tbuckley/cabot-search huggingface dataset:
Serum mucin 5AC (MUC5AC) as a predictor of outcomes and microscopic distant metastasis in pancreatic ductal adenocarcinoma (PDA).
Authors: Ashish Manne, Yonghua Bao, Amir Sara, Ankur Sheel, Ashwini K. Esnakula, Wancai Yang
Journal: Journal of Clinical Oncology (2025)

767 Background: Our prior studies demonstrated that tissue extracellular MUC5AC (EM) detection (EM-D) is associated with early recurrence, and serum MUC5AC (sM) levels have prognostic value in resected PDA following neoadjuvant therapy. This study evaluates the predictive value of post-operative sM before adjuvant therapy (AT). Methods: Serum samples, collected from January 2010 to June 2021 and sourced from the Ohio State University biorepository, were analyzed using enzyme-linked immunoassays with a human MUC5AC kit (NBP2-76703). Multivariate (MV) Cox regression models quantified progression-free survival (PFS) and overall survival (OS), while Wilcoxon tests compared group differences. Results: Nineteen patients had serum samples available post-operative and pre-AT. The cohort's median age was 65 years (range: 48-83), predominantly Caucasian (n=18), and 58% female. Serum was collected a median of 2 weeks (range: 1-16) after surgery, with a mean sM level of 1.1 ng/mL (range: 0.42 to 3.3). Most patients (17/19) received Gemcitabine-based therapy, one received chemoradiation, and another FOLFIRINOX. Among patients, 3 had no recurrence (Nr), 10 experienced distant metastases only (mets), 3 had local recurrence only (Lr-o), and 3 had both Lr and liver recurrence (Liv/Lr). In the MV model, incorporating sM, EM-D, and AT, higher sM levels (HR=2.83, p=0.04) and negative EM-D (HR=6.85, p=0.02) were associated with increased recurrence risk, whereas AT type did not influence recurrence. Regarding OS, sM was significant (HR=2.95, p=0.04) while other factors were not. Elevated sM levels correlated with metastasis risk (mets vs. Liv/Lr vs. Lr-o vs. Nr = 1.54 vs. 0.61 vs. 0.62 vs. 0.92, p=0.01). Patients with locoregional recurrence had significantly lower sM than those with distant metastasis and no recurrence (mets vs. Liv/Lr+Lr-o vs. Nr = 1.54 vs. 0.62 vs. 0.92, p=0.005). In a separate cohort of 10 metastatic patients (mean sM of 1.8 ng/mL, range: 0.43 to 11.2), liver metastases were linked to significantly lower sM than non-liver metastases (0.54 vs. 3, p=0.02), while peritoneal metastases were associated with higher sM levels (3 vs. 0.6, p=0.04). Conclusions: This small study suggests that sM can serve as a biomarker for assessing outcomes and recurrence sites post resection before the initial dose of AT. Elevated sM should prompt suspicion of microscopic metastases, particularly non-liver metastases.
Disparities in liver cancer risk and outcomes in the LGBTQ community: A literature review.
Authors: Fnu Anamika, Akshit Chitkara, Marciano Figueroa, Arshia Adib, Rushin Patel
Journal: Journal of Clinical Oncology (2025)

528 Background: Liver cancer continues to be a significant public health concern, particularly among high-risk groups such as individuals with hepatitis infections, alcohol use disorders, and metabolic diseases. While liver cancer disparities have been well-documented among racial and ethnic minority groups, emerging research highlights significant health inequities within the LGBTQ community, including higher rates of risk factors and limited access to screening and care. This literature review aims to assess the extent of liver cancer disparities within the LGBTQ community and identify gaps in prevention, screening, and treatment. Methods: We performed a systematic search across PubMed, Scopus, and Google Scholar for peer-reviewed studies published between 2000 and 2024. The inclusion criteria focused on studies addressing liver cancer risk, prevalence, or outcomes in LGBTQ populations. Data on key liver cancer risk factors such as hepatitis B and C prevalence, alcohol use, obesity, and access to healthcare services were extracted and synthesized. Additionally, we reviewed public health reports and clinical guidelines relevant to LGBTQ health disparities. Results: The review identified significant disparities in liver cancer incidence and mortality among LGBTQ individuals. Hepatitis B infection rates were about 1.5 times higher, and hepatitis C rates up to 1.7 times higher among LGBTQ populations, particularly among gay and bisexual men. Alcohol use disorder was about 30-40% more prevalent in LGBTQ individuals, which further increases the risk of liver cancer. Screening for liver cancer in LGBTQ populations is underutilized, with rates approximately 20% lower than the general population. There were reported delays in diagnosis in LGBTQ community due to stigma, discrimination, and lack of culturally competent healthcare services. While some interventions targeting LGBTQ health have shown promise, the overall lack of targeted liver cancer prevention and treatment strategies remains a significant barrier. Conclusions: LGBTQ individuals face increased liver cancer risk due to a higher prevalence of key risk factors and inadequate healthcare access. Current screening and preventive strategies are insufficient for addressing these disparities. Targeted interventions, including enhanced screening efforts, hepatitis vaccination and treatment programs, and the development of LGBTQ-specific healthcare protocols, are needed to reduce the liver cancer burden in this underserved population. Policymakers and healthcare providers must address the unique needs of LGBTQ individuals to achieve equitable cancer outcomes. Prevalence of liver cancer risk factors in LGBTQ vs. general population. Risk Factor LGBTQ Population (%) General Population (%) Hepatitis B Infection 15 10 Hepatitis C Infection 18 12 Alcohol Use Disorder 25 16 Metabolic Syndrome 22 18 Screening Rate 40 60
Surrogacy between pathological complete response and overall survival: An individual patient data analysis of eight RCTs on neoadjuvant treatment plus surgery for esophageal cancer.
