Significant Differences In Survival Outcomes Research Articles

Evolution and prognostic significance of HER-2 changes from primary to residual disease in patients with HER-2–negative breast cancer receiving neoadjuvant chemotherapy.

583 Background: HER-2 changes during the neoadjuvant chemotherapy has not been thoroughly evaluated. The current study aimed to analyze the HER-2 status changes from primary to residual disease in HER-2 negative patients after neoadjuvant chemotherapy and evaluate its impact in survival outcomes. Methods: HER-2 negative breast cancer patients with residual disease after NACT who had paired pre- and post-therapeutic HER2 testing results were retrospectively analyzed. Data on clinical and pathological characteristics, treatment information, and survival outcomes were collected for all eligible patients. HER2 changes from the primary to residual disease were described and logistic regression were performed to identify factors associated with HER2 changes. The Kaplan–Meier method and multivariate Cox regression were used for survival analysis. Results: 571 HER-2 negative breast cancer patients with residual disease after NACT were enrolled, including HER2-zero (35.2%, n=201) and HER2-low (64.8%, n=370) patients before NAC. The overall rate of HER-2 changes rate was 32.4% (negative to positive 1.1%, low to zero 15.4%, zero to low 15.9%). Among the patients with HER-2-zero before NAC, patients with HER-2 changes (zero to low) were likely to be hormone receptor positive (68.1% vs 36.7%, P<0.0001) and had a higher proportion of patients with Ki-67≤20 (Ki-67≤20 27.5% vs 15.6%, P=0.035). Among the patients with HER2-low before NAC, a higher proportion of hormone receptor negative were observed in HER2 changes patients (low to zero) (31.8% vs 18.4%, P=0.008) and the Ki-67 is relatively high in HER-2 changes patients (Ki-76 > 20 73.9% vs 65.0% P=0.030). Multivariable logistic regression analyses showed patients with hormone receptor positive before NAC were related to underwent HER2-zero transferring to HER2-low (OR, 3.436, P<0.0001). The median follow-up time was 50.0 months. In the HER-2 zero group, HER2 changes (zero to low) was significantly associated with better DFS comparing with constant HER2-zero (HR0.49, P=0.01) after adjustment, with 4-year DFS rate was 80.1%,55.7% (Log-rank P =0.033). Subgroup analysis showed that in the hormone receptor positive subgroup, patients with HER2 zero to low has a significant better DFS than patients with constant HER2-zero (Log-rank P=0.037). In the HER2-low group, no significant differences in survival outcomes between constant HER2-low and HER2 low to zero (HR1.07, P=0.778). Conclusions: HER2 status showed instability from primary tumor to residual disease after neoadjuvant treatment. HER2 changes (zero to low) was associated with better DFS in HER-2 zero patients.

Prognostic Impact of CDKN2A Mutations Associated With Smoking and Drinking History in Japanese Digestive Cancers.

Organs of the digestive system are frequent sites of cancer development, and digestive tract cancers are the leading causes of death worldwide, including in Japan. Most of these cancers are associated with smoking or drinking habits. This study focused on the clinical and genomic characteristics of patients with these cancers using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, which comprises a large volume of data on Japanese patients who have undergone tumor profiling gene panel tests. The genomic and clinical data from patients with digestive tract cancers registered in C-CAT between 2019 and 2023 were retrospectively reviewed. The data were derived from 412 patients with esophageal squamous cell carcinoma, 558 with gastric adenocarcinoma, 3,368 with colorectal adenocarcinoma, 139 with hepatocellular carcinoma, 2,050 with cholangiocarcinoma, and 2,552 with pancreatic ductal adenocarcinoma. CDKN2A, CDKN2B, and MTAP mutations were associated with both smoking and drinking history, and patients with these mutations had a worse prognosis. Almost all gene alterations in CDKN2B and MTAP were deletions, often accompanied by CDKN2A deletion. CDKN2A mutation emerged as the most decisive prognostic factor among these mutations. Although CDKN2A mutations were frequently seen in esophageal squamous cell carcinoma, cholangiocarcinoma, and pancreatic ductal adenocarcinoma, statistically significant differences in survival outcomes were only identified in the latter two. CDKN2A mutations were associated with smoking and drinking in digestive cancers. This mutation was prevalent among patients with cholangiocarcinoma and pancreatic ductal adenocarcinoma, for whom they could serve as prognostic factors.

