Citations

Purpose: Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroids, and the rate of steroid-induced intraocular pressure (IOP) response. Materials and Methods: Lymphocyte-derived DNA sequencing of CYP3A4 from 10073 patients was completed using the PGRN-Seq assay. Subjects with CYP3A4 intermediate metabolizer or slower phenotypes were identified and compared with controls matched by age, race, and sex. All subjects had at least 3 eye exams with at least an exam while on topical/systemic/local steroid in any body location except the eye. Patients with pre-existing glaucoma or glaucoma suspects were excluded. Results: Of the 10,073 patients, there were 63 patients who had CYP3A4 poor or intermediate metabolizer phenotype. Of the 63 patients, 22 had documented steroid use. Fifty-nine percent (13/22) of patients with CYP3A4 poor/intermediate metabolizer had a steroid-induced IOP response of 3 mm Hg or more, significantly higher compared with 23% (5/22) of matched controls (P=0.031). Although more poor/intermediate metabolizers were steroid responders, the average IOP elevation in steroid responders in both groups was similar (5.0±2.5 mm Hg in CYP3A4 poor/intermediate metabolizers compared with 4.1±2.1 mm Hg in controls, P=0.327). Family history of glaucoma was similar in both groups (7/22 vs. 8/22, P=1.0). Conclusion: Reduced CYP3A4 phenotypes may help identify patients at a higher risk of steroid-induced IOP elevation.

84 Background: Local therapies potentially offer a curative approach for patients with oligometastatic colorectal cancer (CRC). The effectiveness of systemic chemotherapy following definitive local treatment in this setting is not well-defined. Tumor-informed circulating tumor DNA (ctDNA) might guide management strategies after curative-intent local treatment. Methods: This is a single institution retrospective study of patients with CRC who underwent curative-intent local therapy to an isolated site of metastatic disease and had post-intervention tumor-informed ctDNA (Signatera) testing. The study was approved by the institutional review board. Clinical characteristics, including ctDNA results, were collected and evaluated. Kaplan-Meier method and log-rank test were used to calculate and compare disease-free survival (DFS). Factors associated with DFS were analyzed using multivariate Cox proportional hazards model. Results: 45 patients were included with median age of 59 years, 62% being male, 91% white, and 53% with stage IV disease at diagnosis. 37% of the patients had RAS mutations, no patient had BRAF mutation, and 2.2% patient had mismatch repair deficient disease. Isolated liver metastases were present in 80% of patients, lung metastases in 11% and other sites in 9%. 44 patients received chemotherapy prior to definitive treatment, with a median treatment duration of 16 weeks. ctDNA tests were done prior to local therapy in 23 patients, with 14 cases (61%) testing positive. Definitive treatment included resection (58%), ablation (13%), radiotherapy (4%), and multimodality (25%). Post-definitive treatment chemotherapy was administered to 24 (53%) patients. ctDNA positivity following definitive therapy was observed in 10 patients (22%), which was associated with a poorer prognosis, with a median DFS of 5.3 months compared to 21.3 months for the ctDNA-negative group (p<0.001). These findings were confirmed on multivariate analysis. In patients who had negative ctDNA after definitive local treatment, median DFS was 14.9 months for those who received post-intervention chemotherapy versus 21.3 months for those without post-intervention chemotherapy (p=0.835). Conclusions: Patients with negative ctDNA results following definitive local therapy for isolated metastatic CRC have better prognosis. Post-intervention chemotherapy in this group of patients was not associated with improved DFS. ctDNA guided omission of post-intervention chemotherapy following curative-intent local treatment of oligometastatic CRC warrants further study. [Table: see text]

