tbuckley/cabot-search huggingface dataset:
Neoadjuvant immunotherapy for locally advanced/metastatic mismatch repair deficient colorectal cancer: A two-year institutional experience.
Authors: Maeve O'Neill, John Larkin, Paul McCormick, Brian Mehigan, Charles Gillham, Delia Flannery, Katrina O'Connor, David James Gallagher, Grainne M. O'Kane, Michael E Kelly
Journal: Journal of Clinical Oncology (2025)

179 Background: MMRd is a tumour agnostic biomarker predictive of response to immune checkpoint inhibitors (ICIs). Given the poor response to 5-FU based chemotherapy, ICIs are now being explored in early MSI-H CRC. The outcomes on this strategy are limited. Methods: We retrospectively evaluated early outcomes for patients receiving neoadjuvant ICIs for unresectable locally advanced/oligometastatic MMRd colorectal cancer (CRC), where intention of treatment was downstaging to permit curative resection. Following discussion at regional MDT, suitable patients were administered a PD-1 inhibitor 6-weekly until disease progression or improvement rendering suitability for surgical resection (to max of 2 years). Results: From October 2022-September 2024, ten patients with MMRd CRC were commenced on neoadjuvant ICIs. These comprised six right, one left sided colonic and three rectal tumours. Median age at diagnosis was 59 (IQR54–68). Four patients had family history of CRC. One patient had clinical stage II, seven stage III and two patients oligometastatic stage IV disease. All were patients with initially unresectable disease, with potential for curative resection pending response to ICI. Histologically, two tumours were poorly differentiated, two mucinous phenotype and six moderately differentiated adenocarcinomas. BRAF mutation was identified in three patients. None had KRAS mutation. Three rectal cancers received radiotherapy in addition to immunotherapy. Five required a defunctioning stoma either prior to or on ICI. Median follow-up was 12.5 months (IQR7-17). Objective response rate by RECIST 1.1 was 100%, with significant downstaging in 9 of 10 patients. The remaining patient is early in treatment course with no reimaging. To date, complete clinical response (cCR) has been observed in three patients (33%). All 10 patients are alive. Grade 3-4 treatment-related adverse events occurred in two patients (20%) who developed treatment-related strictures (one also had tumour perforation). This was successfully managed with defunctioning ileostomy and antibiotics, with subsequent cCR. Conclusions: We report impressive early outcomes of immunotherapy for locally advanced/metastatic MMRd CRC, with excellent downstaging and high predicted cCR. This highlights the importance of screening all CRC for MSI-H/MMRd. In the setting of initially unresectable CRC, an ICI-first approach can render patients eligible for surgery, however deep responses can result in local effects including strictures and/or perforation.
Clinical outcome of radiofrequency ablation in elderly hepatocellular carcinoma patients over 80 years old.
Authors: Kenta Takaura, Kaoru Tsuchiya, Nobuharu Tamaki, Yutaka Yasui, Hiroyuki Nakanishi, Namiki Izumi, Masayuki Kurosaki
Journal: Journal of Clinical Oncology (2025)

603 Background: The SURF trial showed the efficacy and safety of radiofrequency ablation(RFA). However, patients over 80 years old were excluded from the study. Aims: To evaluate clinical outcomes of RFA for largest hepatocellular carcinoma (HCC) diameter ≤3 cm, and ≤3 HCC nodules in patients over 80 years. Methods: Patients who underwent RFA at our institution for initial treatment of largest HCC diameter ≤3 cm, and ≤3 HCC nodules from January 2011 to December 2023. Treatment outcome and prognosis were examined in the elderly group for cases 80 years or older and in the non-elderly group for cases under 80 years. The Cox proportional hazards model was used to analyze the factors associated with treatment outcome and prognosis. Results: Of the 518 eligible patients, 136 patients were 80 years or older. Median overall Survival (OS) was 80 (95%CI 60-96) vs. 123 (95%CI 101-NA) months (p=0.021) in the elderly vs. nonelderly group. The median recurrence-free survival was 16 (95%CI 14-22) vs. 26 (95%CI 19-30) months (p=0.023), better in the non-elderly group, Interestingly, for liver disease-related deaths, median OS was 97 (95% CI 80-NA) vs. NR (95% CI NA-NA) months (p=0.62) in the elderly vs. non-elderly group. In the multivariate analysis, factors associated with OS were ALBI grade 2 or 3 (HR 1.67, 95%CI 1.07-2.60), DCP ≥ 40mAU/ml (HR 2.08, 95%CI 1.42-3.05), persistent HCV infection (HCV non-SVR) (HR 5.45, 95%CI 3.07-9.67), nonviral liver disease (HR 4.18, 95%CI 2.31-7.55). HCC recurrence was significantly associated with male (HR 1.51, 95%CI 1.18-1.94), elderly group (HR 1.46,95%CI 1.10-1.95), PT ≥80% (HR 0.69, 95%CI 0.53-0.91), DCP ≥40mAU/ml (HR 1.37, 95%CI 1.07-1.76), and HCV non-SVR (HR 1.73, 95%CI 1.35-2.21). The factors associated with liver disease-related death were ALBI grade 2 or 3 (HR 2.16, 95% CI 1.25-3.73), DCP ≥ 40mAU/ml (HR 2.34, 95% CI 1.48-3.70) and HCV non-SVR (HR 2.22, 95% CI 1.39-3.56). Conclusions: In RFA for diameter ≤3 cm, and ≤3 HCC nodules, over 80 years was not a significant factor associated with OS or liver disease-related death. The results support that RFA would be a promising treatment option for HCC patients over 80 years.
The prevalence and prognostic significance of <i>KRAS G12C</i> mutation in metastatic colorectal cancer.
Authors: Joseph Lutz, Mohamed Khamis, Omar Alkharabsheh, Ibrahim Halil Sahin, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2025)