Establishment and validation of a predictive model for tracheotomy in critically ill patients and analysis of the impact of different tracheotomy timing on patient prognosis

BackgroundIn critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial.MethodsClinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group (< = 7 days) and the late tracheotomy group (> 7 days), and the prognosis of the two groups was analyzed.ResultsA total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876–0.919), and 0.896 (95% CI: 0.866–0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p < 0.05), but there was no statistically significant difference in survival outcomes between the two groups.ConclusionThe prediction model constructed and validated based on the MIMIC-IV database can accurately predict the outcome of tracheotomy in critically ill patients. Meanwhile, early tracheotomy in critically ill patients does not improve survival outcomes but has potential advantages in shortening the duration of hospitalization, IMV, and sedation.

Metabolic predictors of COVID-19 mortality and severity: a survival analysis.

The global healthcare burden of COVID-19 pandemic has been unprecedented with a high mortality. Metabolomics, a powerful technique, has been increasingly utilized to study the host response to infections and to understand the progression of multi-system disorders such as COVID-19. Analysis of the host metabolites in response to SARS-CoV-2 infection can provide a snapshot of the endogenous metabolic landscape of the host and its role in shaping the interaction with SARS-CoV-2. Disease severity and consequently the clinical outcomes may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. Hence, the host metabolome can help predict potential clinical risks and outcomes. In this prospective study, using a targeted metabolomics approach, we studied the metabolic signature in 154 COVID-19 patients (males=138, age range 48-69 yrs) and related it to disease severity and mortality. Blood plasma concentrations of metabolites were quantified through LC-MS using MxP Quant 500 kit, which has a coverage of 630 metabolites from 26 biochemical classes including distinct classes of lipids and small organic molecules. We then employed Kaplan-Meier survival analysis to investigate the correlation between various metabolic markers, disease severity and patient outcomes. A comparison of survival outcomes between individuals with high levels of various metabolites (amino acids, tryptophan, kynurenine, serotonin, creatine, SDMA, ADMA, 1-MH and carnitine palmitoyltransferase 1 and 2 enzymes) and those with low levels revealed statistically significant differences in survival outcomes. We further used four key metabolic markers (tryptophan, kynurenine, asymmetric dimethylarginine, and 1-Methylhistidine) to develop a COVID-19 mortality risk model through the application of multiple machine-learning methods. Metabolomics analysis revealed distinct metabolic signatures among different severity groups, reflecting discernible alterations in amino acid levels and perturbations in tryptophan metabolism. Notably, critical patients exhibited higher levels of short chain acylcarnitines, concomitant with higher concentrations of SDMA, ADMA, and 1-MH in severe cases and non-survivors. Conversely, levels of 3-methylhistidine were lower in this context.

Machine learning and multi-omics data reveal driver gene-based molecular subtypes in hepatocellular carcinoma for precision treatment.

The heterogeneity of Hepatocellular Carcinoma (HCC) poses a barrier to effective treatment. Stratifying highly heterogeneous HCC into molecular subtypes with similar features is crucial for personalized anti-tumor therapies. Although driver genes play pivotal roles in cancer progression, their potential in HCC subtyping has been largely overlooked. This study aims to utilize driver genes to construct HCC subtype models and unravel their molecular mechanisms. Utilizing a novel computational framework, we expanded the initially identified 96 driver genes to 1192 based on mutational aspects and an additional 233 considering driver dysregulation. These genes were subsequently employed as stratification markers for further analyses. A novel multi-omics subtype classification algorithm was developed, leveraging mutation and expression data of the identified stratification genes. This algorithm successfully categorized HCC into two distinct subtypes, CLASS A and CLASS B, demonstrating significant differences in survival outcomes. Integrating multi-omics and single-cell data unveiled substantial distinctions between these subtypes regarding transcriptomics, mutations, copy number variations, and epigenomics. Moreover, our prognostic model exhibited excellent predictive performance in training and external validation cohorts. Finally, a 10-gene classification model for these subtypes identified TTK as a promising therapeutic target with robust classification capabilities. This comprehensive study provides a novel perspective on HCC stratification, offering crucial insights for a deeper understanding of its pathogenesis and the development of promising treatment strategies.

Impact of neoadjuvant compared to adjuvant chemotherapy on prognosis in patients with hormone-receptor positive / HER2-negative breast cancer: A propensity score matching population-based study

