Propensity Score Research Articles

Survival associated with metastatic early-onset colorectal cancer among Black patients: A real-world account.

39 Background: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) diagnosed under the age of 50, is a growing health concern. The current study explored the racial differences in EOCRC survival in the United States (US). Methods: This retrospective cohort study was conducted using the TriNetX database, a platform that provides access to deidentified medical records on more than 130 million patients across 94 healthcare organizations in the US. The study cohort included patients with metastatic CRC (mCRC), aged 20 to 50, diagnosed between January 1, 2002, and January 1, 2020, and received frontline chemotherapy with oxaliplatin and 5- fluorouracil or capecitabine. The cohort was divided into Black or African American cohort and White cohort. The primary endpoint, 5-year overall survival (OS), was compared between these cohorts after performing 1:1 propensity score matching (PSM) for baseline demographics and comorbid conditions (Table). Kaplan-Meier curves, log-rank chi-square statistics, and hazard ratios (HR) were used to compare the outcome. Results: The entire cohort consisted of 2,923 patients with a mean age of 44 (±6) years; 48.58% were female. The majority were white (56.38%), followed by 15.56% of unknown race, Black/African American (9.16%), Hispanic (9.34%), and Asian (8.96%). After propensity score matching (PSM), there were 262 patients in both the Black and White groups. In the matched population, the Kaplan-Meier survival curves showed that Black patients had significantly lower 5-year OS rates (24.84%) compared to White patients (33.76%) [Hazard Ratio (HR): 1.39, 95% CI (1.06, 1.85), p<0.05]. There is no significant difference between Black and White population over age of 50 [ HR: 1.06, 95% CI (0.966-1.179), P=0.2]. Conclusions: Survival among Black patients with EOCRC appears to be worse than White patients despite adjustment for confounding variables, supporting further research focusing onto this patient population. Characteristics of the cohorts before and after matching. Black cohort (n = 265) and White cohort (n = 1,632) characteristics before propensity score matching Black cohort (n = 262) and White cohort (n = 262) characteristics after propensity score matching Black patients, n (%) White patients, n (%) Sth diff. Black Patients, n (%) White patients, n (%) Sth diff. Age (Mean ± SD) 36.2 ± 6.18 36.3 ± 6.01 0.022 36.1 ± 6.17 36.2 ± 6.43 0.013 Female 144 (54.5%) 774 (47.4%) 0.142 143 (54.5%) 143 (54.5%) <0.0001 Tobacco use 15 (5.6%) 96 (5.8%) 0.0087 15 (5.7%) 11 (4.2%) 0.0703 Hypertensive diseases 67 (25.3%) 214 (13.12%) 0.3147 65 (24.8%) 64 (24.4%) 0.0089 Ischemic heart diseases 10 (3.7%) 40 (2.4%) 0.0769 10 (3.8%) 10 (3.8%) < 0.0001 Type 2 diabetes mellitus 24 (9%) 89 (5.4%) 0.1403 22 (8.3%) 19 (7.2%) 0.0426 Diseases of arteries, arterioles and capillaries 12 (4.5%) 47 (2.8%) 0.0881 11 (4.1%) 10 (3.8%) 0.0195

Comparison of clinical outcomes in patients with refractory ascites treated with either TIPS, tunneled peritoneal catheter, or ascites pump.

Refractory ascites (RA) remains a serious complication in patients with cirrhosis. Currently, the insertion of a TIPS is considered the standard of care in these patients. To achieve symptom control in those with TIPS contraindications, tunneled peritoneal catheters (PeCa) or ascites pumps were introduced. However, data comparing the available treatment options are scarce. This study aims to compare outcomes among patients with RA treated either with TIPS, PeCa, or ascites pump. All patients with RA and cirrhosis treated at Hannover Medical School between 2009 and 2023 were evaluated. Endpoints included mortality, acute kidney injury (AKI), hyponatremia, peritonitis, and rehospitalization rate. Propensity score matching was conducted to adjust for group differences. First, 31 patients with ascites pump were compared to 62 patients with a PeCa after propensity score matching. There were no differences regarding mortality nor incidences of AKI, hyponatremia, or rehospitalization. However, incidences of peritonitis and explantation were lower in those with ascites pump (HR 0.32, 95% CI: 0.15-0.70, and HR 0.32, 95% CI: 0.14-0.71, respectively). Second, 35 ascites pump patients were matched with 70 individuals with TIPS. No differences regarding mortality or peritonitis incidence were observed. Ascites pump patients showed higher incidences of AKI (HR 4.55, 95% CI: 2.53-8.18) and hyponatremia (HR 4.13, 95% CI: 2.08-8.22). Last, 129 patients with TIPS were compared to 129 with PeCa. Mortality was comparable, while incidences of AKI (HR 5.01, 95% CI: 3.36-7.47), hyponatremia (HR 4.64, 95% CI: 3.03-7.12), and peritonitis (HR 2.19, 95% CI: 1.41-3.41) were higher in those with PeCa. While ascites pump was associated with lower incidences of device infections and explantations, TIPS was associated with the lowest incidence of clinical complications in patients with RA.

Outcomes in management of locally advanced rectal cancer with total neoadjuvant therapy in an underserved population.

