Ikram, Waleed

e23536 Background: Circulating tumor DNA (ctDNA) has gained prominence as a potential indirect marker for minimal residual disease (MRD) in various cancers, including soft tissue sarcomas (STS). Previous studies have suggested that indirect hematologic ratios – such as Neutrophil-Lymphocyte Ratio (NLR), Monocyte-Lymphocyte Ratio (MLR), Platelet-Lymphocyte Ratio (PLR), and Eosinophil-Lymphocyte Ratio (ELR) may correlate with worse outcomes. We sought to evaluate the correlation of NLR, MLR, PLR and ELR in a real world cohort of Non-Hispanic Whites (NHW) and Hispanics (H) with advanced STS. Methods: We performed a retrospective chart review at Dignity Health Cancer institute using our Electronic Medical Records (EMR) and Signatera™ assay to obtain our data points. Inclusion criteria were STS patients of all ages and stages of disease with complete records. We reviewed 33 patient charts, 14 NHW and 19 H patients. Of the NHW population, 11 were male (M) and 3 females (F). For the H population, 14 were M, and 5 were F. We utilized Spearman's rank correlation coefficient to assess monotonic relationships between ct-DNA levels and the hematologic ratios. ct-DNA was quantified through standardized assays per Protocol, with the resultant values treated as continuous variables in our statistical analyses. Power considerations, based on expected effect sizes and type I error rate adjustments were performed. Results: The Spearman’s correlation coefficients and p-values indicated varied associations across ethnic groups. For NHW, the correlations were generally weak and non-significant (NLR: r = 0.18, p = 0.54; MLR: r = -0.04, p = 0.89; PLR: r = 0.35, p = 0.21; ELR: r = 0.001, p = 1.00). Conversely, in the Hispanic cohort, stronger and statistically significant correlations were observed, particularly with NLR (r = 0.78, p < 0.0001) and MLR (r = 0.70, p < 0.001). Overall, the correlations across the entire study population did not reach statistical significance. Conclusions: This study revealed notable racial variations, particularly in the H population, in the relationship between ctDNA levels and hematologic ratios. The noteworthy associations found with NLR (r = 0.78, p < 0.0001) and MLR (r = 0.70, p < 0.001) highlight the possible usefulness of these ctDNA and these indirect biomarkers in assessing disease status in STS. These findings suggest the possibility of using hematologic ratios, particularly in the Hispanic population, as markers of disease progression similar as ctDNA. Hematologic ratios are more easily accessible to the general population compared to ctDNA in many underserved countries and communities. Future studies with larger cohorts are need to further analyze its validity.

e23535 Background: Our study aims to examine the relationship between the presence of circulating tumor DNA (ctDNA) and lactate dehydrogenase (LDH) in patients diagnosed with soft tissue sarcoma (STS). There is emerging yet limited data on the applicability of ctDNA in STS. LDH is a cheaper readily available test that has been associated with unfavorable overall survival in different malignancies. This research aims to understand the correlation between ctDNA and LDH as a tool to assess its utility as indirect markers of response to treatment in STS. Methods: This was a single-center retrospective chart review on patients diagnosed with STS. Eligibility criteria included a confirmed diagnosis and available measurements of both ctDNA and LDH levels. Correlation was compared between Non-hispanic whites (NHW) and Hispanics (H). Data was sourced from our electronic medical record and Signatera™ assay to obtain the primary endpoints. Specimens were standardized in accordance to Natera’s™ specifications. Study endpoints included the correlation coefficients between ctDNA and LDH levels. A two-stage study design was applied for a robust analysis. Spearman's rank correlation coefficient (denoted as r) was employed for statistical analysis, assessing the strength and direction of the monotonic relationship between ctDNA and LDH levels. Marker values were treated as continuous variables in these analyses. All analyses were executed in GraphPad Prism software. Results: The cohort comprised 33 patients with STS (14 NHW, 19 H). The median LDH in H was 189 (interquartile range (IQR) = 184) vs 184 (IQR = 105) in NHW. Comparatively, the median ctDNA in H was 0 (IQR = 39.3) and also 0 (IQR = 11.1) in NHW. The overall correlation between ctDNA and LDH levels was moderate positive (r = 0.5, p = 0.002), indicating a consistent, though not necessarily linear, relationship. Subgroup analysis showed r = 0.19 (p = 0.52) in NHW and r = 0.43 (p = 0.1) in H groups, suggesting ethnic variability in the ctDNA-LDH correlation. These findings were statistically significant within the predefined confidence limits and probability values. Conclusions: Our study demonstrated a significant correlation between ctDNA levels and LDH in STS patients, implying that higher ctDNA may be associated with higher LDH levels. This association can lead clinicians in monitoring LDH more frequently as an indirect marker of response to treatment in STS. This correlation suggests an increased tumor burden with a higher inflammatory response, with variations across different racial groups. The wider availability of LDH testing compared to ctDNA in many centers highlights LDH's potential as an indirect marker for STS. Further research with larger prospective cohorts is essential to confirm LDH's role paired with ctDNA in guiding treatment decisions in STS, enhancing its utility in clinical practice.

