour size, lymph node positive rate (LNR), marital status, and carcinoembryonic antigen (CEA) were independent prognostic factors of OS. Additionally, the age, chemotherapy, tumour grade, primary tumour site, tumour size, LNR, and CEA were independent prognostic factors of CSS. The results of C-indexes and ROC curves indicated that the established nomograms exhibited better discrimination power than TNM classification. The calibration curves demonstrated excellent agreement between the predicted and actual survival rates for 1-, 3-, and 5 year OS and CSS. Meanwhile, the validation cohort demonstrated similar results. Background the clinic context, the DCA showed that these nomograms have higher net benefits, and the RSA showed that patients were further divided into low risk, medium risk, and high risk groups according to the predicted scores from nomograms. And, the Kaplan–Meier curve and log-rank test showed that the survival differences among the three groups are statistically significant.ConclusionsThe prognostic nomograms showed very high accuracy, identifiability, and clinical practicality in predicting the OS and CSS of CRLM patients with unresectable metastases treated by local surgery at 1-, 3-, and 5 years, which might improve individualized predictions of survival risks and help clinicians formulate treatment plans.

Survival Outcomes in Patients with Resectable Gastric Cancer Treated with Total Neoadjuvant Therapy.

Perioperative chemotherapy has become the standard of care for locally advanced gastric cancer. Total neoadjuvant therapy (TNT), including both chemotherapy and chemoradiation, is utilized in other gastrointestinal malignancies. We determined survival in a contemporary cohort of gastric cancer patients treated with TNT. Using a prospective institutional database, patients diagnosed with cT2-4 or cN+ gastric adenocarcinoma (January 2012 to June 2022) who underwent staging laparoscopy, received TNT, and underwent gastrectomy were identified. Overall survival (OS) and disease-specific survival (DSS) were determined using standard statistical methods. The study included 203 patients. The most common TNT sequence was induction chemotherapy followed by chemoradiation (n = 186 [91.6%]). A total of 195 (96.1%) patients completed planned neoadjuvant treatments. Surgery included total gastrectomy in 108 (53.2%), extended (D1+/D2) lymphadenectomy in 193 (95.1%), and adjacent organ resection in 19 (9.4%) patients. Pathologic complete response (pCR) was achieved in 32 (15.8%) patients. The 5-year OS rate was 65.2% (95% confidence interval [CI] 57.8-73.5%), and the 5-year DSS rate was 70.8% (95% CI 63.6-78.9%) in the study cohort. Among patients with pCR, the 5-year OS rate was 89.1% (95% CI 78.1-100.0%), and the 5-year DSS rate was 96.9% (95% CI 91-100%). Posttreatment pathologic N and M stages were the strongest prognostic indicators associated with both OS and DSS. Total neoadjuvant therapy for resectable gastric cancer is associated with a high rate of treatment completion and promising survival outcomes. Prospective comparisons with perioperative treatment are needed to identify patients most likely to benefit from TNT.

The Prediction of DLL4 as a Prognostic Biomarker in Patients with Gastric Cancer Using Anti-DLL4 Nanobody.

Angiogenesis and cancer metastasis depend on the DLL4/Notch signaling pathway. A new approach to treating angiogenesis could inhibit or block this pathway. In the present study, we investigated DLL4 expression as a biomarker capable of predicting survival outcomes in gastric cancer patients using a novel anti-DLL4 Nanobody. By using a recently developed anti-DLL4 Nanobody, the expression of DLL4 was evaluated in tissue samples from 135 gastric cancer patients. It was evaluated whether DLL4 expression is related to clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS). Sixty-five (48%) gastric cancer patients had a positive expression of DLL4 within the tumor tissue. Based on both the univariate and multivariate regression analyses, the expression of DLL4 was strongly associated with RFS (HR, 1.94; p = 0.008) and OS (HR, 2.06; p = 0.004). Moreover, the survival analysis demonstrated that DLL4 expression was a significant independent factor of unfavorable OS (HR, 2.7; p = 0.01) and RFS (HR, 2.3; p = 0.02) in gastric cancer patients. DLL4 expression in gastric cancer patients may predict poor prognosis and survival. Furthermore, the current data demonstrate the potential of Nanobody for detecting DLL4, and it may lead to develop novel therapies and diagnostics for tumors.

