tbuckley/cabot-search huggingface dataset:
The immunogenomic landscape of primary and metastatic gastroesophageal adenocarcinoma.
Authors: Xin Wang, David Chen, Yvonne Bach, Gavin W Wilson, Hiroko Aoyama, Frances Allison, Valentin Sotov, Christine Tran, Michelle Restrepo, Eric Xueyu Chen, Lucy Xiaolu Ma, Elliot Wakeam, Jonathan Yeung, Rebecca KS KS Wong, Patrick Veit-Haibach, Sangeetha Kalimuthu, Ben X Wang, Raymond Woo-Jun Jang, Benjamin Haibe-Kains, Elena Elimova
Journal: Journal of Clinical Oncology (2025)

493 Background: Metastatic gastroesophageal adenocarcinoma (GEA) is a heterogeneous disease with an overall poor prognosis. The tumour microenvironment (TME) between the primary and metastatic compartment is not well characterized. This study aims to describe the immunogenomic features of matched primary and metastatic GEA and their correlation with clinical outcomes. Methods: We performed whole exome sequencing (WES, n=36) and total RNA sequencing (RNA-seq, n=36) on a prospectively collected cohort of metastatic GEA, of which 14 had matched primary and metastatic tissues. We used TME deconvolution (Bagaev et al., 2021) comparing between the primary and metastatic compartments. Using an orthogonal technology, we further integrated immune checkpoint-directed multiplex immunohistochemistry (mIHC) for 22 patients with matched primary and metastatic samples. Results: The median age of our cohort was 61 (range 27-89), primarily male (n=28, 77%), and non-Asian (n=32, 89%). All had metastatic GEA at time of diagnosis. Differential expression showed activation of immune pathways such as tumor necrosis factor signalling and interferon-gamma response in the metastatic compartment. Deconvolution of the TME demonstrated 29% of primary tissues having an immune-inflamed TME compared to 61% of metastatic tissues (p=0.032). Exploring immune cell types, metastatic compartment is characterized by higher abundance of naïve and mature B cell populations (p&lt;0.001), while primary compartment is enriched with CD4+ T cells (p&lt;0.01). In matched cases, only 2 of 14 (14%) had concordant TME subtypes between primary and metastatic samples suggesting high degree of immune divergence. Furthermore, expression of common immune checkpoints aligned more with TME subtypes than within patient compartments suggesting common pathways of immune evasion. M-IHC showed both T-cell and immune checkpoint markers are enriched at the tumor margins compared to the tumor center in both primary and metastatic compartments (CD4; p&lt;0.0001, CD8; p&lt;0.001, CD68; p&lt;0.001). There was a significant increase in the number of CD68+/CD163+/PDL1+ M2-like macrophages in the tumor margins (p&lt;0.0001). Consistent with our deconvolution analysis, there are higher CD4+ T cells in the matched primary compared to metastatic samples. Long-term survivors (&gt;16 months) had decreased number of CD68+ macrophages in the tumor center (p=0.019). Conclusions: Primary and metastatic GEA have divergent TME. This may partially explain varying responses to chemo-immunotherapy approaches. Therapies aimed at modifying TME may provide personalized treatment options.
Racial, gender and socioeconomic disparities in survival outcomes of hepatocellular carcinoma.