e23534 Background: The use of tumor genomic profile (TGP) has led to improved genomic-directed therapies in many solid cancers. Due to its heterogeneity, soft tissues sarcomas (STS) have not benefited much from these genomic advances. Emerging research indicates that about 30% STS have actionable alterations which can lead to potential treatment options (Gounder et al. Nature 2022). Our study aimed to compare the differences in genomic-directed therapy between Non-Hispanic White (NHW) and Hispanic (H) patients with STS at Dignity Health Cancer Institute. Methods: We performed a retrospective analysis of medical records using the electronic medical record. Our study specifically examined patients diagnosed with STS, with a sample size of 14 NHW and 19 H individuals.The eligibility criteria consisted of known diagnosis of STS with completed TGP. We conducted a descriptive analysis using GraphPad Prism Software, where mutations were evaluated as continuous variables. The statistical significance of differences between groups was assessed using an unpaired t-test, with a significance level of < 0.05. Results: We found 73 tumor alterations, with 11 potentially targetable (15.2%). Most patients had negative to low tumor mutational burden (0-2 mut/Mb) with only 2 patients with high TMB ( > 10 mut/Mb). The most common mutations were TP53 and CDK4 with 9 patients (12%) each. The NHW group had an average of 2.57 mutations (standard deviation = 2.87), whereas the H group had an average of 1.42 mutations (standard deviation = 1.35). The median values were 2 and 1, respectively, with no statistically significant difference (p = 0.21). The average for mutations of unknown significance was 1.54 in NHW individuals, while it was 1.00 in Hispanics. In the NHW group showed 11 males and 3 females, while the H group included 14 males and 5 females. There was no significant difference in gender representation between the two groups (p = 1). 3 patients (9%) received non-FDA approved treatments based on TGP (1 CDKN2A-abemaciclib, 1 CDK4-ribociclib and 1 IDH1-ivosidenib) and 2 patients (6.6%) were enrolled in clinical trials. Conclusions: Our investigation reveals that there is no statistically significant disparity in the frequency of mutations between NHW and H groups in our sample. Nevertheless, there was an evident inclination towards an increased frequency of mutations in NHW. Similarly, the occurrence of mutations with uncertain significance was slightly higher in NHWs, although the difference was not statistically significant. Only a minority of patients had targetable mutations or were enrolled in clinical trials. However, the routine use of genomic profiles may lead to more personalized treatments. Our research emphasizes the need to expand the use of comprehensive genomic profiles to increase directed treatments for patients with STS.

