MedStar Georgetown University Hospital Research Articles

Colorectal cancer care disparities in an urban diverse population: A tale of two hospitals in the nation’s capital.

38 Background: Colorectal cancer (CRC) disparities by race and ethnicity are well-documented nationally. In the District of Columbia (DC), Black Americans have an 18% higher incidence and 46% higher mortality rate compared to overall rates among all races/ethnicities. These disparities often stem from long-standing inequities in the social determinants of health, which affect access to cancer prevention, early detection, and treatment. MedStar Georgetown serves a large, urban, diverse population at 2 hospitals: the MedStar Georgetown University Hospital (MGUH) and the MedStar Washington Hospital Center (MWHC). MWHC serves a higher proportion of minoritized patients (pts) with multiple social determinant barriers to care, including those without private health insurance. We hypothesized that disparities would be found in CRC pt care and outcomes when comparing MWHC with MGUH. Methods: We conducted a retrospective study of all CRC pts treated during the 2021-2023 period at MGUH and MWHC using the COTA real-world database. Pt demographics, insurance status, and selected clinical data, including but not limited to treatment site, disease stage, tumor molecular testing, and pt survival, were abstracted for analysis. Descriptive, bivariate, and multivariate analyses focused on gender, race/ethnicity, insurance status, receipt of tumor testing, and the interval between diagnosis and therapy initiation and explored survival by these factors in addition to the site of care (MGUH versus MWHC). Results: Of the 379 CRC pts receiving care at the Lombardi Comprehensive Cancer Center during the study period, 53% were treated at MGUH and 47% at MWHC. CRC pts at MWHC were more likely than CRC pts at MGUH to be Black Americans (65% vs. 28%, p<0.001) and have 3 or more comorbidities (16% vs. 8%, p=0.22) but were less likely to have early onset CRC (p<0.01) and be on private insurance (36% vs. 23%, p=0.01). Pts treated at advanced stages (stages 3-4) were similar between the two hospitals (64%). In spite of these differences, we did not find any differences between MWHC and MGUH in molecular tumor testing (83% vs. 86%, p=0.41), median time (days) to treatment initiation (28 vs. 26 days, p=0.18), or short-term survival (90% vs. 91%, p=0.95). In analyses comparing care/treatment-related factors with race/ethnicity and insurance status across the 2 hospitals, we did not find any statistically significant differences. Conclusions: Contrary to our expectations of finding significant cancer care disparities, we did not observe any differences in molecular tumor testing rates, time to initiation of therapy, or short-term survival by treatment site or race/ethnicity status. Our results suggest that integrated, specialized, guideline-concordant care in comprehensive cancer centers has the potential to eliminate CRC outcome disparities among pts diagnosed at these centers.

Effects of Isoproterenol Administration in Dobutamine Stress Echocardiography.

This study evaluated the safety and efficacy of isoproterenol administration as an adjunct for achievement of target heart rate (HR) during dobutamine stress echocardiography (DSE). In DSE, optimal accuracy is achieved when a target HR of 85% of maximal predicted heart rate (MPHR) is attained. Although rarely studied, intravenous isoproterenol has been used as an adjunct therapy to dobutamine and atropine to increase chronotropic response during pharmacologic stress testing. We identified 5569 DSE studies during which 264 received isoproterenol at MedStar Georgetown University Hospital from August 2011 to March 2023. Of the studies receiving isoproterenol, we collected clinical and echocardiographic parameters from each study to assess the effects of isoproterenol administration, including downstream events. In 264 examinations with isoproterenol, 169 (64%) achieved 85% MPHR. Among these, 103 (39%) developed premature ventricular contractions, 79 (30%) developed symptoms including nausea/vomiting in 44 (17%), and chest pain in 15 (6%). There was a hypertensive response to stress in 53 studies (20%) and a hypotensive response in 37 studies (14%). There was no significant increase in 30-day and 1-year death when compared to studies that did not receive isoproterenol. Isoproterenol can effectively be used as an adjunctive agent in DSE to achieve the requisite hemodynamic stress for evaluation of ischemia, with a similar rate of side effects and complications compared to dobutamine and atropine stress testing.

Ureteroscopy, Laser Lithotripsy, and Stent Replacement for an Obstructing Left Proximal Ureteral Stone with Forniceal Rupture

Watch this full-length, narrated surgical video of a ureteroscopy, laser lithotripsy, and stent replacement for a ureteral stone performed by Dr. Ryan Hankins at MedStar Georgetown University Hospital.

Outcomes with initiation of inpatient immunotherapy.