Authors: Oboseh John Ogedegbe, Olanipekun Lanny Ntukidem, Sakshi Bai, Asfand Yar Cheema, Ahmed Bashir Sukhera, Jorge Rodriguez Vazquez, Gloria Erazo
Journal: Journal of Clinical Oncology (2025)

526 Background: Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer worldwide, with mortality rates increasing globally, particularly in the Western world. The 5‐year survival rate of persons with HCC is less than 20%. It is, therefore, essential to investigate the extent to which social determinants of health influence survival outcomes. In this study, we explored the effect of gender, race/ethnicity and socioeconomic factors on survival outcomes among patients with HCC in the United States. Methods: We extracted data on patients with a histologic diagnosis of hepatocellular carcinoma from the Surveillance, Epidemiology and End Result (SEER) Registry from 2000-2021. The primary outcome of interest was the cause-specific survival of these patients. According to the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) system, the histological code of HCC is 8170/3. We excluded patients of missing or unknown race, income, location, and patients outside the years of study. Cox proportional hazard regression (SPSS) was utilized to determine the association between patients' race/ethnicity, gender, annual median income, location and cause-specific survival. Results: 80,445 met the criteria and were included in our study. Gender proved to be a predictor of survival; compared to females, males had worse outcomes, with males HR 1.040 (95% CI; 1.020-1.060, p = &lt;0.001). Race was a predictor of survival outcomes. Using American Indian/Alaska Native as our reference, Asian/Pacific Islander HR 0.847 (95% CI; 0.790-0.90, p = &lt;0.001), Black HR 1.019 (95% CI; 0.950-1.093, p = 0.603), White HR 0.955 (95% CI; 0.893-1.023, p = 0.186). We also analyzed the effects of socioeconomic factors on survival. Patients with higher annual median income had better outcomes. &gt;$120000 HR 0.817 (95% CI; 0.783-0.851, p = &lt;0.001) while patients with lower annual median income had worse outcomes &lt; $40000 HR 1.217 (95% CI; 1.134-1.305, p &lt; 0.001). The effect of location on survival was not significant. Compared to non-metropolitan areas, metropolitan areas HR 0.988 (95% CI; 0.971–1.004, p = 0.138). Conclusions: Race/ethnicity, income and gender disparities all played a significant role in cause-specific survival in patients with HCC, with improved survival observed in females, Asians and patients with higher annual median income. More efforts are needed to bridge these survival disparities.
Analysis of clinically actionable alterations in baseline tumor versus plasma samples in participants of the TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer.
Authors: Do-Youn Oh, Shukui Qin, Lorenzo Antonuzzo, David Tougeron, Choong-kun Lee, Benjamin R. Tan, Masafumi Ikeda, Julie Wang, Hung-Ying Lin, Young S Lee, Patricia McCoon, Juan W. Valle
Journal: Journal of Clinical Oncology (2025)

625 Background: In the TOPAZ-1 study (NCT03875235), durvalumab + gemcitabine and cisplatin (D+GC) significantly improved overall survival (OS) versus placebo + GC (P+GC) in participants (pts) with advanced biliary tract cancer. Updated results have shown a clinically meaningful long-term OS benefit for D+GC versus P+GC at 3 years. This exploratory analysis tested circulating tumor DNA (ctDNA) in plasma samples for blood-based detection of clinically actionable alterations (CAAs) and investigated the potential of this method to guide treatment decisions. Methods: Baseline genomic alterations were retrospectively assessed in evaluable tumor (FMI biomarker evaluable population [BEP], n=441) and plasma samples (GH BEP, n=643) using FoundationOne (Foundation Medicine Inc., Cambridge, MA) and Guardant INFINITY (Guardant Health, Redwood City, CA) assays, respectively. Mutation prevalence and association with outcomes were compared in the FMI BEP and GH BEP. Positive and negative percent agreement of CAAs detected in tumor versus ctDNA were assessed in 419 pts with both tumor and plasma samples (FMI-GH BEP). Results: The FMI BEP and GH BEP represented 64% and 94% of the TOPAZ-1 final analysis set (685 pts), respectively. The relative prevalence and overall mutational landscape detected in plasma ctDNA was consistent with that observed by tumor profiling, with the notable exception that genes harboring complex alterations (e.g. gene amplification, rearrangements, or homozygous deletions) were less frequently detected in ctDNA (e.g. ERBB2 , FGFR2 , and CKDN2A/2B/MTAP ). The most common alterations (&gt;15% prevalence in both BEPs) observed were in TP53 (49%/52%), KRAS (24%/17%), and ARID1A (21%/16%) (in the FMI/GH BEPs, respectively). The relative prevalence of alterations within geographic and anatomic subgroups was similar in tumor versus plasma for most CAAs. The overall percent agreement in CAAs was ≥93%, and negative percent agreement was ≥97%. However, positive percent agreement was notably low for ERBB2 amplification (52%) and FGFR2 fusions (47%). OS hazard ratios for D+GC versus P+GC in the GH BEP were &lt;1 for both CAAs and wild-type, except for ERBB2 amplification, as previously reported in the FMI BEP. Conclusions: The overall concordance and relative prevalence of simple mutations (e.g. single nucleotide variants) were similar using the FoundationOne tumor assay and Guardant INFINITY ctDNA assay, suggesting that plasma ctDNA testing has potential utility in clinical practice. However, negative status by ctDNA for the complex alterations found in FGFR2 and ERBB2 would require further testing of tumors, based on their low detectability in plasma. Clinical trial information: NCT03875235 .
