Chintakuntlawar, Ashish V.

817 Background: Cancer screening ingastrointestinal (GI) malignancies has translated into an improvement in overall survival due to detection at an earlier stage. The majority of survivors (up to 67%) are over the age of 65. The impact of metabolic profiles on cerebrovascular events amongst this population of cancer survivors is unclear. Methods: Data from the NIS database from 2016 to 2020 were reviewed for patients with seven GI malignancies. Analysis was performed based on the presence or absence of prediabetes using ICD-10 codes. Baseline characteristics, comorbidities, and cerebrovascular outcomes were studied in these 2 cohorts. Results: 1,532,250 hospitalizations of patients with seven GI malignancies, namely colorectal cancer (CRC), pancreatic cancer, hepatocellular carcinoma (HCC), gastric cancer, small intestinal cancer, cholangiocarcinoma, and esophageal cancer, were evaluated and divided into two subgroups: prediabetics (15,610) and non-prediabetics (1,516,640). Prediabetics with GI malignancies as compared to non-prediabetics with GI malignancies were noted to be older (67.7 years vs. 65.64 years), with higher total hospitalization charges (USD 87,267 vs. USD 80,173), greater rates of elective admissions (34.92% vs. 25.89%) but a lower length of stay (6.018 days vs. 6.53 days). Prediabetic patients with GI malignancies were noted to have a higher prevalence of obesity (18.64% vs. 7.69%), dyslipidemia (52.99% vs. 26.16%), and hypertension (49.59% vs. 39.37%). Prediabetics with CRC, as compared to non-prediabetics, had higher adjusted odds ratios (aORs) of occlusion/stenosis of precerebral or cerebral arteries not leading to cerebral infarction, and cerebral infarction, with aORs of 2.03 (95% CI 1.24-3.30, p 0.004), and 1.63 (95% CI 1.01-2.63, p 0.045) respectively. Additionally, prediabetics with pancreatic cancer had a higher aOR of cerebral infarction as compared to non-prediabetics, with aOR of 2.42 (95% CI 1.70-3.44, p<0.001). Conclusions: Prediabetic patients with CRC had higher aORs of cerebral infarction and occlusion/stenosis of precerebral arteries not leading up to cerebral infarction, and prediabetics with pancreatic cancer had twice the risk of cerebral infarction as compared to non-prediabetics. This study highlights the impact of prediabetes, a modifiable risk factor, on cerebrovascular outcomes in patients with GI malignancies.

Abstract Objective Margin distance is a significant prognosticator in oral cavity cancer but its role in HPV‐related oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] remains unclear. Here, we investigate the impact of margin distance on locoregional recurrence in HPV(+)OPSCC. Study Design This is a retrospective cohort study of surgically treated HPV(+)OPSCC patients. Patients received either standard of care (at least 60 Gy with or without cisplatin) or de‐escalated adjuvant therapy (30‐36 Gy with concurrent docetaxel). Margin distance was measured in mm from the primary specimen or in combination with separately submitted margins. Kaplan‐Meier survival analysis with univariate and multivariable Cox regressions were conducted to determine the impact of margin distance on risk of local and locoregional recurrence. Setting Setting for this is 3 tertiary centers between January 2010 and February 2024. Results Among 1102 included patients, 33 (3.0%) had positive final margins. 374 patients had adequate margin distance data available. Margin distance was >3 mm in 73.4%, 1 to 3 mm in 24.5%, and <1 mm in 2.2% of patients. Positive final margins, pT4 disease, pN2 disease, and surgery alone as a treatment modality ( P < .02 for all) was associated with higher risk of 5‐year locoregional recurrence. Margin distance did not significantly impact risk of local or locoregional recurrence even after adjusting for de‐escalated adjuvant therapy ( P > .05). Conclusion Positive final margins after TORS without adjuvant radiotherapy for HPV(+)OPSCC carries a high risk of local recurrence. Margin distance does not appear to significantly impact risk of local or locoregional recurrence, even after de‐escalated adjuvant radiotherapy.

