MetroWest Medical Center

362 Background: Primary small cell carcinoma of the esophagus (SCEC) is a rare and aggressive malignancy, representing <1% of esophageal cancers. Given its rarity, treatment strategies are largely extrapolated from small cell lung cancer. The role of radiotherapy (RT) across disease stages in SCEC, and how outcomes compare with adenocarcinoma and squamous cell carcinoma (SCC), remains poorly defined. Methods: The SEER 18 registries (2000–2022) were queried for patients with histologically confirmed esophageal carcinoma. Histology was grouped as SCEC (ICD-O-3: 8041/3, 8043/3, 8044/3, 8045/3), adenocarcinoma, or SCC. Patients with unknown survival time, non-first primaries, or missing treatment information were excluded. Overall survival (OS) was estimated using Kaplan–Meier methods and compared using log-rank tests. Analyses included SCEC patients treated with RT without surgery, stratified by SEER historic stage (localized, regional, distant), and comparisons across histologic subtypes. Multivariable Cox regression was used to calculate adjusted hazard ratios (HRs). Results: Among 56,126 patients with esophageal carcinoma, SCEC accounted for 403 (0.7%), adenocarcinoma for 66.4%, and SCC for 32.8%. Median OS for SCEC was 9 months (95% CI 8–10), significantly inferior to adenocarcinoma (11 mo, 95% CI 11–12, p <0.001) but not different from SCC (8 mo, 95% CI 8–9). In SCEC patients without surgery, median OS was 6 mo (95% CI 4–8) without RT versus 13 mo (95% CI 11–16) with RT ( p <0.001). Stage-stratified outcomes are summarized in the table: localized SCEC showed a marked OS benefit with RT (7 vs 48 mo, HR 0.18, 95% CI 0.07–0.44, p <0.001). For regional disease, OS was 8 vs 15 mo (HR 0.41, 95% CI 0.15–1.12, p =0.08), and for distant disease, 6 vs 10 mo (HR 0.70, 95% CI 0.46–1.07, p =0.10). Comparisons with non-SCEC histologies revealed that localized SCEC patients receiving RT achieved superior survival (48 mo) compared with 16 mo for both adenocarcinoma and SCC. Conclusions: SCEC is an exceptionally rare esophageal malignancy with poor outcomes relative to adenocarcinoma and SCC. RT provides a substantial survival advantage in localized SCEC, while its effect diminishes in regional and distant disease. These findings support stage-directed RT and highlight the need for prospective studies to optimize treatment in this rare cancer. Overall survival in small cell carcinoma of the esophagus (SCEC) with and without radiotherapy (RT) by stage. Subgroup Median OS without RT (mo) Median OS with RT (mo) HR (95% CI) p value All SCEC (no surgery) 6 (95% CI 4–8) 13 (95% CI 11–16) – <0.001 Localized SCEC 7 48 0.18 (0.07–0.44) <0.001 Regional SCEC 8 15 0.41 (0.15–1.12) 0.08 Distant SCEC 6 (95% CI 3–8) 10 (95% CI 8–13) 0.70 (0.46–1.07) 0.10

