tbuckley/cabot-search huggingface dataset:
Modified Frailty Index (mFI-5) as a prognostic tool of mortality, complications, and readmissions in patients undergoing hepatic ablation for hepatocellular carcinoma.
Authors: Sushrut Ingawale, John Vellek, Arup Ganguly, Mariam Farhan
Journal: Journal of Clinical Oncology (2025)

610 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, often diagnosed late, limiting curative options. Transarterial chemoembolization, Y-90 radioablation, radiofrequency ablation, and thermoablation are commonly used for downstaging, transplant bridging, and palliation in unresectable HCC. Frailty, linked to postoperative complications, has not been studied in hepatic ablation patients. This study evaluates the predictive value of the modified frailty index (mFI-5) for mortality, readmissions, complications, redo procedures, and discharges. Methods: We utilized the National Surgical Quality Improvement Program (NSQIP) database from 2015 to 2019, querying cases of hepatic ablation for CPT codes: 47370 (closed hepatic ablation, single site) and 47380 (open hepatic ablation, single site). Selected cases were analyzed for frailty using the mFI-5 criteria. A multivariate analysis was performed using mFI-5 frailty scores, stratified into non-frail (0), pre-frail (1), frail (2), and severely frail (3+). The outcomes analyzed included mortality, discharge to a destination other than home, major complications, minor complications, readmission, and reoperation. Results: We identified 1921 patients as: 737 non-frail, 701 pre-frail, 442 frail and 41 severely frail. The rates of readmission (5.4%), reoperation (1.4%), major (5.3%) and minor (3.5%) complications were low. Eight patients died following hepatic ablation, and 79 patients were discharged to a destination other than home. In multivariate analysis, most outcomes were not significantly associated with increasing frailty. However, discharge to a destination other than home was significantly more likely in patients with higher frailty scores. In frail patients, the odds ratio (OR) was 2.325 (95% CI 1.228–4.402), and in severely frail patients, this increased to 8.720 (95% CI 3.389–22.435). Conclusions: Hepatic ablation is generally well tolerated with low complication rates; however, frailty significantly influences postoperative outcomes. Frail and severely frail patients are more likely to be discharged to care facilities rather than returning home, suggesting that even in the absence of major complications, these patients require a higher level of post-procedural care. This underscores the need for tailored discharge planning and resource allocation based on patient frailty.
Focusing on clinical trial ineligibility: Nivolumab plus chemotherapy for patients with advanced gastric cancer.
Authors: Iori Motoo, Takayuki Ando, Yurika Nakayama, Yuko Ueda, Shinya Kajiura, Kohei Ogawa, Hiroaki Takagi, Kenichiro Tsukada, Kazuhisa Tabata, Yuno Ohya, Hotaka Tamura, Ayumu Hosokawa, Ichiro Yasuda
Journal: Journal of Clinical Oncology (2025)

355 Background: Nivolumab demonstrates promising efficacy when combined with chemotherapy as first-line treatment in patients with advanced gastric cancer (AGC). However, a large proportion of patients are perceived as ineligible for clinical trials in clinical practice. The aim of this study is to analyze the treatment outcomes and safety among patients deemed ineligible in clinical trials for AGC. Methods: A retrospective examination was conducted involving 187 patients who received treatment for HER2-negative unresectable or recurrent AGC between December 2014 and October 2023 at six institutions. Eleven patients were excluded due to massive ascites or poor performance status (PS). Ineligible patients were defined as meeting any of the seven criteria: age 75 years or over, PS 2, bone marrow dysfunction, hepatic dysfunction, renal dysfunction, serious complications, and extended bone metastasis. Of the 104 patients meeting these criteria, individuals were divided into the ICI group (nivolumab plus chemotherapy) and the non-ICI group (chemotherapy only). A comparative assessment of survival outcomes and tumor responses between the two groups was performed. Additionally, the incidence of immune-related adverse events (irAE) in the ICI group was assessed. Results: The ICI group comprised 57 patients, while the non-ICI group comprised 47 patients. The median follow-up for survival analysis was 11.6 months. In the ICI group, response rate (RR), median progression-free survival (mPFS), and median overall survival (mOS) were 48.7% among patients with measurable lesions, 7.4 months (95%CI, 5.3-10.0), and 15.1 months (95%CI, 13.1-21.0). In the non-ICI group, RR, mPFS, and mOS were 33.3%, 6.4 months (95%CI, 4.1-7.8), and 11.8 months (95%CI, 10.1-14.6). The OS in the ICI group was significantly better than those in the non-ICI group (log-rank p = 0.0436). Furthermore, irAEs were observed in eight patients (14.0%), including hypothyroidism (n=3), arthritis (n=2), hypopituitarism (n=2), and dermatitis (n=1). No patients discontinued treatment due to intolerable irAEs. Conclusions: The combination of nivolumab and chemotherapy showed a favorable outcome even in AGC patients with ineligible group.