208 Background: The use of total neoadjuvant therapy is now standard of care and is favored when treating locally advanced rectal cancer but its treatment is seldom studied in an underserved population. Methods: A retrospective study was conducted on patients with Stage II and III locally advanced colorectal cancer treated with either total neoadjuvant therapy (TNT) followed by resection or conventional therapy (CT) with chemoradiation followed by surgery, with or without adjuvant treatment afterwards. Patients completed treatment between 2015 and 2023 at the Hartford Hospital Helen and Harry Gray Cancer Center at Hartford, Connecticut. Data collected included demographics, type of treatment, tumor location (high vs mid vs low) and pathological response to treatment spread out among the two groups. Propensity score matching was used to minimize baseline differences between the two groups, adjusted for age, gender, ethnicity and tumor location and Fisher’s exact test was performed to then check for significance. Results: Out of the 133 patients analyzed, 90 underwent TNT, and 43 received CT. The average age at diagnosis was 57.5 years (SD: 11.15). In the TNT group, 79 patients (87.7%) achieved either a partial or complete response (PCR), while 11 patients (12.3%) had No response (NR). Tumor locations in the TNT group were distributed as follows: 13.4% (n=12) had high tumors, 34.4% (n=31) had mid tumors, and 52.2% (n=47) had low tumors. In the CT group, 31 patients (72.9%) achieved PCR, while 12 patients (27.9%) had NR. Tumor locations in the CT group were distributed as follows: 9.3% (n=4) had high tumors, 51.2% (n=22) had mid tumors, and 39.5% (n=17) had low tumors. After propensity score matching and adjusting for demographic covariates, the TNT group demonstrated a higher proportion of responders compared to the CT group (p=0.048). Furthermore, 40% (n=36) of patients in the TNT group achieved a complete response, compared to 32% (n=14) in the CT group. Partial response rates were 39.5% (n=17) in the TNT group and 47.8% (n=43) in the CT group. Conclusions: TNT demonstrated superior pathological response rates compared to CT, which supports its growing role in the management of locally advanced rectal cancer even in this underserved population.

The effect of renin-angiotensin system inhibitors on patients with pancreatic cancer receiving systemic treatment: A retrospective cohort study from TriNetX US collaborative networks.

734 Background: This study aimed to assess the impact of renin-angiotensin system inhibitors, including angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), on patients with pancreatic cancer undergoing systemic chemotherapy. Methods: We conducted a global, retrospective collaborative network analysis using TriNetX data from January 1, 2014, to December 31, 2023, to explore this question. The study captured data on pancreatic cancer diagnoses, comorbidities, medications, and survival outcomes. Propensity score matching (PSM) was used to create 1:1 matched groups. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated to assess survival outcomes, while the Kaplan–Meier method was employed to evaluate survival probabilities. Subgroup analyses were performed based on sex, age, surgery, race, and comorbidities. Results: The study included 1,861 patients who were on ARBs/ACEIs and 4,875 patients who were not on these medications at baseline. After 1:1 propensity score matching, both groups were well-balanced with 1,627 patients each. Compared to the non-ARBs/ACEIs group, patients receiving ARBs/ACEIs demonstrated significantly better overall survival (HR: 0.846, 95% CI: 0.753–0.949). Subgroup analyses revealed significantly improved survival outcomes in patients on ARBs/ACEIs, including those without surgery (HR: 0.846, 95% CI: 0.749–0.956), males (HR: 0.762, 95% CI: 0.640–0.908), patients aged 65 years and older (HR: 0.801, 95% CI: 0.709–0.906), and White patients (HR: 0.806, 95% CI: 0.704–0.924). Notably, similar survival benefits were observed in patients with comorbidities such as diabetes, ischemic heart disease, dyslipidemia, and hypertension. Conclusions: In the largest TriNetX matched cohort study on pancreatic cancer, the use of ARBs/ACEIs was associated with a reduced risk of overall mortality. However, prospective studies are needed to further evaluate the effects of concomitant ARB/ACEI use in patients with pancreatic cancer undergoing systemic treatment.

Do Patients With NASH-related Cirrhosis Have Better Overall Survival Compared With Other Etiologies of Cirrhosis? A Population-based Study.

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. We aim to explore the clinical outcomes of NASH cirrhosis compared with other etiologies of cirrhosis. We utilized an EHR-based database (TriNetX) to study the outcomes of NASH cirrhosis. Patients diagnosed with NAFLD or NASH and cirrhosis between January 2016 and December 2019 were identified utilizing appropriate ICD-10-CM codes. The primary outcome was 3-year overall survival. Secondary outcomes were decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. The Control group was patients with other etiologies of cirrhosis than NASH. Study and control groups were matched for demographic characters and comorbidities using propensity score matching. We identified 45,063 patients with NASH cirrhosis. The NASH cirrhosis cohort comprised older (61 vs. 59y) White (78% vs. 64%) women (58% vs. 38%) with more comorbidities (diabetes mellitus, obesity, ischemic heart disease, history of cancer, chronic kidney disease). After propensity score matching, patients with NASH cirrhosis had a better 3-year survival (78% vs. 74%, HR 0.79, 95% CI 0.77-0.82) compared with patients with non-NASH cirrhosis. Hepatocellular carcinoma was diagnosed less commonly in patients with NASH cirrhosis (6.7% vs. 10.6%, P <0.001), and liver transplantation was performed more often for NASH cirrhosis compared with non-NASH cirrhosis [Risk ratio 1.13 (1.08-1.18)]. Patients with NASH cirrhosis probably have better 3-year overall survival than other etiologies of cirrhosis. This is an interesting finding, as patients with NASH are older and have more comorbidities. Improved survival can be partly explained by a higher probability of liver transplantation and improvements in cardiovascular outcomes.