BackgroundThe aim of this population-based cohort study was to investigate the impact of neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy in prognosis among patients with HR+/HER2 negative breast cancer. MethodThis population-based study utilized data from the research database BCBaSe 3.0, based on the Swedish National Quality breast cancer register, including all patients with breast cancer diagnosis in Sweden between 2008 and 2019. Propensity score matching approach was applied. The outcomes of interest consisted of distant-disease free (DDFS), breast-cancer specific (BCSS), and overall survival (OS). ResultsIn total, 14 459 patients were included in the study cohort of whom 2086 received NACT. After 1:1 propensity score matching (PSM), 1539 patients in each study group were available for analyses. No statistically significant difference in survival outcomes were observed between patients treated with NACT compared to those treated with adjuvant chemotherapy (Hazard Ratio (HR) for DDFS: 1.20; 95 % CI: 0.80–1.79; HR for BCSS: 1.16; 95 % CI: 0.54–2.49; HR for OS: 1.14; 95 % CI: 0.64–2.05). ConclusionIn this population-based cohort study of patients with HR+/HER2-breast cancer, the use of NACT seems to be comparable to adjuvant chemotherapy in terms of prognosis, although non-inferiority cannot be proven by this study design. Until further evidence suggesting a survival benefit in favor of either treatment is available, NACT can be pursued when surgical-de-escalation is intended.

Abstract PO4-23-07: Impact of distance between tumor and nipple on locoregional recurrence in breast cancer

Abstract Introduction: Mastectomy is usually recommended for centrally located tumors due to the risk of nipple invasion. While it is well known that there is no significant difference in survival outcomes according to tumor location, central tumors have a higher likelihood of main lactiferous duct invasion, which can result in the migration of tumor cells to the periphery. Therefore, we conducted an investigation specifically focusing on locoregional recurrence (LRR) rates based on the tumor-to-nipple distance (TND). Method: We retrospectively collected the data of patients who underwent breast cancer surgery between 2004-2018 from two institutions. Patients who underwent neoadjuvant chemotherapy were excluded. TND information was obtained from preoperative MRI records. Results: A total of 9,014 patients were included in the study, and the median tumor-to-nipple distance (TND) was 3.4 (0.0-15.0) cm. For all patients, the restricted cubic spline curve analysis showed that the hazard risk of LRR increased with shorter TND. The pattern was more pronounced in the breast-conserving surgery (BCS) group, whereas the mastectomy group showed a relatively constant risk regardless of TND. Thus, we conducted survival analysis for 5,455 patients who underwent BCS. We set the cutoff for TND as 2.5cm as it showed the lowest p-value for LRR rate. Compared to those with TND &amp;gt;2.5cm, patients with TND≤2.5cm showed significantly lower LRR (HR,1.83;95%CI,[1.37-2.46],p&amp;lt; 0.001) and distant metastasis(DM) (HR,1.53;95%CI,[1.16-2.02],p=0.002) rates. Overall survival was not different between two groups (p=0.405). Cox-regression analysis revealed that TND still impacts LRR (HR,1.52;95%CI,[1.11-2.09],p=0.010) but not DM. Importantly, TND still remained significant factor affecting LRR when analyzed as continuous variable (HR,1.04; 95%CI,[1.02-1.06],p&amp;lt; 0.001). The prognostic impact of TND was particularly evident in patients with high mammographic density. Discussion: BCS can be performed for centrally located tumors, as it offers considerable oncologic safety compared to mastectomy. However, for patients who have a fear of recurrence and are reluctant to undergo re-operation, mastectomy would be a good choice. Citation Format: Jong-Ho Cheun, Eunhye Kang, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Ki-Tae Hwang. Impact of distance between tumor and nipple on locoregional recurrence in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-07.

Abstract PS08-01: Antibody-Drug Conjugates (ADCs) in Breast Cancer: Real World Analysis of Outcomes