81 Background: Recent data suggest an association between cardiovascular disease burden and biliary cancer patients. However, the outcomes of hospitalized patients for biliary-pancreatic malignancy with concurrent acute decompensated heart failure (ADHF) are not well understood. Therefore, our objective is to assess the impact of ADHF on patients hospitalized for biliary-pancreatic malignancy. Methods: We used the 2020 U.S. National Inpatient Sample (NIS) to study patients hospitalized for biliary tract and pancreatic malignancy with concurrent acute decompensated heart failure (ADHF) identified by ICD-10 CM codes. Adjusted odds ratios (aORs) for predefined outcomes were determined via multivariable logistic and linear regression analyses. The primary outcome examined was inpatient mortality, while secondary outcomes included complications related to various body systems. Results: We identified 43,009 patients with a primary discharge diagnosis of biliary tract and pancreatic cancer. The mean age was 68.5 years; 49.4% were female. Caucasians accounted for 68%, followed by Hispanics (13%). Of these, 6.27% (3,699/43,009) had a concurrent diagnosis of heart failure. In the survey's multivariable logistic and linear regression analysis, accounting for patient and hospital confounding factors, ADHF demonstrated significant associations with higher in-hospital mortality (aOR 1.63; 95% CI 1.09, 2.44, p = 0.015). In addition, a significant association between ADHF and various adverse in-hospital outcome was observed including prolonged mean length of stay (Beta 1.45; 95% CI 0.67, 2.24, p < 0.001), increased mean total hospital cost (Beta 3,757; 95% CI: 2,641, 36,630, p = 0.024), elevated risk of shock (aOR 2.75; 95% CI: 1.77, 4.26, p < 0.001), higher risk of sepsis (aOR 1.71, 95% CI: 1.09, 2.68, p = 0.018), increased risk of acute respiratory failure (aOR 3.18, 95% CI: 2.25, 4.51, p < 0.001), and heightened risk of acute kidney injury (aOR 1.57; 95% CI: 1.24, 1.99, p < 0.001). Conclusions: Among patients hospitalized for biliary-pancreatic malignancy, concurrent ADHF is linked to increased mortality risk and various in-hospital adverse complications. Additional long-term studies are required for a comprehensive understanding of this association.

80 Background: Disparities in health outcomes exist among racial and ethnic groups in the United States, notably in patients with colon cancer. Metastasis is the primary cause of cancer morbidity and mortality. However, data on the metastasis risks and clinical outcomes on hospitalized individuals with colon cancer is still limited. Therefore, we aim to assess the association between metastatic colon cancer and racial differences. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to explore patients who have colon cancer as the primary diagnosis. Additionally, we identified evidence of metastasis, as recorded by ICD-10-CM. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was racial differences in organ metastasis and secondary outcomes included mortality and length of stay. Statistical significance was established at p-value of 0.05. Results: We identified 80,130 patients with primary diagnosis of colon cancer at discharge. The mean age was 67.4 years; 49.7% were female. Caucasians accounted for 69.3%, with African Americans at 13.3% and Hispanics at 8.2%. 15% of the patients had liver metastasis, whereas 22% had lung metastasis. In a multivariate analysis adjusting for patient, COVID-19, chemotherapy usage and hospital factors, African Americans had higher risk of lung metastasis (aOR 1.22; 95%CI (1.07, 1.40), p = 0.003), higher risk of liver metastasis (aOR 1.51; 95%CI (1.31, 1.74), p = 0.021) and longer length of stay (b = 0.95; 95%CI (0.56, 1.33), p = 0.001). Hispanics also had higher risk of lung (aOR 1.22, p < 0.05) and liver metastasis (aOR 1.24, p = 0.021). We observed an increase in risk of metastasis and mortality but non-statistically significant in some parameters and races, as shown in table provided. Conclusions: In conclusion, our study revealed that racial difference is associated with higher risk of metastasis, as well as other outcomes. To establish a causal relationship between races, metastasis, and mortality in patients with colon cancer, further longitudinal research is necessary. [Table: see text]

74 Background: We identified computed tomography (CT)-derived radiomic features predictive of tumor progression within three months, then examined their ability to prognosticate overall survival (OS) along with clinical features in pancreatic cancer. We evaluated these features in patients with unresected pancreatic cancer who underwent stereotactic body radiation therapy (SBRT) in sequence with chemotherapy, but not surgery. Methods: In this retrospective study, we examined a cohort of 101 patients with stage II-III pancreatic cancer who underwent SBRT with sequential chemotherapy at a single institution (Stanford Health Care) between 1999-2020. From their pre-SBRT contrast-enhanced CT images with segmented tumors, delineating regions-of-interest, we extracted 900 radiomic (quantitative pixel-level imaging characteristic) features. In the first phase, we identified radiomic features that predicted rapid tumor progression within three months following SBRT. We divided the dataset into a training set (n = 53) for model development and a test set (n = 48) for evaluation. Using logistic regression with the Least Absolute Shrinkage and Selection Operator algorithm for feature selection and classification, we built a binary prediction model on the training set to identify patients at risk of progression within three months of SBRT. To fine-tune parameters, we performed five-fold cross-validation (CV) on the training set, repeating each set of parameters five times. We assessed model performance on the test set using the area under the curve (AUC). We selected the model with the best AUC, generating the predictive radiomic feature set. In the second phase, we conducted univariate and multivariate Cox regression analyses to assess the relationship between OS and individual clinical variables (age, sex, stage, vessel involvement, tumor location, performance status, body mass index, biological equivalent dose of radiation) and the radiomic feature set as high versus low risk. Results: Our cohort consisted of 48 men (mean age, 70 years ± 11 [SD]) and 53 women (mean age, 67 years ± 13 [SD]). From the first phase, 32 textural features comprised the radiomic feature set that best predicted rapid tumor progression, with mean AUCs of 0.852 (CV, n=53) and 0.814 (test, n=48). In the univariate Cox model, only the radiomic feature set was predictive of OS (hazard ratio, HR, 1.724, p=0.011). In the multivariate Cox model, radiomic features and age were significant predictors of OS, with HR of 1.819 (p=0.007) and 1.024 (p=0.024), respectively. Conclusions: CT-derived radiomic features predict rapid tumor progression following SBRT, confer nearly a twofold increase in mortality risk, and, along with patient age, enhance the identification of patients with stage II-III pancreatic cancer with poor OS. [Table: see text]