Impact of Ex Vivo Lung Perfusion on Inpatient Cost: A Propensity Score-Matched Analysis of the US Nationwide Healthcare Cost and Utilization Project Database.

The goal of this study was to investigate the association between ex vivo lung perfusion (EVLP) use and inpatient hospitalization cost for lung transplantation in a nationwide sample. Lung transplantation patients in 2018-2020 Nationwide Readmissions Database (NRD) were grouped based on use of EVLP. The primary outcome was total inpatient hospitalization cost. 1:2 propensity score matching by EVLP status was performed followed by multivariable linear regression to determine the association between inpatient cost and EVLP while adjusting for pre-transplant hospital days, high volume EVLP center status, and propensity score. There were 3902 lung transplants and 118 (3%) were recipients of EVLP lungs. Among EVLP patients, the median cost was $871468 (IQR: $608671-1274392), compared to $846516 (IQR: $531462-1439267, p=0.871) among the total non-EVLP cohort. After 1:2 propensity score-matched cohort, recipients of EVLP lungs had longer median hospital length of stay (p=0.046). In the multivariable model using the matched sample, increased cost was not associated with EVLP use (p=0.783); however, high volume EVLP centers were associated with decreased cost (p=0.018). EVLP use was not associated with greater inpatient costs and may be favorable at high volume centers.

Thiazide-Associated Hyponatremia and Mortality Risk: A Cohort Study.

There are likely over 42 million patients with hypertension taking thiazides in the United States and many more worldwide. Hyponatremia is a common complication of thiazide therapy. It is not currently known if thiazide-associated hyponatremia is also associated with increased mortality. The objective of this study was to determine if outpatients who start thiazide diuretic treatment and develop early hyponatremia are at increased risk of mortality when compared with those who do not develop hyponatremia after starting a thiazide. A retrospective cohort study. This study used data from the TriNetX federated health research network comprising deidentified electronic medical records of ∼93 million patients from 76 health care organizations located primarily in the United States. The study population was adult patients 40-90 years old, with essential hypertension and who started on a thiazide diuretic between January 1, 2010, and December 31, 2021. The patients were then subdivided into a hyponatremia cohort and a control cohort. 22,057 patients met the inclusion criteria for the hyponatremia cohort, and 234,466 patients met the inclusion criteria for the control cohort. After propensity score matching, 22,052 remained in both cohorts. The primary outcome is one-year mortality. The hyponatremia cohort developed early hyponatremia defined as a serum sodium≤135mmol/L within 6 months after initiation of thiazide versus a control that had a serum sodium 136-144mmol/L after initiation of thiazide. Primary outcome is mortality. Secondary outcomes include development of sepsis, pneumonia, urinary tract infection, cellulitis, myocardial infarction, stroke, congestive heart failure, ataxia, fall, and hip fracture. The design is a retrospective cohort study, propensity score matched. Patients in the hyponatremia cohort had a higher hazard of mortality than patients in control, HR 1.96 (95% CI, 1.72-2.28; P<0.001). In addition, patients in the hyponatremia cohort had higher hazard of developing sepsis, pneumonia, urinary tract infection, cellulitis, myocardial infarction, stroke, congestive heart failure, ataxia, and hip fracture. The study had a retrospective design. Patients who develop early hyponatremia (serum sodium≤135mmol/L) following initiation of a thiazide diuretic have a higher risk of mortality when compared with those who do not develop hyponatremia after initiation of a thiazide diuretic.

Absence of Viral Replication Is Associated With Improved Outcome in Anti-HCV-Positive Patients With Hepatocellular Carcinoma.

Presence of active hepatitis C virus (HCV) infection may influence the outcome of patients treated for hepatocellular carcinoma (HCC), although this issue has never been adequately assessed in a large series of patients. The aim of this study was to evaluate whether the presence of active HCV affects the survival of patients treated for HCC. This study assessed the outcome of 3123 anti-HCV-positive patients with HCC, subdivided according to the presence of active HCV infection or previous sustained virological response (SVR). Comparisons were also carried out after propensity score matching (PSM) considering demographic, clinical and oncological characteristics. The median overall survival from HCC treatment was longer in patients with SVR than in those with active HCV infection both before (n = 2118: 61.0 months [95% confidence internal (CI): 56.5-65.5] vs. n = 1005: 51.0 months [95% CI: 43.4-58.6]; p = 0.003) and after PSM (n = 1285: 60.0 months [95% CI: 55.3-64.7] vs. n = 926: 54.0 months [95% CI: 46.7-61.3]; p = 0.030). Active HCV infection was associated with a greater risk of mortality (hazard ratio: 1.22-1.27, p = 0.001) independently of liver- and tumour-related variables, and modality of HCC treatment. Death due to liver failure was more common in patients with active HCV infection (24.5% vs. 17.1%; p = 0.001), while non-liver-related causes of death were more common in patients with SVR (25.0% vs. 17.0%; p = 0.001). SVR is associated with a better outcome in patients undergoing HCC treatment, thus suggesting that these patients may benefit from antiviral therapy for HCV independently of cure of HCC.

Durvalumab (DUR) effectiveness in advanced biliary tract cancer (aBTC) patients based on real-world data evidence.

