Kosiorek, Heidi

Abstract Background:Biliary tract cancers (BTC) are rare, chemo resistant and are associated with a poor prognosis. Preclinical and early clinical work had demonstrated interesting anti-tumor activity from targeting fibroblast growth factor receptor (FGFR) pathway. We hypothesized that ponatinib, a multi-targeted tyrosine kinase inhibitor with activity against FGFR, would be active in BTC patients with FGFR alterations.Methods:This was a multi-center, single institution pilot study of ponatinib in patients with advanced, refractory BTC with FGFR alterations. The primary end point was overall response rate, with secondary points of overall survival (OS), progression-free survival (PFS) and Health Related Quality of Life (HRQoL) assessment. Results:Twelve patients were enrolled prior to early termination of the trial. Clinical benefit (defined as complete/partial response + stable disease) of 45.5% was observed. All observed toxicities were manageable and reversible. Toxicities were mild, with lymphopenia (75%), rash (63%) and fatigue (50%) being the most frequent. No significant detriment in global QoL was observed.Conclusions:Ponatinib as a single agent in FGFR altered BTC is tolerable with very modest clinical activity. This is the first report of prospective assessment of FGFR inhibition in BTC using ponatinib, and the first study to report its effect on HRQoL. Further development of ponatinib will involve correlative studies to better refine patient selection, focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy, and studies to better understand mechanisms of treatment resistance.

11026 Background: The Clinical and Translational Science Award (CTSA) Program currently supports more than 50 leading medical research institutions in the U.S. with the aims of training, promoting and developing future translational science researchers, with particular emphasis on advanced Clinical and Translational Research (CTR) education. No prior studies have evaluated career development in oncologists who have completed CTR training. The objective of this study is to examine the impact of advanced CTR training on career development, return-on-investment and research productivity in Oncology specialties. Methods: With IRB approval, we conducted a survey study of U.S.-based Hematology/Oncology (H/O), Radiation Oncology (RO), and Surgical Oncology (SO) members of the American Society of Clinical Oncology who completed CTR training. Data was anonymized and collected through Research Electronic Data Capture (REDCap). Outcomes were compared using Chi-square test for frequency data. Results: We received 225 survey responses (62.1% H/O, 23.3% RO, 13.2% SO, 1.4% others). About 28.4% (n = 64) of the respondents had a PhD or Master's degree in CTR (Group A) compared to 71.6% (n = 161) with graduate certificates or non-degree granting courses in CTR (Group B). Specialty ratio was equally distributed between both groups. Overall, 79.7% vs 57.5%; P < 0.001 of respondents worked in academia, of which 55.2% had tenure track positions. Over 49 different CTSA Programs throughout the U.S. were represented. In terms of impact with new research projects, the ability to secure funding and opportunities for multidisciplinary collaboration, satisfaction with CTR training was higher among Group A compared with Group B (P < 0.001; P < 0.01; P < 0.01 respectively). In terms of research output, higher satisfaction was seen in Group A (67.2% vs 47.4%; P < 0.01), however total publications per year were not statistically significant (P = 0.135). Usefulness of a CTR degree on career advancement, a difference of 50.0% vs 19.1%; P < 0.001 was noted. Similarly, usefulness regarding new job opportunities and return-on-investment also favored Group A (P < 0.001). Overall satisfaction with training was significantly higher in Group A (73.4% vs 48.7%; P = 0.004). Conclusions: This study is the first to report satisfaction ratings for CTR training among oncology specialties. Although no significant difference was observed in terms of publication output, those with higher levels of advanced degrees were more satisfied with their CTR training, and viewed it as more impactful to career advancement and research productivity. The evidence presented is useful for informing career development for oncology residents and fellows offered CTR degrees during their training.