56 Background: We sought to identify the clinical determinants of overall survival (OS) in patients diagnosed with stage II-III pancreatic cancer not undergoing surgery. We curated a relatively homogenous cohort of patients who did not undergo surgical resection, but instead underwent chemotherapy in sequence with stereotactic body radiation therapy (SBRT) to examine the features that differentiated those with poor OS. Methods: In a retrospective study, we examined a cohort of 259 patients with stage II-III pancreatic cancer who underwent chemotherapy in sequence with SBRT without surgery at a single institution (Stanford Health Care). We conducted both univariate and multivariate Cox regression analyses to assess the relationships between OS and individual clinical and tumoral variables, including: age, sex, stage, Karnofsky performance status (KPS), body mass index, vessel involvement, tumor location, and biological equivalent dose [BED] of SBRT as potential determinants. Results: The study cohort consisted of 136 men (52.5%) and 123 women (47.5%) with a median age of 69 (range 38-94). Tumor histology was predominantly ductal adenocarcinoma (n=249, 96.1%), with tumor sites of involvement spanning: uncinate (n=35, 13.5%), head (n=160, 61.8%), body (n=59, 22.8%), and tail (n=5,1.9%). More patients had stage III (n=171, 66%) than stage II (n=88, 34%) disease, and their tumor resectability by NCCN criteria were rated as: unresectable (n=145, 56%), borderline (n=28, 10.8%), resectable (n=11, 4.2%), or unrecorded (n=75, 29%). Tumor progression was observed in local (n=71, 27.4%), regional (n=29, 11.2%), and distant (n=150, 57.9%) sites during the median follow up period of 17 months (range 15-18 months) from diagnosis and 12 months (10-13 months) from SBRT. Death (n=213, 82.2%) during this period was more common than survival (n=46, 17.8%). In univariate analyses, clinical features impacting OS included: KPS (hazard ratio [HR] 0.14, p=0.007); male sex (HR 1.44, p=0.01), pancreatic head tumors (HR 1.44, p=0.011), BED (HR 1.33, p=0.035), and age (HR 1.013, p=0.044). In the multivariate analysis, which incorporated only features significant in the univariate analyses, tumor location at the pancreatic head (HR 1.412, p=0.021) and male sex (HR 1.360, p=0.03) conferred the highest risks for poor OS, with BED bordering on significance (p=0.059) (Table). Conclusions: Among patients with stage II-III pancreatic cancer who underwent chemotherapy in sequence with SBRT, but not surgery, the most significant clinical determinants of poor OS were location of the tumor in the pancreatic head and male sex. Prioritizing additional disease monitoring and alternative therapies for this subset of patients at higher risk of poor survival may be warranted. [Table: see text]

50 Background: A+B is commonly used as first line systemic therapy in HCC patients with CP-B liver function, although in the IMbrave150 clinical trial, its efficacy was only assessed in patients with CP-A liver function. We evaluated outcomes in patients with CP-B liver function and compared to those with CP-A. Methods: We completed a multi-institution, retrospective review of patients with HCC from Mayo Clinic and University Hospitals Seidman Cancer Center, who had received A+B in the first line setting between March 2018 and November 2023. CP score was calculated at time of treatment, response was assessed, and progression free (PFS) and overall (OS) survival were determined using the Kaplan Meier method. Results: Among 322 patients with HCC, median age was 66.5 years, 78.6% were male, and 82.6% were white. Eighty-six patients (27%) had CP-B liver function, while 226 (70%) had CP-A and 10 (3%) had CP-C. Etiology of liver disease in patients with CP-B included hepatitis B in 7.0%, hepatitis C in 38.4%, alcohol use in 30.2%, and metabolic associated steatohepatitis in 20.9%. Median OS in patients with CP-B liver function was 6.4 months, while mOS was 21.6 months for those with CP-A ( p<0.0001). Further stratifying, mOS in those with CP-B7 was 9.1 months, CP-B8 was 5.5 months, and CP-B9 was 4.0 months. 12-month OS in patients with CP-B was 32.4%, compared to 69.3% in CP-A. Median PFS was 4.8 months in those with CP-B and 8.9 months in those with CP-A. Median PFS in those with CP-B7, -B8, and -B9 was 6.4 months, 2.7 months, and 2.7 months, respectively. Among those with CP-B, 1 patient had a complete response, 17 (19.8%) had a partial response, 29 (33.7%) had stable disease, and 37 (43.0%) had progressive disease. Adverse events in CP-B patients included hypertension in 14.0% (grade 3 in 1 patient), bleeding in 16.3% (grade 3 or greater in 11.6%), fatigue in 38.4%, and an immune-related adverse event in 17.4% (grade 3 in 5.8%). Conclusions: Patients with advanced HCC and CP-B7 liver function may still benefit from A+B. Importantly, no additional safety risks were identified in this subgroup. Those with CP-B8 and CP-B9 have significantly worse survival than those with CP-B7 and the likelihood of benefit from systemic therapy is minimal. It is important for providers to address the impact of baseline liver function on expected outcomes in patient with HCC.