Abstract Background The overall survival of patients with advanced thyroid cancers that have progressed following targeted therapies is limited, indicating a strong need for salvage treatments. Methods We retrospectively analyzed patients with refractory advanced thyroid cancer treated with pemetrexed‐carboplatin (PC) at Mayo Clinic since 2019. Results Eleven patients, three with anaplastic thyroid cancer (ATC), seven with differentiated or poorly differentiated thyroid cancer (DTC), and one with oncocytic carcinoma of the thyroid, were treated with novel salvage PC. Patients with DTC ( n = 7) had durable responses with a median progression‐free survival of 29 months. One responder included a patient with ATC whose disease progressed following pembrolizumab/axitinib, lenvatinib, and dabrafenib/trametinib. On this fourth line treatment, the patient remains on therapy to date, over 12 months after initial response. Conclusions This case series reinforces prior published phase I clinical trial data and shows that pemetrexed can have potent efficacy in the treatment of the most advanced thyroid cancers.

6041 Background: Human papillomavirus (HPV) E6/E7 oncoproteins mediate immune evasion by down-regulating Type 1 interferons, TLR9, MHC Class I/II as well as other mechanisms, resulting in persistent infection and initiation of ̃5% of all cancers globally. Similarly, established cancers evade immune surveillance utilizing parallel mechanisms including the expression of checkpoint proteins. PDS0101 is a molecularly targeted immunotherapeutic based on an enantiospecific cationic lipid nanoparticle platform containing HPV16 neoantigens that exhibits anti-tumor activity with checkpoint inhibitors (CPIs) by upregulating Type I interferons and promoting antigen processing and cross presentation. This allows generation of high levels of polyfunctional HPV16-specific CD8 and CD4 T cells in vivo as well as immune memory. VERSATILE-002 (NCT04260126) is a phase 2 study of the combination of PDS0101 and pembrolizumab in treatment of CPI naïve and refractory patients with recurrent or metastatic HPV16-related HNSCC. Herein, we report preliminary safety and efficacy data for CPI naïve patients at a prespecified interim analysis. Methods: Subjects are treated with pembrolizumab 200mg IV every three weeks plus SC PDS0101 following pembrolizumab on days one of Cycles1-4 and Cycle12; pembrolizumab continues up until 35 cycles, disease progression or intolerance to therapy. Results: Eighteen CPI naïve subjects with confirmed HPV16 tumors and a CPS score > = 1, median age 62 yrs (range 46-71), all male, 17 (94%) of whom were White and 16 (88.9%) not Hispanic or Latino, received at least one cycle of combination therapy. At the time of analysis, 17 (94%) subjects had received > = 4 doses of PDS0101 (median 4, range 1-5) and pembrolizumab (median 7, range 1-14). There were no Grade 3 or greater treatment-related toxicities and no drug discontinuation related to toxicity or immune-related AEs. Clinical activity (CR+PR+SD) was seen in 13 (72.2%) of 18 subjects, with best overall reponse per RECIST1.1 documenting: OR in 7 (38.9%; 2 CR, 5PR); stable disease (SD) in 6 (33.3%) and progressive disease in 3 (16.7%); 2 subjects had missing data. Tumor reduction was seen in 4 of 6 (67%) subjects with SD. Nine-month PFS and OS rates (95% CI) were 52% (22.5, 74.7) and 81% (37.8, 95.5) respectively; median PFS and OS have not been reached. Conclusions: The combination of PDS0101 and pembrolizumab demonstrates an excellent safety profile with preliminary evidence of clinical activity in the majority of CPI naïve patients with HPV-related HNSCC. Clinical trial information: NCT04260126.