Efficacy and safety of durvalumab and gemcitabine-based chemotherapy combined with or without lenvatinib in advanced biliary tract cancer.
Authors: Qi Ding, Haobin Yu, Yubei Sun, Gang Wang, Ruipeng Song
Journal: Journal of Clinical Oncology (2025)

595 Background: Immunotherapy in combination with gemcitabine-based chemotherapy, has now become the standard first-line treatment for advanced biliary tract cancer (BTC). Some small-sample studies have shown that immune checkpoint inhibitors (ICIs), when used in combination with lenvatinib and chemotherapy as first-line therapy, exhibit high anti-tumor activity in BTC. Therefore, we conducted a retrospective study to assess the efficacy and safety of durvalumab and gemcitabine-based chemotherapy with or without lenvatinib, in combination for advanced BTC in the real world. Methods: Between January 2021 and September 2024, patients with advanced BTC who received either durvalumab combined with or without lenvatinib, along with gemcitabine-based chemotherapy, were enrolled in this study. The study endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Thirty patients with advanced BTC were included in this study. Fourteen (46.7%) patients had received durvalumab combined with lenvatinib plus chemotherapy. For all the patients, the median OS was 9.5 months(95% CI: 4.98-14.02), and the median PFS was 5.9 months(95% CI: 4.56-7.24). ORR was 43.4% and DCR was 76.7%. Patients with lenvatinib treatment had a longer median PFS (7.1 vs. 4.6 months, P = 0.06) compared with the non-lenvatinib treatment group. However, the median OS was shorter in patients with lenvatinib treatment group (9.0 vs. 9.5 months, P = 0.915). ORR and DCR in patients with lenvatinib were 57.1% and 92.9%, respectively. However, in patients without lenvatinib treatment group, ORR and DCR were only 31.2% and 62.5%, respectively. All patients experienced adverse events (AEs), addition of lenvatinib does not increase the risk of AEs. The data is still being updated. Conclusions: Durvalumab and gemcitabine-based chemotherapy combined with or without lenvatinib has shown to be effective and safe in routine practice. Regarding lenvatinib, its addition has only improved the DCR, ORR, and PFS, but has not been able to prolong OS.
A phase 3 study of first-line sotorasib, panitumumab, and FOLFIRI versus FOLFIRI with or without bevacizumab-awwb for patients with <i>KRAS</i> G12C–mutated metastatic colorectal cancer (CodeBreaK 301).