e18518 Background: Initiatives enhancing equitable oncologic care are an increasingly emphasized priority. Our study aims to identify aspects of breast cancer (BC) care in which differences exist based on insurance coverage status. Methods: We performed a retrospective, case control study consisting of 39 Hispanic ethnicity uninsured patients (UP) with newly diagnosed BC at federally qualified health centers and 119 insured patients (IP) diagnosed at Mayo Clinic Arizona (MCA). Patients were matched 3:1 for age, stage, year of diagnosis, ER and HER2 status. Demographic information, clinical variables, and zip code level specific socioeconomic information were compared. Continuous variables were compared by Wilcoxon rank-sum test and categorical variables by chi-square test. All patients ultimately received their cancer treatment at MCA. Results: Similar treatment patterns with chemotherapy, surgery, and radiation treatment were observed between groups. Primary language was Spanish for 94% of UP and English for 97.5% of IP. The majority of UP were of Hispanic ethnicity (97.4%); IP were 83.2% non-Hispanic White, 9.2% Hispanic, 3.4% African American. Zip code level information reflected more unemployment with a median of 10.6% versus 6.9% p ˂ 0.001, percent of high school or lower (53.0 % v 23.2 %, p ˂ 0.001), and lower income for UP (33733.5 v 64728.0 p values ˂ 0.001). UP BMI was significantly higher (30.6 V 24.7, p=0.005), with presence of more co-morbidities; diabetes (28.2% v 5.0%, p ˂ 0.001), hypertension (35.9 % v 20.2%, p= 0.046), dyslipidemia (28.2% v 12.6%, p = 0.023), metabolic syndrome (p 23.7% v 8.5, p= 0.013), and tobacco use (17.9% v 2.5%, p ˂ 0.001). IP had higher alcohol use (52.9% v 5.3%, p ˂ 0.001). Genetics consultation was performed for 62.2% IP versus 35.9% UP (p=0.004), lower acceptance of oncology nutrition consultation for UP (29.4% vs 7.4%, p= 0.024) Median time from abnormal mammogram to biopsy (25.5 days vs. 14 days, p=0.056), and interval from diagnosis to treatment (62 days vs. 39 days) (p=0.001) were less favorable for UP compared to IP. Conclusions: In comparing the status of UP (primarily Hispanic, Spanish-speaking) and IP (primarily non-Hispanic White, English-speaking) with newly diagnosed BC we identified greater prevalence of co-morbidities and adverse social determinants of health in the former group. We identified access to genetic counseling services, access to oncology nutrition consultation, and timeliness of diagnostic biopsy and initiation of treatment as disparate features in the care pathway. These observations can allow development of tailored interventions to achieve greater equity in delivery of BC care.

4130 Background: Circulating cell-free tumor DNA (ctDNA) genomic profiling is an emerging tool for pancreatic cancer. The impact of detected genomic alterations in tumor response to systemic treatments and outcomes is under investigation. Methods: Patients with advanced pancreatic cancer and ctDNA collected at time of initial diagnosis were retrospectively evaluated. Results of ctDNA analysis were correlated with patients’ demographics, systemic treatment response, progression-free survival (PFS) and overall survival (OS). Results: A total of 104 patients were included in the analysis. The mean age was 70.5 years (SD: 8.3), 50% were male, 37% with locally advanced disease and 63% with metastatic disease. Somatic alterations were detected in 84.6 % of the patients, no genetic alterations were detected in 15.4%, and were associated more with locally advanced pancreatic cancer as opposed to metastatic, p = 0.025. 60.6 % of the cohort had ≥ 2 genomic alterations detected. 28% were treated with FOLFIRINOX and 63% with gemcitabine plus nab-paclitaxel as first-line systemic treatment. Patients with any detectable genomic alterations when compared to patients with no detectable variant had worse median PFS (6.2 versus 15.3 months, p = 0.005) and patients with ≥ 2 detectable genomic alterations had worse median PFS (5.6 versus 11.0 months, p < 0.001) and worse median OS (11.5 versus 24.2 months, p = 0.001). KRAS was detected in 62.5% of the patients and was associated with PD to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (5.8 versus 13.0 months, p < 0.001) and worse median OS (11.5 versus 26.3 months, p = 0.002). TP53 was detected in 60% of patients and was associated with worse median PFS (5.9 versus 10.9 months, p = 0.02) and worse median OS (13.5 versus 24.2 months, p = 0.001). CCND2 was detected in 14% of the patients and was associated with worse median PFS (3.6 versus 8.2 months, p = 0.004). Conclusions: Our study showed that initial detection of ctDNA may identify different genomic alterations that help predict disease outcomes, confirmation of these findings in larger studies are warranted.