598 Background: Based on TOPAZ-1 trial, Durvalumab (DUR) plus gemcitabine and cisplatin significantly improved overall survival (OS) in advanced biliary tract cancer (aBTC) patients. Real-World data evidence can evaluate the benefit of this combination outside controlled studies comparing patients treated with standard chemotherapy with or without DUR. Methods: Using the TriNetX Global Collaborative Network, a platform that operates globally based on anonymized and aggregated clinical data, a sample of aBTC patients from 128 healthcare organizations (HCOs) who met the initial criteria was selected. 5-year overall survival (OS) was analyzed between these cohorts using a Kaplan-Meier analysis. Hazard Ratio (HR) and its 95% confidence interval (95%CI) were calculated to evaluate the difference between cohorts. Propensity Score Matching (PSM) was used to balance the cohorts based on age, gender, and race mitigating possible cofounding variables. All statistical analyses were conducted utilizing the TriNetX Analytics function in the online research. Results: A total of 1099 patients met the study criteria and were included in our study. 399 received DUR plus chemotherapy and 700 received only chemotherapy. Patients treated with DUR showed a significant better OS compared to patients treated with only chemotherapy, both previous to PSM and before PSM (post-PMS median OS 418 days vs 359 days, HR 0.862, 95%CI 0.759-0.979, p=0.022). Conclusions: This is the largest World-Real Data study exploring the effectiveness of Durvalumab in aBTC patients outside clinical trials, confirming a similar benefit than TOPAZ-1 study.

Comparison of efficacy and safety of PD-1 and PD-L1 antibodies in combination with hepatic arterial infusion chemotherapy and target therapy for unresectable intrahepatic cholangiocarcinoma: A multicenter retrospective study.

553 Background: Immune checkpoint inhibitors (ICIs) in combination with hepatic arterial infusion chemotherapy (HAIC) and target therapy have shown promising antitumor activity in unresectable intrahepatic cholangiocarcinoma (iCCA). The present study aimed to compare the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors in this setting. Methods: In this multicenter retrospective study, we included patients with iCCA who received ICIs + HAIC + target therapy from June 2018 to June 2023. Propensity score matching (PSM) was performed to reduce confounding factors. Patients were divided into two groups: those treated with PD-L1 antibody + HAIC + target therapy (Group A) and those treated with PD-1 antibody + HAIC + target therapy (Group B). Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were compared between the two groups. Adverse events were assessed according to CTCAE v5.0. Results: A total of 336 patients met the inclusion criteria and were enrolled for analysis. There were no significant differences in OS, PFS, or ORR between the two groups (median OS: 17.7 vs. 25.3 months, P=0.139; median PFS: 8.3 vs. 10.0 months, P=0.534; ORR: 48.4% vs. 31.1%, P=0.051). Following PSM (ratio = 3, caliper = 0.2), 30 patients in Group A and 83 patients in Group B were included. The ORR, according to the modified RECIST criteria, was significantly higher in Group A compared to Group B (50% vs. 28.9%, P=0.037). However, no significant difference in PFS (median 10.0 vs. 9.0 months, P=0.29) or OS (median 17.6 vs. 22.8 months, P=0.293) was observed between the two groups. Adverse events (AEs) occurred in all 113 patients (100%), wherein grade 3–4 AEs were reported for 12 (10.6%) patients in group A and 45 (39.8%) in group B. There was a tendency for Group A to have a lower incidence of grade 3–4 AEs compared to Group B (40.0% vs. 54.2%, P=0.182),although this difference was not statistically significant. Conclusions: This study found that in the treatment combining ICIs with HAIC and target therapy for unresectable iCCA, Group A demonstrated a superior tumor response and a more favorable safety profile.

Retrospective comparative survival analysis of ablation plus systemic therapy versus systemic therapy alone for breast cancer liver metastases, stratified by extrahepatic metastases status.

Current decision-making for the treatment of breast cancer liver metastases (BCLM) using ablation lacks strong evidence, especially for patients combined with extrahepatic metastases. To assess whether ablation plus systemic therapy (AS) improves survival outcomes in patients with BCLM compared to systemic therapy alone. This retrospective study analyzed patients with BCLM who received either AS or systemic therapy alone. Propensity score matching (PSM) and survival analysis were performed, taking into account factors like the characteristics of primary breast cancer, liver metastases and systemic therapies received. The study included 1021 female patients, with a median follow-up of 39.6 months. Of these patients, 132 underwent AS and 836 received systemic therapy alone. After PSM, among patients with BCLM (≤3 tumors, each ≤3cm), the median overall survival (OS) for those treated with AS or systemic therapy alone was 65.5 and 40.4 months, respectively (HR=0.48, p=.003); in the subset of patients with extrahepatic metastases, the median OS for those treated with AS and systemic therapy alone was 46.4 and 40.8 months, respectively (HR=0.58, p=.047). Among patients with >3cm or >3 lesions, the median OS for those treated with AS or systemic therapy alone was 45.2 and 29 months, respectively (HR=0.67, p=.084). Among patients with BCLM (≤3 tumors, each ≤3cm), AS provide longer survival compared to systemic therapy alone, even with extrahepatic metastases. For patients with larger or more numerous metastases (>3cm or >3 lesions), AS may provide survival benefit, but further validation is needed.

Is treatment delivery of perioperative FLOT therapy in locally advanced OGA associated with recurrence-free survival?