4125 Background: For over two decades, the criteria for liver transplantation (LT) in hepatocellular carcinoma (HCC) have been well-established, yet recurrence remains a major clinical challenge. This recurrence contributes to inferior post-LT survival in HCC patients compared to those without HCC. Prognostic index could serve as a valuable tool to identify patients who may benefit from adjuvant therapies and guide standardized post-LT HCC surveillance, which currently varies across transplant centers. Methods: We developed and validated a predictive model using the United Network for Organ Sharing (UNOS) database, analyzing adult liver transplant recipients with hepatocellular carcinoma (HCC) from 2009 to 2024, including 4,970 patients. Univariable analysis identified variables associated with 1-year, 3-year, and 5-year post-transplant HCC recurrence, applying a strict p-value threshold ( < 0.01). Significant variables were selected for multivariable logistic regression to build the model. Internal validation was performed for each time point using Receiver Operating Characteristic (ROC) curve analysis and confusion matrix evaluation, with the best-performing model selected based on these metrics. Results: The most significant model was derived using 3-year recurrence as the outcome. The final model included the pre-transplant Model for End-Stage Liver Disease (MELD) score (p = 0.02), worst tumor histology grade (p < 0.001), and total tumor diameter (p = 0.03). The final logistic regression equation is as follows: log(1-p/p) = −3.9630 − 0.0621 × Initial MELD score + 0.7657 × Worst tumor histology grade + 0.1084 × Total tumor diameter. Internal validation results showed an AUC of 0.761 (95% CI: 0.718 - 0.804), accuracy of 0.769 (95% CI: 0.757 - 0.7807), sensitivity of 77.2%, and specificity of 65.0% for 1-year recurrence. For 3-year recurrence, the model demonstrated an AUC of 0.733 (95% CI: 0.702 - 0.763), accuracy of 0.6696 (95% CI: 0.6563 - 0.6827), sensitivity of 66.7%, and specificity of 70.9%. For 5-year recurrence, the AUC was 0.714 (95% CI: 0.685 - 0.743), with accuracy of 0.655 (95% CI: 0.641 - 0.668), sensitivity of 65.2%, and specificity of 68.6%. Conclusions: We have developed and validated a predictive model for HCC recurrence following LT using UNOS data. This model shows promising performance, particularly for predicting 1-year recurrence, and may potentially serve as a useful tool for guiding post-transplant management and surveillance strategies.

Abstract Background: Immune checkpoint inhibitors (ICIs) improved outcomes in NSCLC treatment, but causing irAEs. Serum proteomic biomarkers combined with clinical data may offer a better approach for toxicity risk prediction. Methods: To predict five irAE types (pneumonitis, rash, arthritis, thyroiditis, and other adverse events) at multiple time points, pre-treatment serum samples and clinical data (age, gender, smoking history, cancer stage, performance status, and treatment regimen) were analyzed from consecutive 173 NSCLC patients treated with ICI monotherapy or ICI-chemotherapy combination. Serum proteomics was performed via mass spectrometry, and three machine learning models (XGBoost, HistGradientBoosting, and logistic regression) were evaluated using 5-fold cross-validation. Primary outcomes were five toxicity types evaluated at 1, 3, 6 months, and 1 year. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: The median age was 70.7 years, with 50.9% female and 66.5% adenocarcinoma. 16.2% had never smoked, 68.2% former smokers, and 15.0% current smokers. Performance status (PS) was 0 in 17.9%, 1 in 55.5%, 2 in 20.2%, and 3 in 5.2%. The median tumor mutational burden (TMB) was 5.4 mut/Mb, with PD-L1 negative in 30.1%, positive in 58.4%. Treatment regimens included mono-ICI (35.3%), dual ICI (12.7%), and ICI + chemotherapy (52.0%). 91.3% received palliative treatment. Median overall survival (OS) was 20.9 months, progression-free survival (PFS) was 7.1 months, and toxicity-free survival was 35.2 months. The multimodal analysis demonstrated distinct predictive patterns across toxicity types and timepoints. At 30 days, combined modality approaches performed best: Logistic Regression for pneumonitis (AUC=0.60), HistGradientBoosting for rash (AUC=0.60), and XGBoost for arthritis (AUC=0.60). Feature importance analysis identified KRAS mutation status and smoking history as primary predictors for pneumonitis, ECOG status and histology type for rash, disease stage and treatment regimen for arthritis, and PD-L1 expression for other adverse events. Proteomics-based models performed best at 3 months for pneumonitis (AUC=0.60) and thyroiditis (AUC=0.57). Notably, the HistGradientBoosting model achieved superior performance (AUC=0.75) for overall irAE prediction at 9 months using both proteomics and clinical features, demonstrating the value of integrated multimodal analysis. Conclusions: The models showed moderate discrimination, with AUCs ranging from 0.556 to 0.75, particularly excelling in early toxicity prediction. These findings support multimodal machine learning for personalized toxicity risk assessment and proactive management. Citation Format: Junho Song, Leeseul Kim, Donghoon Shin, Jongwoo Kim, Taegyu Um, Allen Cho, Jieun Park, Liam IL-YOUNG Chung, Jeeyeon Lee, Young Kwang Chae. AI-based models integrating serum proteomics and clinical features to predict immune-related adverse events in NSCLC patients undergoing immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3667.