Authors: Jun Okui, Kengo Nagashima, Satoru Matsuda, Yasunori Sato, Hirofumi Kawakubo, Thomas Ruhstaller, Peter C. Thuss-Patience, Thomas Aparicio, Guillaume Piessen, Charlène J. van der Zijden, Bianca Mostert, Bas P.L. Wijnhoven, Takahiro Tsushima, Hiroya Takeuchi, Ken Kato, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2025)

498 Background: Overall survival (OS) is the gold standard endpoint of treatment efficacy but requires an extended follow-up period. This study aimed to determine the validity of pathological complete response (pCR) as a surrogate endpoint for OS. Methods: The individual-level surrogacy between categorical outcome and OS was assessed using Kendall correlation coefficient, τ. Because no method has been reported to estimate τ between categorical variables and OS, we proposed the new method using an inverse probability of censoring weighting (IPCW) estimator adjusted for tied data that occur when applied to categorical outcomes. To evaluate the validity of this new method, we conducted simulations to compare its estimation accuracy with existing methods. A systematic review for all phase III RCTs comparing therapies in perioperative settings for resectable advanced esophageal and gastroesophageal junction cancer was performed and individual patient data (IPD) were requested from all included trials. Finally, surrogacy between pCR and OS was assessed using our proposed method. Results: Across all scenarios with varying τ values, sample sizes, and censoring proportions, the proposed method showed the lowest bias compared to the existing statistical methods. In total, 23 eligible trials were identified and IPD were available from eight RCTs (JCOG1109, JCOG9907, JCOG9204, FFCD9901, FFCD9102, SAKK75/08, CROSS, and KOK), including 1688 patients who received neoadjuvant therapy. For trial-level analysis, pCR showed a strong correlation with a determination of correlation of 0.65 when limited to neoadjuvant chemotherapy (NAC) trials. For individual-level analysis, in patients who received NAC, the hazard ratio (HR) for OS of pCR was 0.25 (95% CI: 0.13 - 0.47), and τ between OS and pCR was 0.225. While in patients who received neoadjuvant chemoradiotherapy (NACRT), the HR was 0.54 (95% CI: 0.45 - 0.66), and τ was 0.189. Additionally, τ between OS and pathological grade (pGrade), OS and tumor regression grade (TRG) was 0.196 and 0.143, respectively. As a reference, hypothetical data showed that in order to achieve a τ of 0.8 between pCR and OS, it is necessary to be able to clearly identify the prognosis to the extent that an HR of 0.09 (95% CI: 0.08 - 0.11) can be obtained. Conclusions: While pCR is sensitive enough to stratify prognosis and exhibit strong trial-level surrogacy, no individual-level surrogacy was demonstrated, making them insufficient to replace OS. It should be noted that there are substantial differences in prognostic stratification and potential use of pCR as primary endpoints in clinical trials.
Phase 1/2 study of FOG-001, a first-in-class direct β-catenin:TCF inhibitor, in patients with colorectal cancer, hepatocellular carcinoma, and other locally advanced or metastatic solid tumors.
