Lower Long-term Survival Research Articles

Chidamide and venetoclax synergistically regulate the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL.

B-cell acute lymphocytic leukemia (B-ALL) is a malignant proliferative B-lymphocyte disease. Although the outcome of B-ALL has greatly improved with combined chemotherapy, immunotherapy, and hematopoietic stem cell transplantation, some patients still experience drug resistance, relapse and a low long-term survival rate, therefore, finding novel approaches to improve the outcome of adult B-ALL patients is critical. Our previous studies revealed that the selective histone deacetylase inhibitor (HDACi) chidamide can inhibit the Wnt/β-catenin signaling pathway by inhibiting MYCN and increasing the expression of DKK3 in B-ALL cells. Some studies have indicated that histone deacetylase inhibitors (HDACis) can dysregulate the B-cell lymphoma-2 (BCL2) protein family, we speculate that chidamide and BCL2 inhibitor venetoclax synergistically inhibit the Wnt/β-catenin signaling pathway by inhibiting MYCN expression and increasing DKK3 expression. In our study, the in vitro and in vivo experiments confirmed that chidamide and venetoclax synergistically inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of HDAC and BCL2, inhibiting the Wnt/β-catenin signaling pathway and B-ALL cell proliferation. These findings indicate that the HDACi chidamide and the BCL2 inhibitor venetoclax can be used in combination to treat B-ALL, providing a new method and strategy for treating B-ALL.

Mutations Matter: Unravelling the Genetic Blueprint of Invasive Lobular Carcinoma for Progression Insights and Treatment Strategies.

Invasive Lobular Carcinoma (ILC) presents a distinct subtype of breast cancer, representing 10-15% of cases, with unique clinical and molecular features. Characterized by a non-cohesive, single-file invasion pattern, ILC is typically estrogen receptor (ER)- and progesterone receptor (PR)-positive but human epidermal growth factor receptor 2 (HER2)-negative. Despite favorable prognostic features, its highly metastatic nature and predilection for atypical sites contribute to lower long-term survival compared to invasive breast carcinoma of no special type (NST). ILC's genetic landscape includes mutations in various genes (CDH1, BRCA2, ATM, etc.) and signaling pathways that impact treatment responses, especially in endocrine treatment. Furthermore, the diverse ILC subtypes complicate its management. Current challenges in chemotherapy, along with the targeted therapies, are also discussed. The present article aims to comprehensively review the recent literature, focusing on the pathological and molecular aspects of ILC, including associated genetic mutations influencing disease progression and drug resistance.

Abstract 4112775: Demographics and Cardiovascular Mortality Among Kaposi Sarcoma Patients in the United States: An Analysis of the SEER Database

Aims and Background: Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus. Despite its significance, there is limited data regarding the causes and mortality factors associated with KS, particularly concerning cardiovascular mortality rates and specific influencing factors. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to gather data from 2000 to 2020. The primary endpoint was overall survival, assessed via log-rank analysis and Kaplan-Meier plots. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated using SAS v9.4, with significance set at p<0.05. Results: We identified 8,247 patients with KS. Most were male (90.6%) and aged 40-59 years old (38.5%). Mortality data from KS showed that 56.3% of diagnosed patients were alive. Among those who died, 49.8% died of infectious causes, 11.4% died of cardiac causes, and the remaining died of other causes, such as leukemias and complications. Advanced age (>80 years) vs. 0-19 year age group (HR: 2.263; 95% CI: 1.068-4.795; p=0.033), non-Hispanic Black race vs. non-Hispanic White race (HR 1.492; 95% CI: 1.369-1.627; p=0.001), and visceral involvement vs. cutaneous KS (HR 1.709; 95% CI: 1.487-1.963; p=0.001) were factors associated with increased mortality. Females had a slightly lower long-term survival than males (p<0.001). Married individuals, higher incomes (≥$75,000), and urban areas of living had higher survival rates compared to widowed patients, lower-income patients (<$75,000), and those in rural locations, respectively (p<0.001, for all). In the subgroup analysis, females (24.3%; n=112) had significantly higher cardiac-related deaths than males (9.5%; n=297) (p<0.0001). Cardiac-related deaths were highest in White patients (16.1%; n=279), followed by Hispanics (10.4%; n=79). Conclusions: Cardiac causes accounted for 11.4% of deaths. Various factors are associated with an increased mortality risk.