Abstract Methods: We estimated the distribution of progression-free survival (PFS), overall survival (OS), and time to treatment failure (TTF) using the Kaplan-Meier method. Differences in survival curves between groups categorized by initial ADC treatment and subsequent ADC treatments were assessed using the log-rank test. Cox proportional hazards regression models were employed to evaluate the association between each survival outcome and various measures of interest, such as age, gender, race, number of prior lines of treatment, hormone receptor status, and HER2 status. Results: The analysis included a total of 469 breast cancer patients, with the distribution of clinical characteristics summarized in Table 1. The median age at the start of ADC treatment was 50 years (range: 20-85). Among the patients, 263 patients (56%) received SC as their initial ADC treatment, while 44% received T-DXd. Additionally, 29 patients received both ADCs during metastatic treatment. The median follow-up time for all patients was 7.9 months (range: 0.1- 39.1). Out of the total patient population, 29% died, while 71% were still alive at the last follow-up. The median OS for all patients was 21.6 months. Median OS of patients receiving SC or T-DXd as their initial ADC treatment, was 14 and 37.1 months, respectively. Patients who received both SC and T-DXd had a median OS of 26.1 months. The median PFS for all patients was 6.0 months. Patients initially treated with SC had a median PFS of 4.7 months, whereas those treated with T-DXd had a median PFS of 9.0 months. In patients who received both, median of PFS was 4.9 months for T-DXd after SC, and 5.0 months for SC after T-DXd. The median TTF for all patients was 6.1 months. Patients initially treated with SC had a median TTF of 4.7 months, while those treated with T-DXd had a median TTF of 9.0 months. In patients who received T-DXd after SC, TTF was 4.9 months and SC after T-DXd was 5.0 months. Clinician-judged responses were seen in 180 (74%)of patients with SC only, 80 (41%) with T-DXd only, 9 (100%) with SC as 2nd ADC and 20 (100%) with T-DXd as 2nd ADC. Furthermore, the analysis explored the association of OS, PFS, and TTF with various measures of interest, including age, gender, race, number of prior lines of treatment, type of treatment, hormone receptor status, HER2 status, Ki67, and best response to ADC. Some notable associations were observed, such as ER-positive status being associated with marginally longer OS compared to ER-negative status (median 24.7 vs. 16.4 months; p=0.06), and HER2-positive status being associated with longer PFS compared to HER2-negative status (median 14.2 vs. 5.4 months; p&amp;lt; 0.001). However, these associations should be interpreted cautiously as they were obtained from univariate analysis. Conclusions: Overall, these results highlight the significant differences in survival outcomes between different ADC treatments in breast cancer patients, likely due to differing patient characteristics. Distribution of clinical characteristics across ADCs Citation Format: Akshara Singareeka Raghavendra, Zhongya Wang, Roland Bassett, Debu Tripathy. Antibody-Drug Conjugates (ADCs) in Breast Cancer: Real World Analysis of Outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-01.

Characteristics and significance of programmed cell death-related gene expression signature in skin cutaneous melanoma.

Programmed cell death (PCD) pathways play crucial roles in the pathogenesis of skin cutaneous melanoma (SKCM). Understanding their prognostic significance and clinical implications is imperative for the development of personalized treatment strategies. A total of 1466 PCD-related genes were analyzed using data from The Cancer Genome Atlas (TCGA)-SKCM cohort (n=353). Prognostic cell death index (CDI) was established and validated through survival analysis and predictive modeling. Functional enrichment, protein-protein interaction (PPI), consensus clustering, and tumor microenvironment assessment and drug sensitivity analysis were performed to elucidate the biological and clinical relevance of CDI. CDI effectively stratified SKCM patients into high and low-risk groups, demonstrating significant differences in survival outcomes. It exhibited predictive value for survival at 1, 3, and 5 years. The concordance index (C-index) was 0.794 in the training set, and 0.792 and 0.821 in the internal and external validation sets, respectively. The corresponding area under curve (AUC) was all above 0.75 in these data sets. Functional enrichment analysis revealed significant associations with immune response and inflammatory processes. PPI analysis identified key molecular modules associated with apoptosis and chemokine signaling. Consensus clustering unveiled three discernible subtypes demonstrating notable disparities in survival outcomes based on CDI expression profiles. Assessment of the tumor microenvironment highlighted correlations with immune cell infiltration such as M1 macrophages and T cells. Drug sensitivity analysis indicated tight correlations between CDI levels and response to immunotherapy. Our comprehensive analysis establishes the prognostic significance of PCD-related genes in SKCM. CDI emerges as a promising prognostic biomarker, offering insights into tumor biology and potential implications for personalized treatment strategies. Further validation and clinical integration of CDI are warranted to improve SKCM management and patient outcomes.

Sex-specific Differences in IDH1-Wildtype Glioblastoma patients in the ReSPOND Consortium.

