Hospital Accreditation Status and Treatment Differences Among Black Patients With Colon Cancer.

Importance: Hospital-level factors, such as hospital type or volume, have been demonstrated to play a role in treatment disparities for Black patients with cancer. However, data evaluating the association of hospital accreditation status with differences in treatment among Black patients with cancer are lacking. Objective: To evaluate the association of Commission on Cancer (CoC) hospital accreditation status with receipt of guideline-concordant care and mortality among non-Hispanic Black patients with colon cancer. Design, Setting, and Participants: This population-based cohort study used the National Program of Cancer Registries, which is a multicenter database with data from all 50 states and the District of Columbia, and covers 97% of the cancer population in the US. The participants included non-Hispanic Black patients aged 18 years or older diagnosed with colon cancer between January 1, 2018, and December 31, 2020. Race and ethnicity were abstracted from medical records as recorded by health care facilities and practitioners. The data were analyzed from December 7, 2023, to January 17, 2024. Exposure: CoC hospital accreditation. Main Outcome and Measures: Guideline-concordant care was defined as adequate lymphadenectomy during surgery for patients with stages I to III disease or chemotherapy administration for patients with stage III disease. Multivariable logistic regression models investigated associations with receipt of guideline-concordant care and Cox proportional hazards regression models assessed associations with 3-year cancer-specific mortality. Results: Of 17 249 non-Hispanic Black patients with colon cancer (mean [SD] age, 64.8 [12.8] years; 8724 females [50.6%]), 12 756 (74.0%; mean [SD] age, 64.7 [12.8] years) were treated at a CoC-accredited hospital and 4493 (26.0%; mean [SD] age, 65.1 [12.5] years) at a non-CoC-accredited hospital. Patients treated at CoC-accredited hospitals compared with those treated at non-CoC-accredited hospitals had higher odds of receiving guideline-concordant lymphadenectomy (adjusted odds ratio [AOR], 1.89; 95% CI, 1.69-2.11) and chemotherapy (AOR, 2.31; 95% CI, 1.97-2.72). Treatment at CoC-accredited hospitals was associated with lower cancer-specific mortality for patients with stages I to III disease who received surgery (adjusted hazard ratio [AHR], 0.87; 95% CI, 0.76-0.98) and for patients with stage III disease eligible for chemotherapy (AHR, 0.75; 95% CI, 0.59-0.96). Conclusions and Relevance: In this cohort study of non-Hispanic Black patients with colon cancer, patients treated at CoC-accredited hospitals compared with those treated at non-CoC-accredited hospitals were more likely to receive guideline-concordant care and have lower mortality risk. These findings suggest that increasing access to high-quality guideline-concordant care at CoC-accredited hospitals may reduce variations in cancer treatment and outcomes for underserved populations.

Trametinib potentiates anti-PD-1 efficacy in tumors established from chemotherapy-primed pancreatic cancer cells.

Despite advances in immune checkpoint inhibitors (ICIs), chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX (5-fluorouracil (5FU), irinotecan, and oxaliplatin) regimen, and ICIs have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in PDAC patients. In this study, we report that neoadjuvant FOLFRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation. We also show elevated MEK/ERK signaling in ex vivo PDAC slice cultures and cell lines treated with a combination of 5FU (F), irinotecan (I), and oxaliplatin (O) (FIO). In addition, we find that the KPC-FIO cells, established from repeated treatment of mouse PDAC cell lines with 6-8 cycles of FIO, display enhanced ERK phosphorylation and demonstrate increased sensitivity to MEK inhibition in vitro and in vivo. Significantly, the KPC-FIO cells develop tumors with a pro-inflammatory immune profile similar to human PDAC tumors following neoadjuvant FOLFIRINOX treatment. Furthermore, we found that the MEK inhibitor Trametinib enables additional infiltration of highly functional CD8+ T cells into the KPC-FIO tumors and potentiates the efficacy of anti-PD-1 antibody in syngeneic mouse models. Our findings provide a rationale for combining Trametinib and anti-PD-1 antibodies in PDAC patients following neoadjuvant or short-term FOLFIRINOX treatment to achieve effective anti-tumor responses.

Utilization of neoadjuvant therapy for localized gastric gastrointestinal stromal tumors and the association with survival.

