Worse 5-year Survival Research Articles

Conditional Survival of Patients With Early-Stage Non-Small Cell Lung Cancer Who Undergo Lobectomy, Segmentectomy, or Wedge Resection Using the NCDB.

Randomized clinical trials have shown that sub-lobar resection for clinical stage (cStage) IA non-small cell lung cancer (NSCLC) is non-inferior to lobar resection. We evaluated traditional and conditional survival differences between lobectomy, wedge resection, and segmentectomy in patients with cStage IA NSCLC. The National Cancer Database (2004-2019) was queried for patients with cStage IA (≤ 2 cm) NSCLC who underwent upfront lobectomy, segmentectomy, or wedge resection. Patients were stratified by extent of resection. Propensity-matched traditional (TSA) and conditional (CSA) survival analyses were performed. Propensity score included age, gender, histology, tumor grade, and Charlson-Deyo score. Number of lymph nodes (LN) harvested was also compared between groups. There were 46 395 patients who met the inclusion criteria, of whom 32 599 (70.3%) received lobectomy, 11 181 (24.1%) wedge resection, and 2615 (5.6%) segmentectomy. Following propensity matching, all groups contained 2615 patients. In the TSA, segmentectomy (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.08-1.32) and wedge resection (HR: 1.41, CI: 1.28-1.56) were associated with worse 5-year survival. This remained significant in CSA at 3- and 5-years post-resection in patients who underwent segmentectomy (HR: 1.24, CI: 1.08-1.43 and HR: 1.23, CI: 1.02-1.49, respectively) and wedge resection (HR: 1.42, CI: 1.24-1.63 and HR: 1.33, CI: 1.11-1.59, respectively). Wedge resection and segmentectomy were associated with a lower number of harvested LN (median = 4 and 6, respectively) compared to lobectomy (8, p < 0.001). Analysis of real-world data suggests that lobectomy is associated with improved traditional and conditional 5-year survival as well as LN harvest.

Left ventricular dilatation in patients with significant aortic regurgitation: association with mortality

Abstract Background In aortic regurgitation (AR), left ventricular (LV) dilatation occurs as a response to volume and pressure overload. Current guidelines recommend the use of LV end-systolic diameter index (LVESDi) to give indication for intervention, but recent studies suggested that volumetric measures may be more accurate in identifying LV remodeling in AR as compared to linear dimensions. Purpose To characterize LV dilatation in patients with significant AR (≥moderate), based on linear and volumetric dimensions, and to determine their prognostic value. Methods A total of 1070 patients (56 ± 18 years,65% male) were included. Cut-off values of 20 mm/m2 for LVESDi and 45 ml/m2 for end-systolic volume index (LVESVi) were used to identify the following LV remodeling patterns: No-significant LV dilatation (N=485), when both LVESDi and LVESVi were below the cut-off values; Discordant LV dilatation (N=279) if only one positive criterion was present; and Concordant LV dilatation (N=306) when both LVESDi and LVESVi were enlarged (Figure 1). The primary endpoint was all-cause mortality. Results Baseline characteristics differed across the 3 LV dilatation groups. Compared to patients with no-significant or discordant LV dilatation, those with concordant LV dilatation were more likely to be men, had a lower prevalence of systemic arterial hypertension and were more symptomatic. Concerning the echocardiographic characteristics, patients with concordant LV dilatation showed more severe AR, worse LV systolic function and larger left atrial volumes compared to the other two LV dilatation groups. During a median follow-up of 89 (IQR,54-132) months, 168 (16%) patients died and 484 (45%) underwent aortic valve surgery (AVS). Patients with concordant LV dilatation had worse 10-year survival (72%) compared to the groups (Figure 2), but benefited more from AVS based on a landmark analysis (p=0.001). In multivariable analysis, a significant association with the risk of all-cause mortality was observed for the presence of discordant (HR 1.645, 95%CI 1.077-2.513;p=0.021) or concordant LV dilatation (HR 2.695, 95% CI 1.710 to 4.249;p&amp;lt;0.001) after adjusting for the variables significant in the univariate analysis such as, age, male gender, NYHA class III-IV, AVS as a time-dependent covariate and LV ejection fraction (LVEF) ≤55%. Moreover, the addition of LV dilatation groups to a basal model including the above mentioned clinical and echocardiographic variables led to a significant increase in the predictivity of the model (Chi-square difference=21.1,p&amp;lt;0.001). Conclusion In patients with significant AR, LV dilatation detected by linear and/or volumetric measures was independently associated with increased mortality. Combining both methods for assessment of LV remodeling may improve risk stratification of these patients.

Frailty and Malnutrition in Surgical Outcomes of Elderly Breast Cancer Patients.