Authors: Kyriakos P. Papadopoulos, Michael Cecchini, Moh'd M. Khushman, Meredith Pelster, Jordi Rodon Ahnert, Shivaani Kummar, Rona Yaeger, Sunil Sharma, Amber L. Wells, Amanda Garofalo, Lalith V Akella, Ziyang Yu, Varsha Iyer, Marie Huong Nguyen, Keith W. Orford, Samuel J. Klempner
Journal: Journal of Clinical Oncology (2025)

TPS322 Background: Wnt/B-catenin pathway activation, which is frequently present in most colorectal cancers and a variety of other solid tumors, is associated with poor prognosis and resistance to immunotherapy. FOG-001 is a Helicon peptide that competitively inhibits the interaction between β-catenin and the T-cell factor (TCF) family of transcription factors. Experiments in patient-derived-xenograft (PDX) models of colorectal cancer (CRC) and hepatocellular carcinoma (HCC) have demonstrated that FOG-001 can inhibit tumor growth and promote tumor regression when administered as monotherapy or in combination with immune checkpoint inhibitors or standard of care therapies, including bevacizumab and 5-FU. Methods: This first-in-human, Phase 1/2, multicenter, open-label, dose escalation (Part 1) and dose-expansion (Part 2) study evaluates the safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor effects of FOG-001 as monotherapy and in combination with other anti-cancer therapies. Eligible patients must have received at least one prior systemic anti-cancer therapy and either progressed on, not responded to, or be unfit for available therapies. In Part 1, FOG-001 is administered intravenously, either weekly or every other week, at escalating dose levels evaluated sequentially in a standard 3+3 design as monotherapy in patients with: (1a) microsatellite stable (MSS) CRC or any solid tumor with a documented Wnt/b-catenin pathway activating mutation (WPAM) and (1c) HCC with WPAM. Part 1b will evaluate PD effects in cohorts of approximately six patients with MSS CRC. Upon selection of the preliminary recommended Phase 2 dose from Part 1a for weekly dosing, combination dose escalation (1d) evaluates the safety/tolerability, PK and anti-tumor effects of FOG-001 in CRC patients combined with FOLFOX+bevacizumab, anti-PD-1/PD-L1 (also includes other solid tumors with known WPAM), or trifluridine/tipiracil+bevacizumab. Part 2 dose expansion evaluates FOG-001 monotherapy in MSS CRC, HCC, and other solid tumors with documented WPAM. Combination dose expansion evaluates the combinations initially evaluated in Part 1d. Primary endpoints are safety/tolerability and preliminary anti-tumor effects (objective response rate). Secondary endpoints are PK, PD, and other anti-tumor responses (e.g., best objective response, duration of response, and progression free survival). Enrollment in Parts 1 and 2 is ongoing in the USA. Clinical trial information: NCT05919264 .
Association of early tumor shrinkage with survival in patients with HER2-positive advanced gastric cancer treated with trastuzumab deruxtecan.
Authors: Koshiro Fukuda, Akira Ooki, Hiroki Osumi, Shota Fukuoka, Koichiro Yoshino, Mikako Tamba, Shohei Udagawa, Keitaro Shimozaki, Mariko Ogura, Takeru Wakatsuki, Keisho Chin, Mitsuhiro Fujishiro, Eiji Shinozaki, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2025)

360 Background: Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate composed of an anti-human epidermal growth factor receptor 2 (HER2) antibody and a cytotoxic topoisomerase I inhibitor, has been approved as third or later-line treatment for unresectable HER2-positive advanced gastric cancer (AGC) based on the results of phase II DESTINY-Gastric 01 trial. However, there are few studies on real-world clinical outcomes and clinicopathological factors associated with efficacy of T-DXd in patients with HER2-positive AGC. Methods: This single-center retrospective study enrolled patients with AGC treated with T-DXd as third- or later-line chemotherapy between March 2018 and December 2023. Early tumor shrinkage (ETS) was defined as the relative change in the sum of longest diameters of RECIST target lesions at 8 ± 2 weeks compared with baseline. Prognostic outcomes were assessed using the log-rank test and Cox proportional hazards regression model. Results: A total of 57 patients were enrolled. The median age was 66 years (range, 31–82); 68% were male; 79% had HER2 3+; 23% had pulmonary metastasis; 67% were treated with T-DXd in the third-line setting. At a median follow-up of 27.6 months, the median progression-free survival (PFS) was 4.5 months (95% confidence interval [CI], 3.8–5.5), and the median overall survival (OS) was 7.3 months (95% CI, 4.9–9.4). Among 40 patients with target lesions, the overall response rate was 35.0% and the disease control rate was 90.0%. Patients with ETS had notably longer PFS (median PFS (months) 8.6 vs 4.1, P &lt; 0.01) and OS (median OS (months) 9.1 vs 6.1, P &lt; 0.01) than those without ETS. In multivariate analysis, ETS was associated with significantly longer PFS (hazard ratio [HR], 0.23; 95% CI, 0.08–0.63; P = 0.004) and OS (HR, 0.27; 95% CI, 0.12–0.65; P = 0.004), whereas pulmonary metastasis was associated with significantly shorter OS (HR 2.46, 95% CI, 1.07–5.65; P = 0.03). Conclusions: This study showed that achieving an ETS was significantly associated with a favorable prognosis in patients with HER2-positive AGC treated with T-DXd.
