Survival Of Patients Research Articles

Plasma Ceramide C24:0/C16:0 Ratio is Associated with Improved Survival in Patients with Pancreatic Ductal Adenocarcinoma

Plasma Ceramide C24:0/C16:0 Ratio is Associated with Improved Survival in Patients with Pancreatic Ductal Adenocarcinoma

Abstract A043: Improving our understanding of social determinants of health and neighborhood deprivation on survival in patients after radical cystectomy for urothelial carcinoma

Abstract A043: Improving our understanding of social determinants of health and neighborhood deprivation on survival in patients after radical cystectomy for urothelial carcinoma

Abstract B009: Analysis of the KRAS mutation spectrum in Black/African American and White/European lung adenocarcinoma patients, and its association with patient survival

Abstract B009: Analysis of the KRAS mutation spectrum in Black/African American and White/European lung adenocarcinoma patients, and its association with patient survival

Radiographical consolidation tumor size and preoperative clinical characteristics are significantly correlated with the postoperative survival of patients with part-solid and pure-solid adenocarcinomas: a propensity score-matched analysis

Radiographical consolidation tumor size and preoperative clinical characteristics are significantly correlated with the postoperative survival of patients with part-solid and pure-solid adenocarcinomas: a propensity score-matched analysis

Abstract C067: Immune thrombocytopenia induced by PD-1/PD-L1 inhibitors in a patient with non-small cell lung adenocarcinoma: A case report and literature review

Abstract Introduction: The introduction of immunotherapy, particularly programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, has transformed the treatment paradigm for non-small cell lung adenocarcinoma (NSCLC), significantly improving patient survival rates. However, alongside their immune-activating effects, these agents can also lead to immune-related adverse events (irAEs), affecting various organ systems. Among these, immune thrombocytopenia (ITP) is a rare but potentially life-threatening complication characterized by the destruction of platelets by autoantibodies, resulting in decreased platelet counts and an increased risk of bleeding. While ITP has been identified as a complication of immunotherapy, particularly PD-1 or PD-L1 inhibitors, its incidence, clinical presentation, and management remain poorly understood. Case Presentation: The 73-year-old female with stage IIIA poorly differentiated NSCLC who received chemotherapy with Taxol/Carboplatin and concurrent radiation therapy followed by a right upper lobectomy, initiated on immunotherapy with durvalumab, a PD-L1 inhibitor, developed severe thrombocytopenia (grade 4) after receiving two cycles of durvalumab. Despite steroid treatment, her condition persisted, indicating immune-related adverse events (irAEs). After confirming the diagnosis through further investigation, including molecular analysis, the patient was treated with intravenous immunoglobulin (IVIG), which significantly increased her platelet counts. Durvalumab was discontinued, and fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, was initiated to manage the irAEs effectively. Discussion: ITP is recognized as an immune-related adverse event (irAE) associated with PD-1 or PD-L1 inhibitors, although it remains rare and poorly understood. Several case reports have highlighted the occurrence of ITP induced by these inhibitors, demonstrating varied clinical presentations and responses to treatment. Mechanisms underlying ITP induction by PD-1/PD-L1 inhibitors are not fully elucidated but may involve immune dysregulation, including CD4+ and CD8+ T cell activation, production of antiplatelet antibodies, and increased expression of PD-L1 on platelets. Management strategies for ITP induced by PD-1/PD-L1 inhibitors include steroids, intravenous immunoglobulin (IVIG) therapy, recombinant human thrombopoietin (TPO), interleukin-6 (IL-6) receptor antagonists, and immunosuppressive agents. However, the effectiveness of these treatments varies among patients, highlighting the need for individualized approaches and further research to optimize management strategies. Conclusion: The prompt recognition and management of ITP induced by PD-1/PD-L1 inhibitors are essential for ensuring favorable patient outcomes. Further research is needed to understand the underlying mechanisms and develop effective prevention and management strategies for this rare but serious immune-related adverse event. Citation Format: Aliya M Khan, Richa Dawar. Immune thrombocytopenia induced by PD-1/PD-L1 inhibitors in a patient with non-small cell lung adenocarcinoma: A case report and literature review [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C067.