Objectives: Refractory septic shock is associated with high morbidity and mortality. Hydroxocobalamin is used to treat postoperative vasoplegia; however, data supporting its use in the setting of refractory septic shock is limited and restricted to case reports. This study evaluates the effect of hydroxocobalamin on mean arterial pressure and vasopressor requirements in a series of patients with refractory septic shock. Design: Single-center, retrospective analysis. Setting: Urban, tertiary-care ICU. Patients: Adult ICU patients with refractory septic shock treated with hydroxocobalamin between August 2018 and January 2020. Interventions: Hydroxocobalamin 5 g IV infusion. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients were included for the analysis. Administration of hydroxocobalamin was associated with an increase in mean arterial pressure at 1, 6, and 24 hours postdose (+16.3, +14.3, and +16.3 mm Hg, respectively; p < 0.001). Increase in mean arterial pressure from baseline remained statistically significant when controlling for sex, age, and comorbid conditions. There was no change in the norepinephrine equivalents patients required 1 hour following hydroxocobalamin administration, but a statistically significant decrease in norepinephrine equivalent was observed at 6 and 24 hours postdose (p < 0.001). Conclusions: Hydroxocobalamin provides sustained hemodynamic benefit at 24 hours in patients with refractory septic shock.

Introduction: Serum folate (SF), vitamin B12 (B12), and iron deficiency (def) are common causes of nutritional anemias (NA). These deficiencies are usually multifactorial, with nutritional and non-nutritional causes playing a role. SF, B12, and iron levels are usually ordered in the setting of anemia, and malnutrition with or without neurologic symptoms. Clinical evidence suggests that these def have a strong dietary component and socioeconomic status (SES). The relationship of NA and area-based SES in the US has not been studied. We aimed to determine the relationship of SES with the prevalence of NA. Methods: We performed a cross-sectional analysis of adult patients with SF, B12 and iron levels at Mayo Clinic Arizona and Florida between 2010 and 2018. Race was classified using the NIH criteria. Normal laboratory values were determined according to our lab reference and the US NHANES III. SF levels (mcg/Lt) were defined as deficient &lt;4, normal ≥4.0, and excess ≥20. B12 levels (ng/L) as deficient &lt;150, borderline 150-400, normal &gt;400-900, and excess ≥900. Iron def was determined by ferritin levels (mcg/L) as low &lt;24, normal 24-336, elevated &gt;336 for men, low &lt;11, normal 11-307, elevated &gt;307 for women. Area-Level SES indicators: Median Household income (MHI), unemployment rate (UR), median gross rent month (MGRM), % uninsured, median house value (MHV), % high school; were geocoded by zip code using the 2014 American Community Survey. Demographics and clinical variables were compared between groups by chi-square test for frequency data or Kruskal Wallis rank-sum test for continuous variables. Results: 202,046 samples from 128,084 patients were analyzed. In the sample-level analysis, there were statistically significant associations between SES and SF def; all SES indicators except UR for B12 def; and no differences for iron def, except % uninsured (Table 1). There was no statistically significant interaction between race and SES for SF def and iron def. Race was a statistically significant modifier between B12 def and MHI (p&lt;0.001), % uninsured (p=0.002), and MHV (p=0.007). Asian and Other race had an increase in odds of B12 def with increasing MHI (Asian OR=1.11 , Other OR=1.18); white race had a decrease in odds of B12 def with increasing MHI (OR=0.95 for a $10,000 increase in MHI). Conclusions: We show significant relationships between SES and NA in the US. Differences were observed between SF def and all the SES indicators without race interactions. There were significant interactions between B12 def, race and SES for pts of White, Asian and Other race. There were no differences between SES and race for iron def. These relationships confirm that NA are related to area-level SES and other social determinants of health. Research regarding the causes of these disparities on a population level are needed. Disclosures No relevant conflicts of interest to declare.