e23533 Background: Circulating tumor DNA (ctDNA) has shown promise as a biomarker for cancer detection and tracking in multiple malignancies like melanoma, colon and lung. Due to the heterogeneity of sarcoma, there has been limited research on ctDNA as a tool for measuring minimal residual disease (MRD). Differences in baseline in ctDNA for STS in racial minorities have been poorly studied. To identify potential racial differences in the efficacy of this tool, this study compares the quantitative values of baseline ctDNA between non-Hispanic white (NHW) and Hispanic (H) patients with soft tissue sarcoma (STS). Methods: The medical records of 33 STS patients who had ctDNA analysis from Natera™ were examined retrospectively at Dignity Health Cancer Institute.There were 19 H patients and 14 NHW patients in the group. All Black (B), Asian (A), and Other (O) racial groups were excluded due to lower numbers. GraphPad Prism software was used to examine the baseline ctDNA levels. Using continuous measures for statistical analysis, we conducted descriptive statistics and determined the mean, standard deviation, and median ctDNA levels for each group. The ctDNA levels were compared between groups using a two-tailed t-test with a significance level of p < 0.05. Results: The average ctDNA levels were 416.675 (standard deviation = 1349.394) in NHW and 300.305 (standard deviation = 1000.543) in H. The median levels were 0 for both groups. The statistical analysis showed that there was no significant differences in the baseline ctDNA levels between the two groups (p = 0.73). Furthermore, the gender distribution among NHW and Hs in the cohort was comparable, with a p-value of 1.00. Conclusions: This study establishes that there is no substantial differences in baseline levels of ctDNA between H and NHW patients with STS. These findings indicate that ctDNA levels in these populations can be equally utilized for diagnostic and monitoring reasons in clinical settings. Nevertheless, to gain a comprehensive understanding of the racial disparities in ctDNA utility and its implications in customized treatment for STS, it is necessary to conduct more extensive research with larger sample sizes and incorporate additional variables.

e23526 Background: Racial, ethnic, and socioeconomic factors have been implicated in the variability of survival rates among soft tissue sarcoma (STS). These disparities are multifactorial and may reflect differences in disease biology, access to care, treatment responses, and others. In situations where different racial groups have equitable access to healthcare, healthcare disparities can decrease, and survival gaps can narrow. Differences in survival in STS in racial minorities have been poorly studied. Recognizing the potential impact of such disparities, our study thereby contributes to the ongoing discourse on healthcare equity in STS outcomes. Methods: We conducted a retrospective analysis of 30 STS patients, stratifying them into Hispanic (H) and non-Hispanic white (NHW) groups at Dignity Health Cancer Institute in Phoenix, Arizona. The Mann-Whitney U test was chosen to compare survival distributions, given the non-normal distribution of our sample. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was applied to determine statistical significance. All analyses were executed in GraphPad Prism software. Results: Our cohort comprised 13 (43%) NHW and 17 (57%) H patients. The mean ages were 57.2 years for NHW and 48.9 years for H, with a balanced gender distribution across groups. The most common subtypes of STS in NHW were liposarcoma (n = 3, 23.1%), and spindle cell carcinoma (n = 2,15.4%). Comparatively, the most common subtypes of STS in H were liposarcoma (n = 5, 29.4%) and leiomyosarcoma (n = 3, 17.6%). All patients were diagnosed with Stage 4 STS. Treatment modalities differed marginally, with NHW patients undergoing more surgical interventions, while H patients were more frequently administered chemotherapy. Median overall survival from the start of first-line therapy was 412 days for NHW and 500 days for H patients. Despite the longer median overall survival observed in Hispanics, the intergroup difference did not reach statistical significance (P = 0.68). Conclusions: The similar survival times between H and NHW STS patients at our institution may hint at an equitable provision of care across racial demographics in a relatively controlled single-center experience. However, the trend of extended survival in the Hispanic group, while not statistically confirmed, raises questions that merit further inquiry. This study serves as a preliminary exploration into racial disparities in STS, advocating for larger-scale research with more diverse patient populations. Further studies are essential to understand these findings and identify and optimize factors contributing to narrowing the survival gap in minorities, with the goal of enhancing STS prognosis for all racial groups.

694 Background: The treatment landscape of localized renal cell carcinoma (RCC) is rapidly evolving. Recent trials have demonstrated contrasting efficacy with adjuvant immunotherapy. Therefore, we sought to assess the mixed treatment comparisons among different adjuvant treatment options using updated data from trials and quantified the absolute effect with these treatments stratified by risk categories. Methods: This living network meta-analysis was conducted using the living interactive evidence (LIvE) synthesis framework. We used stratified baseline risks of disease progression from observational data and at 5, 10, 15 years from the Leibovich risk stratification system (based on risk scores ranging from 0 to ≥15). Corresponding intervention risks were then approximated using relative effect estimates (from NMA) and baseline risks. The difference between CIRs and baseline risks were calculated to present absolute risk differences in each risk category. Results: This NMA included eight RCTs with 8480 participants and seven unique treatment options. Pembrolizumab (pembro; rank 1) was associated with improved disease-free survival (DFS) when compared to atezolizumab (atezo; rank 6; hazard ratio: 0.68; 0.49;0.93), and nivolumab-ipilimumab (nivoipi; rank 5; 0.68; 0.48-0.97). However, no statistically significant difference was observed between pembro and atezo for overall survival (0.53; 0.28-1.01). Survival data for nivoIpi was not reported. No new statistically significant differences were observed since last update. The absolute benefit of atezo and nivoipi was minimal with higher T and N patients (Table). The results were similar with increasing Leibovich risk scores. Conclusions: Current evidence favors the use of a risk adapted approach when offering adjuvant immunotherapy. Adjuvant pembrolizumab remains a preferred treatment in patients with RCC who underwent nephrectomy. [Table: see text]

