Multimodal therapy, combining chemotherapy and surgical resection, is the standard of care for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Patients with poorly differentiated PDAC have suboptimal overall survival (OS), partly owing to the limited understanding of optimal timing for return to intended oncologic therapy (RIOT) after upfront surgery. We aim to evaluate patients with poorly differentiated PDAC who undergo upfront surgical resection and assess how the timing of receipt of adjuvant chemotherapy is associated with OS. Using the National Cancer Database, we identified patients with poorly differentiated nonmetastatic PDAC who received upfront surgical resection followed by adjuvant chemotherapy (2007–2016). Adjusted Cox proportional hazard models evaluated OS on the basis of RIOT timing. Logistic regression was used to identify factors associated with RIOT. Of 2737 included patients, 66.1

PURPOSE:To emulate the Selective Use of Postoperative Radiotherapy After Mastectomy (SUPREMO) phase III clinical trial using real-world data to assess the impact of postmastectomy radiation therapy (PMRT) on overall survival (OS) among patients with intermediate-risk breast cancer. PATIENTS AND METHODS:Using the National Cancer Database, women diagnosed between 2006 and 2013 with intermediate-risk breast cancer (defined as pT1-2N1; pT3N0; or pT2N0 and grade III or with lymphovascular invasion) and 0-3 positive axillary lymph nodes, who underwent total mastectomy, were identified as being in accordance with the SUPREMO trial protocol and included in this study. Multivariable logistic regression, Cox proportional hazards regression, and stabilized inverse probability of treatment weighting were used to explore the relationship between PMRT and OS. The effects of PMRT within subgroups were explored using multivariable interaction models. RESULTS:In total, 49335 patients were included in the study, with 6882 (13.9%) receiving PMRT. Patients with stage T3N0 cancer, 1-3 positive axillary lymph nodes, or positive surgical margins were more likely to receive PMRT. Overall, PMRT was associated with no significant improvement in OS (HR: 0.98, 95% CI, 0.92-1.04). However, improved survival was observed among women with stage T3N0 cancer who received PMRT (HR: 0.72, 95% CI, 0.58-0.89). CONCLUSION:Although PMRT may not be associated with improved OS among all intermediate-risk breast cancer patients with 0-3 positive axillary lymph nodes, the subgroup of patients with stage T3N0 cancer seemed to benefit from PMRT. The study's retrospective nature introduces some uncertainty, but preliminary findings of the SUPREMO trial support these results.

Background and Aims:Studies assessing gastrointestinal stromal tumors (GISTs) have found no survival differences based on margin status; however, small sample sizes, merged anatomic locations, and limited follow-up have been limitations. This study examined the impact of margin status on overall survival in a large national cohort of patients with resected gastric GISTs. Methods:Data on patients with gastric GISTs were abstracted from the National Cancer Database, with data collected over a 16-year period (2004-2020). Exclusion criteria included the presence of other primary tumors, unknown patient/tumor characteristics, macroscopic residual margins, metastasis at diagnosis, and prior chemotherapy. The cohort was stratified according to tumor size. R0 is defined as microscopically negative margin, and R1 is microscopically positive margin. Results:After exclusions, there were 8448 patients in the analysis cohort: 8221 (97.3%) had R0 resections, and 227 (2.7%) had R1 resections. On univariate analysis, tumor size ≤5 cm (P < .001), T1 stage (P < .001), low grade (P < .001), and low mitotic index (P < .001) were associated with a decreased risk of death. Margin status (R0 vs R1) did not have an impact on survival in the combined (P = .249), ≤5 cm (P = .961), ≤3 cm (P = .595), or ≤2 cm (P = .614) cohorts. There was also no difference in the risk of death based on the resection margin, in which the hazard ratio (R1 vs R0) with a 95% confidence interval was 1.206 (.862-1.633). In multivariate analysis, the resection margin status did not affect overall survival (P = .666). Conclusions:Congruent with prior studies, there was no difference in survival when comparing R0 with R1 resections in gastric GIST patients without metastasis over an extended follow-up period. These data may be helpful in assessing suitability for endoscopic resection for patients with gastric GISTs.

Purpose: Previous studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT). Patients and Methods: Using the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: In total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results. Conclusion: In this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.

BackgroundTo determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status. MethodsIn this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed. ResultsWe identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677). ConclusionPostoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.