Multimodal assessment of high-risk human papillomavirus in sinonasal squamous cell carcinoma

High-risk human papillomavirus (hrHPV) is an emerging risk factor for sinonasal squamous cell carcinoma (SNSCC). The goal of this study was to assess the prevalence of hrHPV and subtype distribution in SNSCC and correlation with patient and clinical characteristics. This retrospective cohort study included 43 cases diagnosed with incident primary SNSCC at the University of Cincinnati Medical Center from 2010 to 2015. The prevalence of hrHPV was interrogated using a multi-assay approach that included p16 immunohistochemistry (IHC), RNA in-situ hybridization (ISH), and hrHPV DNA sequencing. The association of hrHPV with 5-year overall survival (OS) and 2-year disease-free survival (DFS) was assessed. Fourteen cases (32.6 %) were classified as hrHPV positive, based on the a priori definition of having either a positive RNAScope™ ISH test or hrHPV DNA and p16-positive IHC; 9 cases (20.9 %) were positive for all three tests. All cases that arose from an inverted sinonasal papilloma (ex-ISP) were negative for hrHPV. HPV16 was the most common subtype among hrHPV positive cases (58.8 %), followed by HPV18 (17.6 %). No significant association was observed between hrHPV and OS or DFS after adjusting for potential confounding. hrHPV is prevalent in a sizable fraction of SNSCC. Additional studies are needed to better elucidate the relationship with patient survival outcomes and determine the optimal testing modality for prognostication.

HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients.

HIGD1B (HIG1 Hypoxia Inducible Domain Family Member 1B) is a protein-coding gene linked to the occurrence and progression of various illnesses. However, its precise function in gastric cancer (GC) remains unclear. The expression of HIGD1B is determined through the TCGA and GEO databases and verified using experiments. The association between HIGD1B and GC patients' prognosis was analyzed via the Kaplan-Meier (K-M) curve. Subsequently, the researchers utilized ROC curves to assess the diagnostic capacity of HIGD1B and employed COX analysis to investigate risk factors for GC. The differentially expressed genes (DEGs) were then subjected to functional enrichment analysis, and a nomogram was generated to forecast the survival outcome and probability of GC patients. Additionally, we evaluated the interaction between HIGD1B and the immune cell infiltration and predicted the susceptibility of GC patients to therapy. HIGD1B is markedly elevated in GC tissue and cell lines, and patients with high HIGD1B expression have a poorer outcome. In addition, HIGD1B is related to distinct grades, stages, and T stages. The survival ROC curves of HIGD1B and nomogram for five years were 0.741 and 0.735, suggesting appropriate levels of diagnostic efficacy. According to Cox regression analysis, HIGD1B represents a separate risk factor for the prognosis of gastric cancer (p<0.01). GSEA analysis demonstrated that the HIGD1B is closely related to cancer formation and advanced pathways. Moreover, patients with high HIGD1B expression exhibited a higher level of Tumor-infiltration immune cells (TIICs) and were more likely to experience immune escape and drug resistance after chemotherapy and immunotherapy. This study explored the potential mechanisms and diagnostic and prognostic utility of HIGD1B in GC, as well as identified HIGD1B as a valuable biomarker and possible therapeutic target for GC.

Survival of patients with mucosal melanoma in Cali, Colombia: a retrospective cohort study