e16342 Background: Pancreatic cancer poses a major challenge due to its high mortality rates and is known as one of the deadliest cancers. The increasing mortality in addition to the aggressive nature of the tumor may be due to major cardiovascular and cerebrovascular events (MACCE). The key to mitigating the risk of pancreatic cancer as well as MACCE, is primary prevention of common risk factors including tobacco use, obesity, dietary factors, alcohol use, and physical activity. Understanding that many of these factors are directly and indirectly influenced by income status, this study aims to explore the relationship between household income on MACCE in pancreatic cancer patients. Methods: Using ICD-10 codes, patients with pancreatic cancer were identified from National Inpatient Sample 2019 database. We included all-cause in-hospital mortality (ACIHM), acute myocardial infarction (AMI), arrythmia, cerebrovascular accident (CVA), and sudden cardiac death (SCD) as MACCE for the outcomes. Baseline characteristics including demographics, comorbidities; and MACCE outcomes were studied using chi-square for categorical or ANOVA for continuous data (statistical significance determined as p-value < 0.05) and results were stratified based on median household income quartiles. Results: Of the 114,235 patients identified with pancreatic cancer who were admitted to the hospital, 25% (28,570) belonged to the first income quartile ($1-47,999), 23.8% (27,235) belonged to the second income quartile ($48,000-60,999), 26.38% (30,135) belonged to the third income quartile ($61,000-81,999), and 24.76% (28,295) belonged to the fourth income quartile ($82,000+). When compared to the patients in the fourth quartile, the adjusted odds ratio (aOR) was found to be higher for all MACCE outcomes for patients in first quartile. The aOR for ACIHM in the first quartile was found to be 1.24 (95% CI 1.06-1.46, p = 0.006) as compared to patients in the fourth quartile. Additionally, the aOR for AMI, was found to be statistically significant in patients belonging to the first quartile at 1.30 (95% CI 1.01-1.70, p = 0.047). Similarly, the aORs for both arrhythmia and SCD were also higher in the population from the first quartile at 3.67 (95% CI 1.10-12.28, p = 0.03) and 1.45 (95% CI 1.01-2.09, p = 0.049). https://docs.google.com/document/d/1v84LyPoGL406_7SDxO1N-wKxwujSgFpf/edit?usp = sharing&ouid = 110330426831507953030&rtpof = true&sd = true. Conclusions: As compared to patients in fourth income quartile, the aOR was found to be higher for all MACCE outcomes for patients in the first income quartile, indicating a vast variation based on income strata. This hints towards a complex interplay of healthcare disparities including but not limited to difficult access to quality healthcare including subspecialities. Further research may be pertinent to explore the causes of this clear disparity to ensure equitable healthcare for all patient population.

e13102 Background: Hereditary mutations of the homologous recombination (HR), the key DNA double-strand break repair pathway, are one of the well-known causes of breast and ovarian cancers. Few reports exist on these mutations and the utilization of PARP inhibitors in the Middle Eastern region. Methods: This is a single-center retrospective study of breast and ovarian cancer patients who underwent genetic testing for g BRCA and HR defects (HRD) respectively between August 2021 and May 2023. Data was summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using RECIST criteria. Results: The prevalence of pathogenic mutations was 22.8%, with 26.3% of breast cancers harboring g BRCA mutations and 24% of ovarian cancers showing HRD positivity. Middle Eastern patients comprised 40% of the g BRCA-positive breast cancer group, while Asians accounted for 66% of the HRD-positive ovarian cancer patients. In mutated breast cancer, 53.3% had a positive family history of cancer. 33.3% of mutated breast cancer group and 66.6% of the ovarian cancer group received PARPis. Objective response to PARPi was 40% and 100% in breast and ovarian cancers, respectively. Conclusions: Our study revealed a high prevalence of g BRCA mutations (26.3%) in breast cancer and HRD positivity (24%) in ovarian cancer). Ethnic profiles differed between these cancers, with Middle Eastern and Southeast Asian patients dominating the breast and ovarian groups, respectively. Interestingly, the TNBC rate in breast cancer remained around 20% regardless of g BRCA status. While disparities between HRD groups were more pronounced in ovarian cancer, as expected, unexpected trends emerged in breast cancer. Further research with larger cohorts is needed to confirm these findings. [Table: see text]