Comprehensive strain assessment and mortality after acute myocardial infarction: a retrospective observational study based on the Essen Coronary Artery Disease registry

Background and aimsCurrent ESC guidelines on the management of patients after acute myocardial infarction only include the evaluation of left ventricular (LV) function by assessment of the ejection fraction in...

Could neoadjuvant radiation dose escalation increase tumor response and recurrence-free survival in patients with locally advanced rectal cancer?

Could neoadjuvant radiation dose escalation increase tumor response and recurrence-free survival in patients with locally advanced rectal cancer?

Detection of serum SNHG22 and its correlation with prognosis of non-small cell lung cancer

BackgroundLung cancer accounts for a significant proportion of cancer-related deaths in China, with the majority of the cases being classified as non-small cell lung cancer (NSCLC). The study aimed to investigate the expression of serum SNHG22 in patients with NSCLC, and its molecular mechanism and prognostic potential in NSCLC.MethodsAdmitted 125 NSCLC patients were selected for the study, along with 125 healthy individuals in the same period. The levels of SNHG22 and miR-128-3p were quantified via RT-qPCR. Correlations between the SNHG22 level and the pathological characteristics of the NSCLC patients were investigated through the application of the chi-square test. The targeting relationship between SNHG22 and miR-128-3p was predicted by online database and confirmed by luciferase activity. The prognostic ability of SNHG22 in NSCLC was assessed by Kaplan-Meier curves and multivariate Cox analysis.ResultsSNHG22 was upregulated in NSCLC and directly targeted miR-128-3p. The rate of overall survival is lower in patients with high-SNHG22 group compared to those with low-SNHG22 group. Silencing SNHG22 impaired the functionality of cells, which was restored by miR-128-3p inhibitor. SNHG22 stands as an independent predictor of poor prognosis in NSCLC patients.ConclusionThe overexpression of SNHG22 in NSCLC is related to lymph node metastasis, TNM stage and patient survival, which is expected to be a prognostic predictor of NSCLC patients.

A Novel Approach for Predicting the Survival of Colorectal Cancer Patients Using Machine Learning Techniques and Advanced Parameter Optimization Methods

Background: Colorectal cancer is one of the most prevalent forms of cancer and is associated with a high mortality rate. Additionally, an increasing number of adults under 50 are being diagnosed with the disease. This underscores the importance of leveraging modern technologies, such as artificial intelligence, for early diagnosis and treatment support. Methods: Eight classifiers were utilized in this research: Random Forest, XGBoost, CatBoost, LightGBM, Gradient Boosting, Extra Trees, the k-nearest neighbor algorithm (KNN), and decision trees. These algorithms were optimized using the frameworks Optuna, RayTune, and HyperOpt. This study was conducted on a public dataset from Brazil, containing information on tens of thousands of patients. Results: The models developed in this study demonstrated high classification accuracy in predicting one-, three-, and five-year survival, as well as overall mortality and cancer-specific mortality. The CatBoost, LightGBM, Gradient Boosting, and Random Forest classifiers delivered the best performance, achieving an accuracy of approximately 80% across all the evaluated tasks. Conclusions: This research enabled the development of effective classification models that can be applied in clinical practice.