All-cause mortality and suicide after pediatric traumatic brain injury: a 20-year nationwide study in Finland

ObjectivesTo assess all-cause mortality and suicides after pediatric traumatic brain injury (pTBI). Study designWe conducted population-based historical cohort study using three nationwide registers from 1998 to 2018 in Finland. All patients that were the age of 0–17 at the time of the pTBI were included. The reference group consisted of children with ankle or wrist fractures. We used Kaplan–Meier and restricted mean survival time (RMST) analysis with 95% confidence intervals (CI) to compare all-cause mortality and suicides between groups. ResultsAfter 20 years of follow-up, there were 479 deaths in the pTBI group (0.67% of 71,963) and 306 deaths in the reference group (0.47% of 64,848). In the pTBI group, 28.6% of the deaths occurred after the first follow-up year, compared to 2.6% in the reference group. In all-cause mortality, survival time was slightly less in the pTBI group with age and gender adjustment throughout the follow-up period [20-year RMST ratio: 0.995; CI (0.994–0.996)]. The leading manners of death were suicides (pTBI group = 28.4%; reference group = 45.5%) and traffic collisions (pTBI group = 37.4%; reference group = 20.8%). Age and gender-adjusted survival time was slightly less for those with suicide as a manner of death in the pTBI group [10-year RMST ratio: 0.999; CI (0.999–0.999); 20-year RMST ratio: 0.999; CI (0.998–0.999)]. ConclusionsChildren and adolescents who sustained a TBI have slightly lower long-term survival time for all-cause mortality, most of which occurs during the first year following injury. There is no clinically meaningful difference in deaths by suicide between the two injury groups.

Long-term survival after TAVI in low-flow, low-gradient aortic valve stenosis.

In patients undergoing transcatheter aortic valve implantation (TAVI), the presence of a low-flow, low-gradient (LFLG) status has been associated with higher mortality at short-term follow-up. We aimed to evaluate long-term survival after TAVI in patients with classical (cLFLG) and paradoxical LFLG (pLFLG) aortic stenosis (AS) compared to high-gradient (HG)-AS. Patients undergoing TAVI at our centre with a hypothetical minimum 5-year follow-up were divided into 3 groups: (1) HG-AS (mean gradient [MG] >40 mmHg), (2) cLFLG-AS (MG <40 mmHg, ejection fraction [EF] <50%), and (3) pLFLG-AS (MG <40 mmHg, EF ≥50%). The primary endpoint of the study was all-cause mortality. Propensity score-weighted survival analysis was performed to adjust for possible baseline confounders. A total of 574 subjects were included (73% HG-AS, 15% pLFLG-AS, 11% cLFLG-AS). The median survival time was 4.8 years, with a maximum of 12.3 years. Patients with cLFLG-AS presented the highest baseline cardiovascular risk. At unadjusted survival analysis, patients with cLFLG-AS showed the worst long-term prognosis, with a rapid decrease in survival within the first year, while pLFLG- and HG-AS patients presented similar survival rates (p=0.023). At weighted long-term analysis, cLFLG- and HG-AS had similar survival rates. Baseline EF was not related to long-term mortality, while patients with a post-TAVI left ventricular ejection fraction (LVEF) improvement >10% lived significantly longer (p=0.02). Classical LFLG-AS patients had lower long-term survival rates as compared to pLFLG-AS and HG-AS patients. However, after adjustment for possible baseline confounders, a low-flow status per se did not have an impact on long-term mortality after TAVI. Post-TAVI LVEF recovery was associated with improved long-term outcome.

Clinical characteristics and long-term outcomes of patients with heart failure with supra-normal ejection fraction: data from LECRA-HF registry