e19076 Background: Non-Hodgkin Lymphoma (NHL) is the seventh most prevalent cancer and has sixth highest malignancy mortality in United States. Owing to the advances in treatment of NHL including targeted therapies, the survival of NHL patients has increased over the past decades. However, inequalities may exist in the access to advanced care, clinical trials, and subspecialist appointments in certain patient populations. We aim to study the racial disparities in major cardiovascular and cerebrovascular events (MACCE) in NHL patients. Methods: Using ICD-10 codes, patients with NHL were identified from National Inpatient Sample 2019 database. We included all-cause in-hospital mortality (ACIHM), acute myocardial infarction (AMI), atrial fibrillation (AF), cerebrovascular accident (CVA), and sudden cardiac death (SCD) as MACCE for the outcomes. Baseline characteristics including demographics, comorbidities; and MACCE outcomes were studied using chi-square for categorical or ANOVA for continuous data (statistical significance determined as p-value <0.05) and results were stratified based on patient’s races. Results: Out of the total sample size of 205220 patients admitted with a diagnosis of NHL, 74.94% (153785) were White, 8.95% (18370) were Black, 9.46% (19415) were Hispanic, 3.48% (7140) were Asian/Pacific Islander, 0.42% (875) were Native American, while 2.75% (5635) belonged to other races. When compared to White patients, ACIHM was significantly higher in Black patients with adjusted odds ratio (aOR) of 1.294 (95% CI 1.099-1.523, p=0.002) and Asian/Pacific Islander patients (aOR 1.279, 95% CI 1.005-1.628, p=0.045). Risk of AMI was lower in Black patients (aOR 0.751, 95% CI 0.587-0.96, p=0.023) as compared to White patients. AF risk was significantly lower in Black, Hispanic, and Other race patients compared to White patients. The odds of developing CVA are higher in Asian/Pacific Islander patients (aOR 1.285, 95% CI 1.002-1.649, p=0.048) and of having SCD are higher in Black patients (aOR 2.052, 95% CI 1.5-2.806, p<0.001) when compared to White patients. Conclusions: In patients with NHL, Black patients had higher ACIHM and SCD while Asian/Pacific Islander patients had higher ACIHM and CVA when compared to White patients. Although the reason of disparity is likely multifactorial, the findings of this study highlight the need for development of healthcare strategies stratified by race which may aid to mitigate the increased risk of MACCE in certain races. Further research involving possible genetic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL becomes imperative.

e13740 Background: Hepatocellular carcinoma (HCC) ranks as the 6th most common cancer and as the 3rd leading cause of cancer-related mortality. With immunotherapy improving survival rates, the relevance of major adverse cardiovascular and cerebrovascular events (MACCE) is increasing. We aim to explore the racial disparities in MACCE among patients with HCC, thus leading to a better understanding of the interplay of these conditions with social determinants of health. Methods: Using ICD-10 codes, patients with HCC were identified from National Inpatient Sample 2019 database. We included all-cause in-hospital mortality (ACIHM), acute myocardial infarction (AMI), atrial fibrillation (AF), cerebrovascular accident (CVA), and sudden cardiac death (SCD) as MACCE for the outcomes. Baseline characteristics including demographics, comorbidities; and MACCE outcomes were compared using chi-square for categorical or ANOVA for continuous data (statistical significance determined as p-value <0.05) and results were stratified based on patient’s races. Results: Out of the total sample size of 89,615 patients admitted with a diagnosis of HCC, 60.14% (53,895) were White, 13.67% (12250) were Black, 15.64% (14015) were Hispanic, 6.48% (5805) were Asian/Pacific Islander, 0.8% (720) were Native American, while 3.27% (2930) belonged to other ethnicities. There were significant racial differences in comorbidities with hypertension being most prevalent in Black patients (42.53%), diabetes mellitus in Native American patients (45.14%) and dyslipidemia in Asian/Pacific Islander patients (32.39%). When compared to White patients, ACIHM was the significantly higher in Black patients with adjusted odds ratio (aOR) of 1.305 (95% CI 1.123-1.517, p=0.001), Asian/Pacific Islander patients with aOR 1.271 (95% CI 1.024-1.578, p=0.03) and Other races patients with aOR 1.578 (95% CI 1.2-2.076, p=0.001). AF was significantly lower in all races when compared to White patients. CVA was significantly higher in Black patients with aOR 1.654 (95% CI 1.329-2.059, p<0.001) compared to White patients. SCD was significantly higher in Asian/Pacific Islander patients with aOR 2.22 (95% CI 1.364-3.612, p=0.001) when compared to White patients. https://docs.google.com/document/d/1wM_b0jmNjChKEfpyj5SL6HmSKEhDo0N3X5H76jC-w0I/edit?usp=sharing Conclusions: In patients with HCC, Asian/Pacific Islander patients had higher ACIHM and SCD while Black patients had higher ACIHM and CVA as compared to White patients. This study highlights the importance for development of healthcare strategies stratified by race which may aid to mitigate the higher risk of MACCE in certain races. Further research involving possible genetic influences and social determinants of health contributing to poorer outcomes in people of color becomes imperative.