OBJECTIVES/GOALS: The goal of this study is to leverage a national database to see if autologous reconstruction rates differ in patient and clinical characteristics, readmission rates, and overall survival (OS) compared to other forms of reconstruction. Autologous reconstruction has not been looked at in this way before. METHODS/STUDY POPULATION: • Aim 1: Use the National Cancer Data Base to construct three patient cohorts for women under 70 and above 18 treated surgically for breast cancer with A) mastectomy only, B) implant-based reconstruction, and C) autologous breast reconstruction. • Aim 2: Examine receipt rates of surgical intervention in Cohorts A vs. B vs. C based on clinical and patient demographic/socioeconomic characteristics. • Aim 3: Compare readmission and overall survival (OS) rates for Cohorts A vs. B vs. C while controlling for age and other key variables. RESULTS/ANTICIPATED RESULTS: Based on the literature, we expect rates of autologous reconstruction (Cohort C) to be lower for patients of minority backgrounds compared to white individuals. In addition, we do not expect overall survival to differ between implant-based (Cohort B) and Cohort C reconstruction. Still, we expect mastectomy-only (Cohort A) survival to vary from the two cohorts even when adjusting for different clinical factors, as similar but smaller studies have shown. Finally, we expect readmission rates to be higher for Cohort C, compared to Cohorts A & B, as it is a more complicated procedure typically done in academic institutions with skilled surgeons. DISCUSSION/SIGNIFICANCE: Autologous reconstruction is now considered the gold standard due to its ability to restore the breast shape with higher patient satisfaction and superior long-term outcomes. Multiple studies have documented ongoing racial disparities in post-mastectomy breast reconstruction and autologous reconstruction, with lower rates and referrals.

Introduction: Region-specific data on individual factors associated with uptake of breast and cervical cancer screening or early testing in diverse Indian populations are limited. Aim: To assess the prevalence and individual determinants of uptake of breast and/or cervical cancer screening or testing among women aged 30-69 years in regionally representative populations of two large Indian cities: New Delhi and Chennai. Methods: We conducted an analysis of the cross-sectional data (2016-2017) nested within the Centre for Cardiometabolic Risk Reduction in South Asia cohort, established in 2010-2011 with 12,271 participants (5365 in New Delhi; 6906 in Chennai). Among 3310 women participants, we evaluated the associations of demographic, socioeconomic, lifestyle, medical, psychosocial, and reproductive factors with breast and/or cervical cancer screening or testing using multivariable logistic regression models with results expressed as adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: At any point prior to 2016-2017, 193 women self-reported having undergone evaluations for breast and/or cervical cancer. The reasons for evaluation were 'general examination' or 'physician's advice' (i.e., screening) or 'being symptomatic' (i.e., early testing). The overall prevalence was 5.8% for screening or testing and 2.5% for screening alone. Formal education (OR:1.88; 95% CI:1.12-3.15), high monthly household income (OR:2.27; 95% CI:1.59-3.25) and less 'fear-of-judgement' (OR:1.65; 95% CI:1.05-2.58) were positively associated with screening or testing uptake. When screening uptake was analysed separately, the results were generally similar. Conclusion: Our findings may have important implications for interventions at community-level (e.g., reducing 'fear-of-judgement', increasing awareness to screening programs and early symptoms) and health-system level (e. g., opportunistic screening).

Despite widespread utilization of immunotherapy, treating immune-cold tumors remains a challenge. Multiomic analyses and experimental validation identified the OTUD4/CD73 proteolytic axis as a promising target in treating immune-suppressive triple negative breast cancer (TNBC). Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization inhibiting tumor immune responses. We further demonstrated the importance of TGF-β signaling for orchestrating the OTUD4/CD73 proteolytic axis within tumor cells. Spatial transcriptomics profiling discovered spatially resolved features of interacting malignant and immune cells pertaining to expression levels of OTUD4 and CD73. In addition, ST80, a newly developed inhibitor, specifically disrupted proteolytic interaction between CD73 and OTUD4, leading to reinvigoration of cytotoxic CD8+ T cell activities. In preclinical models of TNBC, ST80 treatment sensitized refractory tumors to anti-PD-L1 therapy. Collectively, our findings uncover what we believe to be a novel strategy for targeting the immunosuppressive OTUD4/CD73 proteolytic axis in treating immune-suppressive breast cancers with the inhibitor ST80.