Hsa_circ_0006010 and hsa_circ_0002903 in peripheral blood serve as novel diagnostic, surveillance and prognostic biomarkers for disease progression in chronic myeloid leukemia

BackgroundIn the era of tyrosine kinase inhibitor (TKI) treatment, the progression of chronic myeloid leukemia (CML) remains a significant clinical challenge, and genetic biomarkers for the early identification of CML patients at risk for progression are limited. This study explored whether essential circular RNAs (circRNAs) can be used as biomarkers for diagnosing and monitoring CML disease progression and assessing CML prognosis.MethodsPeripheral blood (PB) samples were collected from 173 CML patients (138 patients with chronic phase CML [CML-CP] and 35 patients with accelerated phase/blast phase CML [CML-AP/BP]) and 63 healthy controls (HCs). High-throughput RNA sequencing (RNA-Seq) was used to screen dysregulated candidate circRNAs for a circRNA signature associated with CML disease progression. Quantitative real-time PCR (qRT-PCR) was used for preliminary verification and screening of candidate dysregulated genes, as well as subsequent exploration of clinical applications. Receiver operating characteristic (ROC) curve analysis, Spearman’s rho correlation test, and the Kaplan-Meier method were used for statistical analysis.ResultsThe aberrant expression of hsa_circ_0006010 and hsa_circ_0002903 during CML progression could serve as valuable biomarkers for differentiating CML-AP/BP patients from CMP-CP patients or HCs. In addition, the expression levels of hsa_circ_0006010 and hsa_circ_0002903 were significantly associated with the clinical features of CML patients but were not directly related to the four scoring systems. Furthermore, survival analysis revealed that high hsa_circ_0006010 expression and low hsa_circ_0002903 expression indicated poor progression-free survival (PFS) in CML patients. Finally, PB hsa_circ_0006010 and hsa_circ_0002903 expression at diagnosis may also serve as disease progression surveillance markers for CML patients but were not correlated with PB BCR-ABL1/ABL1IS.ConclusionsOur study demonstrated that PB levels of hsa_circ_0006010 and hsa_circ_0002903 may serve as novel diagnostic, surveillance, and prognostic biomarkers for CML disease progression and may contribute to assisting in the diagnosis of CML patients at risk for progression and accurate management of advanced CML patients.

Effect of electronic alerts on the care and outcomes in patients with acute kidney injury: a meta-analysis and trial sequential analysis

BackgroundAlthough electronic alerts are being increasingly implemented in patients with acute kidney injury (AKI), their effect remains unclear. Therefore, we conducted this meta-analysis aiming at investigating their impact on the care and outcomes of AKI patients.MethodsPubMed, Embase, Cochrane Library, and Clinical Trial Registries databases were systematically searched for relevant studies from inception to March 2024. Randomized controlled trials comparing electronic alerts with usual care in patients with AKI were selected.ResultsSix studies including 40,146 patients met the inclusion criteria. The pooled results showed that electronic alerts did not improve mortality rates (relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.97–1.08, P = 0.44) or reduce creatinine levels (mean difference (MD) = − 0.21, 95% CI = − 1.60–1.18, P = 0.77) and AKI progression (RR = 0.97, 95% CI = 0.90–1.04, P = 0.40). Instead, electronic alerts increased the odds of dialysis and AKI documentation (RR = 1.14, 95% CI = 1.05–1.25, P = 0.002; RR = 1.21, 95% CI = 1.01–1.44, P = 0.04, respectively), but the trial sequential analysis (TSA) could not confirm these results. No differences were observed in other care-centered outcomes including renal consults and investigations between the alert and usual care groups.ConclusionsElectronic alerts increased the incidence of AKI and dialysis in AKI patients, which likely reflected improved recognition and early intervention. However, these changes did not improve the survival or kidney function of AKI patients. The findings warrant further research to comprehensively evaluate the impact of electronic alerts.