391 Background: Although perioperative FLOT therapy is a standard for locally advanced oesophagogastric adenocarcinoma (LA-OGA), completing all cycles, especially in the adjuvant chemotherapy (ACT) phase, is often challenging. This study examined the survival impact of treatment delivery in LA-OGA patients receiving FLOT therapy. Methods: 423 patients who underwent radical resection at The Royal Marsden Hospital from 2017 to 2023 were screened. Major inclusion criteria included patients with LA-OGA (cT2≤ and Nany or Tany and N+), treated with FLOT (at least one cycle of neoadjuvant chemotherapy) and radical resection, with an ECOG performance status of 0–2. Patients were divided into therapy incomplete (Tx Incomp, less than eight cycles of FLOT) and therapy (Tx comp) groups. We performed univariate and multivariate analyses, as well as propensity score matching (PSM) analysis, to evaluate whether treatment delivery was associated with recurrence-free survival (RFS) and overall survival (OS). Kaplan-Meier curves and restricted mean survival times (RMST) up to 36 months were used to evaluate the survival time. The primary endpoint was the 3-year RFS and OS rate. Results: Of the screened patients, 210 met the inclusion criteria, with 79 (38%) in the Tx Incomp and 131 (62%) in the Tx comp group, and 50 (24%) patients did not receive ACT. The median follow-up time was 26.5 months. The 3-year RFS and OS rates in the Tx Incomp and Tx comp groups after PSM were 54% vs 59% (p=0.14) (RMST difference: 4.04 months, p=0.09) and 58% vs 78% (p=0.04) (RMST difference: 6.15 months, p&lt;0.001), respectively. Multivariable analysis showed a significant impact of Tx comp on OS (HR 0.53, 95% CI: 0.32-0.88). In the subgroup of ypN-positive patients, a significant difference of RMST in OS rate was observed between those who started ACT and those who did not start ACT (RMST difference: 7.89 months, p=0.01), whereas no significant difference was found in the ypN-negative group (RMST difference: 0.65 months, p=0.75). Conclusions: This study suggests that completing FLOT therapy is associated with better OS. The impact of ACT might differ according to ypN stage.

Preclinical analysis and clinical validation to identify biomarkers for trifluridine/tipiracil (FTD/TPI) efficacy with or without bevacizumab in patients with metastatic colorectal cancer.

230 Background: We previously identified candidate biomarkers for FTD/TPI efficacy through preclinical and translational studies in patients with metastatic colorectal cancer (mCRC). Recent studies reported that FTD/TPI plus bevacizumab (BEV) improved survival compared to FTD/TPI alone. This study evaluated the clinical significance of these biomarkers in patients with refractory mCRC receiving either FTD/TPI plus BEV or FTD/TPI alone. Methods: Candidate biomarkers were selected based on our transcriptomic and cell biological analyses. We validated these biomarkers in mCRC patients treated with FTD/TPI plus BEV (cohort A) or FTD/TPI alone (cohort B). Blood samples were collected at baseline (BL), before the second cycle (2nd), and progressive disease (PD), with serum biomarker levels measured using ELISA. Change patterns were classified as ‘increased’ or ‘decreased’ from BL. To address the unbalanced distribution of baseline characteristics between cohorts, propensity score matching (PSM) was performed. Results: A total of 112 patients were included, with 34 in each cohort after PSM. Cohort A showed significantly longer overall survival (OS) (14.4 vs 6.2 months, HR 0.53, 95%CI: 0.30-0.93) and higher disease control (DC) (58.8 vs 34.4%, P=0.047) compared to cohort B. In univariate analysis, increased IL-8 or AREG at 2nd and increased IFI16 at PD were associated with poorer clinical outcomes. Grade ≥3 neutropenia (NEU) was linked to better survival in both cohorts. Multivariable analysis identified decreased AREG and Grade ≥3 NEU as better markers for progression-free survival and OS. OS was significantly longer in cohort A compared to B (12.8 vs 5.8 months, HR 0.43, 95%CI: 0.21-0.89) when IL-8 increased at 2nd. Cohort A also had longer OS compared to cohort B when EREG (12.8 vs 6.2 months, HR0.27, 95%CI: 0.11-0,65) or AREG (14.2 vs 9.7 months, HR 0.40, 95%CI: 0.17-0.95) decreased at 2nd. There was no significant interaction between the regimen and biomarkers (IL-8, EREG, and AREG) for OS. Conclusions: Our data suggest that AREG may serve as a prognostic marker for FTD/TPI efficacy. Changes in IL-8, EREG and AREG potentially contribute to the extended survival benefit of combining BEV with FTD/TPI.

Outcomes of neoadjvuant chemotherapy versus chemoradiation for esophageal adenocarcinoma: A National Cancer Database analysis.