Understanding sex-based differences in glioblastoma patients is necessary for accurate personalized treatment planning to improve patient outcomes. To investigate sex-specific differences in molecular, clinical and radiological tumor parameters, as well as survival outcomes in glioblastoma, isocitrate dehydrogenase-1 wildtype (IDH1-WT), grade 4 patients. Retrospective data of 1832 glioblastoma, IDH1-WT patients with comprehensive information on tumor parameters was acquired from the Radiomics Signatures for Precision Oncology in Glioblastoma (ReSPOND) consortium. Data imputation was performed for missing values. Sex-based differences in tumor parameters, such as, age, molecular parameters, pre-operative KPS score, tumor volumes, epicenter and laterality were assessed through non-parametric tests. Spatial atlases were generated using pre-operative MRI maps to visualize tumor characteristics. Survival time analysis was performed through log-rank tests and Cox proportional hazard analyses. GBM was diagnosed at a median age of 64 years in females compared to 61.9 years in males (FDR = 0.003). Males had a higher Karnofsky Performance Score (above 80) as compared to females (60.4% females Vs 69.7% males, FDR = 0.044). Females had lower tumor volumes in enhancing (16.7 cm3 Vs. 20.6 cm3 in males, FDR = 0.001), necrotic core (6.18 cm3 Vs. 7.76 cm3 in males, FDR = 0.001) and edema regions (46.9 cm3 Vs. 59.2 cm3 in males, FDR = 0.0001). Right temporal region was the most common tumor epicenter in the overall population. Right as well as left temporal lobes were more frequently involved in males. There were no significant differences in survival outcomes and mortality ratios. Higher age, unmethylated O6-methylguanine-DNAmethyltransferase (MGMT) promoter and undergoing subtotal resection increased the mortality risk in both males and females. Our study demonstrates significant sex-based differences in clinical and radiological tumor parameters of glioblastoma, IDH1-WT, grade 4 patients. Sex is not an independent prognostic factor for survival outcomes and the tumor parameters influencing patient outcomes are identical for males and females. IDH1-WT = isocitrate dehydrogenase-1 wildtype; MGMTp = O6-methylguanine-DNA-methyltransferase promoter; KPS = Karnofsky performance score; EOR = extent of resection; WHO = world health organization; FDR = false discovery rate.

Mortality rates in Norwegian HEMS—a retrospective analysis from Central Norway

BackgroundHelicopter Emergency Medical Services (HEMS) provide rapid and specialized care to critically ill or injured patients. Norwegian HEMS in Central Norway serves an important role in pre-hospital emergency medical care. To grade the severity of patients, HEMS uses the National Advisory Committee for Aeronautics’ (NACA) severity score. The objective of this study was to describe the short- and long term mortality overall and in each NACA-group for patients transported by HEMS Trondheim using linkage of HEMS and hospital data.MethodsThe study used a retrospective cohort design, aligning with the STROBE recommendations. Patient data from Trondheim HEMS between 01.01.2017 and 31.12.2019 was linked to mortality data from a hospital database and analyzed. Kaplan Meier plots and cumulative mortality rates were calculated for each NACA group at day one, day 30, and one year and three years after the incident.ResultsTrondheim HEMS responded to 2224 alarms in the included time period, with 1431 patients meeting inclusion criteria for the study. Overall mortality rates at respective time points were 10.1% at day one, 13.4% at 30 days, 18.5% at one year, and 22.3% at three years. The one-year cumulative mortality rates for each NACA group were as follows: 0% for NACA 1 and 2, 2.9% for NACA 3, 10.1% for NACA 4, 24.7% for NACA 5 and 49.5% for NACA 6. Statistical analysis with a global log-rank test indicated a significant difference in survival outcomes among the groups (p < 2⋅10− 16).ConclusionAmong patients transported by Trondheim HEMS, we observed an incremental rise in mortality rates with increasing NACA scores. The study further suggests that a one-year follow-up may be sufficient for future investigations into HEMS outcomes.

Development of a promising PPAR signaling pathway-related prognostic prediction model for hepatocellular carcinoma

The peroxisome proliferator-activated receptor (PPAR) signaling pathway plays a crucial role in systemic cell metabolism, energy homeostasis and immune response inhibition. However, its significance in hepatocellular carcinoma (HCC) has not been well documented. In our study, based on the RNA sequencing data of HCC, consensus clustering analyses were performed to identify PPAR signaling pathway-related molecular subtypes, each of which displaying varying survival probabilities and immune infiltration status. Following, a prognostic prediction model of HCC was developed by using the random survival forest method and Cox regression analysis. Significant difference in survival outcome, immune landscape, drug sensitivity and pathological features were observed between patients with different prognosis. Additionally, decision tree and nomogram models were adopted to optimize the prognostic prediction model. Furthermore, the robustness of the model was verified through single-cell RNA-sequencing data. Collectively, this study systematically elucidated that the PPAR signaling pathway-related prognostic model has good predictive efficacy for patients with HCC. These findings provide valuable insights for further research on personalized treatment approaches for HCC.

Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06)

BackgroundImmune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC.MethodsWe retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan).ResultsA total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy.ConclusionsNo significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression.Trial registrationThis study was registered in the Clinical Trial Registry of Korea (https://cris.nih.go.kr: KCT 0007732).