1611 Background: Due to its high prevalence, colorectal cancer (CRC) forms a considerable burden on the healthcare system. Advancements in treatment modalities like immunotherapy have led to significant improvement in the 5-year survival. This, along with the cardiotoxic therapy regimens results in a remarkable incidence of major cardiovascular and cerebrovascular events (MACCE). Thus, it becomes imperative to address the intricacies of factors including racial disparities in MACCE, as these aid with facilitating equitable management of all CRC patients. Methods: Using ICD-10 codes, patients with CRC were identified from National Inpatient Sample 2019 database. We included all-cause in-hospital mortality (ACIHM), acute myocardial infarction (AMI), atrial fibrillation (AF), cerebrovascular accident (CVA), and sudden cardiac death (SCD) as MACCE for the outcomes. Baseline characteristics including demographics, comorbidities; and MACCE outcomes were studied using chi-square for categorical or ANOVA for continuous data (statistical significance determined as p-value < 0.05) and results were stratified based on patient’s races. Results: A total sample patient population of 171,695 patients with a diagnosis of CRC were identified of which 70.71% (121,410) were White, 13.85% (23,790) were Black, 9.15% (15,720) were Hispanic, 3.23% (5,555) were Asian/Pacific Islander, 0.5% (840) were Native American, and 2.55% (4380) belonged to Other races. Substantial differences in the prevalence of comorbidities were noted with hypertension (46.32%) and renal failure (24.74%) being more common in Black patients, diabetes mellitus (37.5%) in Native American patients, and dyslipidemia (37.89%) in White patients. Upon comparison with White patients, the ACIHM was higher in Black patients with adjusted odds ratio (aOR) of 1.23 (95% CI 1.057-1.432, p = 0.007) and Asian/Pacific Islander patients with aOR of 1.359 (1.014-1.823, p = 0.04). While AMI was found to be lower in all races, as compared to White patients, AF was remarkably higher in all races. CVA was higher in Black patients as compared to White patients with aOR of 1.626 (95% CI 1.401-1.886, p < 0.001). SCD was substantially higher in Black patients with aOR 2.059 (95% CI 1.478-2.869, p < 0.001), and in Hispanic patients with aOR 1.743 (95% CI 1.1-2.761, p = 0.018), when compared to White patients. Conclusions: The study noted higher prevalence of MACCE across the board with poorer outcomes in non-White populations, which highlights the urgent need for resource allocation to improve outcomes. This has to be done in pre and post cancer treatment patients, especially in high risk populations. Additionally, the role of cardio-oncology service at every stage of management of CRC appears to be crucial.

Background and Objectives: Non-Hodgkin lymphoma (NHL) has the sixth-highest malignancy-related mortality in the United States (US). However, inequalities exist in access to advanced care in specific patient populations. We aim to study the racial disparities in major adverse cardiovascular and cerebrovascular events (MACCEs) in NHL patients. Materials and Methods: Using ICD-10 codes, patients with NHL were identified from the US National Inpatient Sample 2016–2019 database. Baseline characteristics, comorbidities, and MACCE outcomes were studied, and results were stratified based on the patient’s race. Results: Of the 777,740 patients with a diagnosis of NHL, 74.22% (577,215) were White, 9.15% (71,180) were Black, 9.39% (73,000) were Hispanic, 3.33% (25,935) were Asian/Pacific Islander, 0.36% (2855) were Native American, and 3.54% (27,555) belonged to other races. When compared to White patients, all-cause mortality (ACM) was significantly higher in Black patients (aOR 1.27, 95% CI 1.17–1.38, p < 0.001) and in Asian/Pacific Islander patients (aOR 1.27, 95% CI 1.12–1.45, p < 0.001). Sudden cardiac death was found to have a higher aOR in all racial sub-groups as compared to White patients; however, it was statistically significant in Black patients only (aOR 1.81, 95% CI 1.52–2.16, p < 0.001). Atrial fibrillation (AF) risk was significantly lower in patients who were Black, Hispanic, and of other races compared to White patients. Acute myocardial infarction (AMI) was noted to have a statistically significantly lower aOR in Black patients (0.70, 95% CI 0.60–0.81, p < 0.001), Hispanic patients (0.69, 95% CI 0.59–0.80, p < 0.001), and patients of other races (0.57, 95% CI 0.43–0.75, p < 0.001) as compared to White patients. Conclusions: Racial disparities are found in MACCEs among NHL patients, which is likely multifactorial, highlighting the need for healthcare strategies stratified by race to mitigate the increased risk of MACCEs. Further research involving possible epigenomic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL is imperative.