Centralization of pancreatic cancer treatment within an integrated healthcare system improves overall survival

3585 Background: TP53 mutation is present in approximately 50% of metastatic colorectal cancer (CRC). The spectrum of the TP53 mutations is extremely broad including approximately 80% missense mutations. Several missense mutations have been found to possess gain-of-function (GOF) properties in cell line and animal studies, however, confirmation of the concept of GOF in human malignancies is still lacking. Methods: We investigated the impact of TP53 GOF mutations in patients with metastatic CRC using the NGS data within Kaiser Permanente Northern California (KPNC), a large integrated healthcare system. Results: From November 2017 to January 2021, genomic profiling by StrataNGS was performed on 8658 patients, with 1056 patients being metastatic CRC, among whom 740 patients harbored a TP53 mutation (TP53mut) and 316 patients had wild-type TP53 (TP53wt). Ras (KRAS and NRAS) and BRAF mutation appropriately discriminated the overall survival (OS) of patient populations with either TP53wt or TP53mut, confirming the validity of our dataset. We identified seven GOF TP53 mutations (R175H, R248W, R248Q, R249S, R273H, R273L, R282W) in these CRC patients. We show that different GOF mutation differentially impacts the OS. Patients whose CRC harbored TP53mut R248W, R249S, and R282W (poor prognostic TP53mut, N = 47) had significantly worse OS versus patients whose CRC harbored TP53mut R248Q, R175H, R273H and R273L (N = 160, median OS 29.4 vs 44.2 months, HR 0.47, p = 0.007). The OS of the poor prognostic TP53mut patients was also significantly inferior compared to patients whose CRC harbored all other TP53 mutations (N = 1099, median OS 50.1 months, HR 0.55, p = 0.01) or TP53wt (N = 316, median OS 47,5 months, HR 0.54, p = 0.01). The demographics and the percent of Ras, BRAF, and PI3KCA mutations were similar except that the patients with the poor prognostic TP53mut had significantly higher percent of Ras mutation compared to the rest of the GOF TP53mut patients (p = 0.035). When compared to R248Q alone, R248W confers worse OS (median OS 36.3 vs 63.2 months, p = 0.05). Conclusions: Our data suggest that different TP53 GOF mutations are associated with very different clinical outcomes. Additional studies identifying specific TP53 GOF mutations that impact outcomes may provide further insight for drug development and clinical trial design.

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Healthcare System Variability in Pancreatic Cancer Treatment and Outcomes: A Comparative Analysis Between the US and Ontario

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2021.08.295 ◽

2021 ◽

Vol 233 (5) ◽

pp. e110

Author(s):

Lily V. Saadat ◽

Elizabeth Schofield ◽

Xing Bai ◽

Michael Curry ◽

Allison Lipitz-Snyderman ◽

...

Keyword(s):

Pancreatic Cancer ◽

Comparative Analysis ◽

Cancer Treatment ◽

Healthcare System ◽

The Us ◽

System Variability

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Association of γ-aminobutyric acid type A receptor-associated protein with prognosis in patients after radical pancreatic cancer treatment

10.21203/rs.3.rs-51240/v1 ◽

2020 ◽

Author(s):

Chao Zhang ◽

Wenhao Tang ◽

Yanyuan Tu ◽

Zurong Yuan ◽

Wei Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Cancer Treatment ◽

Survival Time ◽

Cox Regression ◽

Cancer Tissue ◽

Relapse Free Survival ◽

Free Survival ◽

Cancer Tissues

Abstract Purpose: To discuss the value and possible causes of γ-aminobutyric acid type A receptor-associated protein (GABARAP) expression and multiple clinicopathological factors in the prognosis of patients after radical pancreatic cancer treatment.Methods: The pancreatic tissues of 76 pancreatic cancer patients after R0 resection were screened according to the criteria, and the expression levels of GABARAP were determined by using immunohistochemistry (MaxVision) to label the pancreatic cancer tissues and normal pancreatic tissues at the peri-cancer level in these two types of specimens, and the relationship between GABARAP and other factors and the disease-free and overall survival of patients after radical pancreatic cancer treatment was evaluated by single factor survival analysis and Cox regression analysis.Results：The expression ratio of GABARAP in pancreatic cancer tissue was 55.26% (42/76), which was drastically higher than that in normal pancreatic tissue adjacent to cancer (21.42% (12/76). In 76 patients, the middle relapse-free survival time after radical operation for pancreatic cancer was 12.8 months, and the middle overall survival time was 17.8 months. Forty-one patients found relapse on CT, and the recurrence site: local recurrence accounted for 17.1% (7/41) Distant metastasis accounted for 78.0% (32/41), and local recurrence with distant metastasis accounted for 4.9% (2/41). Among the three recurrence methods, there was no drastical difference in survival time from relapse to death (P> 0.05). Cox regression model evaluation showed that GABARAP (P = 0.044) and postoperative adjuvant chemotherapy (P = 0.038) were the overall survival of patients after radical pancreatic cancer Period independent prognostic indicators and both are protective factors for the prognosis of pancreatic cancer patients. Further data analysis found that postoperative chemotherapy had no drastical effect on the relapse-free survival and overall survival of 42 GABARAP-positive patients with cancer tissue, while in 34 GABARAP-negative patients, postoperative chemotherapy drastically increased the total patient Survival period (P = 0.041) but had no drastical effect on the patient's relapse-free survival periodConclusion: The expression of GABARAP in pancreatic cancer tissues was drastically up-regulated, and patients with high expression of GABARAP in pancreatic cancer tissues had better prognosis, but had no drastical effect on the relapse-free survival of patients after radical operation of pancreatic cancer. The expression of GABARAP in pancreatic cancer tissues and Postoperative adjuvant chemotherapy is an independent indicator of patients' prognosis after radical pancreatic cancer resection. Both are protective factors. The high expression of GABARAP in pancreatic cancer may indicate that the adjuvant chemotherapy is low benefit.