Abstract Background Heart failure with preserved ejection fraction (HFpEF) remains insufficiently characterized subgroup of HF with increasing prevalence and limited treatment options. Relationship between clinically assessed left ventricular ejection fraction (LVEF) and survival showed that LVEF ≥65% is associated with higher mortality. Therefore, a novel category of heart failure with supra-normal left ventricular ejection fraction (HFsnEF) was introduced in 2019. However, clinical characteristics and long-term outcomes of HFsnEF patients remain insufficiently elucidated. Purpose We sought to characterize Polish HFsnEF patients and to provide their long-term mortality in comparison to HFpEF. Methods Of 1186 patients enrolled in the single-center Lesser Poland Cracovian Heart Failure (LECRA-HF) Registry between 2009 and 2019 and hospitalized due to HF decompensation 261 (22%) of them were those with LVEF ≥50%. 40 (15.3%) of them were classified as HFsnEF (LVEF ≥65%) and the remaining 221 (84.7%) as HFpEF. The data including patients’ demography, anthropometric measurements, cardiovascular risk factors, prior cardiological treatment and other comorbidities were collected. The long-term follow-up of all-cause mortality was obtained from the Polish National Death Registry. Results HFsnEF patients were less frequently hypertensive (75 vs 88.2%, P=0.026) and had higher baseline LVEF (65 [65-70] vs 55 [50-60] %, P&amp;lt;0.001) than HFpEF subjects. Furthermore, HFsnEF patients presented lower INR (1.1 [1-1.6] vs 1.3 [1.1-1.9], P=0.027) and total protein level (57 [25-63] vs (65.2 [60.2-69.9] g/L, P=0.008) on admission. HFsnEF patients were less frequently treated on discharge with mineralocorticoid receptor antagonists (25 vs 46.2%, P=0.013) as well as loop diuretics (60 vs 76%, P=0.017). The Kaplan-Meier analysis showed that all-cause mortality is higher in HFsnEF than in HFpEF (65.0 vs 55.2%, P=0.044, Figure 1). The independent predictors of long-term mortality were age and diagnosis of HFsnEF (HR 1.037, 95% CI 1.018-1.056 and HR 1.665, 95% CI 1.063-2.608, respectively). Conclusions Our findings indicate that every seventh Polish patient admitted with HFpEF could be classified as HFsnEF. Baseline characteristics of HFsnEF patients are different than HFpEF. Simultaneously, the HFsnEF diagnosis is associated with lower long-term survival.

A New Hope - Patient Specific Bone-Anchored Subperiosteal Implants: Perspective of 3 US Institutions on this Resurrected Treatment Modality

BackgroundSince subperiosteal implants were first developed in the 1940s, they have fallen out of favour due to their high complication rate and low long-term survival rate. Many of these complications were due to micromotion. More recently, patient-specific bone-anchored subperiosteal implants (BASIs) have been developed, which utilize screw fixation to mitigate micromotion. This article discusses the early experience of three US institutions, Duke University, University of Michigan, and Mayo Clinic, describes the recommendations of the BASI’s European designer, and provides our treatment recommendations. ConclusionPatient-specific bone-anchored subperiosteal implants have demonstrated acceptable short-term success. At this point in time, we feel this is a viable treatment option but recommend utilizing traditional treatment modalities, such as standard endosseous implants, prior to utilization of a BASI until additional long-term research has been completed.

Aortic and Mitral Valve Endocarditis-Simply Left-Sided Endocarditis or Different Entities Requiring Individual Consideration?-Insights from the CAMPAIGN Database.

Background: Aortic valve infective endocarditis (AV-IE) and mitral valve infective endocarditis (MV-IE) are often grouped together as one entity: left-sided endocarditis. However, there are significant differences between the valves in terms of anatomy, physiology, pressure, and calcification tendency. This study aimed to compare AV-IE and MV-IE in terms of patient characteristics, pathogen profiles, postoperative outcomes, and predictors of mortality. Methods: We retrospectively analyzed data from 3899 patients operated on for isolated AV-IE or MV-IE in six German cardiac surgery centers between 1994 and 2018. Univariable and multivariable analyses were performed to analyze the risk factors for 30 day and 1 year mortality. A Log-rank test was used to test for differences in long-term mortality. Results: Patients with MV-IE were more likely to be female (41.1% vs. 20.3%.; p < 0.001). Vegetation was detected more frequently in the MV-IE group (66.6% vs. 57.1%; p < 0.001). Accordingly, the rates of cerebral embolic events (25.4% vs. 17.7%; p < 0.001) and stroke (28.2% vs. 19.3%; p < 0.001) were higher in the MV-IE group. Staphylococci had a higher prevalence in the MV-IE group (50.2% vs. 36.4%; p < 0.001). Patients with MV-IE had comparable 30 day mortality (16.7% vs. 14.6%; p = 0.095) but significantly higher 1 year mortality (35.3% vs. 29.0%; p < 0.001) than those with AV-IE. Kaplan-Meier survival analysis showed significantly lower long-term survival in patients with MV-IE (log-rank p < 0.001). Conclusions: Due to the relevant differences between MV-IE and AV-IE, it might be useful to provide individualized, valve-specific guideline recommendations rather than general recommendations for left-sided IE.