BACKGROUND: For gastric gastrointestinal stromal tumors (GISTs), neoadjuvant imatinib is most often reserved for tumors near the gastroesophageal junction, multivisceral involvement, or limited metastatic disease. Whether localized gastric GISTs benefit from neoadjuvant therapy (NAT) remains unknown. We sought to examine factors associated with NAT utilization for localized gastric GISTs and evaluate implications on survival. METHODS: The National Cancer Database identified patients with localized gastric GISTs treated with NAT (2010-2020), excluding tumors extending beyond the gastric wall, located in the cardia, or with metastatic disease. Multivariable logistic regression assessed characteristics of NAT use. After 1:1 propensity score matching, Kaplan-Meier methods and multivariable Cox regression assessed overall survival (OS). RESULTS: Of 7203 patients, 762 (10.6%) received NAT followed by resection. On multivariable analysis, increasing tumor size was associated with NAT use (<2.0 cm vs 2.0-5.0 cm [odds ratio {OR}, 2.03; 95% CI, 1.19-3.47; P = .010] vs >5 cm [OR, 16.87; 95% CI, 10.02-28.40; P < .001]). After propensity score matching, 1506 patients remained. Median OS for NAT was 46.0 months vs 43.0 months for resection (P = .059), which was independently predictive of improved survival on multivariable analysis (hazard ratio [HR], 0.89; 95% CI, 0.80-0.99; P = .041). Subgroup analysis by tumor size showed no survival differences for tumors <2.0 cm or from 2.0 to 5.0 cm. Median OS was higher for tumors > 5.0 cm treated with NAT (NAT, 45.4 months [IQR, 29.5-65.9] vs upfront resection, 42.3 months [IQR 26.9-62.8]) and associated with improved survival on multivariable analysis (HR, 0.88; 95% CI, 0.78-0.99; P = .040). CONCLUSION: Although patients who received NAT had improved survival, this was primarily due to tumors >5.0 cm. Expanding NAT selection criteria to include localized gastric GISTs >5.0 cm may improve outcomes and warrants investigation through clinical trials.

Utilization and survival outcomes of neoadjuvant chemotherapy for early-stage gastric cancer.

BACKGROUND AND OBJECTIVES: Given increased utilization of neoadjuvant therapy (NAT) for gastric adenocarcinoma, practice patterns deviating from standard of care (upfront resection) remain unknown. We sought to identify factors associated with NAT use and survival outcomes among early-stage gastric cancers. METHODS: The National Cancer Database identified patients with early-stage (T1N0M0) gastric cancer (2010-2020). Multivariable logistic regression assessed characteristics associated with NAT utilization compared to upfront surgery. After 1:1 propensity score matching, Kaplan-Meier methods and Cox regression assessed overall survival (OS). RESULTS: Of 6452 patients with early-stage gastric cancer, 626 (9.7%) received NAT. Patients who received NAT were more likely treated at community hospitals, had moderate to poorly differentiated disease, and tumors located in the cardia (all p < 0.05). After propensity score matching, 1,248 patients remained. Median OS for NAT was 37.1 months (IQR 20.2-64.0) versus 45.6 months (IQR 22.5-72.8) for resection (p < 0.001). Treatment with NAT remained independently predictive of worse OS on Cox regression (hazard ratio 1.19; 95% confidence interval 1.05-1.34). CONCLUSIONS: Although patients who received NAT had more aggressive prognostic features, NAT was associated with worse OS despite accounting for this selection bias. These results highlight the importance of adhering to guidelines, regardless of differing disease characteristics, which has significant implications on outcomes.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Survival Among Patients With High-Risk Gastrointestinal Cancers During the COVID-19 Pandemic.