We evaluate the impact of frailty and malnutrition on breast cancer surgery outcomes in older adults using the ACS 5-factor modified frailty index (MFI) and Global Leadership Initiative on Malnutrition (GLIM) definition. Single institution retrospective review of a prospective database of the older adult (>60 years old) breast cancer surgery patients (2000-2016); cases stratified into groups as per MFI (0-2) and GLIM. Characteristics, 90-day post-op events, and 5-year follow-up data were analyzed to report survival and complication outcomes. Among 436 patients at diagnosis, 213 (48.9%) were >80 years old. 377 (86.5%) were alive at 5 years. 274 (62.8%) had MFI > 0, and 69 (15.8%) had malnutrition. Patients ≥ 80, MFI > 0, and PR-negative tumors had worse 5-year survival. There was no survival difference in patients >80 with/without malnutrition (HR = 1.01, p = 0.971), and there was no difference in mastectomy or lumpectomy (p = 0.560) between patients ≥ 80 or patients younger than 80; however, 94% of immediate reconstruction were in pts < 80. On multivariate regression, complications were associated with age < 80, readmission, MFI > 0, and history of HTN; serious complications were associated with age < 80, readmission, anticoagulation, and not receiving endocrine therapy. MFI showed a significant predictive value for 5-year survival for patients ≥ 80 and should be part of the preoperative evaluation.

Spatial multiplexed immunofluorescence analysis reveals coordinated cellular networks associated with overall survival in metastatic osteosarcoma

Patients diagnosed with advanced osteosarcoma, often in the form of lung metastases, have abysmal five-year overall survival rates. The complexity of the osteosarcoma immune tumor microenvironment has been implicated in clinical trial failures of various immunotherapies. The purpose of this exploratory study was to spatially characterize the immune tumor microenvironment of metastatic osteosarcoma lung specimens. Knowledge of the coordinating cellular networks within these tissues could then lead to improved outcomes when utilizing immunotherapy for treatment of this disease. Importantly, various cell types, interactions, and cellular neighborhoods were associated with five-year survival status. Of note, increases in cellular interactions between T lymphocytes, positive for programmed cell death protein 1, and myeloid-derived suppressor cells were observed in the 5-year deceased cohort. Additionally, cellular neighborhood analysis identified an Immune-Cold Parenchyma cellular neighborhood, also associated with worse 5-year survival. Finally, the Osteosarcoma Spatial Score, which approximates effector immune activity in the immune tumor microenvironment through the spatial proximity of immune and tumor cells, was increased within 5-year survivors, suggesting improved effector signaling in this patient cohort. Ultimately, these data represent a robust spatial multiplexed immunofluorescence analysis of the metastatic osteosarcoma immune tumor microenvironment. Various communication networks, and their association with survival, were described. In the future, identification of these networks may suggest the use of specific, combinatory immunotherapeutic strategies for improved anti-tumor immune responses and outcomes in osteosarcoma.

Contemporary Immunosuppression Management and 1-Year Outcomes in Dual Organ Heart Transplantation.

There have been limited reports on immunosuppression strategies and outcomes in dual organ heart transplant populations, primarily from before the 2018 United Network for Organ Sharing (UNOS) heart allocation policy change. Recent data suggested that outcomes with heart-lung and heart-liver transplants remained comparable in the new allocation era, yet heart-kidney recipients have worse 1-year survival. This single-center retrospective study evaluated adult heart-kidney, heart-liver, and heart-lung transplant recipients from September 2019 to May 2023. Immunosuppression regimen, infectious complications, and graft outcomes were collected for 12 months. A total of 36 patients (kidney n = 20, liver n = 9, and lung n = 7) were included in this study. Basiliximab was the most commonly employed induction strategy across the organ groups (12/20 in kidney, 4/9 in liver, and 7/7 in lung). All patients were on triple immunosuppression at 12 months posttransplant with prednisone wean achieved in one heart-liver recipient. Infection complications were frequently reported (95% kidney, 75% liver, 100% lung group). One patient went back to dialysis due to focal segmental glomerulosclerosis. One chronic lung allograft dysfunction was reported, but no other severe biopsy-proven rejection or retransplant was reported. The 1-year survival was 85% (17/20) in heart-kidney, 78% (7/9) in heart-liver, and 86% (6/7) in heart-lung recipients. This study summarized real-world immunosuppression strategies and outcomes in dual organ heart transplant recipients.

Myoferlin: A Potential Marker of Response to Radiation Therapy and Survival in Locally Advanced Rectal Cancer

