Joe Abdo

Background: Immunotherapy has revolutionized oncology care, but clinical response to immune checkpoint inhibitors (ICIs) remains unpredictable, and treatment carries substantial risks and costs. The EpiSwitch^® CiRT blood test is a novel 3D genomic assay that stratifies patients by probability of ICI benefit using a binary, blood-based classification: high (HPRR) or low (LPRR) probability of response. Methods: This interim analysis of the ongoing PROWES prospective real-world evidence study evaluates the clinical utility of CiRT in 205 patients with advanced solid tumors. The primary endpoint was treatment decision impact, assessed by pre-/post-test physician surveys. Secondary endpoints included treatment avoidance, time to ICI initiation, concordance with clinical response, early discontinuation rates, and exploratory health economic modeling. Longitudinal use, resistance monitoring, and equity analysis by social determinants of health (SDoH) were also explored. Results: CiRT results influenced clinical decision-making in a majority of cases. LPRR status was associated with higher rates of treatment avoidance and early discontinuation due to immune-related adverse events (IrAEs). In contrast, HPRR patients experienced greater clinical benefit and longer ICI exposure. CiRT classification was not associated with short-term imaging-based response outcomes, supporting its role as an independent predictor. Given that ICI therapy and supportive care can cost more than $850,000 per patient, CiRT offers potential value in avoiding ineffective treatment and associated toxicities. Conclusions: CiRT demonstrates meaningful clinical utility as a non-invasive, predictive tool for guiding immunotherapy decisions across tumor types. It enables more precise treatment selection, improves patient outcomes, and supports value-based cancer care.

Background: Immunotherapy has revolutionized oncology care, but clinical response to immune checkpoint inhibitors (ICIs) remains unpredictable, and treatment carries substantial risks and costs. The EpiSwitch® CiRT blood test is a novel 3D genomic assay that stratifies patients by probability of ICI benefit using a binary, blood-based classification: high (HPRR) or low (LPRR) probability of response. Methods: This interim analysis of the ongoing PROWES prospective real-world evidence study evaluates the clinical utility of CiRT in 205 patients with advanced solid tumors. The primary endpoint was treatment decision impact, assessed by pre/post-test physician surveys. Secondary endpoints included treatment avoidance, time to ICI initiation, concordance with clinical response, early discontinuation rates, and exploratory health economic modeling. Longitudinal use, resistance monitoring, and equity analysis by social determinants of health (SDoH) were also explored. Results: CiRT results influenced clinical decision-making in a majority of cases. LPRR status was associated with higher rates of treatment avoidance and early discontinuation due to immune-related adverse events (IrAEs). In contrast, HPRR patients experienced greater clinical benefit and longer ICI exposure. CiRT classification was not associated with short-term imaging-based response outcomes, supporting its role as an independent predictor. Given that ICI therapy and supportive care can cost more than $850,000 per patient, CiRT offers potential value in avoiding ineffective treatment and associated toxicities. Conclusions: CiRT demonstrates meaningful clinical utility as a non-invasive, predictive tool for guiding immunotherapy decisions across tumor types. It enables more precise treatment selection, improves patient outcomes, and supports value-based cancer care.

Background/Objectives: Prostate cancer (PCa) remains a major contributor to cancer-related morbidity and mortality worldwide. Current diagnostic strategies, largely based on PSA screening, lack specificity and sensitivity, leading to unnecessary invasive procedures and elevated healthcare costs. This real-world study evaluated the EpiSwitch^® PSE assay, a blood-based test analyzing 3D genome conformation signatures, ability to avoid unnecessary biopsies and the resulting clinical and economical benefits. Methods: 187 patients undergoing evaluation for PCa were tested with the EpiSwitch^® PSE assay. Biopsy confirmation was available for 53 patients, while predictive modeling assessed 134 patients using EpiSwitch PSE results and clinical variables. Results: Among the 187 patients evaluated, predictive modeling showed that up to 79.1% (106/134) of patients could safely defer biopsy based on a low-likelihood EpiSwitch PSE result, while an alternative model showed a 66.4% (89/134) biopsy avoidance rate. The PSE result demonstrated strong concordance with biopsy-confirmed diagnoses and was the most influential predictor in multivariate analysis, followed by PI-RADS score. The test achieved a 100% technical success rate, with an average turnaround time of 4.4 days. Conclusions: Incorporating the EpiSwitch PSE assay into clinical workflows enhances decision-making efficiency, reduces unnecessary biopsies, and improves healthcare resource utilization. These findings support the assay’s strong clinical utility and economic value, highlighting its potential for broader adoption as a minimally invasive reflex test and a pre-biopsy triage tool for the early and accurate detection of prostate cancer. Future studies should include prospective, multicenter trials to confirm these results across broader populations and evaluate longitudinal outcomes of patients managed with PSE-guided care.