Importance: Prior reports demonstrated that patients with cancer experienced worse outcomes from pandemic-related stressors and COVID-19 infection. Patients with certain malignant neoplasms, such as high-risk gastrointestinal (HRGI) cancers, may have been particularly affected. Objective: To evaluate disruptions in care and outcomes among patients with HRGI cancers during the COVID-19 pandemic, assessing for signs of long-term changes in populations and survival. Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database to identify patients with HRGI cancer (esophageal, gastric, primary liver, or pancreatic) diagnosed between January 1, 2018, and December 31, 2020. Data were analyzed between August 23 and September 4, 2023. Main Outcome and Measures: Trends in monthly new cases and proportions by stage in 2020 were compared with the prior 2 years. Kaplan-Meier curves and Cox regression were used to assess 1-year mortality in 2020 compared with 2018 to 2019. Proportional monthly trends and multivariable logistic regression were used to evaluate 30-day and 90-day mortality in 2020 compared with prior years. Results: Of the 156 937 patients included in this study, 54 994 (35.0%) were aged 60 to 69 years and 100 050 (63.8%) were men. There was a substantial decrease in newly diagnosed HRGI cancers in March to May 2020, which returned to prepandemic levels by July 2020. For stage, there was a proportional decrease in the diagnosis of stage I (-3.9%) and stage II (-2.3%) disease, with an increase in stage IV disease (7.1%) during the early months of the pandemic. Despite a slight decrease in 1-year survival rates in 2020 (50.7% in 2018 and 2019 vs 47.4% in 2020), survival curves remained unchanged between years (all P > .05). After adjusting for confounders, diagnosis in 2020 was not associated with increased 1-year mortality compared with 2018 to 2019 (hazard ratio, 0.99; 95% CI, 0.97-1.01). The rates of 30-day (2.1% in 2018, 2.0% in 2019, and 2.1% in 2020) and 90-day (4.3% in 2018, 4.4% in 2019, and 4.6% in 2020) operative mortality also remained similar. Conclusions and Relevance: In this retrospective cohort study, a period of underdiagnosis and increase in stage IV disease was observed for HRGI cancers during the pandemic; however, there was no change in 1-year survival or operative mortality. These results demonstrate the risks associated with gaps in care and the tremendous efforts of the cancer community to ensure quality care delivery during the pandemic. Future research should investigate long-term survival changes among all cancer types as additional follow-up data are accrued.

Association of pathologic factors with postoperative venous thromboembolism after gastrointestinal cancer surgery.

BACKGROUND: Venous thromboembolism (VTE) chemoprophylaxis is the standard of care after gastrointestinal (GI) cancer surgery; however, variation in risk based on pathologic factors (eg, stage and histology) is unclear. This study aimed to evaluate the association of pathologic factors with VTE after GI cancer surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program procedure targeted datasets were queried for patients who underwent colorectal, pancreatic, primary hepatic, and esophageal cancer surgery between 2017 and 2020. Disease-specific and pathologic factors associated with postoperative VTE were evaluated using multivariable logistic regression. RESULTS: Among 70,934 patients who underwent GI cancer surgery, the incidence rates of 30-day postoperative VTE were 3.3% for pancreatic cancer, 3.2% for esophageal cancer, 2.7% for primary hepatic, and 1.3% for colorectal cancer. T stage was associated with VTE for colorectal cancer (T4 vs T1; odds ratio [OR], 1.79; 95% CI, 1.24-2.60), pancreatic cancer (all T stages vs T1; P < .05), and primary hepatic cancer (T4 vs T1; OR, 2.80; 95% CI, 1.55-5.08). N stage was associated with VTE for colorectal cancer (N2 vs N0; OR, 1.33; 95% CI, 1.04-1.68) and pancreatic cancer (N2 vs N0; OR, 1.36; 95% CI, 1.03-1.81). M stage was associated with VTE for colorectal cancer (OR, 1.47; 95% CI, 1.17-1.85) and esophageal cancer (OR, 2.54; 95% CI, 1.24-5.19). Histologic subtype was not associated with VTE, except for pancreatic neuroendocrine tumors vs adenocarcinoma (OR, 1.34; 95% CI, 1.03-1.74). CONCLUSION: Pathologic factors were associated with higher 30-day VTE risk after GI cancer surgery. Acknowledging the association of pathologic factors on VTE is an important first step to considering a more tailored approach to chemoprophylaxis.

Safety and feasibility of establishing an adjuvant hepatic artery infusion program.