Authors: Tae Won Kim, Timothy Price, Julieta Grasselli, John H Strickler, Toshiki Masuishi, Gin Wai Kwok, Suayib Yalcin, Cynthia Chinedu Obiozor, Emily Chan, Priya Gokani, Yu Sunakawa
Journal: Journal of Clinical Oncology (2025)

TPS326 Background: CodeBreaK 300 (NCT05198934) evaluated sotorasib, a selective inhibitor that irreversibly binds to the Kirsten rat sarcoma ( KRAS ) G12C mutant protein, in combination with panitumumab, an anti–epidermal growth factor receptor inhibitor, and showed that 960 mg sotorasib + panitumumab provided a statistically and clinically significant improvement in progression-free survival compared with trifluridine/tipiracil or regorafenib in patients with chemorefractory metastatic colorectal cancer (mCRC) (1). In CodeBreaK 101 (NCT04185883) subprotocol H expansion cohort 2F, the addition of folinic acid, fluorouracil, and irinotecan (FOLFIRI) to this combination in the first-line setting demonstrated a manageable safety profile and promising response rate of 78% in patients with KRAS G12C–mutated mCRC (2). The current study aims to evaluate whether the combination of sotorasib, panitumumab, and FOLFIRI is superior to FOLFIRI with or without bevacizumab-awwb, a VEGF inhibitor, in the first-line setting for mCRC. Methods: CodeBreaK 301 (NCT06252649) is a phase 3, multicenter, randomized, open-label, active-controlled study of sotorasib, panitumumab, and FOLFIRI versus FOLFIRI with or without bevacizumab-awwb as first-line therapy for patients with KRAS G12C–mutated mCRC. Key eligibility criteria include mCRC with KRAS G12C mutation confirmed by central molecular testing, and no prior therapy for metastatic disease. Approximately 450 patients will be randomized 1:1 to receive either sotorasib, panitumumab, and FOLFIRI, or FOLFIRI with or without bevacizumab-awwb. The primary endpoint is progression-free survival assessed by a blinded independent central review of disease response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). The key secondary endpoint is overall survival, and additional secondary endpoints include objective response rate and depth of response. Global enrollment is ongoing. 1. Fakih, NEJM 2023. 2. Siena, ESMO 2024. Clinical trial information: NCT06252649 .
Identification of candidate biomarkers for gastric cancer by bioinformatics analysis of pooled microarray gene expression datasets in Gene Expression Omnibus.
Authors: Fen Wang, Fen Wang
Journal: Journal of Clinical Oncology (2025)

467 Background: Gastric cancer (GC) remains one of the most prevalent malignant diseases worldwide. The high mortality rate is largely due to the limited treatment options and the challenges in diagnosing the cancer at an early stage. Understanding the genetic differences driving the proliferation of GC is crucial for advancing diagnostic methods and developing targeted treatments. This study aims to identify biomarkers involved in the pathogenesis of GC through integrated bioinformatics analysis. Methods: Extracted from the Geo Expression Omnibus, three DataSets (GSE118916, GSE79973, and GSE13861) were analyzed for differentially expressed genes (DEGs) using the R statistical language. The three data sets were then compared for common DEGs, which would serve as the focus of this study. These DEGs were functionally analyzed for pathways by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein–protein interaction (PPI) network was constructed to screen out candidate genes. Results: The results revealed that 123 DEGs of the three datasets containing 26 upregulated genes and 97 downregulated genes were ascertained in our study. The GO and KEGG enrichment analysis results showed that the functions of DEGs were mainly involved in the retinol metabolic process, xenobiotic metabolic process, collagen type I trimer, potassium: proton exchanging ATPase complex, benzaldehyde dehydrogenase (NAD+) activity, alcohol dehydrogenase (NADP+) activity, Collecting duct acid secretion, and Tyrosine metabolism. Through the PPI analysis network, the core genes with the highest degree of 7 nodes were selected: COL1A1, COL1A2, COL11A1, THBS2, ATP4A, COL10A1, and CXCL8. Conclusions: The 7 genes identified in this study may play a vital regulatory role in the occurrence and development of GC and may also be potential therapeutic targets. Further mechanistic studies of the pathogenesis and treatment of GC may be able to identify new targets using these shared pathways. These findings could contribute to a better understanding of the origins of gastric cancer and facilitate the development of early interventions. The bioinformatics analysis conducted in this study offers new insights and directions for further research on gastric cancer.