473 Background: Treatment strategies in resectable gastric cancer (GC) patients include perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC). Treatment delay can lead to metastases with unfavorable outcomes. We aim to identify the distribution of patients upstaged to pathologically node positive disease (pLN+) stratified by time and the optimal treatment in this cohort. Methods: We analyzed resected GC patients in the National Cancer Database (2004-2016) with clinically node negative disease (cLN-). Time from diagnosis to first definitive therapy was stratified as ≤2, >2 to ≤4, and >4 weeks. The distribution of patients upstaged from cLN- to pLN+ disease, the concordance between cLN- and pathologically lymph node negative (pLN-) disease based on treatment strategy, and time to first definitive therapy was analyzed. POC and POCR were compared to evaluate their effect on overall survival (OS) in patients with cLN- upstaged to pLN+ disease. Kaplan-Meier test, log-rank test, multivariable Cox proportional hazards analysis (MVA) were performed. Results: Of the 4,828 gastric cancer patients with cLN- disease, 514 (10.65%) patients received PEC and 4,314 (89.35%) patients received upfront surgery followed by POCR/POC. Distribution of patients stratified by time between diagnosis to first definitive treatment - chemotherapy (PEC) or surgery (POC/POCR), for ≤2 weeks was 9.5% vs. 33%, >2 - ≤4 weeks was 28.4% vs. 24.2% and >4weeks was 62% vs 42.7%, respectively. Patients upstaged from cLN- to pLN+ disease in the PEC group was 43.37%(n=206), and 70%(n=2574) in the upfront surgery group (POC/POCR). Of the 206 (43.37%) patients upstaged from cLN- to pLN+ in the PEC cohort, the upstage rate was 7.77% when chemotherapy was started within 2 weeks of diagnosis, compared to 27.67% with >2 to ≤4 weeks, and 64.56% with >4 weeks. Of the 2,574 (70%) patients upstaged in the upfront surgery cohort (POCR/POC), 30.61% were upstaged in ≤2 weeks, 24.95% in >2 to ≤4 weeks, and 44.44% in ≥4 weeks. On MVA, patients with cLN- disease that were pLN- (POCR=766, POC=341) had no significant difference in OS when treated with POCR (HR 1.11, p=0.39) compared to POC. Patients with pLN+ (POCR=2300, POC=907) disease had an association with improved OS when treated with POCR (HR 0.78, p<0.001) compared to POC. Conclusions: When resectable gastric cancer patients undergoing upfront surgery are upstaged from clinically node negative to pathologically node positive disease, postoperative chemoradiation therapy may be the optimal treatment strategy compared to postoperative chemotherapy. Clinical nodal status may not be an optimal predictor of nodal disease.

XLSX file - 14K, Set of most significantly enriched biological functions as deterermined by IPA analysis based on the gene list in Supplementary Table 5.

ObjectivesIn resource-constrained settings, cancer epidemiology research typically relies on self-reported diagnoses. To test a more systematic alternative approach, we assessed the feasibility of linking a cohort with a cancer registry.SettingData linkage was performed between a population-based cohort in Chennai, India, with a local population-based cancer registry.ParticipantsData set of Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) cohort participants (N=11 772) from Chennai was linked with the cancer registry data set for the period 1982–2015 (N=140 986).Methods and outcome measuresMatch*Pro, a probabilistic record linkage software, was used for computerised linkages followed by manual review of high scoring records. The variables used for linkage included participant name, gender, age, address, Postal Index Number and father’s and spouse’s name. Registry records between 2010 and 2015 and between 1982 and 2015, respectively, represented incident and all (both incident and prevalent) cases. The extent of agreement between self-reports and registry-based ascertainment was expressed as the proportion of cases found in both data sets among cases identified independently in each source.ResultsThere were 52 self-reported cancer cases among 11 772 cohort participants, but 5 cases were misreported. Of the remaining 47 eligible self-reported cases (incident and prevalent), 37 (79%) were confirmed by registry linkage. Among 29 self-reported incident cancers, 25 (86%) were found in the registry. Registry linkage also identified 24 previously not reported cancers; 12 of those were incident cases. The likelihood of linkage was higher in more recent years (2014–2015).ConclusionsAlthough linkage variables in this study had limited discriminatory power in the absence of a unique identifier, an appreciable proportion of self-reported cases were confirmed in the registry via linkages. More importantly, the linkages also identified many previously unreported cases. These findings offer new insights that can inform future cancer surveillance and research in low-income and middle-income countries.