40 Background: Previously we have reported enrollment disparities in PCa clinical trials. Funding source can influence minority representation in clinical trials. Hence, we aimed to evaluate the impact of source of funding on enrollment disparities in PCa clinical trials. Methods: MEDLINE and EMBASE were searched to identify phase II/III PCa trials. All relevant trials reporting age by 65 years were considered eligible for inclusion. Trials recruiting from the United States (US) were considered eligible for analysis by race and ethnicity. The trial proportions of age, or racial/ethnic subgroup category and the global incidence in the corresponding age subgroup (from the global burden of disease database), or the US-population-based incidence in the corresponding racial/ethnic subgroup (from SEER 21 database) were used to compute enrollment incidence ratio (EIR) at each trial. EIRs with corresponding 95% confidence intervals (CI) were then meta-analyzed using a random-effects model and stratified by sources of funding (industry, US-government, and others [academic and non-US govt]). A univariate meta-regression was conducted to assess the temporal changes in EIR by each funding category. Results: Of 127 trials recruiting from the US, 89 (70%) reported race, and 35 (27%) reported ethnicity. Among those, 57 (64%), 14 (16%), and 18 (20%) trials reported industry, US-government, and other sources of funding, respectively. Of those reporting ethnicity, 23 (66%), 4 (11%), and 8 (23%) trials reported industry, US-government, and other sources of funding, respectively. Among the 287 eligible trials, 49 trials (17%) reported age by 65 years. Of those, 36 (73%), 6 (12%), and 7 (13%) reported industry, US-government, and other sources of funding, respectively. In terms of racial/ethnic enrollment, Black patients were significantly under-represented in industry funded trials (0.33; 0.27-0.41). No significant disparity was observed in US-government funded trials (0.75: 0.57-1.00). The P-value of interaction was <0.0001. Hispanics were significantly under-represented in industry funded clinical trials (0.56; 0.43-0.74). The number of US-government funded trials reporting Hispanics were small (<10) which precluded any meaningful statistics. No significant disparity was observed in terms of older adults (EIR: 1.00; 95% CI: 0.95; 1.05) overall and by funding sources. Black patients’ representation in industry funded PCa trials has significantly decreased over the last three decades. No significant change was observed in US-government funded PCa trials over the last three decades (P:0.004). Conclusions: Black and Hispanic men with PCa are likely to be under-represented in industry sponsored clinical trials. Black patients’ representation in industry sponsored trials has declined over time, thus widening the cancer-care inequities in these patients.

Accurate clinical staging of bladder cancer aids in optimizing the process of clinical decision-making, thereby tailoring the effective treatment and management of patients. While several radiomics approaches have been developed to facilitate the process of clinical diagnosis and staging of bladder cancer using grayscale computed tomography (CT) scans, the performances of these models have been low, with little validation and no clear consensus on specific imaging signatures. We propose a hybrid framework comprising pre-trained deep neural networks for feature extraction, in combination with statistical machine learning techniques for classification, which is capable of performing the following classification tasks: (1) bladder cancer tissue vs. normal tissue, (2) muscle-invasive bladder cancer (MIBC) vs. non-muscle-invasive bladder cancer (NMIBC), and (3) post-treatment changes (PTC) vs. MIBC.