Baseline eosinophil proportion is a useful predictor of immune-related adverse events following immune checkpoint inhibitor treatment for recurrent metastatic head and neck cancer

Background Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs. However, predictors of irAEs remain unidentified. Objectives We evaluated the predictors of irAEs and compared the outcomes of ICIs with and without irAEs in patients with recurrent/metastatic head and neck cancers (R/M HNCs). Materials and methods We retrospectively analyzed 157 patients with R/M HNCs who were administered an anti-PD-1 antibody between September 2014 and December 2022. We examined whether various pretreatment factors were associated with irAEs. The overall survival (OS) and progression-free survival (PFS) in patients with and without irAEs were analyzed. Results Overall, 44 patients (28.0%) developed irAEs. The survival curve estimated for patients with and without irAEs showed a significant difference in PFS (p = 0.018), but not in OS (p = 0.208). Multivariate analysis revealed significant differences in relative eosinophil counts (p < 0.001), TP (p = 0.014), and NLR (p = 0.002), which may be independent predictors of irAEs. Conclusion IrAEs may be associated with higher efficacy of ICIs and longer PFS. The relative eosinophil count may be predictors of irAEs and useful in routine medical practice. Using these biomarkers to predict irAEs will help predict ICI effects and manage irAEs.

Effect of Chemotherapy and Surgery Timing on Mortality in Upper and Lower Extremity Osteosarcoma

Abstract Background Surgery with both neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests that up-front surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care (“Neoadjuvant First”) vs upfront surgery first followed by adjuvant chemotherapy (“Surgery First”). Patients and methods Using Surveillance, Epidemiology, and End Results data, we identified patients age 5-29, diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the Surgery First and Neoadjuvant First groups. Results Adjusted 5-year survival was 74% for Surgery First patients and 67% for Neoadjuvant First patients, with a survival difference of 6.9% (95% CI -4.2% - 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8% to 13.7% higher 5-year survival in Surgery First patients. Significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage 3-4 disease (vs stage 1-2 disease). Conclusion The evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the peri-surgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.

Identification of prognostic biomarkers in neuroblastoma using WGCNA and multi-omics analysis

BackgroundNeuroblastoma (NB) is one of the most frequent parenchymal tumors among children, with a high degree of heterogeneity and wide variation in clinical presentation. Despite significant therapeutic advances in recent years, long-term survival in high-risk patients remains low, emphasizing the urgent need to find new biomarkers and construct reliable prognostic models.MethodsIn this study, data from neuroblastoma samples in the ArrayExpress database were utilized to identify key gene modules and pivotal genes associated with NB prognosis by weighted gene co-expression network analysis (WGCNA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis was performed using the DAVID database. Based on these hub genes, survival prognosis models were constructed and validated on an independent validation set in the Gene Expression Omnibus (GEO) database. Differences in biological functions and immune microenvironments and the sensitivity to pharmacological and immunotherapeutic treatments of patients in the high- and low-risk groups were examined by gene set enrichment analysis (GSEA) and immune infiltration analysis.ResultsWGCNA identified 14 gene modules and screened the module with the highest relevance to the International Neuroblastoma Staging System (INSS), containing 60 pivotal genes. GO and KEGG analyses demonstrated that these pivotal genes were mainly implicated in biological processes and signaling pathways including DNA replication, cell division, mitotic cell cycle, and cell cycle. Based on Lasso regression and COX regression analysis, a prognostic model containing DHFR, GMPS and E2F3 was constructed, and the RiskScore was significantly correlated with the 1-, 3- and 5-year survival of the patients. GSEA and immune infiltration analyses revealed significant differences in the levels of cell cycle-related pathways and immune cell infiltration between the high and low RiskScore groups. In particular, patients in the high-risk group are less likely to benefit from immunotherapy and may be better suited for treatment with drugs such as Oxaliplatin and Alpelisib.ConclusionThis research systematically identified biomarkers related to NB prognosis and developed a reliable prognostic model applying WGCNA and multiple bioinformatics methods. The model has important application value in predicting patients’ prognosis, evaluating drug sensitivity and immunotherapy effect, and provides new ideas and directions for precise treatment of neuroblastoma.