BACKGROUND: Hepatic artery infusion (HAI) is less frequently used in the adjuvant setting for resectable colorectal liver metastasis (CRLM) due to concerns regarding toxicity. Our objective was to evaluate the safety and feasibility of establishing an adjuvant HAI program. METHODS: Patients who underwent HAI pump placement between January 2019 and February 2023 for CRLM were identified. Complications and HAI delivery were compared between patients who received HAI in the unresectable and adjuvant settings. RESULTS: Of 51 patients, 23 received HAI for unresectable CRLM and 28 in the adjuvant setting. Patients with unresectable CRLM more commonly had bilobar disease (n = 23/23 vs n = 18/28, p < 0.01) and more preoperative liver metastases (median 10 [IQR 6-15] vs 4 [IQR 3-7], p < 0.01). Biliary sclerosis was the most common complication (n = 2/23 vs n = 4/28); however, there were no differences in postoperative or HAI-specific complications. In the most recent two years, 0 patients in the unresectable group vs 2 patients in the adjuvant group developed biliary sclerosis. All patients were initiated on HAI with no difference in treatment times or dose reductions. CONCLUSION: Adjuvant HAI is safe and feasible for patients with resectable CRLM. HAI programs can carefully consider including patients with resectable CRLM if managed by an experienced multidisciplinary team with quality assurance controls in place.

Assessment of Social Vulnerabilities of Care and Prognosis in Adult Ocular Melanomas in the US.

BACKGROUND: Prior works have studied the impact of social determinants on various cancers but there is limited analysis on eye-orbit cancers. Current literature tends to focus on socioeconomic status and race, with sparse analysis of interdisciplinary contributions. We examined social determinants as measured by the Centers for Disease Control and Prevention (CDC) Social Vulnerability Index (SVI), quantifying eye and orbit melanoma disparities across the United States. METHODS: A retrospective review of 15,157 patients diagnosed with eye-orbit cancers in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017 was performed, extracting 6139 ocular melanomas. SVI scores were abstracted and matched to SEER patient data, with scores generated by weighted averages per population density of county's census tracts. Primary outcome was months survived, while secondary outcomes were advanced staging, high grading, and primary surgery receipt. RESULTS: With increased total SVI score, indicating more vulnerability, we observed significant decreases of 23.1% in months survival for melanoma histology (p < 0.001) and 19.6-39.7% by primary site. Increasing total SVI showed increased odds of higher grading (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.43) and decreased odds of surgical intervention (OR 0.94, 95% CI 0.92-0.96). Of the four themes, higher magnitude contributions were observed with socioeconomic status (26.0%) and housing transportation (14.4%), while lesser magnitude contributions were observed with minority language status (13.5%) and household composition (9.0%). CONCLUSIONS: Increasing social vulnerability, as measured by the CDC SVI and its subscores, displayed significant detrimental trends in prognostic and treatment factors for adult eye-orbit melanoma. Subscores quantified which social determinants contributed most to disparities. This lays groundwork for providers to target the highest-impact social determinant for non-clinical factors in patient care.

Establishing the clinical relevance of grade A post-hepatectomy liver failure.

INTRODUCTION: The International Study Group of Liver Surgery's criteria stratifies post-hepatectomy liver failure (PHLF) into grades A, B, and C. The clinical significance of these grades has not been fully established. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) hepatectomy-targeted database was analyzed. Outcomes between patients without PHLF, with grade A PHLF, and grade B or C PHLF were compared. Univariate and multivariable logistic regression were performed. RESULTS: Six thousand two hundred seventy-four adults undergoing elective major hepatectomy were included in the analysis. The incidence of grade A PHLF was 4.3% and grade B or C was 5.3%. Mortality was similar between patients without PHLF (1.2%) and with grade A PHLF (1.1%), but higher in those with grades B or C PHLF (25.4%). Overall morbidities rates were 19.3%, 41.7%, and 72.8% in patients without PHLF, with grade A PHLF, and with grade B or C PHLF, respectively (p < 0.001). Grade A PHLF was associated with increased morbidity (grade A: odds ratios [OR] 2.7 [95% CI: 2.0-3.5]), unplanned reoperation (grade A: OR 3.4 [95% CI: 2.2-5.1]), nonoperative intervention (grade A: OR 2.6 [95% CI: 1.9-3.6]), length of stay (grade A: OR 3.1 [95% CI: 2.3-4.1]), and readmission (grade A: OR 1.8 [95% CI: 1.3-2.5]) compared to patients without PHLF. CONCLUSIONS: Although mortality was similar between patients without PHLF and with grade A PHLF, other postoperative outcomes were notably inferior. Grade A PHLF is a clinically distinct entity with relevant associated postoperative morbidity.