Efficacy and safety analysis of P-GemDOx regimen and stratified prognosis in patients with early extranodal NK/T cell lymphoma

Objective: To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal natural killer (NK) /T cell lymphoma (ENKTL) . Methods: A retrospective analysis was performed on sixty early-stage ENKTL patients treated with the P-GemDOx regimen who were admitted to the First Affiliated Hospital of Nanjing Medical University between August 2015 and May 2021. The Chi-square test or Fisher's exact test was used to compare group differences, and the Log-rank test was used to compare the differences in survival. Survival outcomes and prognostic factors were examined. Results: After completing 4 to 6 cycles of P-GemDOx chemotherapy, the overall response rate (ORR) was 88.3%, with forty-six patients (76.7% ) achieving complete response (CR). The 4-year progression-free survival (PFS) and overall survival (OS) rates were (66.3±7.1) % and (79.5±6.0) %, respectively. According to the PINK/PINK-E model, there was no significant difference in survival outcomes among risk groups. 23.3% of patients experienced progression of disease within 24 months (POD<24). OS estimates differed significantly (P<0.001) between the POD<24 group (n=14) and the POD≥24 group (n=46). Analysis showed that SUVmax > 12.8 at diagnosis, non-single nasal cavity infiltration, and response less than CR after 4-6 cycles all had a significant association with POD24. We used these data as the basis for predicting POD<24 international prognostic index (POD24-IPI). Patients were stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high risk (two or three risk factors). These groups were associated with 4-year OS rate of 100%, (85.6±9.7) %, and (65.0±10.2) %, respectively (P=0.014). The P-GemDOx regimen was well tolerated, with hematological toxicity being the main side effect. Conclusion: This study demonstrated that the P-GemDOx regimen is effective and safe in the first-line treatment of early-stage ENKTL, and POD24-IPI is a promising prognostic model.

Multi-cohort validation of Ascore: an anoikis-based prognostic signature for predicting disease progression and immunotherapy response in bladder cancer

Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions. Through consensus clustering, we categorized patients from the TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences in survival outcome, clinical features, tumor immune environment (TIME), and potential ICIs response were observed between clusters. We then formulated a four-gene signature, termed "Ascore", to encapsulate this gene expression pattern. The Ascore was found to be closely associated with survival outcome and served as an independent prognosticator in both the TCGA-BLCA cohort and the IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) for bladder cancer immunotherapy response compared to biomarkers like TMB and PD-L1. Finally, we evaluated Ascore’s independent prognostic performance as a non-invasive biomarker in our clinical cohort (Gulou-Cohort1) using circulating tumor cells detection, achieving an AUC of 0.803. Another clinical cohort (Gulou-Cohort2) consisted of 40 patients undergoing neoadjuvant anti-PD-1 treatment was also examined. Immunohistochemistry of Ascore in these patients revealed its correlation with the pathological response to bladder cancer immunotherapy (P = 0.004). Impressively, Ascore (AUC = 0.913) surpassed PD-L1 (AUC = 0.662) in forecasting immunotherapy response and indicated better net benefit. In conclusion, our study introduces Ascore as a novel, robust prognostic biomarker for bladder cancer, offering a new tool for enhancing immunotherapy decisions and contributing to the tailored treatment approaches in this field.

Predicted visceral adiposity index in relation to risk of coronary heart disease and all-cause mortality: insights from NHANES.

The Visceral Adiposity Index (VAI) is a straightforward and gender-specific marker that combines anthropometric measurements with lipid profiles. The objective of this study was to evaluate the relationship between VAI and coronary heart disease (CHD). The study examined data collected from adults during the NHANES 1999-2018 cycle. The analyses were weighted, and multivariable logistic regression models were employed to investigate the association between VAI and CHD. Additionally, subgroup analyses stratified by age were conducted. To evaluate the impact of VAI levels on survival outcomes, the study utilized the Kaplan-Meier method and performed the log-rank test to evaluate the survival outcome of participants with different VAI levels. The study findings revealed a significant association between VAI and CHD, indicating a non-linear relationship where an increase in VAI was associated with an elevated risk of CHD. High levels of VAI were linked to an increased prevalence of CHD (Q4 vs Q1, OR 1.50, 95% CI 1.12-2.01, P=0.01). Additionally, higher levels of VAI were associated with a poorer overall prognosis in terms of survival outcomes. There were no statistically significant differences in survival outcomes among the population with CHD. The results of this study highlighted a significant association between VAI and CHD, with a non-linear relationship observed. High VAI levels were associated with an increased risk of CHD and poor survival outcomes, emphasizing the importance of understanding and managing this risk factor, particularly in older age groups.

Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease: Findings from the Salford Kidney Study.