Nationwide analysis of Medicare expenditure and utilization of EGFR inhibitors from 2018-2022.
Authors: Devang Namjoshi, Mansi Mehta, Vaibhavi Mukhtiar, Gunjan Rana, Kala Seetharaman
Journal: Journal of Clinical Oncology (2025)

112 Background: EGFR inhibitors are used extensively for treatment of metastatic colorectal cancer ranging from first line drugs in combination with chemotherapy to monotherapy for refractory disease. As we increasingly move towards targeted treatments for cancer, financial implications of these drugs must be taken into consideration. In this study we aim to analyze changes in Medicare spending for Cetuximab and Panitumumab to better understand the financial impact of these therapies. Methods: We obtained data from the publicly available Medicare Part D database from Centers for Medicare and Medicaid Services. Data on total spending, total claims, total beneficiaries, average spending per claim, and average spending per beneficiary was extracted from the database. We adjusted the data for 2018 for 2022 using a standard annual inflation rate. Percentage change was calculated using the adjusted data. Results: For Cetuximab, we saw a sharp increase in total spending by 38.77%, from $4,912,903.87 in 2018 to $6,811,781.05 in 2022. The number of claims rose by 31.96%, while the total number of beneficiaries saw a modest increase of 2.44%. Average spending per claim increased by 16.04%, and average spending per beneficiary grew by 49.44%. Panitumumab showed a similar rise in total spending by 43.23%, from $1,594,347.66 in 2018 to $2,283,142.83 in 2022. Claims increased by 25.42%, and beneficiaries grew by 47.83%. Average spending per claim increased by 25.97%, and average spending per beneficiary saw a substantial rise of 65.75%. Conclusions: Our results indicate a significant increase in the financial burden related to EGFR inhibitors. As we move away from chemotherapy and shift our focus to targeted therapies, it is imperative to explore generic alternatives and direct policy changes to ensure equitable access across various racial and socio-economic groups. These findings highlight the need for further research into healthcare policy reforms to ease the burden on our health system. Drug Year Total Spending ($) Total Claims Total Beneficiaries Avg Spending/Claim ($) Avg Spending/Beneficiary ($) Cetuximab 2018 4,912,903.87 551 123 8,072.80 36,163.51 2022 6,811,781.05 727 126 9,369.71 54,061.75 % Change 0.3877 0.3196 0.0244 0.1604 0.4944 Panitumumab 2018 1,594,347.66 5,955 184 242.72 30,714.91 2022 2,283,142.83 7,470 272 305.81 50,736.51 % Change 0.4323 0.2542 0.4783 0.2597 0.6575
Evaluation of the impact of lymph node ratio on survival in patients with pancreatic cancer undergoing neoadjuvant therapy.