Re-exploration for bleeding and long-term survival after adult cardiac surgery: a meta-analysis of reconstructed time-to-event data.

Postoperative bleeding requiring re-exploration is a serious complication that occurs in 2.8-4.6% of patients undergoing cardiac surgery. Re-exploration has previously been associated with a higher risk of short-term mortality. However, a comprehensive analysis of long-term outcomes after re-exploration for bleeding has not been published. The authors performed a systematic, three databases search to identify studies reporting long-term outcomes in patients who required re-exploration for bleeding after cardiac surgery compared to patients who did not, with at least 1-year of follow-up. Long-term survival was the primary outcome. Secondary outcomes were operative mortality, myocardial infarction, stroke, renal and respiratory complications, and hospital length of stay. Random-effects models was used. Individual patient survival data was extracted from available survival curves and reconstructed using restricted mean survival time. Six studies totaling 135456 patients were included. The average follow-up was 5.5 years. In the individual patient data, patients who required re-exploration had a significantly higher risk of death compared with patients who did not [hazard ratio (HR): 1.21; 95% CI: 1.14-1.27; P <0.001], which was confirmed by the study-level survival analysis (HR: 1.32; 95% CI: 1.12-1.56; P <0.01). Re-exploration was also associated with a higher risk of operative mortality [odds ratio (OR): 5.25, 95% CI: 4.74-5.82, P <0.0001], stroke (OR: 2.05, 95% CI: 1.72-2.43, P <0.0001), renal (OR: 4.13, 95% CI: 3.43-4.39 P <0.0001) respiratory complications (OR: 3.91, 95% CI: 2.96-5.17, P <0.0001), longer hospital length of stay (mean difference: 2.69, 95% CI: 1.68-3.69, P <0.0001), and myocardial infarction (OR: 1.85, 95% CI: 1.30-2.65, P =0.0007). Postoperative bleeding requiring re-exploration is associated with lower long-term survival and increased risk of short-term adverse events including operative mortality, stroke, renal and respiratory complications, and longer hospital length of stay. To improve both short-term and long-term outcomes, strategies to prevent the need for re-exploration are necessary.

Outcomes and quality of life in patients receiving durable left ventricular assist device with biventricular support.

Patients requiring biventricular support (BIVAD) face higher morbidity than those undergoing durable left ventricular assist device (LVAD) implantation alone. The goal of the current study was to evaluate quality of life (QOL) of patients with LVAD therapy in the modern era, stratified by use of biventricular support. All patients undergoing LVAD at our center were reviewed between October 2017 and September 2021. Patients were stratified by perioperative use of BIVAD. Patients were administered a telephone survey consisting of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) as well as free-responses regarding satisfaction surrounding their operation. Outcomes included survival, KCCQ-12 metrics, and thematic analysis of free response questions. 92 patients were identified, of whom 26 (28%) received BIVAD support. BIVAD patients had more preoperative ECMO use (54% vs. 12%, p < 0.001) and lower INTERMACS scores (Category 1: 46% vs. 14%, p = 0.001). Three-year survival was 73.8% among LVAD-alone patients and 50.1% among BIVAD patients (log-rank p = 0.022). Median composite KCCQ-12 score was 78 (57-88). No differences in composite or any component scores were noted between groups. 76% of patients report they would be moderately or extremely like to go through surgery again if given repeat choice. The most common themes expressed were overall gratitude (24%) and disappointment with device-related restrictions (20%). Patients requiring BIVAD therapy have more advanced shock, longer associated hospital courses, and lower long-term survival. However, those that survive enjoy similar overall quality of life, and many endorse positive outlooks on their surgical course. Continued assessments of quality of life are important in providing patient-centered LVAD care.

Survivorship after adolescent and young adult cancer: models of care, disparities, and opportunities.