BackgroundMucosa melanoma is a rare condition with aggressive behavior and a less favorable prognosis compared to cutaneous melanoma. The objective of this study was to estimate the overall survival and clinical outcomes of patients diagnosed with mucosal melanoma in a Colombian hospital.MethodsA retrospective cohort study was conducted at Fundación Valle del Lili, a single center located in Cali, Colombia. Patients aged ≥ 18 years, both sexes, diagnosed with mucosal melanoma by histopathology study were included between 2010–2019. Patients who received extra-institutional treatment or whose vital status was unknown during follow-up were excluded. Demographic, clinical and laboratory data were obtained from medical records and laboratory and pathology databases. A descriptive analysis was performed. Survival analysis was conducted using the Kaplan–Meier method.ResultsA total of 23 patients were included. Median age was 63 years old (IQR: 57–68) and 52.2% were woman. Clinical stage was 34.8% early, 26.1% locally advanced and 39.1% metastatic. The main primary locations were nasopharynx (30.4%), genitals (26.1%), rectum (21.7%), oral cavity (13%) and paranasal sinuses (8.7%). The majority received surgery (30.4%) and immunotherapy (26.1%) as first line treatment.Overall survival at one year was 80.8%, at three years 44.3%, and at five years 36.9%.ConclusionMucosal melanoma is a rare, aggressive disease with adverse oncological outcomes due to late diagnosis and limited treatment options. This study provides real-world data in a single-center of Colombia.

The prognostic value of postoperative platelet levels in elderly patients after valve replacement surgery: a retrospective cohort study

BackgroundFurther research is needed to assess the risk and prognosis after valve replacement surgery in elderly patients. This study aims to assess the prognostic value of platelet levels following valve replacement in elderly patients.MethodsA retrospective analysis was conducted on 3814 elderly individuals who underwent valve replacement surgery, categorized into quartiles based on postoperative platelet levels. Univariate and multiple regression analysis were used to assess the risk factors associated with postoperative platelet levels and in-hospital death.The Receiver Operating Characteristic (ROC) curve was utilized to establish the postoperative platelet level threshold indicative of in-hospital mortality risk, while the Kaplan-Meier curve compared the one-year postoperative survival among patients with differing postoperative platelet levels.ResultsThe low postoperative platelet levels group had a higher incidence of massive bleeding (> 400 ml), necessitating platelet transfusion and prolonged cardiopulmonary bypass during surgery (P < 0.001). However, postoperative occurrences of heart failure and stroke did not achieve statistical significance (P > 0.05). Multivariate regression analysis disclosed an association between postoperative platelet levels and in-hospital death (OR: 2.040, 95% CI: 1.372–3.034, P < 0.001). Over the one-year follow-up, patients with low platelet levels postoperatively had poorer overall survival than patients with higher platelet levels (P < 0.001)ConclusionPostoperative platelets can serve as a prognostic indicator after valve surgery in elderly patients as a simple and easily available biochemical indicator. Enhanced monitoring and management postoperative platelet level in the elderly may be beneficial to improve the survival outcome of patients

How Progesterone Receptor Expression Impacts Platinum Sensitivity in Ovarian Clear Cell Carcinoma: Insights from Clinical and Experimental Perspectives.

Ovarian clear cell carcinoma (OCCC) is often considered a relatively platinum-resistant malignancy. The aim of this study was to explore the influence of progesterone receptor (PR) expression levels on platinum sensitivity and survival outcomes in people with OCCC. A retrospective analysis was conducted with 80 people with OCCC who underwent surgery followed by adjuvant chemotherapy. PR expression was assessed via immunohistochemical (IHC) staining and quantified using the H score. The platinum sensitivity and survival outcomes of patients with weak and strong PR expression were compared. Additionally, cisplatin viability and migration experiments were conducted with OCCC cell lines (ES-2 and TOV-21G) with varying PR isoform expressions. Among the 80 patients, 62 were classified as having platinum-sensitive disease, while 18 had platinum-resistant disease. The mean total PR H- score of platinum-sensitive tumors was significantly higher than that of platinum-resistant tumors (p = 0.002). Although no significant differences in progression-free and overall survival were observed between patients with high and low PR expression, those with high PR expression tended to have longer survival. While PR protein was only weakly detectable in ES-2 and TOV-21G cells, a transfection of the PR-A or PR-B gene resulted in a strong expression of PR-A or PR-B, which led to significantly reduced proliferation and migration in ES-2 and TOV-21G cells. Furthermore, overexpression of PR-A or PR-B enhanced cisplatin cytotoxicity in these cell lines. In conclusion, strong PR expression was associated with improved platinum sensitivity and survival outcomes, consistent with our experimental findings. The potential of PR as a tumor sensitizer to cisplatin in OCCC warrants further investigation.