7 Background: Immune checkpoint inhibitors (ICIs) have transformed cancer care; however, studies establishing their benefit have been primarily conducted in robust patients (pts) with good performance status. Administration of ICI to hospitalized pts remains a subject of debate. While there is often a desire to reverse clinical course in patients who are acutely ill, previous studies show minimal benefit from anticancer therapy near the end of life with the potential for toxicity. While ICI are generally better tolerated than traditional cancer therapies, the median time to response ranges from 2-6 months and pts with a poor PS may not derive benefit. ICIs also bring significant financial burdens to pts and healthcare systems. The role of ICIs in the inpatient setting remains unclear. Methods: This study retrospectively examined pts who received PD-(L)1 inhibitors while IP between 2016 and 2023 at MedStar Georgetown University Hospital. Data were collected manually from institutional EMR. Descriptive statistics were used to depict the pt population and show their outcomes. The Kaplan-Meier method estimated survival probabilities from treatment initiation to follow-up or death, with 95% confidence intervals (α = 0.05). The Log rank non-parametric test compared survival distributions among ICIs. Results: Of the 38 pts who initiated ICI as an inpatient, 16 were male (42.1%) and 22 were female (57.9%). The median age was 60 years (31–88 years). Gastrointestinal malignancies were most common indication (31.6%), followed by thoracic/head and neck (21.1%) and hematologic (18.4%) cancers. Among the cohort, 26.3% received nivolumab, 68.4% received pembrolizumab, and 5.3% received a combination of nivolumab and ipilimumab. PD-L1 status was unknown for the majority (79.0%) of pts at time of ICI; 15.8 % were known to be PD-L1 high. Only 14 of 35 (40.0%) patients went on to receive any additional immunotherapy after discharge. The median days to death after discharge was 16 days (0-376 days), with a mean of 36.4 days. The median overall survival was 137 days from IP treatment initiation. The survival probability at 91 days was 65.5% (95% CI: 45.4-79.7) and 31.0% (95% CI: 15.6-47.9) at 182 days. No significant differences were observed between the survival distributions by ICI type (p=0.966) or primary malignancy (p=0.488). Conclusions: Our findings underscore the complexities of initiating inpatient ICI treatment and question its appropriateness. Delaying ICI to outpatient settings may enhance pt tolerance, optimize outcomes, and potentially mitigate unnecessary costs. This approach may allow thorough consideration of performance status outside the hospital, possibly improving treatment effectiveness while reducing futile acute care costs.

Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy

SummaryIndolent CD4+ cytotoxic chimeric antigen receptor (CAR) T-cell lymphoma involving the small intestine was diagnosed in a patient who had previously received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy for treatment of myeloma. Targeted messenger RNA sequencing revealed the presence of CAR gene product in tumor cells. Whole-genome sequencing of samples of tumor and peripheral blood identified a single lentiviral insertion site within the second intron of the SSU72 gene. In addition, numerous genetic alterations that may have contributed to malignant transformation were identified in the tumor sample. (Funded by MedStar Georgetown University Hospital.)

Patients with hepatocellular carcinoma (HCC) who require multiple transarterial chemoembolization (TACE) treatments in quick succession and prediction of outcome.

e16208 Background: TACE has been one of the standard treatments for intermediate-stage HCC patients for over 20 years. The outcome of patients from TACE treatment is variable as the result of the differences in tumor burden, liver function, and comorbidities. Given the advancement made in systemic therapies for advanced-stage HCC, and emerging data on the combination of TACE and immunotherapy, there is an unmet need to identify patients with intermediate-stage HCC who may benefit from early introduction of systemic therapy. The purpose of the study is to identify clinical factors that predict poorer outcomes in patients who receive TACE treatment. Methods: This retrospective analysis is a single-institutional study involving patients from MedStar Georgetown University Hospital. The investigation includes 167 individuals diagnosed with HCC who underwent TACE from 2007 to 2021. The data compiled for analysis encompassed patient demographics, clinical features, risk factors, and treatment outcomes. The log-rank test is used to test whether there is a difference between the survival times of different groups. Results: 167 HCC patients, with 105 in intermediate/advanced BCLC stages B and C were included. The cohort, with a median age of 62, comprised 128 males and 43 females. Cirrhosis was seen in 83% of patients mostly due to viral etiology. Hepatitis C (58%) and hepatitis B (13%) were common, with 4% having both. The remaining 24% had cirrhosis from metabolic-associated fatty liver disease (MAFLD). The median overall survival (OS) durations for patients in BCLC-A (n = 62), BCLC-B (n = 64), and BCLC-C (n = 41) stages who underwent TACE as a component of their comprehensive treatment strategy were 67.9, 29.7, and 30.6 months, respectively (P = 0.035). In 64 subjects with BCLC stage B disease, patients who received 3 or more TACE treatments had higher OS (43.6 months) than those with two or fewer treatments (25.4 months, P = 0.042). Among the patients who had 2 or fewer TACE treatments, 6 patients had liver decompensation and discontinued treatment and 21 patients developed cancer progression and went on to receive systemic therapy. The median time to progression from the last TACE treatment was 5 months. Interestingly, among the patients who received 3 or more TACE treatments, 10 patients who had 3 or more TACE treatments within 6 months from the 1st TACE treatment had an mOS of 25.8 months while 25 patients who had 3 or more TACE treatments over a time span more than 6 months had a mOS of 49.4 months (P = 0.0186). Conclusions: Rapid disease progression in 6 months from the start of TACE treatment was predictive of aggressive tumor biology, and these patients may benefit from the early introduction to systemic therapy. Molecular biomarkers used to predict aggressive tumor biology are an unmet need for selecting patients to receive the combination of TACE and systemic therapy.

Cross-cultural differences in diet and quality of life between Taiwanese and American women during breast cancer treatment.