Survivors of adolescent and young adult (AYA; age 15-39 years at diagnosis) cancer are a growing population with the potential to live for many decades after treatment completion. Survivors of AYA cancer are at risk for adverse long-term outcomes including chronic conditions, secondary cancers, impaired fertility, poor psychosocial health and health behaviors, and financial toxicity. Furthermore, survivors of AYA cancer from racially minoritized and low socioeconomic status populations experience disparities in these outcomes, including lower long-term survival. Despite these known risks, most survivors of AYA cancer do not receive routine survivorship follow-up care, and research on delivering high-quality, evidence-based survivorship care to these patients is lacking. The need for survivorship care was initially advanced in 2006 by the Institute of Medicine. In 2019, the Quality of Cancer Survivorship Care Framework (QCSCF) was developed to provide an evidence-based framework to define key components of optimal survivorship care. In this commentary focused on survivors of AYA cancer, we apply the QCSCF framework to describe models of care that can be adapted for their unique needs, multilevel factors limiting equitable access to care, and opportunities to address these factors to improve short- and long-term outcomes in this vulnerable population.

Comparison of abdominal adipose tissue versus body mass index (BMI) as a predictor of complications and survival in liver transplantation

IntroductionBecause of the obesity epidemic, more obese patients are on liver transplant (LT) waiting lists. The diseases associated with obesity may increase complications and limit survival after LT. However, there is no established measure or cut-off point to determine this impact and aid decision making. The aim of the present study is to evaluate obesity in patients undergoing LT via BMI and CT-based measurement of adipose tissue (AAT). These parameters will be used to predict the risk of postoperative complications and 5-year survival. MethodsA retrospective, single-center study was carried out at a tertiary Spanish hospital, including all patients who received LT between January 2012 and July 2019 (n = 164).The patients were adults who underwent LT using the ‘piggyback’ technique, preserving the recipient vena cava. Visceral adipose tissue (VAT) and BMI were calculated to examine correlations with postoperative complications and 5-year survival. ResultsNo significant association was found between postoperative complications by Comprehensive Complication Index, BMI, AAT/height, subcutaneous fat/height and VAT/height.Kaplan-Meier curves for 5-year survival compared LT recipients with BMI < 30.45 versus ≥30.45, with an estimated survival of 58.97 months versus 43.11 months, respectively (P < .001) (Fig. 3) and for LT recipients with an AAT/height <27.35 mm versus ≥27.35 mm, with an estimated survival of 57.69 months versus 46.34 months (P = .001). ConclusionsThis study does not show a higher rate of postoperative complications in obese patients. There is a significantly lower long-term survival in patients with AAT/height ≥27.35 mm and BMI ≥ 30.45. BMI is a valid estimate of obesity and is predictive of survival.

Novel Systemic Inflammatory Markers Predict All-Cause Mortality in Patients Undergoing Endovascular Abdominal Aortic Aneurysm Repair.

Clinically useful predictors for risk stratification of long-term survival may assist in selecting patients for endovascular abdominal aortic aneurysm (EVAR) procedures. This study aimed to analyze the prognostic significance of peroperative novel systemic inflammatory markers (SIMs), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), hemoglobin-to-red cell distribution width ratio (HRR), systemic immune-inflammatory index (SIII), and systemic inflammatory response index (SIRI), for long-term mortality in EVAR. A retrospective analysis was performed on 147 consecutive patients who underwent their first EVAR procedure at the Department of Vascular Surgery, Beijing Hospital. The patients were divided into the mortality group (n = 37) and the survival group (n = 110). The receiver operating characteristic curves were used to ascertain the threshold value demonstrating the most robust connection with mortality. The Kaplan-Meier survival analysis was performed between each SIM and mortality. The relationship between SIMs and survival was investigated using restricted cubic splines and multivariate Cox regression analysis. The study included 147 patients, with an average follow-up duration of 34.28 22.95 months. Deceased patients showed significantly higher NLR (p 0.001) and reduced HRR (p 0.001). The Kaplan-Meier estimates of mortality were considerably greater in the higher-NLR group (NLR 2.77) and lower-HRR group (HRR 10.64). The hazard ratio (HR) of 0.833 (95% confidence interval (95% CI): 0.71-0.97, p 0.021) was determined to be statistically significant in predicting death in the multivariable analysis. Preoperative higher-NLR and lower-HRR have been associated with a lower long-term survival rate in abdominal aortic aneurysm (AAA) patients undergoing elective EVAR. Multivariate Cox regression showed that decreased preoperative HRR is an independent risk factor that increases mortality risk following EVAR. SIMs, such as the NLR and HRR, could be used in future clinical risk prediction methodologies for AAA patients undergoing EVAR. However, additional prospective cohort studies are needed to identify these findings.