Comparative restricted mean survival time (RMST) analysis of survival in advanced hepatocellular carcinoma (aHCC) from pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW.
Authors: Roberto A. Pazo Cid, Carmen Blanco Abad, Paula Gomila Pons, Ana Comin Orce, Marta Gascon Ruiz, Sara Elena Campos Ramírez, Pablo Gomez, Maria Alvarez Alejandro, Irene Torres, Luis Sarría, Raquel Larrosa, Alejandro Serrablo, Javier Fuentes Olmo
Journal: Journal of Clinical Oncology (2025)

597 Background: In advanced hepatocellular carcinoma (aHCC), the evaluation of overall survival (OS) and progression-free survival (PFS) through restricted mean survival time (RMST) provides a nuanced understanding of treatment efficacy. The RMST analysis serves as a valuable complement to the hazard ratio (HR) analysis, offering insights into the average survival time over a specified period. This study compares RMST analyses of OS at 24 and 36 months, and PFS at 12 and 18 months, across five pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW. Methods: Data from the experimental arms of the five phase III trials were analyzed. The RMST was calculated using the area under the Kaplan-Meier survival curves up to the specified time points. Specifically, OS was evaluated at 24 and 36 months, and PFS at 12 and 18 months. The RMST provides an estimate of the average time that patients survive (for OS) or remain progression-free (for PFS) within a specific timeframe. Kaplan-Meier survival curves were digitized if not available in raw form, and the area under the curve (AUC) was computed using numerical integration methods. RMST values were extracted from the AUC for the specified periods. This approach accounts for censored data and provides a robust comparison of survival times across different treatment groups. Results: The results for OS RMST at 24 and 36 months and PFS RMST at 12 and 18 months are summarized in the table. Conclusions: Angiogenesis inhibitor + immune checkpoint inhibitor combinations (Atezolizumab + Bevacizumab; Sintilimab + IBI305) provide the most favorable RMST outcomes in terms of OS and PFS. Restricted mean survival time (RMST) comparison of OS and PFS (months). aHCC 1L Phase III Trials Treatment Arm OS 24m OS 36m PFS 12m PFS 18m IMbrave-150 1, 2 Atezolizumab + Bevacizumab 17.50 22.79 9.69 13.29 ORIENT-32 3 Sinitilimab + IBI305 17.01 21.09 9.18 12.54 CARES-310 4 Camrelizumab + Rivoracenib 16.34 19.75 9.29 12.14 HIMALAYA 5, 6 Tremelimumab + Durvalumab 15.36 18.76 8.95 12.02 CM-9DW 7, 8 Nivolumab + Ipilimumab 15.87 20.08 8.74 11.78 1 Finn et al. N Engl J Med 2020;382:1894-905; 2 Cheng et al. J Hepatol 2022;76:862-873; 3 Ren et al. Lancet Oncol 2021;22:977–90; 4 Qin et al. Lancet 2023;402:1133–46; 5 Abou-Alfa et al. NEJM Evid 2022;1(8):EVIDoa2100070; 6 Sangro et al. Ann Oncol 2024;35:448-457; 7 Galle et al. J Clin Oncol 2024;42(suppl 17):abstr LBA4008; 8 Decaens et al. Ann Oncol 2024;35:S657.
Exploration of novel biomarkers and novel therapies for immune checkpoint inhibitors (ICIs) in genetic variants of esophageal squamous cell carcinoma (ESCC): A study of 1,059 Japanese cases.