e23187 Background: Limited research has examined the role of different food types (vegetables, fruits, meat, fat, and whole grains) on quality of life (QoL) among cancer patients undergoing active treatment. This study aimed to examine what different food intakes are associated with QoL among American and Taiwanese women who are newly diagnosed with breast cancer (BC). Methods: This ongoing observational study enrolled 77 American (Black, Latina, and non-Hispanic White) adult women from MedStar Georgetown University Hospital and 79 Taiwanese women from National Taiwan University Hospital. They were diagnosed with stage 0-III primary BC within six months prior to enrollment, were undergoing surgery, chemotherapy, and radiation, with no other cancers. Patient-reported overall health and QoL were assessed using the two global health items from the EORTC-QLQ30. Three random 24-hour diet recalls (two weekdays and one weekend) were administered using the NIH-developed ASA24 program. Linear regression was conducted to examine the associations between food categories and QoL outcome, adjusting for nationality, age, cancer stage, treatment type, body mass index, physical activities, financial problems, and appetite loss. Results: American and Taiwanese patients displayed differing food intake during BC treatment. Taiwanese patients consumed less starchy vegetables and total fat (both p < .01) than American patients, on average. Multivariate results indicated that QoL was positively associated with higher total vegetable intake (excluding starchy vegetables and legumes; β = 5.38, 95% CI: 0.22, 1.20), controlling for other food types and covariates. Starchy vegetables and legumes showed non-significant negative effects on QoL. QoL was positively associated with total fat intake (β = 0.11, 95% CI: 0.02, 0.21). Total meat, fruit, and whole grain intakes were not significantly associated with QoL. Conclusions: The associations between food intakes and QoL were not affected by nationality, regardless of food type. Non-starchy vegetables and adequate total fat intakes may support BC patients undergoing treatments. More research is needed to verify the identified associations and explore how cancer treatment affects the digestion of certain food types and their potential impact on QoL. This study provides cross-cultural insights into potential nutritional influence on QoL among patients undergoing cancer treatment.

Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer in Men With Hip Prostheses: A Cautionary Note.

Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements. 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC).The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal).During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy. The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy.The rates of late > Grade 3 GU toxicity and> Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities.Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral.Three underwent salvage cryotherapy and three received salvage ADT. In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT.However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hopethat recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes.

Expanded Indications for Nipple-Sparing Mastectomy and Immediate Breast Reconstruction in Patients Older Than 60 Years.

Although nipple-sparing mastectomy (NSM) and immediate breast reconstruction (IBR) have long been praised for excellent cosmetic results and the resultant psychosocial benefits, the feasibility and safety of these procedures in patients older than 60 years have yet to be demonstrated in a large population. Patients undergoing NSM with or without IBR at the MedStar Georgetown University Hospital between 1998 and 2017 were included. Patient demographics, surgical intervention, and complication and recurrence events were retrieved from electronic medical records. Primary outcomes were recurrence and complication rates by age groups older and younger than 60 years. There were 673 breasts from 397 patients; 58 (8.6%) older than 60 years and 615 (91.4%) younger than 60 years with mean follow-up of 5.43 (0.12) years. The mean age for those older than 60 was 63.9 (3.3) years, whereas that for those younger than 60 was 43.1 (7.9) years (P < 0.001). The older than 60 group had significantly higher prevalence of diabetes, rates of therapeutic (vs prophylactic) and unilateral (vs bilateral) NSM, and mastectomy weight. However, there were no significant differences by age group in complication rates or increased risk of locoregional or distant recurrence with age. Based on similar complication profiles in both age groups, we demonstrate safety and feasibility of both NSM and IBR in the aging population. Despite increased age and comorbidity status, appropriately selected older women were able to achieve similar outcomes to younger women undergoing NSM with or without IBR.

Supportive Care of Hematopoietic Stem Cell Donors.

Supportive care needs for hematopoietic stem cell recipients have been studied. Less is known about the care needs of stem cell donors. Care challenges arise at donor selection, preparation for the donation, the donation procedure and the immediate and long-term after-care. Care needs were analyzed for 1,831 consecutive bone marrow and peripheral stem cell donors at MedStar Georgetown University Hospital between January 2018 and August 2023 in support of a review of the current literature. During the selection, related donors may experience psychological pressures affecting their motivation, while donation centers may be willing to accept co-morbidities in these donors which might preclude donation in unrelated peers. For bone marrow donations, it is important to select donors not only according to optimal genetic matching criteria but also according to suitable donor/recipient weight ratios, to facilitate sufficient stem cell yields. During the donation preparation phase, side effects and complications related to stem cell stimulation must be anticipated and managed for peripheral cell donors, while the pros and cons of autologous blood donation should be evaluated carefully for bone marrow donors. The stem cell donation procedure itself carries potential side effects and complications as well. Peripheral cell donors may require a central line and may encounter hypocalcemia, thrombocytopenia, and anemia. Bone marrow donors face risks associated with anesthesia, blood loss and pain. Post-procedure care focusses on pain management, blood cell recovery and the psychological support necessary to regain a high quality-of-life existence. Hematopoietic stem donors are giving part of themselves to save another's life. They deserve comprehensive supportive care to accompany them throughout the donation process.

Investigating Metabolic and Immunologic Consequences of Nucleotide Substitutions in Acute Myeloid Leukemia