Background: The COVID pandemic has resulted in significant changes many aspects of daily living. To understand the impact that COVID-19 has had on the myeloproliferative neoplasm (MPN) patient population, we conducted an internet based survey. Methods: Survey: This survey was hosted Mayo Clinic's secured REDCap system for online surveys with a link to the survey alongside a brief description posted via the www.mpnqol.com website, as well as other MPN organizational partners. Survey responses were completely anonymous. Questions included MPN-Total symptom score (TSS), NCCN distress thermometer (NCCN-DT), questions regarding impact on medical care, and questions from CDC COVID-19 community survey question bank regarding the impact of social distancing as well as changes in health behaviors. Distress thermometer, MPN-TSS, and/or questions related to the impact of COVID-19 on MPN treatment were analyzed by: MPN diagnosis, among those with ET, PV, or MF diagnoses; medication status; stay at home order; community spread; and country. Associations were tested using Kruskal-Wallis or Wilcoxon rank sum tests (for continuous variables) or Fisher Exact tests (for categorical variables). Analysis: Results: Patient Demographics (Table 1): 1560 people responded to the survey, 1217 were eligible for analysis. Median age was 62 (range: 21-93), and 298 (24.6%) respondents were male. There were respondents from USA, Australia, Canada, Netherlands, Ireland, and UK. 233 patients (19.2%) have myelofibrosis, 419 (34.6%) polycythemia vera and 543 (44.8%) essential thrombocythemia. At the time of the COVID outbreak, 1026 (84.3%) were on MPN directed medical therapy, including ruxolitinib (15.3%), interferon (14.7%), hydroxyurea (42.7%) and ASA (47.7%). 165 (13.6%) respondents received COVID testing, of which 5 had positive tests. Impact on MPN Care (Table 2): We sought to understand how patient's clinical care changed. Over half respondents who spoke to their MPN doctor had a telemedicine visit after COVID19 (57.1%). 422 (36.5%) patients spaced out visits, of which 99 (22.7%) felt there were consequences. A change in therapy due to COVID-1 occurred in only 5.4% of patients. MPN Symptom Burden and QoL: Data captured on the NCCN-DT had a median of 4 (0-10). MPN-SAF-TSS composite score was collected in 1150 respondents, median score was 26 (0-90). These scores are higher than those previously reported. Pandemic Impact on Lifestyle (Table 1): 595 (49.5%) of patients report living in a community where there is significant COVID-19 spread. 946 (78.9%) reported that COVID-19 has impacted their day to day life. 198 (17.2%) of patients agreed, or strongly agreed that COVID had a significant impact on their finances. 799 (67.8%) had a stay at home order. Of those who quarantined (112), the median duration was 30d (1-120). The majority of people increased hand-washing, and cleaning habits. 954 (81.7%) respondents reported wearing masks in public. 908 (76.8%) reported increased stress from social distancing. The majority of respondents report using healthy coping habits, such as reaching out to friends/loved ones, breathing and relaxation, as well as healthy diet. Less than 15% of patients report unhealthy coping strategies, such as use of opioids, benzodiazepines, alcohol, or cannabis Factors associated with response: There were no differences in responses based on type of MPN. If a patient was on medication, they were more likely to have spoken to their provider (p&lt;0.001). If there was a stay at home order in place, there was a higher MPN-TSS score (p&lt;0.001). If the respondent lived in an area of high community spread, they had a higher NCCN-DT score (p&lt;0.001). Patients in the USA had a higher NCCN-DT score (p=0.001), were more likely to stretch out the duration of time between visits (p&lt;0.001) and less likely to have a telemedicine visit (p&lt;0.001). Although fewer respondents in the USA thought COVID-19 was a serious disease (p=0.02), a higher percentage of respondents wore masks (p &lt;0.001). Conclusions: In our survey of MPN patients, there were many changes noted in clinical care. The use of telemedicine was common, and at least a third had significant changes in their care. Most experienced increased stress, however, employed healthy coping strategies. Only a minority of patients had a COVID test, and only 5 were positive, further data will be needed to understand the impact of COVID infection. Figure 1 Disclosures Harrison: Roche: Honoraria; Incyte Corporation: Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Sierra Oncology: Honoraria; Promedior: Honoraria; Shire: Honoraria, Speakers Bureau; AOP Orphan Pharmaceuticals: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau; CTI Biopharma Corp: Honoraria, Speakers Bureau. Pemmaraju:Affymetrix: Other: Grant Support, Research Funding; Plexxikon: Research Funding; Incyte Corporation: Honoraria; Roche Diagnostics: Honoraria; Blueprint Medicines: Honoraria; Novartis: Honoraria, Research Funding; SagerStrong Foundation: Other: Grant Support; DAVA Oncology: Honoraria; Samus Therapeutics: Research Funding; Cellectis: Research Funding; Daiichi Sankyo: Research Funding; Celgene: Honoraria; AbbVie: Honoraria, Research Funding; Stemline Therapeutics: Honoraria, Research Funding; MustangBio: Honoraria; LFB Biotechnologies: Honoraria; Pacylex Pharmaceuticals: Consultancy. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Blueprint: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gupta:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol MyersSquibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding; Pfizer: Consultancy. Mascarenhas:Celgene, Prelude, Galecto, Promedior, Geron, Constellation, and Incyte: Consultancy; Incyte, Kartos, Roche, Promedior, Merck, Merus, Arog, CTI Biopharma, Janssen, and PharmaEssentia: Other: Research funding (institution). Shimoda:Kyowa Hakko Kirin Co., Ltd.: Research Funding; Pfizer Inc.: Research Funding; Otsuka Pharmaceutical: Research Funding; Celgene: Honoraria; Perseus Proteomics: Research Funding; PharmaEssentia Japan: Research Funding; AbbVie Inc.: Research Funding; Astellas Pharma: Research Funding; Merck & Co.: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceutical Company: Honoraria; Novartis: Honoraria, Research Funding; Shire plc: Honoraria; Asahi Kasei Medical: Research Funding; Japanese Society of Hematology: Research Funding; The Shinnihon Foundation of Advanced Medical Treatment Research: Research Funding. Kiladjian:AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Komatsu:AbbVie: Other: member of safety assessment committee in M13-834 clinical trial.; Otsuka Pharmaceutical Co., Ltd., Shire Japan KK, Novartis Pharma KK, PharmaEssentia Japan KK, Fuso Pharmaceutical Industries, Ltd., Fujifilm Wako Pure Chemical Corporation, Chugai Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Takeda Pharmaceutica: Research Funding; Meiji Seika Pharma Co., Ltd.: Patents & Royalties: PCT/JP2020/008434, Research Funding; PPMX: Consultancy, Research Funding; Otsuka Pharmaceutical Co., Ltd., PharmaEssentia Japan KK, AbbVie GK, Celgene KK, Novartis Pharma KK, Shire Japan KK, Japan Tobacco Inc: Consultancy; Takeda Pharmaceutical Co., Ltd, Novartis Pharma KK, Shire Japan KK: Speakers Bureau. Abello:Takeda: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Gomez-Almaguer:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Mauro:Novartis: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Sun Pharma/SPARC: Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Honoraria, Other: Travel, Accommodation, Expenses, Research Funding. Mesa:Samus Therapeutics: Research Funding; Novartis: Consultancy; Genentech: Research Funding; Incyte: Research Funding; Bristol Myers Squibb: Research Funding; AbbVie: Research Funding; CTI BioPharma: Research Funding; Sierra Oncology: Consultancy; LaJolla Pharmaceutical Company: Consultancy; Promedior: Research Funding.