XLSX file - 15K, Set of most significantly enriched canonical pathways as deterermined by IPA analysis based on the gene list in Supplementary Table 5.

Introduction: Pancreatic cancer is the fourth leading cause of cancer death in the United States and has a 5-year relative survival rate of 12.5% for all stages combined. The majority of patients presenting with pancreatic adenocarcinoma are not candidates for resection, and many resectable patients do not undergo surgery. The introduction of endoscopic ultrasound-guided radiofrequency ablation has introduced an additional non-surgical option for local treatment for pancreatic tumors. The current study examined the US epidemiology of patients with pancreatic adenocarcinoma potentially meeting the criteria for non-surgical local ablative intervention. Methods: Data was abstracted from the Surveillance, Epidemiology, and End Results (SEER) database. Adult patients with histologically confirmed pancreatic adenocarcinoma, registered in the years 2004–2015 were included. Eligible tumors were defined as tumors less than 3cm, with no lymph node involvement or metastatic disease. Patients were excluded if they had distant disease, lymph nodes not examined, or unknown tumor size. Results: A total of 25,891 patients met the inclusion criteria. Of those patients, 13,682 (52.8%) had a tumor size < 3cm, with no nodal involvement and no metastatic disease. T-stage distribution was T1 6.43%, T2 23.9%, T3 48.8%, and T4 20.9%. Surgery was not recommended or was contraindicated in 70.6% of the cohort. Surgery was performed in 22.1%. Surgery was recommended but not performed in 5.4%. The 5-year survival for those who received surgery was 32.8% compared to 2.2% for those patients who were not recommended for surgery. Approximately 77.5% of patients with non-metastatic pancreatic adenocarcinoma, no lymph node involvement, and a tumor size of < 3cm did not receive surgical resection. Conclusion: There is a large unmet need for additional local ablative options for the adjunctive management of patients with pancreatic adenocarcinoma.

Introduction: Insulinomas are the most common functioning endocrine neoplasm of the pancreas and cause hypoglycemic episodes due to intermittent secretion of insulin. While surgical resection is indicated for most tumors, there is a considerable risk of morbidity and mortality associated with the surgical management of insulinomas. The aim of this study was to examine the population of patients with insulinomas who could be eligible for non-surgical local ablative intervention. Methods: Data was extracted from National Cancer Database (NCBD). Adult patients with microscopically confirmed insulinoma, registered in the years 2004–2020 were included. Patients were excluded if there was no report on metastasis or unknown tumor size. Results: A total of 193 patients met the inclusion criteria. Of those patients, 53.9% were female, with an average Charlson Comorbidity Index of 0.31, and an age range of 18-90 years with a mean of 47.45 years. The tumor size range was 1mm to 150mm with a mean of tumor size of 26.59mm and a median of 19mm. 34.7% of tumors occurred in the tail of the pancreas, 24.4% in the head of the pancreas, 16.6% in the body of the pancreas, and 4.7% in the neck of the pancreas. Forty patients had metastatic involvement. Of the 99 patients in which lymph nodes were examined, 71 cases reported all examined nodes negative, 10 cases reported 1 positive lymph node, 4 cases reported 2 positive nodes, and 14 cases reported 3 or more lymph nodes positive. Of the 130 cases with recorded TMN stage, 45.1% were stage I, 7.8% were stage II, 0.5% were stage III, and 14.0% were stage IV. Surgery was performed in 81.4% of patients with an average of 7.45 days until discharge following surgery. Of those patients, 26.5% recorded local excision of the tumor, and 73.6% recorded major abdominal surgery. Conclusion: Reflecting the symptomatic nature of the tumors, approximately 73.6% of patients with insulinomas received major abdominal surgery. A local ablative option for the management of patients with insulinoma might reduce the need for major pancreatic surgery in this population.

XLSX file - 9K, Prediction Model based on Clinical Variables alone, namely, tGleason score, Log(prePSA + ), pStage, Surgical Margin Status, and Age.