Background Stressors, conventionally defined as cell extrinsic factors with the ability to promote clonal evolution, have been implicated as modulators of cancer development and progression. Smoking has previously been linked to unique single-base substitutions (SBSs), which may facilitate the development and progression of acute myeloid leukemia (AML). Similar to smoking in lung cancer, we previously reported unique C&amp;gt;A single-base substitutions (SBSs) in AML. SBS4 mutational signature (COSMIC database) is characterized by C&amp;gt;A transversions and may induce “immunogenicity”. Interestingly, C&amp;gt;A associates with G&amp;gt;A in elderly AML with previous smoking history (Patel, ASH, 2022). In recent years, high body mass index (BMI) has been associated with risk for clonal hematopoiesis (CH). However, a SBS correlation with metabolic parameters (i.e. lipid studies and BMI) remains uncharacterized. In this study, we aimed to: (1) confirm the association of smoking with C&amp;gt;A and G&amp;gt;A SBSs in an expanded cohort of leukemia patients and (2) to investigate metabolic and immunologic factors associated with these SBSs among patients with leukemia. Methods After IRB approval, we conducted a retrospective analysis of AML patients (pt) from Baylor and MedStar Georgetown University Hospital (MGUH). Genetic data using next generation sequencing (NGS), as well as demographic and clinical information was obtained. For patients from MGUH, FASTA nucleotide sequences were obtained by subjecting mutations to transcript expression and cDNA alignment in the NCBI gene database. MHC I binding neopeptides were identified by mapping FASTA nucleotide sequences and HLA class I alleles in the Net MHC pan 4.1 database. SBSs with neopeptides that exhibited binding were grouped for further analysis of associations. Descriptive statistics were obtained using SAS software. Results Our expanded database included 85 pt with AML that had NGS performed at diagnosis. This increased the number of SBSs in our database from 148 to 213. Median age was 64.8 years (y) (range, 22-89). 42/85 patients (49.4%) had a positive smoking exposure. 41/213 (19.2%) of SBSs were C&amp;gt;T, 14/213 (6.6%) were C&amp;gt;A, 12/213 (5.6%) were G&amp;gt;C, 68/213 (31.9%) were G&amp;gt;A, 12/213 (5.6%) were A&amp;gt;C, 8/213 (3.8%) were A&amp;gt;T, 25/213 (11.7%) were G&amp;gt;T, 13/213 (6.1%) were A&amp;gt;G, 4/213 (1.9%) were T&amp;gt;A, 6/213 (2.8%) were T&amp;gt;C, 8/213 (3.8%) were C&amp;gt;G, and 2/213 (0.9%). 4/80 (5%) of G&amp;gt;A transitions were in pts age &amp;lt;40y, 18/80 (22%) age 40-59 y, and 58/80 (73%) &amp;gt;60y ( Fig 1A). Smoking significantly increased association with C&amp;gt;A transversion rate from 2.44% to 12.94% ( p=0.003). C&amp;gt;A combined with G&amp;gt;A showed an increased smoking rate of 50.59% vs 29.27%( p=0.002). When compared with patients without a smoking exposure, patients with C&amp;gt;A or G&amp;gt;A mutations and a smoking exposure had significantly higher total cholesterol of 165.2mg/dL compared to 125.8mg/dL ( p=0.02) and LDL of 101.8mg/dL compared to 74.5mg/dL ( p=0.04). Interestingly, higher frequency of G&amp;gt;T, (previously recognized to be associated with oxidative damage) was observed among AML patients aged 40-59 exhibiting higher body mass index (BMI) ( Fig 1B). Given dominance of G&amp;gt;A expression in older AML pt, we investigated MHC class I neopeptide immunogenicity initiated by G&amp;gt;A mutations as a suggestion of functional interference. Among pathogenic G&amp;gt;A variants demonstrating TCR-reactivity, 1/18 (5.6%) vs 7/21 (33.3%) neopeptides were observed in AML pt less than 60 y vs older than 60 y ( p = 0.03). Discussion Our data confirm the association of smoking exposure with C&amp;gt;A and G&amp;gt;A mutagenicity. Subsequent analysis demonstrated a significant association with increased TC and LDL levels, indicating an altered lipidome may affect the acquisition of these mutations in AML patients with smoking exposure. We have also seen that G&amp;gt;A is enriched in older AML patients. In this pt subgroup, our data suggests that neopeptides derived from G&amp;gt;A SBS retain immunogenic potential. While this has been previously associated with aging, other etiologic associations have yet to be established. Additionally, younger obese AML pt exhibit increased susceptibility for G&amp;gt;T mutagenesis possibly as result of oxidative stress. Continued work is needed to elucidate the spectrum of stressors associated with mutational signatures in AML and their underlying mechanisms, as this will have important biologic implications for preventative and therapeutic interventions.

Fluoroquinolone-Resistant Enterobacteriaceae Prevalence for Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (aHSCT) in the Treatment of Multiple Myeloma (MM)