416 Background: While neoadjuvant chemoradiation (NCRT) has been the acceptable standard of care for esophageal adenocarcinoma (EAC), there has been a paradigm shift from recent trials have shown that neoadjuvant chemotherapy (NAC) is either equivalent or superior to NCRT. We sought to examine the outcomes of NAC versus NCRT in esophageal cancer from the National Cancer Database (NCDB). Methods: Utilizing the NCDB, we identified esophagectomy patients with EAC who underwent multiagent NCT versus multiagent NCRT. Overall Survival (OS) was analyzed with the Kaplan-Meier method and multivariate analysis (MVA) was performed to identify predictors of OS. Propensity score matching (PSM) was used to correct for baseline differences between groups. Results: After PSM, we identified 1007 patients in each group. Groups were equally balanced in age, gender, T/N stage, grade, and facility volume. There was improved lymphadenectomy and higher use of adjuvant therapy in NCT patients. There were significant improvements in R0 resection and pathologic response associated with NCRT patients. There was a significant improvement in OS in NCT versus NCRT. The median and 5-year OS was 42.7 months and 42% in NCT patients versus 34.2 months and 35% in NCRT patients (p = 0.001). For pathologic complete responders, median and 5-year OS was 101 months and 64% in NCT patients versus 71.2 months and 53% in NCRT patients (p = 0.04). On MVA, improved mortality was associated with female gender, pathologic N0, &gt;10 nodes removed, pathologic partial or complete response, R0, well/moderate grade, NCT, adjuvant chemotherapy, and higher facility volume. There was also no survival benefit to adjuvant chemoradiation. Conclusions: Despite higher R0 and pathologic response associated with NCRT, NCT was superior to NCRT for OS in EAC patients. NCRT needs to be re-examined in its role as a treatment recommendation for operable EAC patients. Multivariate analysis for overall survival. Variable HR 95% CI P value Age 1.01 1.00 – 1.02 0.004 SexMaleFemale Reference0.79 0.64 – 0.98 0.03 Charlson Deyo score01 Reference1.05 0.91 – 1.21 0.54 Pathologic N-stageN0N+ Reference1.82 1.58 – 2.10 &lt;0.001 LN removed&lt;10&gt;10 Reference0.81 0.68 – 0.97 0.02 ResponseNonePartialComplete Reference0.810.61 0.69 – 0.940.50 – 0.75 0.008&lt;0.001 Margin statusR0R1 Reference1.24 1.01 – 1.52 0.04 GradeWell/moderatePoor Reference1.35 1.18 – 1.54 &lt;0.001 Preop radiationYesNo Reference0.77 0.67 – 0.88 &lt;0.001 Adjuvant therapyNoneChemotherapyChemoradiation Reference0.770.83 0.65 – 0.920.64 – 1.08 0.0040.17 Facility volumeLow (≤10/year)Medium (11-19/year)High (≥20/year) Reference0.860.78 0.72 – 1.030.67 – 0.90 0.10&lt;0.001

Association between chronic ambient heavy metal exposure and mental health in Korean adult patients with asthma and the general population.

Insufficient evidence is available to confirm the effect of exposure to airborne metals on mental disorders, particularly among asthmatics. We aimed to investigate the effect of airborne metal exposure on mental health responses in asthmatics and the general population. Using nationally representative cross-sectional data, a total of 47,796 adults were analyzed. We assessed the associations between mental health factors, such as perceived stress, depressive symptoms, and suicidal ideation, and individuals' annual average exposure to airborne metals, including lead, cadmium, chromium, copper, manganese, and iron, over 14 years using multiple logistic regression. The associations were compared using the propensity score matching (PSM) method. The odds ratios (OR) and 95% confidence intervals (CI) for mental health outcomes were calculated for an interquartile range (IQR) increase in the concentration of each airborne metal. Exposure to airborne metals was significantly associated with increased odds of adverse mental health in asthmatics. Significant associations between all ambient heavy metal contaminants and suicidal ideation were found in both asthmatic patients and the general population. After PSM, exposure to all ambient heavy metal contaminants showed significant associations with suicidal ideation in patients with asthma, whereas only iron exposure was significantly associated with suicidal ideation in the general population. After adjusting for perceived stress and depressive symptoms, similar patterns were also observed. Exposure to lead (OR: 1.99; 95% CI: 1.45-2.72) showed particularly a strong association with suicidal ideation in asthmatics. This study suggests that exposure to airborne metals significantly increases depressive symptoms and suicidal ideation, especially in individuals with asthma. Additional clinical research is needed to better understand these associations.

Aflibercept (AFL) vs. ramucirumab (RAM) -based therapy in patients with advanced colorectal cancer: Efficacy comparison using real-world data evidence from TriNetX platform.

71 Background: FOLFIRI in combination with Aflibercept (AFL) or Ramucirumab (RAM) prolongs overall survival compared with FOLFIRI alone in patients with advanced colorectal cancer (aCCR) as second-line therapy, however, there are no comparative studies between them. Methods: Utilizing the TriNetX Global Collaborative Network, a platform that operates globally based on anonymized and aggregated clinical data, a sample of aCCR patients from 128 healthcare organizations (HCOs) who met the initial criteria was selected. 5-year overall survival (OS) was analyzed between these cohorts using a Kaplan-Meier analysis. Hazard Ratio (HR) and its 95% confidence interval (95%CI) were calculated to evaluate the difference between cohorts. Propensity Score Matching (PSM) was used to balance the cohorts based on age, gender, and race mitigating possible cofounding variables. All statistical analyses were conducted utilizing the TriNetX Analytics function in the online research platform. Results: A total of 1046 patients met the study criteria and were included in our study. 523 received AFL and 523r received RAM-based therapy. Patients treated with AFL showed a significant better OS compared to patients treated with RAM, both previous to PSM and before PSM (post-PMS median OS 430 days vs 317 days, HR 0.797, 95%CI 0.683-0.930). Conclusions: In this study, based on Real World data, Aflibercept showed superior results to Ramucirumab in advanced colorectal cancer patients treatment. To date this is the largest study comparison between this two therapeutic options.

Individual patient data (IPD) pooled analysis on the optimal therapeutic management of patients with microsatellite instability-high (MSI) resectable gastroesophageal adenocarcinoma (GEA).