No survival benefit of primary tumor resection for non-small cell lung cancer patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

Non-small cell lung cancer (NSCLC) patients with pleural dissemination are generally contraindicated for surgery. This study aimed to investigate the survival benefits of primary tumor resection for NSCLC patients with unexpectedly detected pleural disseminated nodules during thoracotomy in the era of targeted therapy. Of the 4984 patients with NSCLC who underwent surgery without induction therapy between 2000 and 2021, we retrospectively evaluated 90 (1.8%) patients with unexpectedly detected pleural disseminated nodule. Survival analyses were performed with Kaplan-Meier methods and Cox proportional hazards regression. Among the evaluated patients, 58 were male, the median age was 67, and 77 (86%) were diagnosed with adenocarcinoma. Exploratory thoracotomy was performed in 21 (23%), and primary tumor resection was performed in 69 (77%) patients, including pneumonectomy in four, lobectomy in 39, and sublobar resection in 26. Epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase rearrangement were detected in 33 (37%) and 4 (4%) cases, respectively. Among them, 31 patients received targeted therapy. The overall survival (OS) was not significantly different between patients with primary tumor resection and exploratory thoracotomy (5-year OS rate: 30.2% vs. 27.8%, p = 0.81). Multivariable analysis revealed that sex (p = 0.02) and targeted therapy (p < 0.01) were independent prognostic factors for OS. Survival outcomes in patients who received targeted therapy were significantly better regardless of primary tumor resection. Primary tumor resection might not affect the survival in NSCLC patients with unexpectedly detected pleural disseminated nodules in the era of targeted therapy.

Does autoimmune disease impair the survival of hepatocellular carcinoma patients undergoing liver resection? A multi-institutional observational study

BackgroundPatients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies.MethodsOperated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality.ResultsFrom 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (–) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence.ConclusionOur study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings.

Childhood Cancers; Diagnostic Challenges in Sub-Sahara Africa

Childhood cancers pose a significant public health challenge in sub-Saharan Africa due to late diagnoses, limited treatment options, and poor long-term survivorship. This paper aims to describe the key childhood cancers affecting the region, explore barriers to diagnosis and treatment, and propose potential solutions. The most common childhood cancers in Nigeria and other sub-Saharan countries include leukemia, brain tumors, lymphomas such as Burkitt's lymphoma, and solid tumors like neuroblastoma and Wilms' tumor. However, lack of diagnostic capacity, scarce chemotherapy resources, and high costs frequently delay diagnosis and prevent optimal treatment. Poverty is also associated with worse survival outcomes for pediatric cancer patients. Solving this crisis requires coordinated, multi-pronged efforts. Areas of focus include establishing childhood cancer surveillance and control policies, training primary providers to recognize early signs and symptoms, strengthening referral networks, increasing pediatric oncology services in underserved areas, expanding research on childhood cancers unique to the region, and enhancing financial access to treatment. With government support for childhood cancer programs and global partnerships to address shortages in skilled staff and technologies, survival rates have the potential to significantly improve for Africa's children with cancer. Keywords: Childhood cancer, malignancy, Diagnosis, Challenges.

Clinicopathologic characteristics and prognostic factors of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study.

To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.

Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.

Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited. This retrospective study analyzed 97 patients treated at Yale for melanoma between 2002-2020. Bulk-RNA sequencing of patient tumor samples from the Skin Cancer SPORE Biorepository was used to evaluate for differential gene expression of MIF, DDT, CD74, and selected inflammatory markers, and gene expression was correlated with patient survival outcomes. Our findings revealed a strong correlation between MIF and DDT levels, with no statistically significant difference across common melanoma mutations and subtypes. Improved survival was associated with lower MIF and DDT levels and higher CD74:MIF and CD74:DDT levels. High CD74:DDT and CD74:MIF levels were also associated with enrichment of infiltrating inflammatory cell markers. These data suggest DDT as a novel target in immune therapy. Dual MIF and DDT blockade may provide synergistic responses in patients with melanoma, irrespective of common mutations, and may overcome ICI resistance. These markers may also provide prognostic value for further biomarker development.

A Multi-Omics Analysis of an Exhausted T Cells' Molecular Signature in Pan-Cancer.