Protein Tyrosine Kinase 7 (PTK7) in Breast Cancer: A Retrospective Analysis of Tumour Expression and Association with Clinical Outcome

Protein tyrosine kinase 7 (PTK7), originally known as colon carcinoma kinase (CCK4), is an evolutionary conserved, catalytically defective transmembrane receptor involved in Wnt signalling. PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has been investigated in phase I clinical trials for triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer. PTK7 protein expression was evaluated in 1136 early-stage invasive breast tumours by immunohistochemistry. In addition, PTK7 mRNA expression in the METABRIC (n = 1980) and the TCGA breast cancer cohorts (n = 1082) was evaluated. Associations between PTK7 expression and clinicopathological criteria and patient outcome were determined. No association between PTK7 protein expression and breast cancer-specific survival was observed; however, PTK7 mRNA expression in the METABRIC cohort was associated with breast cancer-specific survival (p &lt; 0.001). PTK7 protein and mRNA expression were associated with breast cancer-specific survival of patients with a poor prognostic Nottingham Prognostic Index (NPI) and a moderate prognostic NPI, respectively. Taken together, these data indicate that PTK7 expression is associated with patient outcome in subgroups of breast cancer patients.

Investigating MATN3 and ASPN as novel drivers of gastric cancer progression via EMT pathways

Abstract Gastric cancer (GC) is a leading cause of cancer-related deaths globally, necessitating the identification of novel therapeutic targets. This study investigates the roles of MATN3 and ASPN in GC progression via the epithelial-mesenchymal transition (EMT) pathway. Analysis of the Cancer Genome Atlas—Stomach Adenocarcinoma (TCGA-STAD) dataset revealed that both MATN3 and ASPN are significantly upregulated in GC tissues and correlate with poor patient survival. Protein–protein interaction and co-expression analyses confirmed a direct interaction between MATN3 and ASPN, suggesting their synergistic role in EMT activation. Functional assays demonstrated that MATN3 promotes GC cell proliferation, migration, and invasion, while its knockdown inhibits these malignant behaviors and induces apoptosis. ASPN overexpression further amplified these oncogenic effects. In vivo, studies in a mouse model corroborated that co-overexpression of MATN3 and ASPN enhances tumor growth and metastasis. These findings highlight the MATN3-ASPN axis as a potential therapeutic target in GC, offering new insights into the molecular mechanisms driving GC progression.

Pulmonary and extra-pulmonary effects of lung transplantation in an Italian cohort of patients with systemic sclerosis

Abstract Objectives Lung transplantation (LuTx) is a life-saving intervention for Systemic Sclerosis (SSc) patients with end-stage lung disease. The aim of this study was to evaluate patients’ survival and LuTx outcomes on systemic disease manifestations. Methods A retrospective evaluation was conducted on SSc patients who underwent LuTx between 2010 and 2021. Outcomes assessed at baseline, 6, 12, and 24 months post-LuTx included skin involvement by modified Rodnan skin score (mRSS), global disease activity using a modified EUSTAR index (0–9 scale). Lung function rescue was evaluated by forced vital capacity (FVC). Patient survival was assessed by Kaplan-Meier analysis. Results 13 SSc patients were included, with a male/female ratio 9/4 and a median age of 48.7 years. Nine patients were affected by diffuse cutaneous scleroderma (dcSSc) and four by limited cutaneous scleroderma (lcSSc). FVC significantly increased from 56% of the predicted value at baseline to 78% at 2 years (p= 0.003). mRSS decreased from 7.4 ± 3.8–3.3 ± 2.5 in patients with dcSSc (p= 0.02). The modified EUSTAR index score decreased from 2.54 ± 1.8 at baseline to 0.49 ± 0.5 at 2 years (p= 0.02). Survival rate was 92.3% at 2 years, and 76.9% at 5 years. No unexpected adverse events were observed. Conclusions In SSc patients undergoing LuTx, an excellent 2-year survival was observed, without any disease-related adverse events. Our study supports LuTx as a viable option in SSc patients with end-stage lung disease. Apart from expected recovery of lung function, LuTx was associated with improvement of mRSS and global systemic disease activity.