Authors: Ryuichi Morita, Takeshi Ishikawa, Toshifumi Doi, Junichiro Itani, Daiki Sone, Naoto Iwai, Masahiro Iwasaku, Ken Inoue, Osamu Dohi, Naohisa Yoshida, Kazuhiko Uchiyama, Tomohisa Takagi, Hideyuki Konishi, Koichi Takayama, Yoshito Itoh
Journal: Journal of Clinical Oncology (2025)

495 Background: In Japan, cancer genome profiling (CGP) tests will be covered by insurance in 2019, and more than 1,000 ESCC cases have been accumulated in the national database. ICIs are currently the key drugs for esophageal cancer, and MSI and TMB status can work as biomarkers for ICIs in solid tumors. Therefore, to improve the prognosis of esophageal squamous cell carcinoma (ESCC), we aim to search for gene variants that may predict the efficacy of ICIs and explore the possibility of new treatment from genetic data accumulated in the Japanese nation-wide C-CAT database. Methods: We retrospectively analyzed 1,059 ESCC cases from C-CAT data accumulated from June 2019 to February 2024. We used the registered clinical and genetic information to examine gene variants and carcinogenic pathways that could serve as biomarkers for ICIs. Results: Of the 1059, 152 (14.4%) had TMB-H and 3 (0.3%) had MSI-H, with a median TMB of 5.0 Muts/Mb (range: 0-268). XPO1 and TP53 were found to be positively and negatively correlated as genes affecting TTF in nivolumab monotherapy (FDR P value &lt; 0.01). TMB has the potential to be a biomarker for ICI, but TMB was significantly higher in the group with variants in the ARID family ( ARID2 , ARID1A plus ARID5B ) (median TMB 5.0 vs 8.0 Muts/Mb, P&lt;0.001). In addition, 709 patients (66.9%) had any variants in three pathways (TP53, RTK and cell cycle), which are thought to be involved in the carcinogenesis of ESCC. PIK/Akt/mTOR and epigenetic modulation pathways were also found to be abnormal in many cases, and abnormalities in the epigenetic modification pathway were found to contribute significantly to TMB-H (FDR P value&lt;0.01, Logarithmic value=19.2). Conclusions: This is the first case-specific report on the relationship between mutations in the ARID family and TMB in ESCC and the signalling pathways leading to carcinogenesis. In the present study, the association between the ARID family and TMB, and between abnormalities in the epigenetic modification pathway and TMB, which has been previously reported in other cancer types but not in esophageal cancer, suggests that multiple pathological mutations including these may be new biomarkers for ICI in 1059 Japanese patients. Furthermore, multiple pathways are often involved in ESCC carcinogenesis at the same time, and a separate, combined approach that takes these into account may be necessary in the development of new drugs.
Influence of MRP4 levels on clinical outcomes in biliary tract cancer.
Authors: Gerardo F. Arroyo, Ana Sahores, Ana Carolina Ituarte, Cristina Inklemona, Sandra Rojo, Ruben Dario Kowalyszyn, Carlos Davio, Maria May
Journal: Journal of Clinical Oncology (2025)

624 Background: Biliary tract cancer (BTC) are rare tumors with a poor prognosis.Multidrug resistance protein 4 (MRP4) is a transmembrane efflux transporter that influences on cellular growth and differentiation. Recent studies have linked high MRP4 levels to increased aggressiveness in pancreatic cancer and other tumor types. This study aimed to evaluate the role of MRP4 in BTC and its association with clinical outcomes in a real-world cohort from endemic areas in Argentina. Methods: We conducted a retrospective analysis of clinical outcomes and MRP4 expression in paraffin-embedded tissue samples from 78 patients with BTC. Immunohistochemistry staining was performed, and MRP4 expression was scored based on staining intensity and the percentage of positive cells. A score exceeding 100 was classified as high MRP4 levels. Statistical analyses included Chi-square, Kaplan-Meier survival curves, and log-rank tests, with significance set as p &lt;0.05 (two-tailed). Results: High MRP4 levels were observed in 46 out of the 78 samples (59%). Patients with gallbladder cancer (n=64) and elevated MRP4 levels had significantly poorer overall survival (OS) compared to those with low MRP4 levels (median 11.3 and 14.5 months, high and low, p =0.038). In the broader BTC cohort evaluable for survival (n=73; 64 gallbladder, 7 cholangiocarcinoma, 1 ampulla of Vater, and 1 biliary undefined) patients with elevated MRP4 levels had non-significant shorter OS (median 12.4 and 13.5 months, high and low, p =0.17). Poorly differentiated tumors were more likely to express high MRP4 levels ( p =0.06). High MRP4 expression was found in 59% of localized stages (0-II) and in 57% of advanced stages (III, IV and relapsed). Conclusions: High MRP4 expression is common in BTC, particularly gallbladder cancer, and could be a marker of poor prognosis. MRP4 levels appear more elevated in poorly differentiated tumors, and are similar in both, early and advanced stages, suggesting its involvement in early tumor progression. Further prospective studies are needed to confirm MRP4 as a biomarker. If MRP4 is a driver gene, targeting with inhibitors could represent a promising therapeutic strategy for these challenging tumors.