Fenestrated/Branched Endovascular Aortic Repair Patients With Peripheral Artery Disease Have Significantly Lower Long-Term Survival and Higher Incidence of Postoperative Mesenteric Ischemia

Fenestrated/Branched Endovascular Aortic Repair Patients With Peripheral Artery Disease Have Significantly Lower Long-Term Survival and Higher Incidence of Postoperative Mesenteric Ischemia

Examining the impact of median arcuate ligament-induced celiac artery compression on target vessel patency, long-term survival and device integrity in fenestrated and branched endovascular repairs

ObjectiveTo evaluate the impact of celiac artery (CA) compression by median arcuate ligament (MAL) on technical metrics and long-term CA patency in patients with complex aortic aneurysms undergoing fenestrated/branched endograft repairs (F/B-EVARs). MethodsSingle-center, retrospective review of patients undergoing fenestrated/branched endovascular aortic aneurysm repairs and requiring incorporation of the CA between 2013 and 2023. Patients were divided into two groups—those with (MAL+) and without (MAL−) CA compression—based on preoperative computed tomography angiography findings. MAL was classified in three grades (A, B, and C) based on the degree and length of stenosis. Patients with MAL grade A had ≤50% CA stenosis measuring ≤3 mm in length. Those with grade B had 50% to 80% CA stenosis measuring 3 to 8 mm long, whereas those with grade C had >80% stenosis measuring >8 mm in length. End points included device integrity, CA patency and technical success—defined as successful implantation of the fenestrated/branched device with perfusion of CA and no endoleak. ResultsOne hundred and eighty patients with complex aortic aneurysms (pararenal, 128; thoracoabdominal, 52) required incorporation of the CA during fenestrated/branched endovascular aortic aneurysm repair. Majority (73%) were male, with a median age of 76 years (interquartile range [IQR], 69-81 years) and aneurysm size of 62 mm (IQR, 57-69 mm). Seventy-eight patients (43%) had MAL+ anatomy, including 33 patients with MAL grade A, 32 with grade B, and 13 with grade C compression. The median length of CA stenosis was 7.0 mm (IQR, 5.0-10.0 mm). CA was incorporated using fenestrations in 177 (98%) patients. Increased complexity led to failure in CA bridging stent placement in four MAL+ patients, but completion angiography showed CA perfusion and no endoleak, accounting for a technical success of 100%. MAL+ patients were more likely to require bare metal stenting in addition to covered stents (P = .004). Estimated blood loss, median operating room time, contrast volume, fluoroscopy dose and time were higher (P < .001) in MAL+ group. Thirty-day mortality was 3.3%, higher (5.1%) in MAL+ patients compared with MAL− patients (2.0 %). At a median follow-up of 770 days (IQR, 198-1525 days), endograft integrity was observed in all patients and CA events—kinking (n = 7), thrombosis (n = 1) and endoleak (n = 2) —occurred in 10 patients (5.6%). However, only two patients required reinterventions. MAL+ patients had overall lower long-term survival. ConclusionsCA compression by MAL is a predictor of increased procedural complexity during fenestrated/branched device implantation. However, technical success, long-term device integrity and CA patency are similar to that of patients with MAL− anatomy.

Pathological and Molecular Diagnosis of Uveal Melanoma.

(1) Background: Uveal melanoma (UM) is a common malignant intraocular tumor that presents with significant genetic differences to cutaneous melanoma and has a high genetic burden in terms of prognosis. (2) Methods: A systematic literature search of several repositories on uveal melanoma diagnosis, prognosis, molecular analysis, and treatment was conducted. (3) Results: Recent genetic understanding of oncogene-initiation mutations in GNAQ, GNA11, PLCB4, and CYSLTR2 and secondary progression drivers of BAP1 inactivation and SF3B1 and EIF1AX mutations offers an appealing explanation to the high prognostic impact of adding genetic profiling to clinical UM classification. Genetic information could help better explain peculiarities in uveal melanoma, such as the low long-term survival despite effective primary tumor treatment, the overwhelming propensity to metastasize to the liver, and possibly therapeutic behaviors. (4) Conclusions: Understanding of uveal melanoma has improved step-by-step from histopathology to clinical classification to more recent genetic understanding of oncogenic initiation and progression.

