Citations

11009 Background: Gender & racial/ethnic leadership disparities have been independently identified in academic hematology/oncology (HO) and radiation oncology (RO). Here, we evaluate gender and racial/ethnic intersectionality from the trainee to the leadership level. Methods: All ACGME accredited HO and RO training program websites were queried to identify constituent trainees, academic faculty, program directors (PD) and department chairs (DC), with a leadership position defined as PD or DC. Individual gender & race/ethnicity was determined using externally validated software tools (Gender-API, NamSor, & Onolytics), publicly available descriptors, and image review. We grouped individuals into 6 categories: White Male (WM), White Female (WF), Asian Male (AM), Asian Female (AF), Underrepresented Groups in Medicine (as defined by AAMC) Male (URMM) and Female (URMF). The chi-squared goodness-of-fit test was applied to examine if deviations exist between the observed vs. expected proportions of gender/race dyads in trainees, PD, and DC compared to academic faculty. Results: We identified 7,722 individuals from 2019-2020: 1,759 trainees (HO=1525; RO=234), 5,726 faculty (HO=4834; RO=892), 242 PD (HO=149; RO=93) and 237 DC (HO=144; RO=93). Leadership positions were most often comprised by WM (52.6%), and least often comprised by URMF (2.9%). Combined HO/RO analysis revealed significant differences in the observed representation of trainees & DC vs expected levels based on total faculty, respectively: WM (33.7% & 60.3% vs. 42.3%), WF (19.2% & 13.9% vs. 22.3%), AM (20.75% & 16.9% vs. 16.4%), AF (17.9% & 2.5% vs. 12.7%), URMM (4.09% & 5.5% vs. 3.5%) and URMF (4.3% & 0.8% vs. 2.8%), p<0.01. No differences were seen between PD vs total faculty. On subset analysis, there were significant differences observed in HO programs at the trainee, PD and DC levels compared to total faculty, whereas significant differences in RO programs were seen only at the DC level [Table]. Conclusions: Gender & racial/ethnic disparity is present in academic oncology. Specifically, women of all races/ethnicities are proportionally underrepresented in DC positions in HO and RO programs. These data can serve as a benchmark to raise awareness and monitor progress towards a more balanced workforce in oncology.[Table: see text]

11007 Background: The proportion of women & underrepresented groups in medicine (URM) in the field of hematology and oncology remains low, particularly in academic leadership positions. Editorial board appointments allow physicians to have a substantial impact on the nature of the published scholarly work and serve as a platform for academic opportunities. We aimed to assess gender and race/ethnicity representation in editorial board positions in hematology and oncology journals. Methods: Editorial leadership board members from 60 journals from oncology, hematology, radiation oncology, and surgical oncology were reviewed, 54 journals were included in the analysis. Gender and race/ethnicity were determined based on publicly available data for editor-in-chief (EiC) and second-in-command (SiC) (including deputy, senior, or associate editors). Descriptive statistics and chi-squared were estimated. Results: A total of 793 editorial board members are included in the analysis. 72.6 % were men and 27.4 % were women. 71.3% of editorial leadership were non-Hispanic white with Asian editorial board members representing the second largest majority at 23.3%. The editorial position was significantly different among men and women (p = 0.038) with women filling only 15.9% (10/63) of the EiC positions. Of these 10 women, the racial breakdown was 90% white and 10% Asian. In the prevalence odds ratio (pOR), women were about half as likely to be in the EiC position compared with men [pOR: 0.47, 95%CI (0.23, 0.95, p = 0.03)]. Women represented 28.4% (207/730) of SiC editorial positions. White editors had the highest representation at 71.0% in the SiC editorial positions, followed by Asian editors at 16.0%. Notable differences were seen in gender proportions between journal specialties (p = 0.001); with surgical oncology and hematology having the lowest female representation at 11.9% and 22.7%, respectively. Conclusions: Women and UIM are markedly underrepresented in leadership roles on Editorial Boards in hematology and oncology journals. Importantly, the representation of minority women physicians in EiC positions is at an inexorable zero which is a sign of unconscious attitudes that may exclude women and minorities from certain positions. It is imperative that we work to move towards a more diverse and inclusive editorial board to ensure critical perspectives are heard and scientific discovery is fostered.[Table: see text]

10500 Background: Inherited pathogenic variants in ATM, CHEK2, and PALB2 confer moderate to high risks of breast cancer. The optimal approach to screening in these women has not been established. Methods: We used two simulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) and data from the Cancer Risk Estimates Related to Susceptibility consortium (CARRIERS) to project lifetime breast cancer incidence and mortality in ATM, CHEK2, and PALB2 carriers. We simulated screening with annual mammography from ages 40-74 alone and with annual magnetic resonance imaging (MRI) starting at ages 40, 35, 30, and 25. Joint and separate mammography and MRI screening performance was based on published literature. Lifetime outcomes per 1,000 women were reported as means and ranges across both models. Results: Estimated risk of breast cancer by age 80 was 22% (21-23%) for ATM, 28% (26-30%) for CHEK2, and 40% (38-42%) for PALB2. Screening with MRI and mammography reduced breast cancer mortality by 52-60% across variants (Table). Compared to no screening, starting MRI at age 30 increased life years (LY)/1000 women by 501 (478-523) in ATM, 620 (587-652) in CHEK2, and 1,025 (998-1,051) in PALB2. Starting MRI at age 25 versus 30 gained 9-12 LY/1000 women with 517-518 additional false positive screens and 197-198 benign biopsies. Conclusions: For women with ATM, CHEK2, and PALB2 pathogenic variants, breast cancer screening with MRI and mammography halves breast cancer mortality. These mortality benefits are similar to those for MRI screening for BRCA1/2 mutation carriers and should inform practice guidelines.[Table: see text]