Authors: Maren Thomas, Jamie Huston, Ravi Shridhar, Kenneth Lee Meredith
Journal: Journal of Clinical Oncology (2025)

702 Background: Pancreatic cancer continues to have a dismal prognosis despite improvements in surgical care. Resection status and lymph node status continues to be key factors impacting prognosis. There remains significant debate on the utility of increasing nodal harvest in patients undergoing surgery, while others report an improvement in survival. We sought to evaluate the impact of lymph node positivity to lymph nodes resected in patients with pancreatic cancer undergoing resection. Methods: Utilizing the National Cancer Database, we identified patients diagnosed with pancreatic cancer who underwent neoadjuvant chemotherapy (NCT) or neoadjuvant chemoradiation (NCR) followed by resection. We then stratified by nodal status and calculated a LN+/LNR (lymph node resected) ratio. Pearson’s Chi-square test was used to compare categorical variables. Survival analysis was estimated by the Kaplan-Meier method and associated log-rank test. Propensity score matching (PSM) was completed for variables of age, sex, tumor size, LN removed, LN positive, pathogenic T- stage and N-stage, grade, 30- and 90-day mortality, R0 resection, facility volume, response, adjuvant therapy, and LNR. Significance was considered at p-value ≤0.05. Results: We identified 4117 patients with a median age of 65 (25-90). There were 2323 patients who underwent NCT and 1794 who underwent NCR. The median LN resected in the NCT was 18 vs 15 in the NCR, p&lt;0.001. However, there were more LN+ in the NCT vs NCR, 2.1 vs 0.9, p&lt;0.001. The R0 resection rates were lower in the NCT vs NCR 81% vs 86%, p&lt;0.001. Additionally, complete response rates were higher amongst the NCR, 9.2% vs 4.7%, p&lt;0.001. Lymph node ratios were consistently higher in the NCT cohorts among all ratio strata, p&lt;0.001. Patients with pN+ disease had a median and 5-year survival of 26.4mo and 17% compared to their pN- counterparts at 38.8mo and 36%, p&lt;0.001. Patients treated with NCT demonstrating a LNR of 0.01-0.1 had median and 5-year survival of 32.8 and 27%, LNR 0.11-0.4 (25.5mo and 12%), and LNR&gt;0.4 (19.1mo and 10%), p&lt;0.001. Patients treated with NCR demonstrating a LNR of 0.01-0.1 had median and 5-year survival of 29.1 and 21%, LNR 0.11-0.4 (25.8mo and 17%), and LNR&gt;0.4 (21.3mo and 5%), p&lt;0.001. PSM confirmed a higher LNR in the NCT cohort compared to NCR, p&lt;0.001, however survival was also longer in these patients among the LNR 0.01-0.1, and 0.11-0.4, p&lt;0.001. Conclusions: Lymph node status in patients with pancreatic cancer continues to be a significant prognostic indicator of survival. Moreover, lymph node ratio may be a more accurate predicter of survival in patients undergoing neoadjuvant chemotherapy and neoadjuvant chemoradiation.
Development and validation of a prognostic model for advanced gastric and oesophageal carcinoma (AGOC) using individual patient data from two clinical trials.
Authors: Sayeda Kamrun Naher, David Espinoza, Peter S. Grimison, Kohei Shitara, Nick Pavlakis, David Goldstein, Martin R Stockler, Rebecca Mercieca-Bebber, Katrin Sjoquist
Journal: Journal of Clinical Oncology (2025)

499 Background: Estimating survival in advanced gastric and oesophageal carcinoma (AGOC) remains a significant challenge. We developed a prognostic model incorporating readily accessible patient and clinical data and specific patient-reported outcomes (PROs), utilizing individual participant data from two randomized trials. Methods: We used data from 2 trials comparing regorafenib to placebo; AGITG INTEGRATE IIa (n=251) for model development and AGITG INTEGRATE (n=152) for validation. Both trials enrolled metastatic or AGOC following failure of 1 or more prior lines of systemic therapy. Candidate variables were chosen from systematic literature review and expert consultation. Significant prognostic factors for inclusion in the multivariable model were identified using univariable Cox proportional hazards models with p-value threshold of 0.1. Multivariable models were developed via Lasso regression. An initial model was created using clinical variables alone, followed by the integration of PROs. C statistics were used to discriminate the model’s efficiency. Results: Univariable analysis identified 9 clinical variables and 4 PRO domains as significant, including body mass index (BMI)(p=0.08), ECOG PS (0.02), extent of cancer (p&lt;0.001), liver involvement (p=0.04), treatment with regorafenib (p=0.005), neutrophil-lymphocyte ratio (NLR) (p&lt;0.001), LDH (p&lt;0.001), albumin (p&lt;0.001), and CA 19-9 (p=0.007). Significant baseline PROs included appetite loss (p&lt;0.001), constipation (p&lt;0.001), fatigue (p&lt;0.001), and pain (p&lt;0.001). Gastrectomy violated the Cox model proportional hazards assumption necessitating that the analysis be stratification by gastrectomy. The primary model (M1) incorporated region (Asia vs non-Asia, p=0.25, was included because it was significant in previous analysis (INTEGRATE), ECOG PS status, cancer extent, treatment with regorafenib, NLR, BMI, LDH, CA 19-9, and albumin. The final model (M2), which included PROs, demonstrated superior discriminative ability with the highest c-statistic values in both the gastrectomy and non-gastrectomy strata. The c-statistic increased from 0.695 for M1 to 0.723 for M2, indicating the added prognostic value of including PROs. Conclusions: The prognostic model that integrated both clinical data and PROs, proved robust for predicting survival in AGOC. The addition of PROs significantly enhanced prognostic accuracy, highlighting their importance in survival models. Further validation and refinement of the model is ongoing.