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No Racial Disparities in Pancreatic Cancer within an Integrated Healthcare System

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2020.08.407 ◽

2020 ◽

Vol 231 (4) ◽

pp. e154

Author(s):

Sidney Thanh-Liem Le ◽

C.K. Chang

Keyword(s):

Pancreatic Cancer ◽

Racial Disparities ◽

Healthcare System ◽

Integrated Healthcare

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525 THE IMPACT OF RACE ON PANCREATIC CANCER TREATMENT AND SURVIVAL IN THE NATIONWIDE VETERANS AFFAIRS HEALTHCARE SYSTEM

Gastroenterology ◽

10.1016/s0016-5085(21)00999-9 ◽

2021 ◽

Vol 160 (6) ◽

pp. S-106

Author(s):

Ann Xu ◽

Jennifer R. Kramer ◽

Daniela Abrams ◽

Taher Jamali ◽

Yan Liu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Treatment ◽

Healthcare System ◽

Veterans Affairs ◽

The Impact

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Faculty Opinions recommendation of Novel telestroke program improves thrombolysis for acute stroke across 21 hospitals of an integrated healthcare system.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732320662.793540848 ◽

2017 ◽

Author(s):

David Liebeskind

Keyword(s):

Acute Stroke ◽

Healthcare System ◽

Integrated Healthcare

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Targeting EGFR in Pancreatic Cancer Treatment

Current Drug Targets ◽

10.2174/138945012800564158 ◽

2012 ◽

Vol 13 (6) ◽

pp. 802-810 ◽

Cited By ~ 77

Author(s):

T. Troiani ◽

E. Martinelli ◽

A. Capasso ◽

F. Morgillo ◽

Michele Orditura ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Treatment

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Clinical, behavioural and social factors associated with racial disparities in COVID-19 patients from an integrated healthcare system in Georgia: a retrospective cohort study

BMJ Open ◽

10.1136/bmjopen-2020-044052 ◽

2021 ◽

Vol 11 (5) ◽

pp. e044052

Author(s):

Felipe Lobelo ◽

Alan Bienvenida ◽

Serena Leung ◽

Armand Mbanya ◽

Elizabeth Leslie ◽

...

Keyword(s):

Quality Of Care ◽

Racial Disparities ◽

Clinical Outcomes ◽

Healthcare System ◽

Retrospective Cohort ◽

Chronic Obstructive ◽

Integrated Healthcare ◽

Icu Admission ◽

Hospitalised Patients

ObjectivesTo identify sociodemographic, clinical and behavioural drivers of racial disparities and their association with clinical outcomes among Kaiser Permanente Georgia (KPGA) members with COVID-19.DesignRetrospective cohort of patients with COVID-19 seen from 3 March to 29 October 2020. We described the distribution of underlying comorbidities, quality of care metrics, demographic and social determinants of health (SDOH) indicators across race groups. We also described clinical outcomes in hospitalised patients including length of stay, intensive care unit (ICU) admission, readmission and mortality. We performed multivariable analyses for hospitalisation risk among all patients with COVID-19 and stratifyied by race and sex.SettingKPGA, an integrated healthcare system.Participants5712 patients who all had laboratory-confirmed COVID-19. Of them, 57.8% were female, 58.4% black, 29.5% white, 8.5% Hispanic and 3.6% Asian.ResultsBlack patients had the highest proportions of living in neighborhoods under the federal poverty line (12.4%) and in more deprived locations (neighbourhood deprivation index=0.4). Overall, 14.4% (n=827) of this cohort was hospitalised. Asian patients had the highest rates of ICU admission (53.1%) and mechanical ventilation (21.9%). Among all patients, Hispanics (adjusted 1.60, 95% CI (1.08, 2.37)), blacks (1.43 (1.13, 1.83)), age in years (1.03 (1.02, 1.04)) and living in a zip code with high unemployment (1.08 (1.03, 1.13)) were associated with higher odds of hospitalisation. COVID-19 patients with chronic obstructive pulmonary disease (2.59 (1.67, 4.02)), chronic heart failure (1.79 (1.31, 2.45)), immunocompromised (1.77 (1.16, 2.70)), with glycated haemoglobin >8% (1.68 (1.19, 2.38)), depression (1.60 (1.24, 2.06)), hypertension (1.5 (1.21, 1.87)) and physical inactivity (1.25 (1.03, 1.51)) had higher odds of hospitalisation.ConclusionsBlack and Hispanic KPGA patients were at higher odds of hospitalisation, but not mortality, compared with other race groups. Beyond previously reported sociodemographics and comorbidities, factors such as quality of care, lifestyle behaviours and SDOH indicators should be considered when designing and implementing interventions to reduce COVID-19 racial disparities.

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