29 Background: Previous research highlights central nervous system (CNS) malignancy as significant contributors to disability-adjusted life-years. However, there's a lack of information on the impact of COVID-19 infection in hospitalized CNS malignancy patients. Methods: Using the 2020 U.S. National Inpatient Sample (NIS), we investigated the impact of COVID-19 infection affected patients primarily hospitalized for CNS malignancy. We calculated adjusted odds ratios (aORs) for specific outcomes using multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including system-based complications. Results: We identified 37,385 patients diagnosed with CNS malignancy, averaging 53.6 years old, with 57.76% being female. Among them, 0.84% (315/37,385) were also diagnosed with COVID-19. After adjusting for patient and hospital factors, COVID-19 infection was linked to higher in-hospital mortality (aOR 4.12, 95% CI: 1.55, 10.89, p = 0.004), longer stays (Beta-coefficient 6.06, 95% CI: 2.97, 9.14, p < 0.001), increased total hospital costs (Beta-coefficient 11,855, 95% CI: 1,410, 22,301, p = 0.026), elevated risks of shock (aOR 3.96, 95% CI 1.03, 15.10, p = 0.018), acute respiratory failure (aOR 4.33, 95% CI: 1.83, 10.22, p = 0.001), and sepsis (aOR 3.96, 95% CI: 1.03, 15.10, p = 0.044). Conclusions: Our study reveals that COVID-19 infection is associated with higher in-hospital mortality and multiple adverse outcomes in patients hospitalized for CNS malignancy. Further longitudinal studies are necessary to thoroughly investigate the causality of these clinical outcomes in this population.

213 Background: Lung cancer patient often encounter disparities in health outcomes, especially in difference racial and ethnic groups. Metastasis is the primary cause of cancer morbidity and mortality. However, data on the metastasis risks and clinical outcomes on hospitalized individuals with lung cancer is still limited. Therefore, we aim to assess the association between metastatic lung cancer and racial differences. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to explore patients who have lung cancer as the primary diagnosis. Additionally, we identified evidence of metastasis, as recorded by ICD-10-CM. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was racial differences in organ metastasis and secondary outcomes included mortality and length of stay. Statistical significance was established at p-value of 0.05. Results: We identified 103,335 patients with primary diagnosis of lung and bronchus cancer at discharge. The mean age was 68.9 years; 50.5% were female. Caucasians accounted for 74.3%, with African Americans at 12.1% and Hispanics at 4.6%. 10% of the patients had brain metastasis, whereas 14% had bone metastasis. In a multivariate analysis adjusting for patient, COVID-19, chemotherapy usage and hospital factors, African Americans had higher risk of brain metastasis (aOR 1.18; 95%CI (1.02, 1.37), p = 0.002), higher risk of bone metastasis (aOR 1.16; 95%CI (1.02, 1.33), p = 0.025), higher risk of mortality (aOR 1.21; 95% CI (1.01, 1.45), p = 0.039) and longer length of stay (b = 0.85; 95%CI (0.55, 1.16), p = 0.001). Hispanics also had higher risk of brain (aOR 1.36, p < 0.05) and prolonged length of stay (b 0.79, p < 0.005). We observed an increase in risk of metastasis and mortality but non-statistically significant in some parameters and races, as shown in table provided. Conclusions: In conclusion, our study revealed that racial difference is associated with higher risk of metastasis, as well as other outcomes. Further longitudinal research is necessary to establish a causal relationship between races, metastasis, and mortality in patients with lung cancer. [Table: see text]