Abstract Introduction: For locally advanced head and neck squamous cell carcinoma (HNSCC), definitive chemoradiation therapy, or surgery followed by radiation with or without chemotherapy, are the standard of care treatment options. However, recurrence rates remain high. Neoadjuvant immunotherapy is currently being explored with promising results, including a 2.9% pathological complete response rate (pCR) and a 70-90% disease-free survival (DFS) rate at 1 year with anti-PD-(L)1 therapy. Combining the anti-CTLA-4 to anti-PD-(L)1 could further improve outcomes. Here we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of combined neoadjuvant immunotherapy with anti-CTLA-4 and anti-PD-(L)1. Methods: A literature search was performed on PubMed, Embase, ASCO, ESMO and ClinicalTrials.gov from the date of inception through 07/22/2024. We used MeSH terms and keywords for HNSCC and neoadjuvant immunotherapy. No filters were applied for the search. Data were extracted following the PRISMA guidelines. Only prospective trials were included. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions and risk ratios (RR) with 95% confidence intervals (CI) were computed. Results: A total of 99 HNSCC patients (oral cavity: 62.9%, oropharynx: 23.5%, larynx: 6.8%, hypopharynx: 6.8%) treated with combined neoadjuvant anti-PD-(L)1 and anti-CTLA-4 therapies from five studies were included in this meta-analysis. The median age was 63 years (range, 22-85), and the number of neoadjuvant therapy cycles (range, 1-2) were similar across the studies.. The tumor stages distribution were as follows: 30% stage II, 21% stage III, 40% stage IV, and 9% had recurrent disease . HPV was positive in 33.4% of patients and 72.2% were current/former smokers. The rates of pCR, major pathological response (MPR), and objective response rate (ORR) were 2.83% (95% CI, 1.63-4.90), 7.55% (95% CI, 3.03-18.83), and 10.61% (95% CI, 3.17-35.5), respectively. The 1-year DFS (82.6%) was reported in only 1 study. The 1-year overall survival (OS) ranged from 87% to 95.7%. No surgical delays were reported and all the patient received the surgery. The rate of grade >3 treatment-related adverse events was 7.29%. (95% CI, 2.30-23.48). The most frequently reported grade 3 adverse events included ALT increase (n=5), followed by diarrhea/colitis (n=4), GGT increase (n=4), and infusion/allergic reaction (n=2). Conclusions: The findings suggest that combining anti-CTLA-4 to anti-PD-(L)1 in the neoadjuvant setting do not deepen the pathological responses seen with single agent anti-PD-(L)1 when compared to the historical controls. Moreover, longer follow-up is necessary to assess potential differences in DFS and OS. Citation Format: Donghoon Shin, Robin Park, Sunggon Lee, Woo Joo Lee, James Yu, Moazzam Shahzad, Guilherme Rabinowits. Neoadjuvant combined anti-PD-1 and anti-CTLA-4 inhibitor therapy for locally-advanced resectable head and neck squamous cell carcinoma: systematic review and meta-analysis [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A039.

Isolated pulmonic valve endocarditis is a rare entity attributedto multiple factors, including lower pressures on the right side of the heart, as well as lower oxygen content of venous blood. Herein, we present a challenging case of isolated pulmonic valve endocarditis complicated with septic emboli and high-grade methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. A 31-year-old female presented to the emergency department with fever, chills, fatigue, left-sided pleuritic pain, shortness of breath, and an 8-pound weight loss for the past two weeks. She is an active intravenous drug user. Notable was a grade four diastolic murmur most prominent on the upper left sternal border.Chest CT with contrast showed multiple pulmonary emboli with cavitating nodules suspicious of a septic etiology. Transthoracic echo revealed an isolated large irregularly shaped (3.0 cm x 1.5 cm) vegetation on the pulmonic valve with moderate-to-severe pulmonary regurgitation. The course was notable for persistent high-grade MSSA bacteremia for a total of 10 days, which was treated with ertapenem and cefazolin. The patient did not undergovalve replacement. Close outpatient follow-up was established with a recommendation to treat with an additional two doses of dalbavancin 1,500 mg one week apart. Isolated pulmonic valve endocarditis is a very rare entity. Prompt recognition of isolated pulmonic valve endocarditis and multidisciplinary management is key to improving outcomes among patients with this extremely rare condition.