Prostate cancer (PCa) remains a major contributor to cancer-related morbidity and mortality worldwide. Current diagnostic strategies, largely based on PSA screening, lack specificity and sensitivity, leading to unnecessary invasive procedures and elevated healthcare costs. This real-world study evaluated the EpiSwitch® PSE assay, a blood-based test analyzing 3D genome conformation signatures, in 187 patients undergoing evaluation for PCa. Biopsy confirmation was available for 53 patients, while predictive modeling assessed 134 patients using EpiSwitch PSE results and clinical variables. Across models, up to 79.1% of patients could safely defer biopsy based on PSE results, highlighting the test’s potential to reduce invasive procedures without compromising diagnostic safety. The PSE result, whether high or low, consistently emerged, alongside the PI-RADS score, as the strongest predictor of cancer risk, highlighting the PSE score as the primary driver of this outcome. Incorporating the EpiSwitch PSE assay into clinical workflows enhances decision-making efficiency, reduces unnecessary biopsies, and improves healthcare resource utilization. These findings support the assay’s strong clinical utility and economic value, highlighting its potential for broader adoption as a minimally invasive reflex test and a pre-biopsy triage tool for prostate cancer early and accurate detection.

Asia comprises 60% of the global male population, yet Asian men’s health issues, such as prostate cancer, remain sparse in the literature. Clinical researchers have often overlooked prostate cancer in Asian men, as available statistics suggest that Asian men are less likely to develop prostate cancer compared to Caucasian, Black, and Hispanic males. However, cultural investigations have indicated these figures may be influenced by factors such as cultural taboos, superstition and misconception, limited access to diagnostic tools and healthcare facilities, and epidemiological factors in terms of lifestyle, environmental exposure, and genetics. In particular, the lack of diagnostic resources, coupled with cultural stigmas surrounding cancers affecting the genitalia in Asian societies, may contribute to significant underreporting. Rapid aging population growth in East Asia and the continuing shift in Asiatic lifestyles towards Westernization will likely contribute to a continued rise in prostate cancer incidence among Asian men in the coming years. A comprehensive review of novel and commercially available prostate cancer detection tests demonstrates that accurate, less-invasive tools could relieve many of the pressures surrounding Asian men and their prostate health.

Esophageal cancer (EC) is the deadliest cancer worldwide, with a 92% annual mortality rate per incidence. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of ECs, with EAC having one of the worst prognoses in oncology. Limited screening techniques and a lack of molecular analysis of diseased tissues have led to late-stage presentation and very low survival durations. The five-year survival rate of EC is less than 20%. Thus, early diagnosis of EC may prolong survival and improve clinical outcomes. Cellular and molecular biomarkers are used for diagnosis. At present, esophageal biopsy during upper endoscopy and histopathological analysis is the standard screening modality for both ESCC and EAC. However, this is an invasive method that fails to yield a molecular profile of the diseased compartment. To decrease the invasiveness of the procedures for diagnosis, researchers are proposing non-invasive biomarkers for early diagnosis and point-of-care screening options. Liquid biopsy involves the collection of body fluids (blood, urine, and saliva) non-invasively or with minimal invasiveness. In this review, we have critically discussed various biomarkers and specimen retrieval techniques for ESCC and EAC.

Introduction: The incidence of esophageal adenocarcinoma (EAC) has increased more than any other cancer in our lifetime. Barrett’s esophagus (BE) is the only known precursor to EAC. At present, HER-2 and anti-PD-L1 therapies are FDA-approved for EAC, and off-label use of EGFR-directed therapy has been reported. Our study aims to use liquid chromatography mass spectrometry (LC/MS) to measure the expression of oncoproteins that are currently approved-drug targets in EAC and explore new promising targets for drug development and diagnostic applications for EAC and BE. Methods: EAC patients who underwent esophagectomy without chemo-radiation were identified. BE patients with subsequent progression to EAC and those without progression for >10 years were identified. Normal esophageal mucosa tissues with no history of progression were analyzed for baseline expression. Tissue sections were microdissected to isolate pure EAC, BE and normal mucosal cells from stroma. These biopsies were solubilized for LC/MS-based quantification of 80+ clinically relevant tumor markers including novel markers which are believed to play a role in the disease progression from BE to EAC. The expression trends of these markers were scrutinized by immunofluorescence (IF) in a subset of specimens/biomarkers to confirm mass spec results. Results: A total of 159 tissues were analyzed via LC-MS. In 55 EAC tissues - HER2, PD-L1 and EGFR were overexpressed in 16.3%, 0%, and 0% of patients, respectively. New markers DAD1 and S100P were noted to have high (7,634.0 and 27,222.6 attomoles/ug) and consistent (98.1% and 94.5%) overexpression in EAC samples. Expression of HER2, S100P and DAD1 were significantly higher in EAC compared to 23 normal esophageal mucosa specimens. There was no statistical difference in the expression of PD-L1 and EGFR between EAC and healthy mucosal samples. 45 BE biopsies progressed to EAC within a mean of 380 days, while the remaining 36 BE specimens did not progress over a 10-year period. 8 novel biomarkers were expressed at a higher level in BE tissue that progressed to cancer when compared to esophageal tissue that remained stable over 10 years. The expression trends observed via LC/MS were confirmed via IF in DAD1, S100P and two other novel markers. Discussion: LC-MS revealed low prevalence of target proteins in currently approved EAC therapies and high levels of newly discovered disease drivers that should be explored as possible therapy targets or diagnostic markers. The differential overexpression of the novel markers in progressive and non-progressive BE tissues, as well as the consistent overexpression of these markers in EAC tumors, demonstrates the potential for early detection of esophageal carcinogenesis and/or reveals potential therapeutic programs for an indication that lacks highly efficacious targeted therapy options. Citation Format: Christopher Hartley, Ajay Bansal, Catherine Hagen, Olivia Driscoll, Seyun Oh, Joe Abdo, Sumeet K. Mittal. Mass spectrometry detects lower frequency of routine markers and consistent overexpression of novel disease drivers in Barrett's-related esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2805.