Hypertension is commonly observed in patients living with chronic kidney disease (CKD). Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD. There remains variability in antihypertensive treatment practices. To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients. The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002. All patients are followed up annually, and their medical records including the list of medications are updated until they reach study endpoints [starting on renal replacement therapy or reaching estimated glomerular filtration rate (eGFR) expressed as mL/min/1.73 m2 ≤ 10 mL/min/1.73 m2, or the last follow-up date, or data lock on December 31, 2021, or death]. Data on antihypertensive prescription practices in correspondence to baseline eGFR, urine albumin-creatinine ratio, primary CKD aetiology, and cardiovascular disease were evaluated. Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis. Kaplan-Meier analysis demonstrated differences in survival probabilities. Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included. The median age was 65 years. A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages (53% of eGFR ≤ 15 mL/min/1.73 m2 vs 26% of eGFR ≥ 60 mL/min/1.73 m2, P < 0.001). An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased (category A3: 62% vs category A1: 40%, P < 0.001), with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers. The prescription of three or more antihypertensive agents was associated with all-cause mortality, independent of blood pressure control (hazard ratio: 1.15; 95% confidence interval: 1.04-1.27, P = 0.006). Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed (log-rank, P < 0.001). Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm. Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents. Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.

Abstract B112: Disparities in cervical cancer survival among Hispanic subpopulations living in the United States

Abstract Purpose: The Hispanic population bears a high burden of cervical cancer; however, disaggregated data, which is vital in equitable resource allocation, lacks in this group. Our study evaluated disparities in cervical cancer survival among Hispanic subpopulations receiving guideline-concordant care and identified factors affecting survival. Methods: Data from the National Cancer Database was used to identify patients with cervical cancer from 2004-2019. The Hispanic cohort was analyzed in its entirety, and by region of origin. Nine quality metrics were established to assess guideline-concordant care for eligible patients across various cancer stages. Demographic data, treatment modalities, and survival were described. Demographic and clinical variables were stratified by Hispanic subpopulation and compared using chi-squared tests. Kaplan-Meier curves were employed to examine cervical cancer survival among the Hispanic subpopulation for each quality metric. Marginal Poisson log-linear models were utilized to evaluate the association Hispanic subpopulation and the receipt of eligible quality metrics, and obtain adjusted relative risks (aRR), while controlling for potential confounders. Results: A total of 77,567 patients were included, 4363 (5.6%) of which identified as Hispanic. Compared to non-Hispanic White (NHW) and non-Hispanic Black (NHB) populations, larger proportion of the Hispanic population was uninsured (19.16%, p &amp;lt; 0.001) and more likely to live in neighborhoods with lowest rates of high school diploma attainment (61.43%, p &amp;lt;0.001). Significant differences in neighborhood income, education level, insurance status, and stage at presentation among Hispanic subpopulations were identified (p&amp;lt;0.001). Survival among patients with stage IA2-IIA2 patients undergoing radical hysterectomy was lowest among NHB and Cuban patients when compared to NHW and other Hispanic patients (p&amp;lt;0.001). Survival among stage IB2-IVA patients undergoing primary radiation and concurrent chemotherapy was also lowest among Cuban, NHW and NHB patients when compared to other populations, and highest among Mexican populations (p&amp;lt;0.001). Among patients with stage IVB disease receiving chemotherapy, Dominican populations had the highest survival rates p&amp;lt;0.001). Compared to Mexican patients, Cuban patients were 1.18 times as likely to receive timely initiation of treatment in early stage (RR 1.18, 95% CI 1.03-1.34, p=0.01). Patients of South or Central American origin (RR 1.18, 95%CI 1.09-1.28, p&amp;lt; 0.001), Cuban (RR 12.5, 95%CI 1.1-1.43, p&amp;lt;0.001), and Dominican (RR1.19, OR 1.01-1.4, p=0.03) were more likely to undergo timely initiation of treatment in locally advanced disease when compared to Mexican patients. Conclusion: Significant differences in survival outcomes for patients with cervical cancer were identified among our cohort, as well as within the Hispanic population. Variation in initial of treatment, treatment type received, and social factors may contribute to these disparities. Citation Format: Andreea Dinicu, Shayan Dioun, Yongzhe Wang, Yongmei Huang, Jason Wright, Ana Tergas. Disparities in cervical cancer survival among Hispanic subpopulations living in the United States [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B112.