Background: Fluoroquinolones (FQL) are commonly used in antimicrobial prophylaxis in immunocompromised cancer patients (pts) during prolonged neutropenia. A possibly high and increasing proportion of pts harboring FQL-resistant Enterobacteriaceae (FRE) challenges the assumption that prophylaxis with FQLs is still of benefit in preventing sepsis. Previous studies reported that colonization of FRE in allogeneic transplant patients may be an infection risk factor (cf. Satlin et al. Clin Infect Dis 202;73:1257-65). This prospective study aims to determine the prevalence of FRE in defined pt populations in two metropolitan areas treated with dose-intense melphalan with autologous peripheral blood stem cell (PBSC) transplantation, and to determine the possible clinical effects of FRE in the host microbiome on transplant outcomes. Methods: Pts eligible for this prospective, ongoing study have a diagnosis of MM and are undergoing autologous PBSC transplantation after conditioning with dose-intense melphalan 200 mg/m 2 at Hackensack University Medical Center (HUMC) and MedStar Georgetown University Hospital (MGUH). Peri-rectal swabs are scheduled before chemotherapy mobilization of PBSC given with FQL prophylaxis, before transplant admission with initiation of antimicrobial prophylaxis, at time of hospital discharge, and 3 months after aHSCT. Prophylaxis is discontinued with fever or hospital discharge. Blood cultures are obtained at time of fever (&amp;gt;38 °C) with adjustments in antibiotics per standard of care. A central catheter is placed for venous access in all patients throughout their transplant course. Pts are discharged after achieving neutrophil (ANC) engraftment and control of conditioning regimen toxicities. Bacterial cultures from perirectal swabs (fresh or frozen for shipping) were purified on CHROMagar™ Orientation Plates and grown in the presence of ≥5 ug/ml ciprofloxacin to select for quinolone-resistant organisms. Results: To date, 39 pts are evaluable (Table 1). PBSC were mobilized using filgrastim/plerixafor (G-Moz) or cyclophosphamide/etoposide/dexamethasone (CDE) followed by filgrastim with levofloxacin prophylaxis. The quantity of CD34+ cells infused is in Table 1. All pts achieved ANC engraftment at a median of 10.8 days (range 9-14) and were hospitalized for a median of 13 days (range 11-24). 37/39 pts collected swabs before transplant admission (and swabs were obtained at discharge for the other 2 pts). 13/37 (35%) admission swabs demonstrated FRE colonization (Table 2). 6/33 swabs at time of discharge were positive for FRE including for 4 pts negative for FRE on transplant admission with a total of 17/39 pts (44%) showing FRE colonization at some point during the transplant admission. Samples collected at 3 months after transplantation for 24 pts reaching that timepoint showed FRE colonization for 4 pts including 2 pts not previously testing positive at time of transplantation. 27/107 samples tested positive for FRE and 21/39 pts (54%) had at least one FRE positive culture. Seven pts (20%) developed neutropenic fever but no pt experienced a blood-stream infection (BSI). One pt developed Clostridium difficile colitis during the period of neutropenia. One pt tested positive for MRSA colonization at admission but did not develop fever or BSI. One pt was readmitted after initial hospital discharge for evaluation of fever without a source of infection determined. Ten pts (5 FRE colonized during transplant course) were given prednisone for persistent diarrhea attributed to engraftment syndrome (cf: Spitzer TR. Bone Marrow Transplant 2001;27:893-8) commencing at a median of 10 (range, 8-13) days after aHSCT and not associated with CDE mobilization or detection of FRE. Nineteen other patients, 8 of whom tested positive for FRE, did not receive corticosteroids for management of regimen-related toxicities (an additional 7 pts received preplanned corticosteroids starting at day +8). No center effect is yet evident. Conclusions: FRE are detected in a high proportion of pts undergoing aHSCT in the treatment of MM. However, FQL prophylaxis is not associated with FRE BSI in this ongoing study. FRE colonization is not predictive of delayed engraftment or prolonged hospitalization, and does not appear predictive of non-infectious diarrhea.

Timing of Thrombosis with Myeloproliferative Neoplasm Diagnosis Among Veterans and Civilians

Rates of Arterial (AT) and Venous Thrombosis (VT) are increased in Veterans with Myeloproliferative Neoplasms (Vet-MPN), including Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF), compared to matched controls (J Clin Oncology 2023 41:16_suppl, 7011). The timing of first AT or VT episode in Vet-MPNs remains undefined when compared to Civilians with MPN (Civ-MPN). These findings could elucidate optimal timing for risk mitigation strategies to prevent thrombotic complications and should help to determine duration of thrombotic risk and need for systemic anticoagulation prophylaxis. The Veterans Affairs Informatics and Computing Infrastructure (VINCI) database was queried from January 1, 2006 to January 26, 2023 to identify Vet-MPNs, AT, and VT through ICD-9 and -10 codes. This process yielded 2,752 Vet-MPN and 583,803 Veterans without MPN from Illinois, the state most representative of the US population. These cohorts were compared to data derived from a retrospective chart review of Civ-MPN cared for between January 1, 2019 to December 31, 2022, at MedStar Georgetown University Hospital and MedStar Washington Hospital Center. Service-Connected Exposures (SCE) to potential carcinogens among Veterans were verified through their duration and location of service. We subdivided time to first AT and VT from MPN diagnosis as follows: more than 3 months prior to MPN diagnosis, within 3 months of diagnosis, 3 months to 1 year post diagnosis, 1 to 5 years, and more than 5 years after MPN diagnosis. Mean data from various cohorts were analyzed utilizing Fisher's exact test. Vet-MPN experienced a statistically higher incidence of AT compared to Civ-MPN (p=.0019) and Civ-MPN experienced a statistically higher incidence of AT compared to Veterans without MPN (p=0.02) which served as a control. In contrast, there was a higher incidence of VT among both Vet- and Civ-MPN cohorts compared to Veterans without MPN (p&amp;lt;.0001) (Table 1). The mean ages at MPN diagnosis and onset of first AT were similar (≥63 years) in both Civ- and Vet-MPN. In contrast, the mean age of MPN diagnosis and age of first VT were considerably earlier for Civ-MPN (51 years) versus both Vet-MPN with VT and Veterans without MPN with VT (≥67 years). There was a higher prevalence of hypertension, hyperlipidemia, diabetes, heart failure, and smoking among Veterans with or without MPN compared to Civ-MPN with either AT or VT (Table 1). A trend toward statistical significance was observed for the presence of hypertension and hyperlipidemia (p=0.049 and p=0.02, respectively) in Vet-MPN compared to Civ-MPN, while Veterans without MPN had a statistically higher prevalence of hyperlipidemia (p=0.02) and heart failure (p=0.001) in AT. Notably, a trend toward statistical significance in VT was observed for the presence of diabetes among all Veterans with or without MPN compared to Civ-MPN (p=0.01 and p=0.007, respectively). There was a biphasic distribution in time to onset of first AT and VT in all Vet- and Civ-MPN cohorts (Figure 1). There was a higher cumulative incidence of first AT and VT in Vet-MPN at more than 3 months prior to MPN diagnosis compared to Civ-MPN with AT and VT (Figure 1). On the other hand, the Civ-MPN cohort had a late surge of first VT more than 5 years after MPN diagnosis compared to the other MPN cohorts. A biphasic distribution in time to onset of first AT and VT was also observed among the Vet-MPN cohort when stratified by SCEs from World War II, the Korean War, the Vietnam War, and the Gulf War. The vast majority of both AT and VT in Vet-MPN from all SCE examined experienced onset of thrombotic events more than 3 months prior to MPN diagnosis. Most VT in Gulf War Vet-MPN occurred within 3 months of MPN diagnosis. In conclusion, the predominant risk for developing thrombotic complications in MPN, particularly in Vet-MPN, occurs in a biphasic pattern, beginning more than 3 months prior to MPN diagnosis and becoming apparent again at more than 5 years after MPN diagnosis. These findings suggest that the MPNs convey an enduring hypercoagulability potential throughout the natural history of the disease. There appears to be an accelerated onset of thrombotic complications earlier in the course of disease in Vet-MPN, perhaps reflecting their SCE with toxic carcinogens. More work is necessary to determine epigenetic influences on MPN natural history.