Updated trends in incidence and mortality of pancreatic cancer. an analysis of the Surveillance, Epidemiology, and End Results (SEER) database.
Authors: Olanipekun Lanny Ntukidem, Oboseh John Ogedegbe, Sakshi Bai
Journal: Journal of Clinical Oncology (2025)

786 Background: Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. The prognosis for pancreatic cancer remains poor despite advances in cancer therapy. In this study, we provide updated trends in pancreatic cancer incidence and mortality using the SEER database, with a subset analysis of age and gender. Methods: Using the SEER Stat software, we gathered data from the Surveillance, Epidemiology, and End Results (SEER) database (2000–2021). We employed Jointpoint regression to analyze the secular trend of incidence and incidence-based mortality (IBM), which we classified and arranged according to age and sex. Results: 235,116 cases met the inclusion criteria for our study. These included diagnosed cases of pancreatic cancer from 2000 to 2001. The total age-adjusted incidence rate was 12.5 per 100,000. 118,791 (50.5%) were males and 116,325 (49.5%) were female. While the annual percentage change (APC) from 2000-2019 was 0.92 (p &lt; 0.05), signifying an annual cumulative increase, APC from 2019-2021 was -0.085, signifying an annual cumulative decrease. For males, the APC was 0.94 (p &lt; 0.05) from 2000 to 2018 and -0.55 from 2018-2021, and for females, the APC was -0.89 (p &lt; 0.05) from 2019-2021. The pancreatic cancer IBM APC from 2000-2022 was 22.60 (p &lt; 0.05) and 0.54 (p &lt; 0.05) from 2002-2021. For males, IBM APC was 21.10 (p &lt; 0.05) from 2000-2002 and 0.58 from 2002-2021. For females, IBM APC was 25.15 from 2000-2002 and 0.42 from 2002-2021. We also studied pancreatic cancer IBM based on age. For 30-49 years, APC from 2000-2002 was 34.65 (p &lt; 0.05), and -0.64 (p &lt; 0.05) from 2002-2021. For 50-69 years, APC from 2000-2002 was 28.05 (p &lt; 0.05) and 0.3 from 2002-2021. For 70+ years, APC from 2000-2002 was 21.28 (p &lt; 0.05) and 0.73 from 2002-2021. Conclusions: There was a statistically significant rise in incidence and incidence-based mortality across the board, underscoring the need for improved diagnostic and therapeutic modalities of management of pancreatic cancer.
Leveraging large-scale PDO-based assays to optimize antibody-drug conjugate efficacy in CRC.