PurposePatients with locally advanced rectal cancer often require neo-adjuvant chemoradiotherapy to downstage the disease, but the response is variable with no predictive biomarkers. We have previously revealed through proteomic profiling that myoferlin is associated with response to radiotherapy. The aims of this study were to further validate this finding and explore the potential for myoferlin to act as a prognostic and/or therapeutic target. Materials and MethodsImmunohistochemical analysis of a tissue microarray for 111 patients was used to validate the initial proteomic findings. Manipulation of myoferlin was achieved using siRNA, a small molecular inhibitor (wj460) and a CRISPR-Cas9 knockout cell line. Radiosensitisation following treatment was assessed using 2D clonogenic assays, 3D spheroid models and patient derived organoids. Underlying mechanisms were investigated using electrophoresis, immunofluorescence and immunoblotting. ResultsAnalysis of both the diagnostic biopsy and tumour resection samples confirmed that low myoferlin expression correlated with a good response to neoadjuvant LCRT. High myoferlin expression was associated with spread to local lymph nodes and worse 5-year survival (p = 0.01, HR 3.5, 95%CI [1.27, 10.04]). This was externally validated using the S:CORT database. Quantification of myoferlin using immunoblotting in immortalised colorectal cancer cell lines and organoids demonstrated that high myoferlin expression was associated with increased radioresistance. Biological and pharmacological manipulation of myoferlin resulted in significantly increased radiosensitivity across all cell lines in 2D and 3D models. Following irradiation, myoferlin knockdown cells had a significantly impaired ability to repair DNA double strand breaks. This appeared to be mediated via non-homologous end-joining. ConclusionsWe have confirmed that high expression of myoferlin in rectal cancer is associated with poor response to neoadjuvant therapy and worse long-term survival. Furthermore, the manipulation of myoferlin led to increased radiosensitivity in vitro. This suggests that myoferlin could be targeted to enhance the sensitivity of rectal cancer patients to radiotherapy and further work is required.

Impact of heart failure hospitalizations on clinical outcomes after mitral transcatheter edge-to-edge repair: Results from the EXPAND study.

This analysis aimed to compare the clinical outcomes associated with heart failure (HF) readmissions and to identify associations with HF hospitalizations (HFH) in patients treated with the MitraClip™ NTR/XTR System in the EXPAND study. The global, real-world EXPAND study enrolled 1041 patients with primary or secondary mitral regurgitation (MR) treated with the MitraClip NTR/XTR System. Echocardiograms were analysed by an independent echocardiographic core laboratory. The study population was stratified into HFH and No-HFH groups based on the occurrence of HFH 1 year post-index procedure. Clinical outcomes including MR severity, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and all-cause mortality were compared (HFH: n = 181; No-HFH: n = 860). Both groups achieved consistent 1-year MR reduction to ≤1+ (HFH vs. No-HFH: 87.3% vs. 89.5%, p = 0.6) and significant 1-year improvement in KCCQ scores (+16.5 vs. +22.3, p = 0.09) and NYHA functional class. However, more patients in the No-HFH group had 1-year NYHA class ≤II (HFH vs. No-HFH: 67.9% vs. 81.9%, p < 0.01). All-cause mortality at 1 year was 36.8% in the HFH group versus 10.4% in the No-HFH group (p < 0.001). The HFH rate decreased by 63% at 1 year post-M-TEER versus 1 year pre-treatment (relative risk 0.4, p < 0.001). Independent HFH associations were MR ≥2+ at discharge, HFH 1 year prior to treatment, baseline NYHA class ≥III, baseline tricuspid regurgitation ≥2+, and baseline left ventricular ejection fraction ≤40%. This study reports the impact of HFH on clinical outcomes post-treatment in the EXPAND study. Results demonstrate that the occurrence of HFH was associated with worse 1-year survival, and treatment with the MitraClip system substantially reduced HFH and improved patient symptoms and quality of life.

The associations of food environment with gastrointestinal cancer outcomes in the United States.

Social conditions and dietary behaviors have been implicated in the rising burden of gastrointestinal cancers (GIC). The "food environment" reflects influences on a community level relative to food availability, nutritional assistance, and social determinants of health. Using the US Department of Agriculture-Food Environment Atlas (FEA), we sought to characterize the association of food environment on GIC presenting stage and long-term survival. Patients diagnosed with GIC between 2013 and 2017 were identified using the SEER database. FEA-scores were based on 282 county-level food security variables, store-restaurant availability, SNAP/WIC enrollment, pricing/taxes, and producer vicinity adjusted-for factors of socioeconomic status, race-ethnicity, transportation access, and comorbidities. Relative FEA rankings across US counties were averaged into a composite score and assigned to patients by county-of-residence. The association of FEA, cancer stage, and survival were analyzed using multiple logistic regression and cox-proportional hazard models relative to White/non-White race/ethnicity. Among 287,148 patients, the most common GIC-sites were colon (n = 97,942, 34%), pancreas (n = 49,785, 17.3%), liver (n = 31,098, 11.0%) and esophagus (n = 16,271, 5.7%). A worse food environment was independently associated with increased odds of late-stage diagnosis (esophageal odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05; hepatic OR: 1.06, 95% CI: 1.03-1.08; pancreatic OR: 1.04, 95% CI: 1.01-1.06) among all patients; in contrast, food environment was associated with colorectal cancer stage among non-White patients only (OR: 1.04, 95% CI: 1.03-1.06). Worse food environment was associated with worse 3-year survival (colon OR: 1.03, 95% CI: 1.01-1.04; hepatic OR: 1.12, 95% CI: 1.08-1.17; gastric OR: 1.07, 95% CI: 1.01-1.13). Similar associations were noted relative to overall survival among the entire cohort (biliary tract hazard ratio [HR]: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.02, 95% CI: 1.01-1.04; hepatic HR: 1.07, 95% CI: 1.06-1.09; pancreatic HR: 1.04, 95% CI: 1.02-1.05; rectum HR: 1.03, 95% CI: 1.01-1.04; gastric HR: 1.05, 95% CI: 1.03-1.07), as well as among non-White patients (biliary HR: 1.04, 95% CI: 1.01-1.07; colon HR: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.05, 95% CI: 1.02-1.08; hepatic HR: 1.08, 95% CI: 1.06-1.10) (all p < 0.003). Food environment was independently associated with late-stage tumor presentation and worse 3-year and overall survival among GIC patients. Interventions to address inequities across communities relative to food environments are needed to alleviate disparities in cancer care.