Findings on the effects of iron on heart failure (HF) hospitalizations and mortalityamong patients with iron deficiency (ID) and HF remain conflicting across different studies. We performed a meta-analysis of clinical trials assessing the clinical, hematic and cardiovascular benefits of treating ID in HF patients. We completed a systematic search for studies comparing IV iron to placebo in HF patients with ID. The primary outcomes were rates of HF hospitalization and all-cause mortality. Secondary outcomes included change in hematic values, New York HeartAssociation (NYHA) class and ejection fraction. We applied a random-effects model with planned sensitivity analyses of studies with skewed effect sizes. Nine studies were included with a total of 2,261 patients. Analysisrevealed that treatment of HF patients with IV iron replacement significantly reduced the odds of HF hospitalization (odds ratio (OR): 0.44; 95% confidence interval (CI): 0.24 to 0.78; p=0.005, I2=67%),) but did not significantly impact all-cause mortality compared to placebo (OR:0.89; 95%, CI:0.67 to 1.19; p=0.44, I2: 0%). Analysis showed that IV iron treatment group had significantly higher serum ferritin, transferrin saturation and hemoglobin (Hb) levels. They also had lower NYHA class -1.90 (95% CI (-2.91 to -0.89); p<0.001, I2:89%) with higher ejection fraction 0.50 (95% CI (0.09 to 0.90) p=0.016, I2:86%). Treatment with IV iron in HF patients with ID is associated with a significant reduction of HF hospitalization but no effects on all-cause mortality. There were also significant increases in hematic values and ejection fraction with a reduction in NYHA class.

The relationship between hyperhomocysteinemia (HHcy) and obesity with low skeletal muscle mass (LMM) has not been established. We aim to assess the association between HHcy and the coexistence of obesity and LMM in asymptomatic adult population. We conducted a population-based cross-sectional study among asymptomatic individuals who underwent measurements of plasma homocysteine and body composition analysis. HHcy was defined as > 15 umol/L, obesity as body mass index ≥ 25 (kg/m2), and LMM as skeletal muscle index less than 2 SD below the sex-specific mean of young adults. The participants were classified into ‘control’, ‘obesity alone’, ‘LMM alone’, and ‘obesity with LMM’. Among 113,805 participants, the prevalence of HHcy was 8.3% in control, 8.7% in obesity alone, 10.0% in LMM alone, and 13.0% in obesity with LMM (p for trend < 0.001). In a multivariable logistic regression analysis, the associations showed a positive trend for HHcy along the groups from obesity alone, to LMM alone, and to obesity with LMM. HHcy was independently associated with the presence of LMM alone (adjusted odds ratio 1.186 [95% confidence interval 1.117–1.259]) and obesity with LMM (1.424 [1.134–1.788]), respectively. This study demonstrated that HHcys was more strongly associated with coexistence of obesity and LMM than either condition alone in the adult population.

This study aimed to compare the efficacy and tolerability of pre-operative platinum/5-fluorouracil (P5F) and carboplatin/paclitaxel (CP), in combination with radiation therapy in older adults with locally advanced, stage I-III esophageal cancer. We retrospectively reviewed 51 patients aged ≥70 years who underwent chemoradiotherapy followed by esophagectomy for stage I-III esophageal cancer between 2008 and 2018. Pathological complete response (pCR) and survival rates were compared across the two chemotherapy regimen arms. Treatment completion (p=0.28), pCR (p=0.89), and partial response rates were similar across both chemotherapy groups. Overall survival (OS) and disease-free survival (DFS) were similar across both groups with HR=0.80 (p=0.62) and HR=0.72 (p=0.72) respectively. The lesser toxic CP regimen may be used in older patients with locally advanced esophageal cancer, with tumor response and survival rates similar to P5F chemotherapy.