Nimotuzumab combined with chemotherapy plus immunotherapy as first-line treatment for advanced esophageal squamous cell carcinoma.
Authors: Quanli Han, Qi Wang, Zhi Cui, Muhong Deng, Yue Ma, Fang Pang
Journal: Journal of Clinical Oncology (2025)

344 Background: Esophageal squamous cell carcinoma (ESCC) is the primary type of esophageal cancer with poor prognosis in China. Chemotherapy plus immunotherapy as first-line standard treatment has limited benefit in advanced ESCC patients. Nimotuzumab, a humanized anti-EGFR antibody, exhibited favorable efficacy in advanced ESCC with good safety profile. We explored the efficacy and safety of nimotuzumab as first-line therapy for patients with advanced ESCC. Methods: In this retrospective study, patients were aged ≥ 18 years with histologically diagnosed advanced ESCC, ECOG of 0-3, given nimotuzumab (400 mg, Q3W) combined with chemotherapy (paclitaxel: 300-400mg and platinum: 400-500mg or tegafur: 60mg/bid, Q3W) plus immunotherapy (PD-(L)1: 200-240 mg, Q3W). They assigned into two groups: metastasis group and locally advanced group. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR) and safety. Results: As of July 2024, 58 patients were enrolled (metastasis group: n=20, locally advanced group: n=38). The median age was 59.5 years (range: 44-80). The median follow-up was 32.59 months (95% CI: 23.0, 36.7). The ORR was 74.1% (95% CI: 0.6, 0.8). Survival analysis showed that the 1-year OS was 79.16% (95% CI: 64.5, 88.3) and 2-year OS was 57.38% (95% CI: 41.3, 70.5), 1-year PFS and 2-year PFS was 64.41% (95% CI: 49.4, 76.0) and 32.80% (95% CI: 19.7, 46.5), respectively. The median OS (mOS) was 31.01months, the median PFS (mPFS) was 17.84 months. Nimotuzumab plus chemotherapy and immunotherapy displayed a favorable survival outcomes both in metastasis group and locally advanced group with OS (1-year OS: 77.76% and 80.37%; 2-year OS: 62.21% and 55.91%) and PFS (1-year PFS: 53.46% and 69.99%; 2-year PFS: 25.06% and 36.66%), the mOS was not reached and 31.01 months, mPFS was 18.27 months and 16.69 months, respectively. There were 74.1% patients occurred grade 1-2 adverse events (AEs), and 13.8% occurred grade 3-5 AEs. The most common AEs included nausea (60.3%), myelosuppression (51.7%), leukopenia (41.4%), thrombocytopenia (29.3%), and neutropenia (24.1%). No serious treatment-related AEs or death recorded. Conclusions: This study demonstrated a favorable survival profile and acceptable toxicity in first-line treatment of advanced ESCC patients with nimotuzumab regimen. Further prospective study needed to certify in order to benefit more patients.
Long-term outcomes and surgical conversion following immunotherapy in MSI-H biliary tract cancers.