Donor Age More Than 20 Years Greater Than Recipient Age Is Associated With Worse 5-Year Survival in Young Adult Heart Transplantation.

Prior studies indicate donor age-recipient age (DA-RA) difference may be of prognostic value in adolescents, although not adults. We aim to analyze the relationship between DA-RA difference and long-term survival of young adult heart transplantation (HTx) recipients. First-time, single-organ HTx recipients aged 18-30 who underwent HTx between 2010 and 2020 were analyzed from the United Network for Organ Sharing (UNOS) registry. Four cohorts were created based on DA-RA difference. The primary outcome was 5 year post-HTx survival. Secondary outcome was post-HTx complications. One thousand eight hundred three donor-recipient pairs were divided into four groups: DA-RA < 0, 0 ≤ DA-RA < 10, 10 ≤ DA-RA < 20, and DA-RA ≥ 20 with 682 (37.8%), 651 (36.1%), 356 (19.7%), 114 (6.3%) pairs in each cohort, respectively. The estimated 5 year survival of the DA-RA ≥ 20 cohort was 66.5% compared to the other three groups at ~75%. After adjustment, DA-RA ≥ 20 was independently associated with worse survival compared to DA-RA < 0 (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.06-2.27; log-rank p = 0.008). There was no significant difference in complication incidence across cohorts. Among young adults, accepting a donor heart more than 20 years older than the recipient was associated with worse 5 year survival. We did not detect a significant difference up to 20 years. This information may help guide appropriate donor selection in the young adult population.

Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma

Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma. To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma. This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least 1 tumor marker measured at MD Anderson between March 2016 and May 2023. Data were analyzed from January to December 2023. Association of serum tumor markers with survival in patients with appendiceal adenocarcinoma. Cox proportional hazards regression analyses were also performed to assess associations between clinical factors (serum tumor marker levels, demographics, and patient and disease characteristics) and patient outcomes (overall survival). A total of 1338 patients with appendiceal adenocarcinoma were included, with a median (range) age at diagnosis of 56.5 (22.3-89.6) years. The majority of the patients had metastatic disease (1080 patients [80.7%]). CEA was elevated in 742 of the patients tested (56%), while CA19-9 and CA125 were elevated in 381 patients (34%) and 312 patients (27%), respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; elevated vs normal was 81% vs 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9-5.6), 84% vs 92% for CA19-9 (HR, 2.2; 95% CI, 1.4-3.4), and 69% vs 93% for CA125 (HR, 4.6; 95% CI, 2.7-7.8) (P < .001 for all). Quantitative evaluation of tumor markers was associated with outcomes. Patients with highly elevated (top 10th percentile) CEA, CA19-9, or CA125 had markedly worse survival, with 5-year survival rates of 59% for CEA (HR, 9.8; 95% CI, 5.3-18.0), 64% for CA19-9 (HR, 6.0; 95% CI, 3.0-11.7), and 57% for CA125 (HR, 7.6; 95% CI, 3.5-16.5) (P < .001 for all). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were all still associated worse survival (HR for CEA, 3.4; 95% CI, 2.5-4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2-2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4-6.4; P < .001). Interestingly, tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 vs 15.0; difference, 3.3; 95% CI, 0.9-3.7; P < .001). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with an 11-fold increased risk of death in patients with all 3 tumor markers elevated relative to those with none elevated. Somatic mutations in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.

Coronary artery calcium and cardiovascular outcomes in patients with lymphoma undergoing autologous hematopoietic cell transplantation.

Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2-fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). The median age at HCT was 55.7 years (range, 18.5-75.1 years), 59% were male, and 60% were non-Hispanic White. The prevalence of CAC was 37%. The 5-year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1-100 (20%), and >100 (32%) (p=.001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2-7.5) and worse 5-year survival (77% vs. 50%; p<.001; HR, 2.0; 95% CI, 1.1-3.4), compared to those without CAC. CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision-making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT.

TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma.