T cells are essential tumor suppressors in cancer immunology, but their dysfunction induced by cancer cells can result in T cell exhaustion. Exhausted T cells (Tex) significantly influence the tumor immune environment, and thus, there is a need for their thorough investigation across different types of cancer. Here, we address the role of Tex cells in pan-cancer, focusing on the expression, mutations, methylation, immune infiltration, and drug sensitivity of a molecular signature comprising of the genes HAVCR2, CXCL13, LAG3, LAYN, TIGIT, and PDCD1across multiple cancer types, using bioinformatics analysis of TCGA data. Our analysis revealed that the Tex signature genes are differentially expressed across 14 cancer types, being correlated with patient survival outcomes, with distinct survival trends. Pathway analysis indicated that the Tex genes influence key cancer-related pathways, such as apoptosis, EMT, and DNA damage pathways. Immune infiltration analysis highlighted a positive correlation between Tex gene expression and immune cell infiltration in bladder cancer, while mutations in these genes were associated with specific immune cell enrichments in UCEC and SKCM. CNVs in Tex genes were widespread across cancers. We also highlight high LAYN methylation in most tumors and a negative correlation between methylation levels and immune cell infiltration in various cancers. Drug sensitivity analysis identified numerous correlations, with CXCL13 and HAVCR2 expressions influencing sensitivity to several drugs, including Apitolisib, Belinostat, and Docetaxel. Overall, these findings highlight the importance of reviving exhausted T cells to enhance the treatment efficacy to significantly boost anti-tumor immunity and achieve better clinical outcomes.

Timing of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer

Whole genome duplication is frequently observed in cancer, and its prevalence in our prior analysis of end-stage, homologous recombination deficient high grade serous ovarian cancer (almost 80% of samples) supports the notion that whole genome duplication provides a fitness advantage under the selection pressure of therapy. Here, we therefore aim to identify potential therapeutic vulnerabilities in primary high grade serous ovarian cancer with whole genome duplication by assessing differentially expressed genes and pathways in 79 samples. We observe that MHC-II expression is lowest in tumors which have acquired whole genome duplication early in tumor evolution, and further demonstrate that reduced MHC-II expression occurs in subsets of tumor cells rather than in canonical antigen-presenting cells. Early whole genome duplication is also associated with worse patient survival outcomes. Our results suggest an association between the timing of whole genome duplication, MHC-II expression and clinical outcome in high grade serous ovarian cancer that warrants further investigation for therapeutic targeting.

Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma.

Personalized and tumor-informed circulating tumor DNA (ctDNA) testing is feasible and allows for molecular residual disease (MRD) identification in patients with pancreatic ductal adenocarcinoma (PDAC). In this retrospective analysis of commercial cases from multiple US institutions, personalized, tumor-informed, whole-exome sequenced, and germline-controlled ctDNA levels were quantified and analyzed in patients with PDAC. Plasma samples (n = 1329) from 298 clinically validated patients were collected at diagnosis, perioperatively (MRD-window; within 2-12 weeks after surgery, before therapy), and during surveillance (>12 weeks post-surgery if no ACT or starting 4 weeks post-ACT) from November 2019 to March 2023. Of the initially diagnosed patients with stages I-III PDAC who went for resection, the median follow-up time from surgery was 13 months (range 0.1-214). Positive ctDNA detection rates were 29% (29/100) and 29.6% (45/152) during the MRD and surveillance windows, respectively. Positive ctDNA detection was significantly associated with shorter DFS within the MRD window (median DFS of 6.37 months for ctDNA-positive vs 33.31 months for ctDNA-negative patients; HR: 5.45, P < .0001) as well as during the surveillance period (median DFS: 11.40 months for ctDNA-positive vs NR for ctDNA-negative; HR: 12.38, P < .0001). Additionally, DFS was significantly better with KRAS wildtype status followed by KRASG12R (HR: 0.99, P = .97), KRASG12D (HR: 1.42, P = .194), and worse with KRASG12V (HR: 2.19, P = .002) status. In multivariate analysis, ctDNA detection at surveillance was found to be the most significant prognostic factor for recurrence (HR: 24.28, P < .001). Perioperative tumor-informed ctDNA detection in PDAC is feasible across all stages and is associated with patient survival outcomes.