Prospective Evaluation of Circulating Tumor DNA using Next Generation Sequencing as a Biomarker during Neoadjuvant Chemotherapy in Localized Pancreatic Cancer.

OBJECTIVE: In this prospective study, we aim to characterize the prognostic value of circulating tumor DNA (ctDNA) by next-generation-sequencing (NGS) in patients undergoing neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Circulating tumor DNA is a promising blood-based biomarker that is prognostic in several malignancies. Detection of ctDNA by NGS may provide insights regarding the mutational profiles in PDAC to help guide clinical decisions for patients in a potentially curative setting. However, the utility of ctDNA as a biomarker in localized PDAC remains unclear. METHODS: Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine between October 2020 and October 2022. Blood samples were collected to perform targeted tumor agnostic NGS utilizing the Tempus x|F 105 gene panel at three timepoints: pre-therapy (at diagnosis), post-NAC, and after local therapy, including surgery. The relationship between ctDNA detection and CA19-9, and the prognostic significance of ctDNA detection were analyzed. RESULTS: 56 patients were included in the analysis. ctDNA was detectable in 48% at diagnosis, 33% post-NAC, and 41% after local therapy. After completion of NAC, patients with detectable ctDNA had higher CA19-9 levels versus those without (78.4 vs. 30.0, P=0.02). The presence of baseline ctDNA was associated with a CA19-9 response; those without ctDNA had a significant CA19-9 response following NAC (109.0 U/mL vs. 31.5 U/mL; P=0.01), while those with ctDNA present at diagnosis did not (198.1 U/mL vs. 113.8 U/mL; P=0.77). In patients treated with NAC, the presence of KRAS ctDNA at diagnosis was associated with and independently predicted worse progression-free-survival. CONCLUSION: This report demonstrates the prognostic value of ctDNA analysis with NGS in localized PDAC. NGS ctDNA is a biomarker of treatment response to NAC. KRAS ctDNA at diagnosis independently predicts worse survival in patients treated with NAC.

Comparison of perioperative and histopathologic outcomes among neoadjuvant treatment strategies for locoregional gastric cancer.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NAC) and chemoradiation (NCRT) have demonstrated improved survival for gastric cancer. However, the optimal neoadjuvant treatment remains unclear. We sought to evaluate perioperative and histopathologic outcomes among neoadjuvant treatments for locoregional gastric cancer. METHODS: The National Cancer Database queried patients who received NAC or NCRT followed by resection for T2-T4 and/or node-positive gastric cancer (2006-2018). Logistic and Poisson regression assessed perioperative (30-day readmission, 30- and 90-day mortality, length of stay [LOS]) and histopathologic outcomes (pathologic complete response [PCR], margin status, and negative pathologic lymph nodes [ypN0]). Kaplan-Meier methods and Cox regression assessed overall survival (OS). RESULTS: Of 9831 patients, 4221 (42.9%) received NAC and 5610 (57.1%) NCRT. There were no differences in perioperative outcomes, apart from patients treated with NCRT exhibiting increased LOS (incidence rate ratio 1.09, 95% confidence interval [CI] 1.03-1.16). Patients who received NCRT were more likely to achieve PCR, margin-negative resection, and ypN0 (all p < 0.05). Median OS was 36.8 months for NAC and 33.6 months for NCRT (p < 0.001). NCRT independently predicted worse OS (vs. NAC, hazard ratio 1.10, 95% CI 1.03-1.18). CONCLUSION: NCRT was associated with better histologic tumor response although NAC was associated with improved OS. Better understanding prognostication through histologic assessment following neoadjuvant therapy is needed.

Association Between Racial and Socioeconomic Disparities and Hospital Performance in Treatment and Outcomes for Patients with Colon Cancer.