Authors: Lélia Polit, Jacques RR Mathieu, Cartry Jerome, Sabrina Bedja, Alice Boileve, Michel Pierre Ducreux, Fanny Jaulin, Gustave Ronteix
Journal: Journal of Clinical Oncology (2025)

261 Background: Clinical trials are one of the major barriers in contemporary drug development. Functional assays based on patient-derived organoids (PDO) are a promising new tool for derisking clinical development of new therapies, but their use has been limited due to small cohort sizes and the absence of systematic validation studies. Using the largest cohort of matched PDOs, longitudinal clinical data, transcriptomic and WES data in CRC, we explore the use of large PDOs collections to characterize ADC efficacy and affinity through systematic mapping of the relationship between target antigen affinity and payload efficacy. Methods: We have assembled a collection of 85 PDOs from colorectal cancer (CRC), generated from primary tumour samples and metastatic biopsies. Patients ranged from 32 to 89 years old and had experienced an average of 1.54 lines of treatment prior to the PDO-generating tissue sampling. Using gene expression levels of well known target antigens such as CEACAM5, ERBB2, MSLN and TROP2 as a proxy for protein concentration, we explore the relationship between the target antigen affinity and the efficacy of a subset of common payloads including topoisomerase and microtubule inhibitors. This allows us to identify the relationship between two of the three main vectors of ADC efficacy in CRC. Results: We show that topoismerase inhibitor and microtubule inhibitor efficacy relates to the RNA expression level of multiple target antigens commonly used in active clinical trials in CRC. These data match the target antigen and payload couples currently under development or approved in the clinic. We are developing a tool to optimize clinical trial design. This approach will allow us to match patients more accurately with the appropriate payload, ensuring a higher likelihood of response. Conclusions: We report that large-scale PDO-based assays can be a useful tool to anticipate clinical readouts. This work suggests that well-characterized PDO collections could also help redefine patient populations, increasing the likelihood of identifying those more likely to respond to a given ADC, and thus improving the success rates of clinical studies for new treatments in CRC.
A comparison of real-world outcomes by mismatch repair status in patients with stage II/III rectal cancer in the Netherlands.
Authors: Renee A Lunenberg, Ingrid Franken, Frederieke H van der Baan, Femke P C Sijtsma, Geraldine R Vink, Miriam Koopman, Martijn P.W. Intven, Manon Braat, Leon Moons, Miangela M Lacle, Marloes Elferink, Susan Boklage, Jamie Garside, Rob van Wuijtswinkel, Jeanine Roodhart
Journal: Journal of Clinical Oncology (2025)

260 Background: A subset of rectal tumours (~3–5%) have mismatch repair deficiency (dMMR); the remaining are classified as MMR proficient (pMMR). A recent trial for stage II/III dMMR rectal cancer (RC) showed that 6 months of neoadjuvant treatment with dostarlimab, a programmed cell death protein 1 inhibitor, induced a 100% clinical complete response rate and allowed for organ preservation. Using real-world data from the Netherlands, a dMMR patient cohort was compared to a matched pMMR cohort to assess if clinical outcomes differed, even after matching for baseline characteristics. Methods: Utilizing data from the Netherlands Cancer Registry, this retrospective analysis assessed patients with stage II/III RC treated from 2015–2022 with known MMR status. The dMMR cohort was matched 1:2 to a cohort of pMMR patients on age, year of diagnosis, tumour clinical (cT) stage, and node clinical (cN) stage. Event-free survival (EFS; defined as first occurrence of locoregional failure, distant metastasis, a new primary colorectal tumour, or death from any cause) and overall survival (OS) were compared using Kaplan-Meier methodology and a univariable Cox model. Results: Among the 7939 patients included, 184 (2.3%) had dMMR tumours. After matching and a loss of 8 dMMR patients due to ineligibility, 176 dMMR patients were compared to 363 pMMR patients. Matching successfully removed differences in age, cT, and cN stage; however, dMMR patients continued to have more BRAF mutants (p=0.014), more poorly differentiated tumours (p&lt;0.001) and more variation in histology (p=0.01). dMMR patients had a statistically significant lower risk of experiencing an event (hazard ratio [HR] 0.54 [95% confidence interval (CI) 0.38–0.77], p&lt;0.001), with a 3-year EFS of 79.6% (95% CI 73.7–86.1) compared to pMMR patients (64.7% [95% CI 59.8–70.1]). For OS, there was no significant difference between the dMMR and pMMR cohorts (HR 0.73 [95% CI 0.47–1.16], p=0.181); however, within the small group of patients with an event, OS at 1 year for dMMR patients was 68.4% (95% CI 55.1–84.9) compared to 93.5% (95% CI 89.5–97.7) for pMMR patients (p=0.001). Conclusions: dMMR RC is rare, and tumour characteristics differ from those of patients with pMMR tumours (1). After controlling for clinical stage and age, this study suggests dMMR patients have improved EFS compared to pMMR patients. There is no significant difference in OS between groups but dMMR patients with an event have worse OS than pMMR patients, highlighting an additional need to prevent recurrence of disease within dMMR patients.1. Lunenberg, R et al. Poster presented at ESMO Congress (Presentation 569P), 13-17 Sept 2024, Barcelona, Spain.