Treatment resistance and relapse are common problems in head and neck squamous cell carcinoma (HNSCC). Except for p16, no clinically accepted prognostic biomarkers are available for HNSCC. New biomarkers predictive of recurrence and survival are crucial for optimal treatment planning and patient outcome. High translocator protein (TSPO) levels have been associated with poor survival in cancer, but the role of TSPO has not been extensively evaluated in HNSCC. TSPO expression was determined in a large population-based tissue microarray cohort including 611 patients with HNSCC and evaluated for survival in several clinicopathological subgroups. A TCGA HNSCC cohort was used to further analyze the role of TSPO in HNSCC. TSPO expression was downregulated in more aggressive tumors. Low TSPO expression associated with worse 5-year survival and was an independent prognostic factor for disease-specific survival. Subgroup analyses showed that low TSPO expression associated with worse survival particularly in p16-positive oropharyngeal cancer. In silico analyses supported the prognostic role of TSPO. Cellular respiration had the highest significance in pathway analyses for genes expressed positively with TSPO. Decreased TSPO expression associates with poor prognosis in HNSCC. TSPO is a prognostic biomarker in HNSCC to potentially guide treatment stratification especially in p16-positive oropharyngeal cancer.

Risk factors and associated outcomes of postoperative delirium after open abdominal aortic aneurysm repair

ObjectiveOpen abdominal aortic aneurysm repair (OAR) is a major vascular procedure that incurs a large physiologic demand, increasing the risk for complications such as postoperative delirium (POD). We sought to characterize POD incidence, identify delirium risk factors, and evaluate the effect of delirium on postoperative outcomes. We hypothesized that POD following OAR would be associated with increased postoperative complications and resource utilization. MethodsThis was a retrospective study of all OAR cases from 2012 to 2020 at a single tertiary care center. POD was identified via a validated chart review method based on key words and Confusion Assessment Method assessments. The primary outcome was POD, and secondary outcomes included length of stay, non-home discharge, 90-day mortality, and 1-year survival. Bivariate analysis as appropriate to the data was used to assess the association of delirium with postoperative outcomes. Multivariable binary logistic regression was used to identify risk factors for POD and Cox regression for variables associated with worse 1-year survival. ResultsOverall, 198 OAR cases were included, and POD developed in 34% (n = 67). Factors associated with POD included older age (74 vs 69 years; P < .01), frailty (50% vs 28%; P < .01), preoperative dementia (100% vs 32%; P < .01), symptomatic presentation (47% vs 27%; P < .01), preoperative coronary artery disease (44% vs 28%; P = .02), end-stage renal disease (89% vs 32%; P < .01) and Charlson Comorbidity Index score >4 (42% vs 26%; P = .01). POD was associated with 90-day mortality (19% vs 5%; P < .01), non-home discharge (61% vs 30%; P < .01), longer median hospital length of stay (14 vs 8 days; P < .01), longer median intensive care unit length of stay (6 vs 3 days; P < .01), postoperative myocardial infarction (7% vs 2%; P = .045), and postoperative pneumonia (19% vs 8%; P = .01). On multivariable analysis, risk factors for POD included older age, history of end-stage renal disease, lack of epidural, frailty, and symptomatic presentation. A Cox proportional hazards model revealed that POD was associated with worse survival at 1 year (hazard ratio, 3.8; 95% confidence interval, 1.6-9.0; P = .003). ConclusionsPOD is associated with worse postoperative outcomes and increased resource utilization. Future studies should examine the role of improved screening, implementation of delirium prevention bundles, and multidisciplinary care for the most vulnerable patients undergoing OAR.

Polypharmacy and potentially-inappropriate medications are prevalent in the elderly cancer patients receiving systemic cancer therapy and they co-relate with adverse outcomes

ObjectivesCancer is the disease of the ageing. Most of the elderly cancer patients have pre-existing illnesses requiring complexity of medical care. Excessive medications would lead not only futility, but also result in adverse outcomes especially if such over-prescription is not appropriate. This study was intended to determine the prevalence of polypharmacy (PP) and potentially-inappropriate medications (PIMs) among elderly cancer patients eligible for active cancer care and their associations with hospitalization and mortality.Materials and methodsThis was a prospective cohort study conducted among the elderly non-hematologic cancer patients (≥ 65 years old) whom a medical oncologist had decided suitable for systemic cancer therapy. Demographic data including age, sex, primary site of cancer, cancer stage at diagnosis, Charlson Comorbidity Index (CCI), numbers and kinds of medications used both prior to and during cancer treatment were recorded. Hospitalizations not related to systemic cancer therapy administration and mortality were prospectively monitored. All of the patients had to be followed at least one year after cancer diagnosis.ResultsThere were 180 eligible participants. Median age in years (IQR) was 68 (65–73). One hundred patients (55.56%) were male and 80 patients (44.44%) were female. Breast (35, 19.44%), lung (31, 17.22%) and colorectal (18, 10%) cancers were the most common diagnoses. Eighty-six patients (47.78%) had metastatic disease at cancer diagnosis. One hundred twenty-two patients (67.78%) had PP (5 or more medications a day) and thirty-six patients (20%) had hyper-PP (10 or more medications a day). One hundred twenty five of the whole cohort (69.4%) had PIMs. Patients with more serious CCI scores were associated with PP and hyper-PP. While patients with primary lung cancer was only the only factor associated with PIMs. When excluding opioids, laxatives and anti-emetics, the most frequently prescribed drugs during cancer treatment, the so-called corrected PP did not associate with worse 1-year survival. Factors correlated with 1-year mortality were more advanced age group (70 years old or more) (OR 2.24; 95% C.I., 1.14–4.41; p = 0.019), primary lung cancer (OR 2.89; 95% C.I., 1.45–5.78; p = 0.003), metastatic disease at cancer diagnosis (OR 4.57; 95% C.I., 1.90–10.97; p = 0.001), and unplanned hospitalizations (OR 3.09; 95% C.I.,1.60–5.99; p = 0.001). While male gender (OR 2.35; 95% C.I., 1.17–4.71; p = 0.016), metastatic stage at cancer diagnosis (OR 2.74; 95% C.I., 1.33–5.66; p = 0.006) and corrected PP (OR 1.90; 95% C.I. 1.01–3.56; p = 0.046) were the significant predictive factors of unplanned hospitalizations.ConclusionAmong elderly cancer patients suitable for systemic cancer therapy, around two thirds of patients had PP and PIMs. Higher CCI score was the only significant predictor of PP and hyper-PP; while primary lung cancer was the sole independent factor predicting PIMs. PP was associated with unplanned hospitalizations, albeit not the survival.