Medicaid expansion has been associated with improved colorectal cancer screening rates and earlier stage diagnosis, but its impact on survival among colon cancer patients is unknown. We hypothesized that patients with invasive, nonmetastatic colon cancer residing in Medicaid expansion states (MES) would have better survival rates compared to patients in non-expansion states (NES). Methods This retrospective study of 86 413 patients (40-64 years old) undergoing surgical resection for a new diagnosis of invasive, nonmetastatic colon cancer included in the National Cancer Database (NCDB) from 2010 to 2015 compared overall survival (OS) in MES to NES. Cox proportional hazard models, fit for OS, and propensity score-matching (PSM) analysis were performed. Results In this sample, 51 297 cases (59.2%) lived in MES and 35 116 (40.8%) in NES. Medicaid expansion states had earlier pathological stage compared to NES (stage I 25.38% vs 24.17%, stage II 32.93 vs 33.4%, and stage III 41.69 vs 42.43%; P < .001). 5-year OS in MES was higher than NES (79.1% vs 77.3%; P < .001); however, on both multivariable analysis (MVA) and PSM analysis, MES did not have significantly different OS from NES (hazard ratio (HR), .99, 95% confidence interval (CI), .95-1.03; P = .570; HR, .99, 95% CI, .95-1.03; P = .68). Conclusion Among NCDB patients with invasive, nonmetastatic colon cancer residing in MES at time of diagnosis was associated with earlier pathological stage. However, on both MVA and PSM analysis, OS was not significantly different in MES vs NES. Research on patient outcomes, such as receipt of guideline concordant care, can further inform the impact of insurance coverage expansion efforts on cancer outcomes.

BACKGROUND Patient-reported outcomes (PROs) assessment is a necessary component of surgical outcome assessment and patient care. This study examined the success of routine PROs assessment in an academic-based thoracic surgery practice.METHODS PROs, measuring pain intensity, physical function, and dyspnea, were routinely obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System (PROMIS) on all thoracic surgery patients beginning in April 2018 through January 2021. Questionnaires were administered electronically through a web-based platform at home or during the office visit. Completion rates and barriers were measured.RESULTS A total of 9725 thoracic surgery office visits occurred during this time frame. PROs data were obtained in 6899 visits from a total of 3551 patients. The mean number of questions answered per survey was 22.4 +/- 2.2. Overall questionnaire completion rate was 65.7%. A significant decline in survey completion was noted in April 2020, after which adjustments were made to allow for questionnaire completion through a mobile health platform. Overall monthly questionnaire completion rates ranged from 20% (April 2020) to 90% (October 2018). Mean T scores were dyspnea, 41.6 +/- 12.3; physical function, 42.7 +/- 10.5; and pain intensity, 52.8 +/- 10.3.CONCLUSIONS PROs can be assessed effectively in a thoracic surgery clinic setting, with minimal disruption of clinical activities. Future efforts should focus on facilitating PROs collection from disadvantaged patient populations and scaling implementation across programs.

BACKGROUND Esophagectomy is an important, but potentially morbid, operation used to treat benign and malignant conditions that may significantly impact patient quality of life (QOL). Patient-reported outcomes (PROs) are measures of QOL that come directly from patient self-report. This study characterizes patterns of change and recovery in PROs in the first year after esophagectomy. METHODS Longitudinal QOL scores measuring physical function, pain, and dyspnea were obtained from esophagectomy patients during all clinic visits. PRO scores were obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System from April 2018 to February 2021. Mean PRO scores over 100 days after surgery were compared with baseline PRO scores using mixed-effects modeling with compound symmetry correlational structure. RESULTS One hundred three patients with PRO results were identified. Reasons for esophagectomy were malignancy (87.4%), achalasia (5.8%), stricture (5.8%), and dysplasia (1.0%). When comparing mean PRO scores at visits <= 50 days after surgery with preoperative PRO scores, physical function scores declined by 27.3% (P<.001), whereas dyspnea severity and pain interference scores had increased by 24.5% (P<.001) and 17.1% (P<.001), respectively. Although recovery occurred over the course of the 100 days after surgery, mean physical function scores and dyspnea scores were still 12.7% (P=.02) and 26.4% (P=.001) worse, respectively, than mean preoperative levels. CONCLUSIONS Despite declines in QOL scores immediately after esophagectomy, recovery back toward baseline was observed during the first 100 days. These findings are of considerable importance when counseling patients regarding esophagectomy, tracking recovery, and implementing quality improvement initiatives. Further long-term follow-up is needed to determine recovery beyond 100 days. (C) 2023 by The Society of Thoracic Surgeons