Abstract PO1-06-08: Treatment utilization by race and insurance type among triple negative breast cancer patients

Abstract Introduction Triple negative breast cancer (TNBC) is associated with poorer prognosis and its lower long-term survival rates disproportionately affect people of racial and ethnic minority groups. Ensuring timely and effective treatment for all patients regardless of race or insurance status is critical. The objective of this study is to describe treatment patterns by line of therapy, race, and insurance type to identify barriers to accessing healthcare using a physician survey and patient-chart review. Methods This study employed a 60-minute physician survey and linked retrospective chart review of patients’ charts conducted June-July 2022. Participating oncologists across the US (34% Central; 19% Southeast; 18% Northeast; 21% West; 9% East Coast) were required to be board-certified, in practice 3 to 30 years post-residency, and managing at least 7 patients with TNBC in the past 3 years. Oncologists extracted patient-level data from 2-4 patient records for the chart review. A convenience sample of charts oversampled patients on Medicaid, Black and Latina patients, and patients with later stage TNBC to allow for robust disparities analysis. Data collection included provider characteristics, treatment by line of therapy (LOT), rationale for treatment decisions, barriers experienced in accessing care, and support services used. Results Participating oncologists (n=101, 73% male; 62% community vs 39% academic setting) provided data on 283 patients with TNBC [99% female; median age = 46.0 years; race = Black (42%), Latina (31%), White (25%) or Other (2%); geographic location = Urban (53%), Suburban (39%), Rural (8%)]. White patients were more likely to be covered by private insurance (73%) compared to Black (25%) and Latina patients (32%). Black and Latina patients were more likely to be covered by Medicaid (White, 16%; Black, 71%; Latina, 52%). Over half of patients needed prior authorization for first-line (1L) treatment; mean wait time for prior authorization was 1.5 weeks. Black patients (58%) were more likely to require prior authorization in 1L as compared to White patients (49%); There were no significant differences in prior authorization requirements based on type of insurance (Medicaid, Medicare, Private/Commercial Insurance). Of the 283 patients treated with 1L therapy, 111 patients received second-line (2L) treatment [Black (n=52, 44%), Latina (n=29, 32%), White (n=26, 37%), Other (n=4, 71%)], and 45 patients received third-line (3L) treatment [Black (n=25, 21%), Latina (n=9, 10%), White (n=9, 13%), Other (n=2, 33%)]. Chemotherapy was the most common 1L (75%) and 2L (51%) treatment. Targeted therapy (TT), defined as immunotherapy, hormone therapy or antibody–drug conjugates, was most common in 3L (64%). A smaller proportion of Black patients who progressed to 3L received TT (n=13, 52%) compared to White (n=8, 89%) and Latina (n=7, 78%) patients. A larger proportion of patients with private/commercial insurance (n=18, 95%) received TT in 3L as compared to patients with Medicaid (n=10, 42%) or Medicare (0%). Conclusions Findings indicated disparities both in pre-treatment barriers (specifically prior authorization) and the utilization of targeted therapy in later lines of therapy among Black patients. Although treatment patterns did not seem to differ by race in early lines of therapy, numerical differences in treatment patterns by race and insurance type emerged in later lines of therapy. Given the poor prognosis for patients diagnosed with TNBC and its disproportionate impact on communities of color, future policy efforts should be focused on achieving equity in treatment initiation and use of TT in TNBC patients. Citation Format: Natalia Sadetsky, Langa Bakhuluma-Ncube, Emily Fox, Laura Okpala, Matt O'Hara, Jennifer Parr. Treatment utilization by race and insurance type among triple negative breast cancer patients [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 PO1-06-08.

Prognostic Value of Mitral Annular Calcification in Liver Transplant Patients: Implication in Posttransplant Outcomes.