Procyanidin C1 inhibits tumor growth and metastasis in colon cancer via modulating miR-501-3p/HIGD1A axis

IntroductionAlthough colon (COAD) and rectal adenocarcinoma (READ) combined to refer to colorectal cancer (CRC), substantial clinical evidence urged that CRC should be treated as two different cancers due to compared with READ, COAD showed higher morbidity and worse 5-year survival. ObjectivesThis study has tried to screen for the crucial gene that caused the worse prognosis and investigate its mechanism for mediating tumor growth and metastases in COAD. Meanwhile, the potential anti-COAD compound implicated in this mechanism was identified and testified from 1,855 food-borne chemical kits. This study aims to bring a new perspective to the development of new anti-COAD drugs and personalized medicine for patients with COAD. Methods and resultsThe survival-related hub genes in COAD and READ were screened out from The Cancer Genome Atlas (TCGA) database and the results showed that HIGD1A, lower expressed in COAD than in READ, was associated with poor prognosis in COAD patients, but not in READ. Over-expressed HIGD1A suppressed CRC cell proliferation, invasion, and migration in vitro and in vivo. Meanwhile, the different expressed microRNA profiles between COAD and READ showed that miR-501-3p was highly expressed in COAD and inhibited HIGD1A expression by targeting 3′UTR of HIGD1A. MiR-501-3p mimics promoted cell proliferation and metastasis in CRC cells. In addition, Procyanidin C1 (PCC1), a kind of natural polyphenol has been verified as a potential miR-501-3p inhibitor. In vitro and in vivo, PCC1 promoted HIGD1A expression by suppressing miR-501-3p and resulted in inhibited tumor growth and metastasis. ConclusionThe present study verified that miR-501-3p/HIGD1A axis mediated tumor growth and metastasis in COAD. PCC1, a flavonoid that riched in food exerts anti-COAD effects by inhibiting miR-501-3p and results in the latter losing the ability to suppress HIGD1A expression. Subsequently, unfettered HIGD1A inhibited tumor growth and metastasis in COAD.

Long-term prognostic factors for PRRT in neuroendocrine tumors.

Peptide receptor radionuclide therapy (PRRT) is an effective and well-tolerated treatment option for patients with neuroendocrine tumors (NETs) that prolongs progression-free survival (PFS). However, the limited overall survival (OS) rates in the prospective phase III study (NETTER1) highlighted the need to identify patient-specific long-term prognostic markers to avoid unnecessary side effects and enable better treatment stratification. Therefore, we retrospectively analyzed prognostic risk factors in NET patients treated with PRRT. A total of 62 NET patients (G1: 33.9%, G2 62.9%, and G3 3.2%) with at least 2 cycles of PRRT with [177Lu]Lu-HA-DOTATATE (mean 4 cycles) were analyzed. Of which, 53 patients had primary tumors in the gastroenteropancreatic (GEP) system, 6 had bronchopulmonary NET, and 3 had NET of unknown origin. [68Ga]Ga-HA-DOTATATE PET/CT scans were performed before PRRT start and after the second treatment cycle. Different clinical laboratory parameters, as well as PET parameters, such as SUVmean, SUVmax, and PET-based molecular tumor volume (MTV), were collected, and their impact on the OS was investigated. Patient data with a mean follow-up of 62 months (range 20-105) were analyzed. According to interim PET/CT, 16 patients (25.8%) presented with partial response (PR), 38 (61.2%) with stable disease (SD), and 7 (11.3%) with progressive disease (PD). The 5-year OS was 61.8% for all patients, while bronchopulmonary NETs showed poorer OS than GEP-NETs. Multivariable Cox regression analysis showed that chromogranin A level and MTV together were highly significant predictors of therapeutic outcome (HR 2.67; 95% CI 1.41-4.91; p = 0.002). Treatment response was also influenced by the LDH level (HR 0.98; 95% CI 0.9-1.0; p = 0.007) and patient age (HR 1.15; 95% CI 1.08-1.23; p < 0.001). ROC analysis revealed baseline MTV > 112.5 ml [Sens. 91%; Spec. 50%; AUC 0.67 (95% CI 0.51-0.84, p = 0.043)] and chromogranin A >1,250.75 μg/l [Sens. 87%; Spec. 56%; AUC 0.73 (95% CI 0.57-0.88, p = 0.009)] as the best cutoff values for identifying patients with worse 5-year survival. Our retrospective analysis defined MTV and chromogranin A in combination as significant prognostic factors for long-term OS. Furthermore, an interim PET/CT after two cycles has the potential in identifying non-responders who may benefit from a change in therapy at an early stage.