Overall Survival and Cancer-Specific Mortality in Patients with Prostate Cancer Undergoing Definitive Therapies: A Narrative Review

The overall survival (OS) of patients with prostate cancer (PCa) who receive locally definitive therapy is generally better than that of patients who do not receive definitive therapy. There is no difference in the incidence of local recurrence or distant metastasis between treatment modalities. Because the prognosis of PCa is relatively good, many studies have focused on quality of life after treatment as an endpoint. However, a limited number of patients develop biochemical recurrence after definitive treatment for PCa and subsequently develop distant metastasis or die from PCa. Therefore, we believe that preventing local recurrence and distant metastasis and prolonging the OS should be emphasized when selecting a treatment modality for PCa. In this review, the significance and usefulness of radical prostatectomy and radiation therapy as the main modalities of definitive therapies for local PCa and locally advanced PCa were evaluated, as well as the outcomes of OS and PCa-specific mortality and the treatment options after biochemical recurrence to improve the oncological outcomes.

Effect of radiation after surgery on the prognosis of children with Wilms tumor

Background To explore the association between radiation after surgery and the 5-year overall survival (OS) and 5-year cancer-specific survival (CSS) in patients with Wilms tumor. Methods In this cohort study, 1564 participants were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The univariate and multivariable COX proportional risk model as well as competitive risk model were used to explore the covariates associated with 5-year OS and 5-year CSS of patients with Wilms tumor and the correlation between radiation after surgery and 5-year OS or 5-year CSS of patients with Wilms tumor, respectively. The Kaplan-Meier curves of participants were plotted. Results The median follow-up was 126.00 (84.00, 178.00) months. Patients receiving surgery had higher 5-year survival probability than those not receiving surgery, while participants receiving radiation after surgery showed poor 5-year survival than those not. After adjusting for covariates including age and SEER stage, increased risk of 5-year overall mortality in patients with Wilms tumor [hazard ratio (HR) = 1.62, 95% confidence interval (CI): 1.10–2.41). After the adjustment for confounding factors including age, SEER stage and ethnicity, increased risk of 5-year cancer-specific mortality of patients with Wilms tumor was observed in those receiving radiation after surgery (HR = 1.77, 95%CI: 1.13–2.79). Conclusion Radiation after surgery was associated with poor prognosis of patients with Wilms tumor, which indicated that the clinicians should assess whether the patient was suitable for using radiation after surgery.

Combination of immune checkpoint inhibitors and radiotherapy in locally advanced esophagogastric junction adenocarcinoma: A review

AbstractEsophagogastric adenocarcinoma (EGJ‐AC) poses a significant global health burden, characterized by high incidence rates and poor prognosis. Despite advancements in treatment modalities, including surgery, chemotherapy, and radiation therapy (RT), locally advanced EGJ‐AC management remains challenging. Various preclinical and clinical studies have provided insights into the synergistic effects of combining immune checkpoint inhibitors (ICIs) with RT, further supporting the combination therapy in EGJ‐AC. Immunotherapy, particularly ICIs, has emerged as a promising therapeutic approach in various malignancies, including EGJ‐AC. This narrative review aims to critically examine the rationale behind combining ICIs with standard treatment modalities, including RT or chemoradiotherapy, in the preoperative setting for locally advanced EGJ‐AC. A comprehensive literature search identified eight phase 2 randomized clinical trials evaluating the safety profile and oncologic outcomes of adding ICI agents to neoadjuvant chemoradiotherapy in this population. The results of enrolled trials show that the combination of ICIs with standard treatment modalities is a promising approach for improving survival and pathological response in patients with locally advanced EGJ‐AC. This combination treatment was associated with mostly grade 1–2 immune‐related toxicities, indicating its safety and tolerability. There were higher rates of complete or major pathologic responses compared to historical controls. Further studies, including large‐scale randomized controlled trials, are needed to address remaining questions regarding the efficacy, safety, and long‐term outcomes of combination therapy in this population.