With the rise of metabolic diseases and aging in liver transplant (LT) candidates, mitral annular calcification (MAC) is more recognizable. Despite cardiovascular risk becoming a leading cause of mortality in LT recipients, the influence of MAC remains unexamined. This study investigates the prevalence, related factors, and impact of MAC on LT outcomes. We explored 4148 consecutive LT patients who underwent routine pretransplant echocardiography from 2008 to 2019. Multivariate logistic analysis and the tree-based Shapley additive explanation scores in machine learning were used to evaluate the significant and important related factors. The primary outcome was 30-d major adverse cardiac events (MACE), and the secondary outcome was a median of 5-y cumulative all-cause mortality. MAC was found in 123 (3.0%) patients. Significant and important related factors included age, alcoholic liver disease, chronic kidney disease, hyperuricemia, hypertension, and coronary artery disease. The MACE rate was higher in patients with MAC compared with those without MAC at 30 d ( P < 0.001, adjusted hazard ratio 1.67; 95% confidence interval, 1.08-2.57). Patients with MAC had poorer cumulative overall survival probability compared with those without MAC ( P = 0.0016; adjusted hazard ratio 1.47; 95% confidence interval, 1.01-2.15). Specifically, women with MAC had a poorer survival probability compared with men without MAC (65.0% versus 80.7%, P < 0.001) >10 y post-LT. The presence of MAC before LT was linked to increased 30-d MACE and lower long-term survival rates, especially in women. Identification and management of MAC and potential risk factors are crucial for improving post-LT survival.

O247: In vitro exposure of gastric cancer cell line AGS to the cannabinoid cannabidiol (CBD) results in cytotoxicity in a dose-dependent manner

Abstract Introduction Current curative therapeutic regimens for gastric cancer combine chemotherapy with surgery, though this approach is associated with morbidity and mortality and relatively low long-term survival when compared to other solid organ and gastro-intestinal tumours. Cannabinoids are known to have anti-cancer properties in some tumours, though their role in gastric cancer is relatively unknown. This study aimed to determine if the non-psychoactive cannabidiol (CBD) induces cytotoxicity in the gastric cancer cell line AGS. Method The gastric cancer cell line AGS was maintained as per recommended guidelines. When cells reached 70% confluence, they were seeded in 96 well plates and treated with CBD or cisplatin at concentrations ranging from 0.2 μM to 100 μM or vehicle control. After 96 hours contact time, cell viability was assessed using a colorimetric cell viability assay (MTT assay). Experiments were repeated independently four times. Cell viability at each concentration was recorded and half maximal inhibitory concentration (IC50) was calculated. Results were expressed as the mean ± SE mean. Results Treatment with cisplatin induced significant cytotoxicity in a dose dependent manner with an IC50 concentration of 1.8 ± 0.3μM. Treatment with CBD also induced cytotoxicity in a dose dependent manner. Cytotoxic effects were observed with concentrations as low as 3.1μM (78% viability). The IC50 concentration for CBD was 10.2 ± 2.5 μM. Conclusions CBD induced significant cytotoxicity at micromolar concentration in stomach carcinoma cells. Further studies should be carried out to investigate the mechanisms of action that underpin the observed in vitro cytotoxic effect.

Comparison of abdominal adipose tissue versus body mass index (BMI) as a predictor of complications and survival in liver transplantation

IntroductionBecause of the obesity epidemic, more obese patients are on liver transplant (LT) waiting lists. The diseases associated with obesity may increase complications and limit survival after LT. However, there is no established measure or cut-off point to determine this impact and aid decision making. The aim of the present study is to evaluate obesity in patients undergoing LT via BMI and CT-based measurement of adipose tissue (AAT). These parameters will be used to predict the risk of postoperative complications and 5-year survival. MethodsA retrospective, single-center study was carried out at a tertiary Spanish hospital, including all patients who received LT between January 2012 and July 2019 (n = 164).The patients were adults who underwent LT using the ‘piggyback’ technique, preserving the recipient vena cava. Visceral adipose tissue (VAT) and BMI were calculated to examine correlations with postoperative complications and 5-year survival. ResultsNo significant association was found between postoperative complications by Comprehensive Complication Index, BMI, AAT/height, subcutaneous fat/height and VAT/height.Kaplan-Meier curves for 5-year survival compared LT recipients with BMI < 30.45 versus ≥30.45, with an estimated survival of 58.97 months versus 43.11 months, respectively (P < .001) (Fig. 3) and for LT recipients with an AAT/height <27.35 mm versus ≥27.35 mm, with an estimated survival of 57.69 months versus 46.34 months (P = .001). ConclusionsThis study does not show a higher rate of postoperative complications in obese patients. There is a significantly lower long-term survival in patients with AAT/height ≥27.35 mm and BMI ≥ 30.45. BMI is a valid estimate of obesity and is predictive of survival.