Limited cumulative experience with ex vivo lung perfusion is associated with inferior outcomes after lung transplantation

ObjectiveEx vivo lung perfusion (EVLP) allows for prolonged preservation and evaluation/resuscitation of donor lungs. We evaluated the influence of center experience with EVLP on lung transplant outcomes. MethodsWe identified 9708 isolated, first-time adult lung transplants from the United Network for Organ Sharing database (March 1, 2018-March 1, 2022), 553 (5.7%) involved using donor lungs after EVLP. Using the total volume of EVLP lung transplants per center during the study period, centers were dichotomized into low- (1-15 cases) and high-volume (>15 cases) EVLP centers. ResultsForty-one centers performed EVLP lung transplants, including 26 low-volume and 15 high-volume centers (median volume, 3 vs 23 cases; P < .001). Recipients at low-volume centers (n = 109) had similar baseline comorbidities compared with high-volume centers (n = 444). Low-volume centers used numerically more donation after circulatory death donors (37.6 vs 28.4%; P = .06) and more donors with Pao2/Fio2 ratio <300 (24.8 vs 9.7%; P < .001). After EVLP lung transplants, low-volume centers had worse 1-year survival (77.8% vs 87.5%; P = .007), with an adjusted hazard ratio of 1.63 (95% CI, 1.06-2.50, adjusting for recipient age, sex, diagnosis, lung allocation score, donation after circulatory death donor, donor Pao2/Fio2 ratio, and total annual lung transplant volume per center). When compared to non-EVLP lung transplants, 1-year survival of EVLP lung transplants was significantly worse at low-volume centers (adjusted hazard ratio, 2.09; 95% CI, 1.47-2.97) but similar at high-volume centers (adjusted hazard ratio, 1.14; 95% CI, 0.82-1.58). ConclusionsThe use of EVLP in lung transplantation remains limited. Increasing cumulative EVLP experience is associated with improved outcomes of lung transplantation using EVLP-perfused allografts.

Factors Associated With Survival Disparities Between Non-Hispanic Black and White Patients With Uterine Cancer

Disparities in survival exist between non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) patients with uterine cancer. To investigate factors associated with racial disparities in survival between Black and White patients with uterine cancer. This cohort study used data from the National Cancer Database on 274 838 Black and White patients who received a diagnosis of uterine cancer from January 1, 2004, to December 31, 2017, with follow-up through December 2020. Statistical analysis was performed in July 2022. Overall survival by self-reported race and evaluation of explanatory study factors associated with hazard ratio (HR) reduction for Black vs White patients. A propensity scoring approach was applied sequentially to balance racial differences in demographic characteristics, comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, and treatment. The study included 32 230 Black female patients (mean [SD] age at diagnosis, 63.8 [10.0] years) and 242 608 White female patients (mean [SD] age at diagnosis, 63.5 [10.5] years) and had a median follow-up of 74.0 months (range, 43.5-113.8 months). Black patients were more likely than White patients to have low income (44.1% vs 14.0%), be uninsured (5.7% vs 2.6%), present with nonendometrioid histologic characteristics (46.1% vs 21.6%), have an advanced disease stage (34.1% vs 19.8%), receive first-line chemotherapy (33.8% vs 18.2%), and have worse 5-year survival (58.6% vs 78.5%). Among patients who received a diagnosis at younger than 65 years of age, the HR for death for Black vs White patients was 2.43 (95% CI, 2.34-2.52) in a baseline demographic-adjusted model and 1.29 (95% CI, 1.23-1.35) after balancing other factors. Comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, treatment, and unexplained factors accounted for 0.8%, 7.2%, 11.5%, 53.1%, 5.8%, 1.2%, and 20.4%, respectively, of the excess relative risk (ERR) among the younger Black vs White patients. Among patients 65 years or older, the HR for death for Black vs White patients was 1.87 (95% CI, 1.81-1.93) in the baseline model and 1.14 (95% CI, 1.09-1.19) after balancing other factors. Comorbidity score, neighborhood income, insurance status, histologic subtype, disease stage, treatment, and unexplained factors accounted for 3.0%, 7.5%, 0.0%, 56.2%, 10.6%, 6.9%, and 15.8%, respectively, of the ERR among Black vs White patients aged 65 years or older. This study suggests that histologic subtype was the dominant factor associated with racial survival disparity among patients with uterine cancer, while insurance status represented the main modifiable factor for women younger than 65 years. Additional studies of interactions between biology and social determinants of health are merited.