249 Background: Since 1975, Esophageal adenocarcinoma (EAC) incidence has increased more than any other cancer (̃700%). Pre-malignant metaplastic tissue, or Barrett's Esophagus (BE), is the only known precursor for EAC. Periodic histological assessment of endoscopic biopsy along dysplasia-carcinoma sequence is used to assess progression risk. Current surveillance protocols have clinical limitations as 80% of patients still present with stage II-IV EAC. The aim of this study is to compare novel proteomic expression patterns to distinguish stable BE patients from those who developed EAC using the STLA101 assay. Methods: After Institutional Review Board approval patients with BE/GERD were identified. Two cohorts were selected: progressors (progressed to EAC at subsequent interval of 0.5-3 years) and non–progressors (̃10 yrs of f/u surveillance without progression along dysplasia/carcinoma path). 24 normal esophageal mucosa samples with no h/o of BE were also retrieved for baseline expression levels. Tissue sections were microdissected to isolate pure BE cells from surrounding stromal cells. BE cells underwent a multi-step process where tissue was heated and digested to produce a liquid biopsy for mass spec. Isotopically labeled control peptides representing the STLA101 panel were spiked in with digested tissue samples to quantify all of the markers simultaneously using a Triple-quad mass spectrometer. Results: A total of 95 tissues were analyzed. 29 BE biopsies progressed to EAC within a mean of 380 days while the remaining 28 BE and 14 GERD specimens did not progress over a 10-yr period. All 8 biomarkers were expressed at a higher level in BE tissue that progressed to cancer when compared to BE/GERD tissue that remained stable over 10 years. The assay had a 100% technical success rate as no samples yielded “non-detectable” data points. Conclusions: The differential overexpression of the STLA101 panel on progressive and non-progressive BE tissues demonstrates the clinical utility of STLA101 as a predictive biomarker panel for early detection of esophageal carcinogenesis. Non-progressive BE tissues were similar to normal mucosa, therefore, patients whose BE tissue samples resemble this profile may receive a reduced screening cadence. On the other hand, patients with overexpression of the STLA101 panel may be eligible to receive more frequent screening or therapeutic intervention.

343 Background: Esophageal adenocarcinoma (EAC) continues to have extremely poor prognosis despite advances in surgical and oncological regimens. Targeted and immune therapy hold promise to improve outcomes in solid tumors including EAC. At present HER-2 and anti-PD-L1 therapies are approved by the FDA for EAC. Additionally, off-label use of EGFR directed therapy has been reported. The aim of this study is to measure expression of 80+ oncoproteins in EAC using multiplexed mass spectrometry to elucidate expression of currently approved-drug targets and explore promising new targets for drug development. Methods: After Institutional Review Board approval (Mayo Clinic and KUMC), EAC patients whose tumors were resected via esophagectomy before chemotherapy and/or radiation were identified. Normal esophageal mucosa samples with no history of EAC were also retrieved for analysis. Tissue sections were microdissected to exclude stroma from adenocarcinoma cells. Isolated EAC cells were solubilized for mass spectrometry-based quantitation of more than 80 clinically relevant tumor markers. Results: 55 EAC tissues were analyzed. HER2, PD-L1 and EGFR were overexpressed only in 16.3%, 0%, and 0% of patients, respectively. New oncoproteins #2 and #6 were noted to have high (7,634.0 and 27,222.6 attomoles/ug) and consistent (98.1% and 94.5%) overexpression in EAC samples. Expression of HER2, oncoproteins #2 and #6 were significantly higher in EAC compared to normal esophageal mucosa. There was no statistical difference in the expression of PD-L1 and EGFR between EAC and normal samples. Conclusions: Mass spectrometry revealed a very low prevalence of target oncoproteins in EAC for currently used drugs. Our study potentially reveals alternate markers which are near universally present at high levels and should be further explored for targeted treatment.[Table: see text]