The Human Leukemia Immunopeptidome Is Driven By Pathogenic Molecular Variant Biotypes

Background Historically, acute myelogenous leukemia (AML) has been characterized as having a low somatic mutational burden and is predicted to have low neoantigen levels compared to solid tumors. However, recent data has shown that AML is an immunogenic malignancy and oncogenic driver mutations promote immune escape through immunoediting. Downregulation of human leukocyte antigen (HLA) class II HLA-DRB1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 gene expression on leukemia cells has previously been associated with immune escape in AML following allogeneic hematopoietic stem cell transplantation (allo-HCT). While allo-HCT and cellular therapies are well-known potentially curative treatment options in AML, the human leukemia immunopeptidome has still not been well characterized. Here, we sought to uncover the human leukemia immunopeptidome by detecting differential major histocompatibility complex (MHC) class I neopeptide expression using molecular biotype subgroups. Methods We conducted retrospective analysis on 31 patients with hematopoietic malignancies including AML, chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), MDS, chronic myelogenous leukemia (CML) and other hematopoietic malignancies (i.e. NK cell leukemia) at MedStar Georgetown University Hospital. Mutations were identified using next generation sequencing and separated into the following annotated molecular biotypes based on the mechanism of pathogenesis: Group 0 (G0) DNA repair, G1 splicing, G2 transcription factor, G3 kinase activation, G4 epigenetic modification, G5 chromatin remodeling, G6 cohesin, G7 tumor suppressor (i.e. p53), G8 telomere maintenance, G9 histone modification, G10 nucleotransport (i.e. NPM1) and G11 cell cycle regulation. FASTA nucleotide sequences were obtained by subjecting mutations to transcript expression and cDNA alignment in the National Center for Biotechnology Information (NCBI) gene database. MHC class I binding neopeptides were identified by mapping patient FASTA nucleotide sequences and HLA class I alleles in the Net MHC pan 4.1 database. Neopeptides were grouped by % Rank and categorized as weak binding (WB) if &amp;gt; 0.5 and strong binding (SB) if ≤0.5. Descriptive and inferential statistics were performed using SAS. Results Thirty-one patients were evaluated including 17 AML (54.8%), 5 MDS (16.1%), 3 CMML (9.7%), 2 MDS/MPN (6.5%), 1 CML (3.2%) and 3 hematopoietic malignancies (9.7%). The median age was 65 years (range 28 -89); 43.8% were female and 43.3% were African American (AA). 144mutations were identified; thus far, 82 mutations have been subjected to FASTA NP_ protein extraction. The G3 biotype had the highest frequency of neopeptide bindings (n=59) followed by G2 (n=50) and G4 biotypes (n=42) ( Fig.1). Among patients with MDS, smokers were more likely to exhibit neopeptide binding compared to non-smokers (p=0.032). Patients with neopeptide binding had a longer median overall survival (mOS) compared to patients without neopeptide binding (mOS = 566 vs 114 days, p=0.0174) (Fig 2). Data exploration allowed isolation of a 54-year-old Asian male with Li-Fraumeni syndrome and p53 mutated AML who demonstrated high affinity neopeptide binding to HLA-B*39:01 with %Rank 0.08. Additionally, a 34 -year-old AA female with FLT3 mutated AML showed very high affinity neopeptide binding to HLA-A*29:02 with %Rank 0.007 as well as evidence of somatic HLA-A*03:01 deletion. Conclusions Pathogenic molecular variant biotypes constitute a novel immune signature, the human leukemia immunopeptidome. Smoking increased the likelihood of MHC class I neopeptide binding among patients with MDS. The presence of neopeptide binding predicted improved mOS in patients with myeloid malignancies. Further investigation of the human leukemia immunopeptidome may provide additional prognostic significance above that of standard molecular and cytogenetic risk stratification.

The Secret Life of Junior Pathologists: Challenges and Future Directions.

Transition from pathology trainee to independent pathologist is stressful. No study has examined junior pathologists' challenges and concerns during this transition. To identify challenges and concerns of junior pathologists. Junior pathologists were defined as those who had been practicing independently for up to 5 years after completion of residency/fellowship. An institutional review board-approved electronic survey was created and distributed to recent pathology graduates of MD Anderson Cancer Center (Houston, Texas) and MedStar Georgetown University Hospital (Washington, District of Columbia). The survey was open from October 13, 2022, to January 31, 2023. The survey included 16 multiple-choice and free-text questions. Responses were received from 39 junior pathologists. Participants working in academic settings indicated independence, work-life balance, and professional identity formation as challenges; those in nonacademic settings indicated pathology reporting, efficiency, and administration as challenges. Areas where participants wished they received more guidance differed by practice setting: participants in academic settings more often chose effective time management and importance of turnaround time (35% [7 of 20] versus 0% [0 of 14], P = .03) and tumor board conference presentation skills (25% [5 of 20] versus 0% [0 of 14], P = .06), while those in nonacademic settings more often chose Current Procedural Terminology (CPT) coding, billing, and cost-effective patient care (79% [11 of 14] versus (35% [7 of 20]; P = .02). More female than male participants indicated that they wished they had received more guidance in leadership and soft skills (79% [11 of 14] versus 28% [5 of 18]; P = .01). This study identified challenges experienced by junior pathologists. Collective efforts from training programs, experienced pathologists, and professional organizations can explore ways to improve the transition experience.