455 Background: Patients with resectable MSI/dMMR GEA showed improved survival and modest if any benefit from chemotherapy. Preoperative treatment with immune checkpoint inhibition (ICI) showed high rate of major-complete pathologic response in single arm trials possibly allowing the design of chemotherapy/surgery-free approaches. Methods: This was a multinational IPD analysis including patients with resectable GEA with MSI/dMMR status enrolled in INFINITY and NEONIPIGA phase II trials, with dual CTLA-4/PD-(L)1 ICI followed by surgery +/- adjuvant ICI; PROSECCO retrospective study, with perioperative FLOT chemotherapy and surgery, and the dataset of our previous IPD analysis on MAGIC, CLASSIC, ARTIST and ITACA-S randomized trials of patients treated with surgery alone or plus older perioperative/adjuvant chemo(radio)therapy regimen. Primary endpoint was the evaluation of rates of pathologic complete response (pCR) defined as TRG1a Becker and major-complete pathologic response (pCR/MPR) defined as TRG1a/b Becker according to preoperative treatment schedule in patients who underwent surgery. Univariable and multivariable analyses were conducted using a random effects logistic model adjusted with propensity score. Secondary endpoints were event-free survival (EFS) and overall survival (OS) according to the therapeutic strategy in the overall study population. Multivariable mixed-effects Cox models weighted with propensity score were performed. Results: The IPD included 197 patients. Of these, 49 received ICI +/- surgery, 27 FLOT chemotherapy plus surgery, 33 surgery alone and 88 older chemo(radio)therapy regimens plus surgery. In the 69 patients resected after neoadjuvant ICI or FLOT standard of care treatment, ICI demonstrated a higher rate of pathologic response compared to chemotherapy (pCR 61.9% vs 3.7%, OR 54.8 p=0.002; pCR/MPR 78.6% vs 10%, OR 39.3 p&lt;0.001). In ITT population, no significant difference in OS and EFS was shown in patients treated with ICI, FLOT plus surgery, old chemo(radio)therapy plus surgery or surgery alone. Conclusions: In resectable MSI/dMMR GEA, upfront ICI showed comparable survival outcomes to surgery alone, with limitations of study design and sample size. The impact on survival of ICI versus surgery alone should be investigated prospectively to avoid overtreatment or identify specific risk categories with benefit. The high rate of major-complete pathologic response may allow to study or perform organ sparing surgery procedures or non-operative management to reduce surgical morbidity/mortality and improve quality of life. OS EFS HR 2.5-97.5% CI p HR 2.5-97.5% CI p Ref: Surgery only - - - - - - Chemo+surgery 1.16 0.27-4.98 0.84 1.10 0.39-3.07 0.85 FLOT+surgery 1.10 0.19-6.22 0.92 2.38 0.90-6.27 0.08 ICI +/- surgery 1.97 0.43-8.96 0.38 1.39 0.51-3.77 0.52

The impact of frailty on patient selection and outcomes for open versus endovascular treatment of unruptured intracranial aneurysms: A propensity-score matched analysis.

Endovascular treatment (EVT) has been demonstrated to have improved post-operative outcomes and fewer complications compared to open microsurgical clipping of unruptured intracranial aneurysms (UIAs). Our study analyzes patient selection and outcomes for open versus EVT stratified by frailty measured using the Risk Analysis Index (RAI). This was a retrospective study of patients who underwent open or EVT for an UIA at our institution between March 2017 and June 2022. Propensity-score matching (PSM) was performed using the 1:1 nearest neighbour method to create two groups (open and EVT) matched by demographics and treatment modality. RAI-measured frailty was used to categorize patients into 4 tiers: robust (0-10), pre-frail (11-20), frail (21-30) and severely frail (≥31). Outcomes of interest were length of stay (LOS), functional dependence at discharge and 30-day readmission. After PSM, 209 patients were stratified into two groups, open and EVT, respectively. Patients who received EVT were older compared to open surgery (mean±SD: 62.6±11.4 vs. 60.8±10.6, P<0.05), however, RAI-measured frailty did not differ significantly between the two groups (median (IQR) open: 3 (2-7), vs. EVT: 3 (2-9)), P=0.090. Among robust and pre-frail patients, EVT was associated with significantly shorter LOS compared to open surgery, median (IQR): 1 (1-2) vs. 3 (2-4) and 1 (1-2), vs. 3 (2-6); P<0.001, respectively). Neither functional dependence at discharge nor 30-day readmission rates were different after stratification by frailty. Patients in the robust and pre-frail tiers experienced significantly shorter LOS after EVT compared to open surgery. We would like to encourage the use of frailty assessment as a pre-operative risk stratification tool patients undergoing treatment of UIAs.

Long-course chemoradiation vs short-course radiation in total neoadjuvant therapy for rectal cancer: Propensity score case-matched analysis.