23 Background: Identification of factors associated with enrollment disparities in clinical trials can narrow cancer care inequities. Funding source can influence minority representation in clinical trials. Therefore, we aimed to assess the impact of funding sources on enrollment disparities in colorectal (CRC) clinical trials. Methods: CRC phase II/III randomized controlled trial (RCTs) identified through MEDLINE and EMBASE from each database’s inception through 2022 were considered eligible. Trial level enrollment incidence ratios (EIR) were computed; defined as the ratio of trial proportions of a gender, age, or racial/ethnic subgroup category and the global incidence in the corresponding gender/age subgroup (from the global burden of disease database), or the US-population-based incidence in the corresponding racial/ethnic subgroup (from SEER 21 database). EIRs were then meta-analyzed using a random-effects model for each funding source category (US- government, industry, others). Temporal trends were analyzed using a univariate meta-regression. Results: Using data from 287 RCTs, women were significantly under-represented in the industry sponsored trials (EIR: 0.85 [95% CI: 0.83 - 0.88]) but not in US-government sponsored trials (0.92 [0.84-1.00]). A total of 87 RCTs reported age proportions; older adults (above 65 years) were significantly under-represented in the industry sponsored (0.84 [0.74-0.96]) and as well as in US-government sponsored CRC trials (0.52 [0.44-0.61]). Only 56 and 15 trials reported race and ethnicity, respectively. Limited data on racial/ethnic enrollment revealed significant under-representation of Black (0.45 [0.36 -0.57]) and Hispanic (0.45 [0.31-0.66]) patients across industry sponsored CRC trials. In contrast, no significant disparity was observed in the inclusion of Asian race in the industry sponsored trials. The number of US-government sponsored trials reporting racial/ethnic subgroups were small ( < 10) which precluded any meaningful statistics. Trends show that the representation of women has improved ( P: 0.02) while the representation of Black ( P: 0.007) and Hispanic patients ( P: 0.04) has worsened over the last three decades in industry sponsored CRC trials. Conclusions: The reporting of race/ethnicity is suboptimal in CRC trials especially in those sponsored by US government. Older adults may be under-represented regardless of funding source. Women, Blacks and Hispanics may be under-represented in industry sponsored CRC clinical trials. While representation of women appears to be improving, representation of Black and Hispanic patients has worsened in industry sponsored CRC clinical trials over the last three decades.

ImportanceProstate cancer (PCa) is marked by disparities in clinical outcomes by race, ethnicity, and age. Equitable enrollment in clinical trials is fundamental to promoting health equity.ObjectiveTo evaluate disparities in the inclusion of racial and ethnic minority groups and older adults across PCa clinical trials.Data SourcesMEDLINE, Embase, and ClinicalTrials.gov were searched to identify primary trial reports from each database's inception through February 2021. Global incidence in age subgroups and US population-based incidence in racial and ethnic subgroups were acquired from the Global Burden of Disease and Surveillance, Epidemiology, and End Results 21 incidence databases respectively.Study SelectionAll phase 2/3 randomized PCa clinical trials were eligible for age disparity analyses. Trials recruiting exclusively from the US were eligible for primary racial and ethnic disparity analyses.Data Extraction and SynthesisThis study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were pooled using a random-effects model.Main Outcomes and MeasuresEnrollment incidence ratios (EIRs), trial proportions (TPs) of participants 65 years or older or members of a racial and ethnic subgroup divided by global incidence in the corresponding age group, or US population–based incidence in the corresponding racial and ethnic subgroup, were calculated. Meta-regression was used to explore associations between trial characteristics and EIRs and trends in EIRs during the past 3 decades.ResultsOf 9552 participants among trials reporting race, 954 (10.8%) were African American/Black, 80 (1.5%) were Asian/Pacific Islander, and 8518 (78.5) were White. Of 65 US trials, 45 (69.2%) reported race and only 9 (13.8%) reported data on all 5 US racial categories. Of 286 global trials, 75 (26.2%) reported the enrollment proportion of older adults. Outcomes by race and age were reported in 2 (3.1%) and 41 (15.0%) trials, respectively. Black (EIR, 0.70; 95% CI, 0.59-0.83) and Hispanic (EIR, 0.70; 95% CI, 0.59-0.83) patients were significantly underrepresented in US trials. There was no disparity in older adult representation (TP, 21 143 [71.1%]; EIR, 1.00; 95% CI, 0.95-1.05). The representation of Black patients was lower in larger trials (meta-regression coefficient, −0.06; 95% CI, −0.10 to −0.02; P = .002).Conclusions and RelevanceThe results of this meta-analysis suggest that Black and Hispanic men are underrepresented in trials compared with their share of PCa incidence. The representation of Black patients has consistently remained low during the past 2 decades.