The predictive value of liver tests for the presence of liver metastases.

To analyze the predictive value of biochemical liver tests in patients with malignant melanoma, breast, colorectal or lung cancers at the time of diagnosis of liver metastases. A retrospective review of patients with the above-mentioned solid tumors at MedStar Georgetown University Hospital from 2016-2020. The highest optimal cutoff according to sensitivity and specificity for the presence of liver metastases was for AST ≥1.5×ULN for melanoma, lung, and breast cancers and ≥2×ULN for colorectal cancer, ALT ≥1.25×ULN for melanoma, breast and colorectal cancers and ≥1.5×ULN for lung cancer, and ALP ≥1.5×ULN for melanoma, breast and colorectal cancers. Using thresholds of liver enzymes above the ULN may improve the diagnostic accuracy for the presence of liver metastases.

High levels of expression of Trop-2 in thymic epithelial tumors

BackgroundTrophoblastic antigen 2 (Trop2) is a cell surface glycoprotein expressed in multiple types of cancers, including breast cancer, non-small cell lung cancer, and gastrointestinal cancers. Trop2 expression and the use of Trop2-directed therapy such as antibody-drug conjugate (ADC) have not yet been investigated in thymic epithelial tumors (TETs). MethodsPatients with TETs treated at MedStar Georgetown University Hospital were retrospectively identified. Of the patients for whom tumor samples and normal thymus tissue were available, immunohistochemistry (IHC) membranous staining for Trop2 and PD-L1 were performed. Positivity for Trop2 required at least 10% of the tumor cells to be stained, with an intensity scored of 1+ (weak), 2+ (moderate), and 3+ (strong). Cases with CPS ≥ 5% were considered positive for PD-L1. Results30 TET samples from 29 patients (17 patients with thymoma and 12 patients with thymic carcinoma) were identified. One patient with thymic carcinoma had two samples from different time points. From the same set of patients, 13 samples of normal thymus tissue were available. In normal thymus tissue, eight samples (62%) showed no positivity of Trop2, while five samples (38%) showed 1 + IHC staining. In the thymoma samples, four (24%) showed 0 or 1 + IHC staining, while 13 (76%) showed 2 + or 3 + staining. Of the 13 thymic carcinoma samples, three samples (23%) showed 1 + IHC staining while seven (54%) showed 2 + staining and three (23%) showed 3 + staining. There was no statistically significant correlation found between PD-L1 expression and Trop-2 expression in thymoma or thymic carcinoma. ConclusionsTrop2 is readily expressed in TETS with a higher degree of expression in thymic carcinoma. The expression of Trop-2 was lower in normal thymic tissue compared with TETs. The increased expression of Trop-2 in TETs suggests that Trop2 is an attractive therapeutic target for Trop-2 directed therapy.

Discordant Race and Ethnicity Documentation in the Georgetown Multiple Sclerosis and Neuroimmunology Center (P4-9.005)

<h3>Objective:</h3> We aimed to evaluate the reliability of R/E documentation in the EHR of MedStar Georgetown University Hospital. <h3>Background:</h3> The incidence and prevalence of multiple sclerosis (MS) appears to vary by race and ethnicity (R/E), and prognosis has been reported to be worse in Black and Hispanic/Latinx MS patients compared to White MS patients. Frequently, studies rely on electronic health records (EHR), but discrepancies in R/E documentation may be a potential source of errors in health disparities assessment. <h3>Design/Methods:</h3> Self-reported data from the MS-ADVANCE study at Georgetown University was compared to demographics extracted from the MedStar Georgetown University Hospital EHR. Concordance was defined as the percent agreement between self-reported R/E and R/E demographic information found in the EHR. <h3>Results:</h3> R/E data from 197 participants in the MS-ADVANCE study were analyzed. Most participants self-reported as Non-Hispanic White (n=142), which generally matched EHR documentation (concordance 92.6%). Similarly, 86% of Non-Hispanic Black (n=43) and 100% of Asian individuals (n=2) were accurately identified in the EHR. However, only 2 of 8 self-identified Hispanic/Latinx patients were identified as such in the EHR (concordance 25%). <h3>Conclusions:</h3> This is the first study evaluating concordance of self-reported R/E information compared to EHR documentation in patients with MS. While concordance was generally good in most groups, R/E information in the EHR was often incorrect for Hispanic/Latinx patients. Because most epidemiological analyses extract data from electronic records, this considerable observed discrepancy in R/E documentation may impact our understanding of prevalence, incidence, and prognosis in Hispanic/Latinx individuals with MS. Since obtaining reliable demographic information is crucial to determine quality of care and health outcomes, improvement in data collection is necessary when exploring healthcare disparities in Hispanic/Latinx individuals living with MS. <b>Disclosure:</b> Dr. Manrique has nothing to disclose. Miss Peres Da Silva has nothing to disclose. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Osborne has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myer Squibb. Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon. Dr. Osborne has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Peter Angelos Law Firm. Dr. Osborne has received publishing royalties from a publication relating to health care. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Tornatore has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sanofi Genzyme. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Biogen. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Celgene. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Shin has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mallinckrodt. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shin has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Sanofi Genzyme. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Celgene. Dr. Shin has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Shin has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shin has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Mallinckrodt.