BACKGROUND: Disparities in colon cancer care and outcomes by race/ethnicity, socioeconomic status (SES), and insurance are well recognized; however, the extent to which inequalities are driven by patient factors versus variation in hospital performance remains unclear. We sought to compare disparities in care delivery and outcomes at low- and high-performing hospitals. METHODS: We identified patients with stage I-III colon adenocarcinoma from the 2012-2017 National Cancer Database. Adequate lymphadenectomy and timely adjuvant chemotherapy administration defined hospital performance. Multilevel regression models evaluated disparities by race/ethnicity, SES, and insurance at the lowest- and highest-performance quartile hospitals. RESULTS: Of 92,573 patients from 704 hospitals, 45,982 (49.7%) were treated at 404 low-performing hospitals and 46,591 (50.3%) were treated at 300 high-performing hospitals. Low-performing hospitals treated more non-Hispanic (NH) Black, Hispanic, low SES, and Medicaid patients (all p < 0.01). Among low-performing hospitals, patients with low versus high SES (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.82-0.92), and Medicare (OR 0.90, 95% CI 0.85-0.96) and Medicaid (OR 0.88, 95% CI 0.80-0.96) versus private insurance, had decreased odds of receiving high-quality care. At high-performing hospitals, NH Black versus NH White patients (OR 0.83, 95% CI 0.72-0.95) had decreased odds of receiving high-quality care. Low SES, Medicare, Medicaid, and uninsured patients had worse overall survival at low- and high-performing hospitals (all p < 0.01). CONCLUSION: Disparities in receipt of high-quality colon cancer care occurred by SES and insurance at low-performing hospitals, and by race at high-performing hospitals. However, survival disparities by SES and insurance exist irrespective of hospital performance. Future steps include improving low-performing hospitals and identifying mechanisms affecting survival disparities.

Access, Outcomes, and Costs Associated with Surgery for Malignancy Among People Experiencing Homelessness.

BACKGROUND: Little is known about surgery for malignancy among people experiencing homelessness (PEH). Poor healthcare access may lead to delayed diagnosis and need for unplanned surgery. This study aimed to (1) characterize access to care among PEH, (2) evaluate postoperative outcomes, and (3) assess costs associated with surgery for malignancy among PEH. METHODS: This was a retrospective cohort study of patients in the Healthcare Cost and Utilization Project (HCUP) who underwent surgery in Florida, New York, or Massachusetts for gastrointestinal or lung cancer from 2016 to 2017. PEH were identified using HCUP's "Homeless" variable and ICD-10 code Z59. Multivariable regression models controlling patient and hospital variables evaluated associations between homelessness and postoperative morbidity, length of stay (LOS), 30-day readmission, and hospitalization costs. RESULTS: Of 67,034 patients at 566 hospitals, 98 (0.2%) were PEH. Most PEH (44.9%) underwent surgery for colorectal cancer. PEH more frequently underwent unplanned surgery than housed patients (65.3% vs 23.7%, odds ratio (OR) 5.17, 95% confidence interval (CI) 3.00-8.92) and less often were treated at cancer centers (66.0% vs 76.2%, p=0.02). Morbidity rates were similar between groups (20.4% vs 14.5%, p=0.10). However, PEH demonstrated higher odds of facility discharge (OR 5.89, 95% CI 3.50-9.78) and readmission (OR 1.81, 95% CI 1.07-3.05) as well as 67.7% longer adjusted LOS (95% CI 42.0-98.2%). Adjusted costs were 32.7% higher (95% CI 14.5-53.9%) among PEH. CONCLUSIONS: PEH demonstrated increased odds of unplanned surgery, longer LOS, and increased costs. These results underscore a need for improved access to oncologic care for PEH.

Associations of social vulnerability with truncal and extremity melanomas in the United States.