The role of adjuvant chemotherapy after radical surgery in patients with lymph node-positive bladder cancer or locally advanced (pT3, pT4a) bladder cancer: A meta-analysis and systematic review.

This study aims to evaluate the impact of adjuvant chemotherapy (AC) on survival outcomes in patients with lymph node-positive bladder cancer or locally advanced (pT3, pT4a) bladder cancer after surgery. We also seek to identify which patients with pN+ bladder cancer are most likely to benefit from AC after radical cystectomy (RC). We searched databases including Embase, PubMed, Cochrane, and ClinicalTrials.gov to identify relevant literature published in English up to February 2024. We used Stata to compare various parameters. The study has been registered in PROSPERO. A total of 21 studies were analyzed, including 1 randomized controlled trial, 6 prospective studies, and 14 retrospective studies, encompassing 12,888 patients. The meta-analysis showed that for patients with lymph node-positive bladder cancer, the adjuvant chemotherapy (AC) group had higher overall survival (OS) (I2=58.2%, HR 0.69; 95% CI: 0.57-0.83; P=0.019) and recurrence-free survival (RFS) (I2=66.6%, HR 0.71; 95% CI: 0.57-0.89; P=0.006) compared to the radical cystectomy (RC) group. For patients with pT3 and pT4a bladder cancer, the AC group had higher overall survival (OS) (I2=57.3%, HR 0.77; 95% CI: 0.67-0.89; P=0.022) and cancer-specific survival (CSS) (I2=47.2%, HR 0.75; 95% CI: 0.64-0.88; P=0.0048) compared to the RC group. At the same time, according to the different chemotherapy regimens, we divided the cisplatin-based chemotherapy regimen and carboplatin based chemotherapy or other regimens into two subgroups for analysis, and found that the OS (I2=41.4%, HR 0.64; 95%CI: 0.51~0.80; P=0.000) was better than carboplatin and other chemotherapy regimens (I2=64.1%, HR 0.77; 95%CI: 069~0.86; P=0.000); Lymph node density (LND) was found to be an independent predictor of overall survival (HR=1.6; 95% CI: 1.31-1.95; P=0.0000). This study found that postoperative adjuvant chemotherapy (AC) improves overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) in patients with pT3, pT4a, It was also confirmed that cisplatin-based chemotherapy regimen was more beneficial for patients with bladder cancer; and lymph node-positive bladder cancer. Additionally, our analysis revealed that patients with lymph node-positive bladder cancer benefit more from postoperative AC. It was further demonstrated that cisplatin-based chemotherapy regimens are more beneficial than other regimens for patients with locally advanced bladder cancer.

The efficacy of cone-beam computed tomography-guided transcatheter arterial chemoembolization in hepatocellular carcinoma survival: A systematic review.

Cone-beam computed tomography (CBCT)-guided transcatheter arterial chemoembolization (TACE) represents an alternative treatment option for advanced hepatocellular carcinoma (HCC) patients, yet a comprehensive evaluation of CBCT guidance on this procedure and CBCT's impact on patient survival remains lacking. We aimed to assess the efficacy and benefits of CBCT-guided TACE in improving survival outcomes for patients with HCC and show the importance of CBCT in interventional radiology. Meta-analysis was conducted to evaluate CBCT-guided TACE compared to conventional TACE in the treatment of HCC. PubMed and Cochrane library databases were searched for studies published. Outcomes of interest included 1- or 3-year local progression-free survival (LPFS) rates, overall survival (OS) rates, and tumor response results. A total of eight studies were included in the meta-analysis, comprising 1176 patients. The analysis showed that CBCT-guided TACE improved 1-year LPFS (odds ratio [OR] = 2.81, P < 0.001), 3-year (OR = 4.42, P = 0.002), and the 3-year OS rates (OR = 3.03, Confidence Interval = 1.65-11.80, P = 0.14) compared to conventional TACE. CBCT-guided TACE enhances survival outcomes for patients with HCC; by addressing this research gap, our study endeavors to encourage clinicians and researchers to pursue this medical technology by providing a robust synthesis of current evidence.