Vitreoretinal Lymphoma with Intraretinal Infiltration, Simulating Retinal Necrosis

To describe the clinical features and outcomes of vitreoretinal lymphoma (VRL) with intraretinal infiltration, a pseudonecrotic variant. Retrospective, comparative analysis. Patients with biopsy-proven VRL at a single center from August 2016 to April2022. A retrospective record review was conducted for clinical, imaging, and laboratory data. Clinical features, visual, and survival outcomes. We included 67 eyes of 40 patients with biopsy-proven VRL. Pseudonecrotic retinal lesions (PRLs) were found in 24 (35.8%) eyes of 19 patients; these eyes were classified as a pseudonecrotic variant, whereas the remaining 43 (64.2%) eyes were classified as nonnecrotic. Comparison (pseudonecrotic vs. nonnecrotic) revealed that eyes with PRLs at presentation had a worse median best-corrected visual acuity (BCVA; 2.4 vs. 0.5 logarithm of the minimum angle of resolution [logMAR], P < 0.0001) and severe ocular manifestations (P < 0.0001), including optic disc swelling (79.2% vs. 0%), retinal vasculitis (93.8% vs. 4.7%), retinal hemorrhage (83.3% vs. 0%), and retinal detachment (RD) (79.2% vs. 0%). Follow-up data were available for 20 eyes (17 patients) in the pseudonecrotic group and 43 eyes (21 patients) in the nonnecrotic group. An equally worse median BCVA was noted in pseudonecrotic eyes at 6 months after treatment and the final follow-up as compared with nonnecrotic eyes (2.4 vs. 0.3 logMAR, P < 0.0001). The median follow-up period did not differ significantly (16.6 vs. 18.4 months, P= 0.47). Initial BCVA (β= 0.300, P= 0.003), presence of anterior chamber cell (β= 0.472, P= 0.013), and RD (β= 1.137, P < 0.0001) were significantly associated with poor visual outcomes in multivariate linear regression analysis (adjusted R2= 0.693). There were no significant differences in survival outcomes. Vitreoretinal lymphoma can present as pseudonecrotic retinopathy, with more advanced clinical presentations and worse final visual outcomes. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Analysis of Post-Transplant Clinical Outcomes and Prognostic Factors in FLT3-ITD Mutated Acute Myeloid Leukemia Patients Under ELN 2022 Risk Stratification

Background In 2022 European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML), one of the most important changes made to the genetic risk classification of AML is that the FLT3-ITD allelic ratio (AR) is no longer considered in the risk classification; consequently, AML with FLT3-ITD (without adverse-risk genetic lesions) are now categorized in the intermediate-risk group, irrespective of the allelic ratio or concurrent presence of NPM1 mutation. Aims To investigate the survival outcomes of FLT3-ITD mutated AML patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), based on prognostic stratification defined by the 2017 and 2022 ELN guidelines, and to analyze the risk factors affecting transplant prognosis. Methods A total of 163 FLT3-ITD mutated AML patients underwent allo-HSCT were enrolled in this study. Bone marrow aspirates were obtained, cytogenetic and molecular characteristics were collected at the time of diagnosis. Genetic risk category was classified according to the 2017 and 2022 edition of the European LeukemiaNet (ELN) recommendations. HLA-haploidentical donor transplants were performed if no HLA matched sibling or unrelated donor was available. Patients received myeloablative conditioning with a modified Bu/Cy/Flu/Ara-c (busulfan/cyclophosphamide/fludarabine/cytarabine) or MCBC (melphalan/cladribine/busulfan/cyclophosphamide) preparative regimen. The therapeutic process and clinical outcomes were retrospectively analyzed. Results We assessed 163 adults with FLT3-mutated AML (median age 37 years) allografted between 2017 and 2022 in our clinical center. The median follow-up of alive patients was 24.9 months. The 2-year relapse-free survival (RFS) and overall survival (OS) were 67.2% and 71.9%, respectively. The 2-year incidences of relapse and non-relapse mortality were 27.9% and 12.5%, respectively. There was no significant difference in survival outcomes between the intermediate and high-risk groups after transplantation, both defined by the 2017 and 2022 ELN guidelines. High FLT3-ITD allelic ratio (≥0.5) at initial diagnosis was associated with elevated WBC counts ( P&amp;lt;0.001), but did not affect the response ratefollowing induction chemotherapy ( P=0.059) . Patients with high allelic ratio were more likely to benefit from maintenance therapy after transplantation ( P=0.048 for OS). In univariate analysis, presence of NPM1 mutation and the allelic ratio of FLT3-ITD did not affect any of the transplant outcomes. In multivariate analysis, MRD-negative at transplantation, occurrence of chronic GVHD and posttransplant maintenance therapy improved OS and RFS. Conclusion Allo-HSCT can overcome the poor prognosis in patients with FLT3-ITD mutated AML. Neither the presence of NPM1 mutation nor the FLT3-ITD allelic ratio affected survival. Prevention of disease relapse after transplantation remains a challenge. The main prognostic factors affecting transplant outcomes included pre-transplant MRD status and the application of maintenance therapy. Thus, introduction of FLT3 inhibitors as post-transplant maintenance therapy and the development of highly sensitive MRD assays will further reduce disease recurrence and improve survival.