156 Background: Short-course radiotherapy (Short-TNT) is not widely used in the United States as part of total neoadjuvant therapy (TNT) for rectal cancer, due to concerns for lower tumor regression, increased local recurrence, and poorer quality of surgical specimens compared to long-course chemoradiotherapy (Long-TNT). However, there have been few studies that directly compared outcomes of Long-TNT versus Short-TNT. This study aimed to evaluate outcomes of Short-TNT versus Long-TNT. Methods: Consecutive patients with stage II-III rectal cancer who underwent TNT at an NCI-designated comprehensive cancer center from 2019 to 2022 were identified. Outcomes after Short-TNT and Long-TNT were compared using 1:1 propensity score matching. Results: Among 318 patients, 170 (85 Short-TNT, 85 Long-TNT) were eligible for the matched analysis (Table). The median follow-up was 31 months. The two groups were similar in tumor distance from anal verge (5cm vs. 6cm), clinical stage (stage III: 90.6% vs. 89.4%), radiologic high-risk features, and treatment sequence (induction chemotherapy: 30.5% vs. 28.2%). The Long-TNT was associate with a higher proportion of nonoperative management (38.8% vs. 24.7%, p=0.03). A local regrowth rate with long-TNT was not lower than short-TNT (39.4% vs. 28.6%, p=0.42). There were no differences in rates of clinical complete plus near-complete response (52.9% vs. 52.9%, p=1.00), overall complete response (pathologic plus sustained clinical complete response; 32.2% vs. 29.9%, p=0.74), and surgical outcomes including retrieved lymph nodes number (19 vs. 22, p=0.27), sphincter preservation (46.2% vs. 62.5%, p=0.10), distal margin (3cm vs. 3.5cm, p=0.77), CRM+ (83.8% vs. 3.1%, p=0.42) and postoperative complications (overall: 34.6% vs. 25.0%, p=0.14; ≥Grade3: 5.8% vs. 9.4%, p=0.60). Conclusions: Short-TNT had a comparable overall complete response rate with equivalent surgical outcomes to Long-TNT. Short-TNT should be revisited in the US as a viable alternative TNT strategy both for nonoperative management and for treatment of locally advanced rectal cancer. Propensity score case-matched analysis. Outcomes Total (n=170) Long-TNT (n=85) Short-TNT (n=85) p value Clinical complete/near complete response, number (%) 90 (52.9) 45 (52.9) 45 (52.9) 1.00 Non-operative management, number (%) 54 (31.8) 33 (38.8) 21 (24.7) 0.03 Overall complete response, number (%)* 54 (31.0) 26 (30.6) 28 (32.9) 0.74 Surgical outcomes Surgery (n=116) Surgery after Long-TNT (n=52) Surgery after Short-TNT (n=64) Sphincter-preserving surgery, number (%) 64 (55.2) 24 (46.2) 40 (62.5) 0.10 Circumferential resection margin +, number (%) 4 (3.4) 2 (3.8) 2 (3.1) 0.42 Distal margin, cm (range) 3.4 (0.1-12) 3 (0.2-6.5) 3.5 (0.1-12) 0.77 Major complications (≥Grade3), number (%) 9 (7.8) 3 (5.8) 6 (9.4) 0.60 *Pathologic + sustained clinical complete response.

Perioperative chemotherapy with either S-1 or 5-fluorouracil plus oxaliplatin and docetaxel for locally advanced gastric or gastroesophageal junction adenocarcinoma: A prospective trial and matched comparison.

396 Background: Perioperative triplet chemotherapy improves the survival and surgical outcome of patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in addition to curative surgery. 5-fluorouracil (5-FU), docetaxel, oxaliplatin and leukovorin (FLOT) has been suggested as the treatment of choice. S-1, an oral fluoropyrimidine chemotherapeutic, also shows compelling efficacy as one of the triplet backbone and is exempt from a prolonged infusion time. However, a comparison over efficacy and tolerability between S-1 or 5-FU-containing triplet has not been investigated. Methods: The study contains two parts. The first part was a prospective single-arm multi-centered phase II trial with eight cycles of perioperative leucovorin, oxaliplatin, docetaxel and S-1 (LOTS) in patients with ≥T3 any N or ≥T2N(+) non-metastatic gastric/GEJ adenocarcinoma. The primary endpoint was the treatment response assessed by pathological tumor regression (TRG). After confirming the result passing the statistical threshold, we compared them with an identical and independent patient population who received perioperative FLOT under a prospective observation. A propensity score matching (PPSM) was used to balance the heterogeneity between the two groups. The efficacy, survival and tolerability were compared in a post-hoc manner. Results: From Feb 2017 to Jan 2024 with a comparable median follow-up time (LOTS, 18.7 ms; FLOT, 18.9 ms), a total of 45 and 154 patients were enrolled and received either LOTS or FLOT treatment. After a one-to-two PPSM procedure, the baseline characteristics of patients were comparable (LOTS, n=45; FLOT, n=90). Patients had similar curative resection rates (LOTS, 91%; FLOT, 86%; p=.359) and above nearly complete pathological regression rates (TRG 0-1: LOTS, 23%; FLOT, 27%; p=.669). The 24-ms recurrence-free (RFS) and overall survival (OS) rates were also comparable (LOTS vs. FLOT: 66 vs. 59% in RFS, p=.463; 73 vs. 68% in OS, p=.491). The toxicities were tolerable, except that more diarrhea and nausea events were reported in the LOTS group, whereas neutropenia, thrombocytopenia and mucositis were significantly prominent in the FLOT group. Conclusions: Perioperative LOTS shows reasonable therapeutic efficacy and survival as compared with FLOT in patients with locally advanced gastric/GEJ cancer. While the toxicity profile is distinctive from FLOT, it could be a potential alternative regimen with the convenience to save the prolonged infusion time. Clinical trial information: NCT04999332 . Pathological outcome. Prior to LOTS treatment (n=45) After LOTS treatment (n=43) Prior to FLOT treatment (n=90) After FLOT treatment (n=86) p in LOTS vs. FLOT CAP TRG, n (%) 0.669 0 - - 1 (2.3) - - 3 (3.5) 1 - - 9 (20.9) - - 20 (23.3) 2 - - 14 (32.6) - - 23 (26.7) 3 - - 19 (44.2) - - 40 (46.5)