Authors: Priyanshi Shah, Anina Peersen, Amit Mahipal, Fang-Shu Ou, Nguyen H. Tran
Journal: Journal of Clinical Oncology (2025)

592 Background: Deficient mismatch repair/microsatellite instability (MSI-H) in biliary tract cancers (BTC) is rare, estimated to be 1-5%. MSI-H across solid tumors has shown unprecedented durable response to immune checkpoint inhibitors (ICI) regardless of anatomic location. Here we describe the clinical outcomes of unresectable BTC patients with MSI-H treated with ICIs and their conversion to surgery. Methods: We conducted a multicenter, retrospective analysis of patients (pts) with advanced BTC who had been identified with MSI-H by molecular analysis performed between 2017 and 2024 at Mayo Clinic and University Hospitals Seidman Cancer Center. The outcomes of interest were overall survival (OS), defined as time from initiation of first-line systemic treatment to death; Time-to-treatment failure (TTF), defined as time from initiation of treatment to cessation due to any cause; and response. All analyses were done descriptively. Results: We identified 22 MSI-H pts with BTC, 19 with cholangiocarcinoma and 3 with gallbladder cancer. Median age at diagnosis was 61 (range 26-86), 20 (90.9%) were Caucasian, 9 (40.9%) were male gender, and 5 (22.7%) had etiology as Lynch syndrome. Twelve (54.5%) pts had metastatic disease at diagnosis. Twenty pts (90.9%) received first line systemic therapy, of whom 11 (55%) continued onto second line. Among the 20 pts that received first line therapy, median TTF was 7.6 months (95% CI: 4.8-14.3), objective response was observed in 7 (35%) pts, and disease control was observed in 15 pts (75%). Among the 11 pts that continued onto second line systemic treatment, objective response was observed in 4 pts (36%) and disease control was observed in 6 pts (55%). Among the 20 pts that received first line therapy, 19 (95%) ever received ICI +/- chemotherapy as a part of their treatment plan. Two-year OS for pts who ever received ICI was 63% (95% CI: 41%-96%). In total, 4 pts (20%) were restaged to resectable following treatment with an ICI, underwent resection, and currently have no evidence of disease. Conclusions: Administration of ICI during treatment plan in pts with MSI-H confirmed durable response and even downstage pts to resectable stage for curative intent. Testing for MSI-H should be performed upfront to guide treatment decision.
Clinical-pathologic characteristics in young patients with metastatic colorectal cancer: Experience from a specialized cancer institute in Peru.
Authors: Eder Christian Veramendi Cabana, Stephanie Elizabeth Chaupis Acosta, Cindy Calle, Armando MARTIN Sanchez Yarleque, Paola Mejía, Jackeline Macetas, Angela Leonardo, Juan Carlos Carlos Haro Varas, Victor Roman Paitan Amaro, Cristian Pacheco, Monica Calderon, Victor Castro Oliden
Journal: Journal of Clinical Oncology (2025)

279 Background: Colorectal cancer (CRC) represents the third cause of malignant neoplasm in the world and the second in terms of mortality. CRC is a major cause of cancer-related morbidity and mortality in Peru. Diagnosis at younger ages represents a challenge. In this study, we evaluated prognostic factors in patients who were metastatic at diagnosis or progressed to metastatic disease during follow-up. Methods: A descriptive cross-sectional study, between 2013 and 2022, 66 patients under 40 years old and stage IV at diagnosis were analyzed. Parameters evaluated were age, gender, comorbidity, performance status and stage of the disease at the diagnosis, localization, surgery undergone, systemic treatment regimen, response to first-line treatment, incidence of K-RAS, sites and number of metastases, expression of tumor predictors (CEA levels), and survival times. A multivariate analysis was conducted with factors that were considered statistically significant in the univariate analysis. Results: Median age was 35 years [29.25-37] and the female/male ratio was 34/32. From 66 patients at stage IV disease, 30 patients (45.5%) were right-side, 36 (54.5%) were left-side colon cancer. At the end of follow-up, 51 patients had died, and 15 survived. Overall survival (OS) was significantly better in patients older than 35 years old (p&lt;0,05), those who underwent primary tumor surgery (p&lt;0,001), negative perineural invasion (p&lt;0.0045). The treatment most common was CAPOX with a median OS of 17 months (p&lt;0.013). The multivariate analysis shows that patients who did not undergo primary surgery had worse disease-specific OS (hazard ratio, CI 2.21.95% [1.15-4.25], p&lt; 0.018) and there was no statistical difference between chemotherapy regimens and treatment line. Conclusions: In young patients with metastatic CRC, Primary tumor surgery and negative perineural invasion are significant factors influencing overall survival. Patients older than 35 years and those who underwent surgery showed better survival. These findings reflect the importance of early colorectal cancer screening and improve the risk assessment.