Hyperglycemia is associated with worse 3-year survival in older patients admitted to the intensive care unit after non-cardiac surgery: Post hoc analysis of a randomized trial.

Hyperglycemia is common in critically ill patients after surgery and is associated with worse perioperative outcomes. Yet, the impact of postoperative hyperglycemia on long-term outcomes remains unclear. We therefore analyzed the association between early postoperative hyperglycemia and 3-year overall survival in older patients who were admitted to the intensive care unit after surgery. This was a post hoc analysis of database obtained from a previous randomized trial and 3-year follow-up. The underlying trial enrolled 700 patients aged 65 years or older who were admitted to the intensive care unit after elective non-cardiac surgery. Early postoperative time-weighted average blood glucose was calculated and was divided into three levels, i.e., <8.0 mmol/L, from 8.0 to 10.0 mmol/L, and >10.0 mmol/L. The primary outcome was 3-year overall survival. The association between time-weighted average blood glucose level and 3-year overall survival was analyzed with Cox proportional hazard regression models. Subgroup analyses were also performed in patients with or without diabetes, and in patients following cancer or non-cancer surgery. A total of 677 patients (mean age 74 years, 60% male sex) were included in the final analysis. Within 3 years after surgery, deaths occurred in 22.1% (30/136) of patients with time-weighted average blood glucose <8.0 mmol/L, compared with 35.7% (81/227) of those from 8.0 to 10.0 mmol/L (unadjusted hazard ratio 1.75, 95% CI 1.15 to 2.67, P = 0.009), and 36.9% (116/314) of those >10.0 mmol/L (unadjusted hazard ratio 1.91, 95% CI 1.28 to 2.85, P = 0.002). After adjustment for confounding factors, the risk of 3-year mortality remained higher in patients with time-weighted average blood glucose from 8.0 to 10.0 mmol/L (adjusted hazard ratio 2.28, 95% CI 1.47 to 3.54, P < 0.001) and in those >10.0 mmol/L (adjusted hazard ratio 2.00, 95% CI 1.29 to 3.10, P = 0.002). Similar results were obtained in the subgroups of patients without diabetes and patients following cancer surgery. For older patients admitted to the intensive care unit after elective non-cardiac surgery, high early blood glucose (time-weighted average blood glucose ≥ 8.0 mmol/L) was associated with poor 3-year overall survival. The impact of moderate glycemic control on long-term survival deserves further investigation.

Abstract PR004: In vitro and in vivo CRISPR screens in colorectal cancer organoids identify suppressors of metastasis

Abstract Colorectal cancer (CRC) is the 2nd-leading cause of cancer-related deaths worldwide and metastatic disease remains a major unmet clinical need. Nevertheless, the molecular underpinnings of metastatic spread and colonization of distant sites remain elusive. To systematically identify functional genes contributing to metastasis in a physiologically relevant model of CRC, we developed a novel platform enabling robust, pooled CRISPR/Cas9 screening in primary colonic organoids engineered with common CRC driver mutations in Apc, Kras, and Tp53. We performed parallel in vitro invasion and in vivo metastasis gain-of-function CRISPR/Cas9 knockout screens with high-content gRNA libraries to uncover novel suppressors of metastasis. We confirmed resulting hits as bona-fide metastatic suppressors using both pooled validation screens and single-gene approaches. Genes scoring in both in vitro and in vivo screens included previously identified regulators of migration and invasion, such as Ctnna1, and genes scoring only in the in vivo screen included novel negative regulators of metastasis such as Bcl2l13. These hits in the murine system were supported by human TCGA data, indicating that low expression of these genes is associated with worse 5-year survival in colon and rectal adenocarcinoma patients (COAD and READ). Utilizing transwell and live-imaging assays, we found that sgRNAs targeting Ctnna1 markedly enhanced invasion and migration of CRC organoids while sgRNAs targeting Bcl2l13 had no effect, an observation consistent with our in vitro screen. Therefore, while loss of Ctnna1 enhances metastasis by augmenting invasion and migration, loss of Bcl2l13 acts through alternative mechanisms. Single cell RNA sequencing of primary and metastatic lesions derived from Bcl2l13 knockout and control CRC tumors identified novel putative pathways promoting metastatic spread via migration-independent mechanisms, including upregulation of hypoxia signalling and recruitment of pro-tumorigenic macrophages. Thus, our CRISPR/Cas9 screening pipeline is a viable approach for the identification of novel regulators of CRC metastasis in vitro and in vivo, uncovering both motility and migration-dependent and independent paths to metastatic success. These findings will help untangle the complex web of molecular events underlying CRC metastasis and provide clinically-relevant insights into the process of human CRC metastasis. Citation Format: Zvi Cramer, Xin Wang, Nicolae Adrian Leu, Keara Monaghan, Joshua H. Rhoades, Yuhua Tian, Joshua Rico, Diego Mendez, Ricardo Petroni, Melissa S. Kim, Ning Li, Christopher J. Lengner, M. Andres Blanco. In vitro and in vivo CRISPR screens in colorectal cancer organoids identify suppressors of metastasis [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr PR004.