4079 Background: Cell-free circulating tumor DNA (ctDNA) holds significant promise and is being used for clinical decision making in multiple tumors. This study aimed to evaluate the prognostic value of pre-treatment ctDNA in metastatic biliary tract cancers (BTC) treated with platinum based first-line chemotherapy treatment. Methods: We performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis we considered the detected gene with highest variant allele frequency (VAF). Results of ctDNA analysis were correlated with patients’ demographics, progression-free survival (PFS) and overall survival (OS). Results: The median age of patients was 67 y/o (27-90). 54 (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma and six gallbladder cancer. 46 (68.6%) of the patients were treated with cisplatin plus gemcitabine, 14 (21%) patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations while 7 (10.4%) patients were treated on a clinical trial with gemcitabine and cisplatin plus additional targeted agents (CX4945 or PEGPH20). TP53, KRAS, APC, FGFR2 and IDH1 were the genes with highest frequency as dominant clone. The median dominant clone allele frequency (DCAF) was 3% (0-97%). DCAF >3% was associated with statistically significant worse PFS (median PFS: 4.05 vs. 7.70 months, p=0.046) and OS (median OS: 10.8 vs. 18.8 months, p=0.056). Each 1% increase in DCAF is associated with a hazard ratio of 26.21 in OS when adjusting for subtypes, age, treatment type, and CA19-9 [Table]. Conclusions: Patients with metastatic BTC with DCAF > 3% at diagnosis have worse PFS and OS compared to patients with low ctDNA when treated with upfront platinum-based chemotherapy.[Table: see text]

Abstract Venetoclax (Ven) combined with a hypomethylating agent (HMA) has now emerged as an effective treatment regimen for acute myeloid leukemia, in both de novo and relapsed/refractory setting. The current multicenter study retrospectively examined Ven + HMA treatment outcome among 32 patients (median age 69 years; 59% males) with blast‐phase myeloproliferative neoplasm (MPN‐BP). Pre‐leukemic phenotype included essential thrombocythemia (ET)/post‐ET myelofibrosis (34%), polycythemia vera (PV)/post‐PV myelofibrosis (38%) and primary myelofibrosis (28%). Twenty‐nine study patients were fully annotated cytogenetically and molecularly (NGS): 69% harbored complex karyotype and/or mutations, including TP53 (41%), IDH1/2 (21%), ASXL1 (21%), N/KRAS (14%), SRSF2 (10%), EZH2 (10%) and U2AF1 (7%). All patients received Ven combined with either azacitidine ( n = 12) or decitabine ( n = 20); either up front ( n = 23) or after failing another induction therapy ( n = 9). Complete remission with (CR) or without (CRi) count recovery was achieved in 14 (44%) patients and was more likely to occur in the absence of pre‐leukemic PV/post‐PV myelofibrosis phenotype ( p < .01), complex karyotype ( p < .01) or K/NRAS ( p = .03) mutations; seven of eight patients (88%) without vs four of 21 (19%) with complex karyotype or K/NRAS mutation achieved CR/CRi ( p < .01); all 11 informative patients with pre‐leukemic PV/post‐PV myelofibrosis phenotype displayed complex karyotype ( p < .01). In contrast, neither TP53 ( p = .45) nor IDH1/2 ( p = .63) mutations affected response. Compared to historical controls treated with HMA alone ( n = 26), the CR/CRi rate (44% vs 4%) and median survival (8 vs 5.5 months) were more favorable with Ven + HMA, but without significant difference in overall survival. Importantly, six patients with CR/CRi subsequently received allogeneic hematopoietic stem cell transplant (AHSCT). Note, Ven + HMA produces robust CR/CRi rates in MPN‐BP, especially in the absence of RAS mutations and complex karyotype, thus enabling AHSCT, in some patients.

Abstract Purpose Recent advances in molecular diagnostic technologies allow for the evaluation of solid tumor malignancies through noninvasive blood sampling, including circulating tumor DNA profiling (ctDNA). Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, often because of late presentation of disease. Diagnosis is often made using endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, which often does not yield enough tissue for next-generation sequencing. With this study, we sought to characterize the ctDNA genomic alteration landscape in patients with advanced PDAC with a focus on actionable findings. Materials and Methods From December 2014 through October 2019, 357 samples collected from 282 patients with PDAC at Mayo Clinic underwent ctDNA testing using a clinically available assay. The majority of samples were tested using the 73-gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. Clinical data and outcome variables were available for 165 patients; with 104 patients at initial presentation. Results All patients included in this study had locally advanced or metastatic PDAC. Samples having at least one alteration, when variants of unknown significance (VUS) were excluded, numbered 266 (75%). After excluding VUS, therapeutically relevant alterations were observed in 170 (48%) of the total 357 cohort, including KRAS (G12C), EGFR, ATM, MYC, BRCA, PIK3CA, and BRAF mutations. KRAS, SMAD, CCND2, or TP53 alterations were seen in higher frequency in patients with advanced disease. Conclusion Our study is the largest cohort to date that demonstrates the feasibility of ctDNA testing in PDAC. We provide a benchmark landscape upon which the field can continue to grow. Future applications may include use of ctDNA to guide treatment and serial monitoring of ctDNA during disease course to identify novel therapeutic targets for improved prognosis. Implications for Practice Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis often due to late presentation of disease. Biopsy tissue sampling is invasive and samples are often inadequate, requiring repeated invasive procedures and delays in treatment. Noninvasive methods to identify PDAC early in its course may improve prognosis in PDAC. Using ctDNA, targetable genes can be identified and used for treatment.