BACKGROUND: Prior studies in social determinants (SDoH) of truncal-extremity melanomas (TEM) have analyzed race, income, and environmental factors relative to their effect on health disparities. However, they are limited by the narrow scopes of SDoH and study population, while lacking analyses of interrelational contribution of SDoH on TEM disparities. METHODS: This retrospective cohort study of adult TEM patients (1975-2017) assessed linear regression trends in months of survival, as well as logistic regression trends in advanced presenting stage, surgery, and chemotherapy receipt across TEM subtypes with increasing overall social vulnerability and vulnerability in 15 SDoH variables grouped into socioeconomic status (SES), minority-language status (ML), household composition (HH), and housing-transportation (HT) themes measured by the SVI. SVI measures are ranked/compared across all US counties for relative vulnerability in a specific SDH and their total composite while accounting for sociodemographic-regional differences. RESULTS: Across 325 760 TEM patients, increasing overall social vulnerability demonstrated significant decreases in the survival period for 7/13 TEM histology types (p < 0.001), with relative decreases in the survival period as high as 44.0% (67.0-37.5 months) for epithelioid cell. SES and HH were the highest-magnitude contributors to these overall trends. For many patients with TEM, increased odds of advanced presenting stage (highest with acral-lentiginous: odds ratio [OR], -1.18; 95% confidence interval [CI], 1.02-1.36), decreased odds of indicated surgery receipt (lowest with amelanotic, 0.79; 0.71-0.87), and increased odds of indicated chemotherapy (highest with melanoma in giant nevi: 1.50; 1.01-2.44) were observed; SES and ML followed by HH and HT contributed to these trends. CONCLUSIONS: There were detriments in TEM care & prognosis in the United States with increasing social vulnerability. Identifying which SDH quantifiably are associated more with disparities in interrelational, real-world contexts is important to provide nuance to inform future research and initiatives to address TEM disparity.

Iron drives anabolic metabolism through active histone demethylation and mTORC1.

All eukaryotic cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here we report a previously undescribed eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of a high-affinity leucine transporter, LAT3, and RPTOR. By directly suppressing leucine availability and RAPTOR levels, iron deficiency supersedes other nutrient inputs into mTORC1. This process occurs in vivo and is not an indirect effect by canonical iron-utilizing pathways. Because ancestral eukaryotes share homologues of KDMs and mTORC1 core components, this pathway probably pre-dated the emergence of the other kingdom-specific nutrient sensors for mTORC1.

Venous Thromboembolism Chemoprophylaxis Adherence Rates After Major Cancer Surgery.

Importance: Venous thromboembolism (VTE) represents a major source of preventable morbidity and mortality and is a leading cause of death in the US after cancer surgery. Previous research demonstrated variability in VTE chemoprophylaxis prescribing, although it is unknown how these rates compare with performance in the Veterans Health Administration (VHA). Objective: To determine VTE rates after cancer surgery, as well as rates of inpatient and outpatient (posthospital discharge) chemoprophylaxis adherence within the VHA. Design, Setting, and Participants: This retrospective cohort study within 101 hospitals of the VHA health system included patients aged 41 years or older without preexisting bleeding disorders or anticoagulation usage who underwent surgical treatment for cancer with general surgery, thoracic surgery, or urology between January 1, 2015, and December 31, 2022. The VHA Corporate Data Warehouse, Pharmacy Benefits Management database, and the Veterans Affairs Surgical Quality Improvement Program database were used to identify eligible patients. Data analysis was conducted between January 2022 and July 2023. Exposures: Inpatient surgery for cancer with general surgery, thoracic surgery, or urology. Main Outcomes and Measures: Rates of postoperative VTE events within 30 days of surgery and VTE chemoprophylaxis adherence were determined. Multivariable Poisson regression was used to determine incidence-rate ratios of inpatient and postdischarge chemoprophylaxis adherence by surgical specialty. Results: Overall, 30 039 veterans (median [IQR] age, 67 [62-71] years; 29 386 men [97.8%]; 7771 African American or Black patients [25.9%]) who underwent surgery for cancer and were at highest risk for VTE were included. The overall postoperative VTE rate was 1.3% (385 patients) with 199 patients (0.7%) receiving a diagnosis during inpatient hospitalization and 186 patients (0.6%) receiving a diagnosis postdischarge. Inpatient chemoprophylaxis was ordered for 24 139 patients (80.4%). Inpatient chemoprophylaxis ordering rates were highest for patients who underwent procedures with general surgery (10 102 of 10 301 patients [98.1%]) and lowest for patients who underwent procedures with urology (11 471 of 17 089 patients [67.1%]). Overall, 3142 patients (10.5%) received postdischarge chemoprophylaxis, with notable variation by specialty. Conclusions and Relevance: These findings indicate the overall VTE rate after cancer surgery within the VHA is low, VHA inpatient chemoprophylaxis rates are high, and postdischarge VTE chemoprophylaxis prescribing is similar to that of non-VHA health systems. Specialty and procedure variation exists for chemoprophylaxis and may be justified given the low risks of overall and postdischarge VTE.