Differences in Stroke Outcomes and Experiences between White and Minority Patients and Providers (P7-5.029)

<h3>Objective:</h3> Our primary aim was comparing provider and patient surveys regarding stroke care. Our secondary aim was comparing patient responses by race/ethnicity. <h3>Background:</h3> Race disparities exist in treatment, lived experiences, and outcomes of stroke survivors. Stroke providers and patients differ in values and concerns during recovery. Aligning patient and provider concerns may foster better therapeutic relationships. <h3>Design/Methods:</h3> A 28-question patient survey and 25-question provider survey were created to gain insight into experiences with stroke care at MedStar Georgetown University Hospital (MGUH). Of 200 patients admitted to MGUH stroke service from September 2021 to March 2021, 39 completed the patient survey. All 40 providers (physicians and nurses from emergency medicine, neurology and critical care) completed their provider surveys. Statistical analyses included Fisher’s exact test. <h3>Results:</h3> White patients were older and had higher education than racial/ethnic minority patients but similar health-insurance status. Providers were mostly white and female. White patients agreed their health care team effectively communicated to understand their condition significantly more than minority patients (p=0.033). White patients perceived significantly more support from their health care team than minority patients (p=0.05). Providers viewed managing chronic stroke effects (77%) and difficulty following lifestyle changes (46%) as the biggest challenges in patients’ long-term care. Racial/ethnic minority patients expressed concern with understanding stroke risk factors (35%) and responsibilities at work and home (35%). White patients reported concerns managing effects of their strokes (33%), risks of recurrence (25%), and worries about home responsibilities (25%). <h3>Conclusions:</h3> This pilot survey-based study demonstrated differences in care experiences and post-stroke concerns between white and racial/ethnic minority patients. Most providers viewed managing chronic effects as the biggest challenge for patients, which was more consistent with white patients. Racial differences between providers and minority patients may contribute to differences in long-term stroke concerns. Limited by sample size, a larger multi-center study is planned to increase generalizability. <b>Disclosure:</b> Mr. Shankar has received personal compensation for serving as an employee of Medstar Georgetown. Ms. Sumling has received personal compensation for serving as an employee of Georgetown Medstar. Dr. Denny has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbott Laboratory. The institution of Dr. Denny has received research support from NIDDILIR. Dr. Denny has received publishing royalties from a publication relating to health care.

Abstract P4-03-42: Evaluating the Impact of Race and Body Mass Index on the Diagnosis and Prognosis of Early Onset Breast Cancer

Abstract Background: Early-onset breast cancer is typically defined as a diagnosis of disease before age 40-45. Prior studies have shown interesting associations between race and obesity on the incidence and prognosis of breast cancer. Data from the SEER program at the National Cancer Institute has shown increased mortality amongst African American women (0.2%) compared to Non-Hispanic White (NHW) women (0.1%) who were diagnosed with breast cancer at age 45 years or younger. This is despite a similar risk of diagnosis between racial groups of this age range (1.27%, 1.27%). Other large studies have shown that African American patients tended to present with more advanced disease had worse clinical outcomes. Our study sought to determine the impact of race and obesity on the diagnosis and prognosis of early onset breast cancer amongst the patient population at Georgetown University Hospital (GUH). Methods: We compiled a database of all new patients, 652 in total, seen at Lombardi Cancer Center at Medstar GUH from 10/2020- 6/2022. We reviewed patient charts in the EMR and documented age at diagnosis, race, ethnicity, stage at diagnosis, and BMI. The BMI was categorized by underweight (BMI &amp;lt; 18.5), healthy weight (BMI 18.5-24.9), overweight (BMI 25-25.9), obese (BMI 30-34.9), and morbidly obese (BMI ≥ 35). Stage at diagnosis was determined by comparing the pathology report with the NCCN guidelines version 4.2022. We identified 136 patients who were diagnosed at GUH at age 45 years old or younger and compared our findings to SEER data from 2017-2019. Results: Out of 136 patients who met our age criteria, 131 had racial data available: 29 AA (0.22), 68 NHW (0.52), 4 Hispanic (0.03), 30 Other (0.23). Out of the 34 patients with advanced disease (stage 3 and 4) 16 were NHW (0.47), 4 were AA (0.12), 2 were Hispanic (0.06) and 12 were Other (0.35). 131 patients had BMI data available: 5 underweight (0.04), 56 healthy weight (0.43), 41 overweight (0.31), 21 obese (0.16), and 8 morbidly obese (0.06). 18 patients with advanced disease were overweight or obese, out of which 11 were NHW (0.61), 3 were AA (0.16), 3 were Other (0.16), and 1 was Hispanic (0.06). Conclusion: In contrast with the SEER data, our study found that the patient population at GUH had a much higher proportion of Non-Hispanic White (NHW) patients who were diagnosed with advanced disease compared to African American (AA) patients. It also found a higher proportion of NHW patients amongst those who were diagnosed with advanced stage disease and were overweight or obese compared to AA patients. This data suggests that in our patient population, Non-Hispanic White women who were overweight or obese at the time of diagnosis of early onset breast cancer (≤ 45 years old) were more likely to be diagnosed with advanced stage disease than women in other demographic groups. It is possible that this discrepancy is related to racial variations in receptor status. Further investigation is required to correlate these associations in clinical practice with other known demographic variables and disease-specific risk factors in order to better understand how they impact the diagnosis and prognosis of early-onset breast cancer. Citation Format: Austin Kordic, Amanda Reyes, Nadia Ashai. Evaluating the Impact of Race and Body Mass Index on the Diagnosis and Prognosis of Early Onset Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-42.