289 Background: Kristen rat sarcoma virus ( KRAS ) mutations are reported in 40-45% of colorectal cancer (CRC), and they are associated with poor prognosis. KRAS G12C mutation is reported in 3-4% of CRC patients and may be associated with worse prognosis compared to RAS non-G12C mutations. Here, we explored the prevalence and prognostic significance of KRAS G12C mutation compared to RAS non-G12C and BRAF V600E in a cohort of CRC patients from a tertiary cancer center in the United States (US). Methods: The cBioCancer Genomics Portal was used to obtain genomic data. The prevalence of KRAS G12C mutation, RAS non-G12C ( KRAS G12D, KRAS G13D, KRAS G12V, KRAS A146T, KRAS G12A, KRAS G12S, KRAS G13C, KRAS V14I, KRAS Q61H, KRAS G12R, KRAS Q61R, KRAS K117N, NRAS Q61K , NRAS Q61R , NRAS Q61L , NRAS Q61H , NRAS G13D , NRAS G13C NRAS G13R NRAS G12D , NRAS G12C , NRAS G12V, NRAS G12V and NRAS G60V ) mutations and BRAF V600E mutations was calculated. The median overall survival (mOS) was explored in CRC (MSK, Cancer Cell 2018 cohort). Patients in this cohort were not treated with KRAS G12C targeted therapy. Survival analysis was performed using the Kaplan-Meier method with log-rank test comparisons. Results: In this cohort of patients with stage IV CRC (N=1134), the prevalence of KRAS G12C mutation in patients with stage IV CRC was 3.1%. In patients with RAS non-G12C mutations, BRAF V600E mutation, and RAS/BRAF V600E wild-type (WT), the prevalence was 41.7%, 7.5%, and 47.7% respectively. The mOS in KRAS G12C mutation, RAS non-G12C mutations, BRAF V600E mutation, and RAS/BRAF V600E WT was 65 months (m), 55m, 19m and 105m respectively. Compared to RAS non-G12C , the mOS of CRC patients with KRAS G12C was (65m vs 55m, p=0.54) . Compared to patients with BRAF V600E mutation, the mOS was better in patients with KRAS G12C (65m vs. 19m, p &lt;0.0001) and in patients with RAS non-G12C (55m vs. 19m, p &lt;0.0001). Conclusions: The prevalence of KRAS G12C mutation in this cohort was relatively similar to other reports at 3.1%. Consistent with several other reports, there was no statistically significant difference in the mOS between patients with KRAS G12C mutation and patients with RAS non-G12C mutations. Patients with BRAF V600E mutations had worse mOS compared to patients with KRAS G12C mutation and RAS non-G12C mutations. The reported high mOS in this cohort is possibly due to selection bias (patients able to afford and receive treatment at this tertiary center).
CK2 expression gastrointestinal cancer: Exploring clinical characteristics and cancer genetics.
Authors: Nicholas Wilson, Cristián Figueroa, Isabelle Kreber, Isabel M. Dominguez
Journal: Journal of Clinical Oncology (2025)

834 Background: The expression of protein kinase CK2 subunits (CSNK2A1, CSNK2A2, CSNK2A3, and CSNK2B) in gastrointestinal cancers has not been fully characterized. In this study, we seek to evaluate how changes in CK2 subunit expression are associated with GI cancer clinical characteristics and genetics. Methods: Data analysis was performed with data from The Cancer Genome Atlas (TCGA). R version 4.2.2 was used for analysis. We provide an analysis of several cancer cohorts looking at CK2 subunit expression, as well as cancer mutations, copy number alterations, and clinical characteristics. Results: From the TCGA datasets containing mRNA expression data, we assessed hepatocellular carcinoma (n=361), colorectal adenocarcinoma (n=339), gastric adenocarcinoma (n=306) and diffuse type gastric adenocarcinoma (n=69), pancreatic adenocarcinoma (n=169), esophageal adenocarcinoma (n=89) and squamous cell carcinoma (n=95), and cholangiocarcinoma (n=36). We explored associations between CK2 subunit expression and GI cancer-specific known driver mutations, of which we report the following significant findings (p &lt; 0.05 for all). Mutations in TP53 were associated with increased expression of CSNK2A1 in hepatocellular carcinoma and stomach adenocarcinoma, increased CSNK2A2 in colorectal adenocarcinoma, and CSNK2B in colorectal adenocarcinoma, pancreatic adenocarcinoma, and stomach adenocarcinoma. Mutations in KRAS were associated with increased expression of CSNK2A1 and CSNK2B in pancreatic adenocarcinoma. Mutations in BRAF were associated with decreased expression of CSNK2A2 and CSNK2B in colorectal adenocarcinoma. We also noted significant changes in CSNK2 subunit expression when looking at mutations and copy number alterations in signaling pathways such as Wnt, NOTCH, PI3K, TGFβ, and more. We also explored associations between CK2 subunit expression and GI cancer clinical characteristics, of which we report the following significant findings (p &lt; 0.05 for all). In colorectal adenocarcinoma, increased CSNK2A2 expression was associated with lymph node invasion and advanced clinical stage. In hepatocellular carcinoma, increased CSNK2A1 and CSNK2A3 expression was associated with greater tumor grade, tumor size, and more advanced clinical staging. Increased CSNK2A2 expression was associated with greater tumor size, more advanced clinical staging, and vascular invasion. Increased CS2NKB expression was associated with increased tumor grade, size, and vascular invasion. In pancreatic adenocarcinoma, increased CSNK2A3 expression was associated with a worse response to the first treatment course. Conclusions: Our results suggest that changes in protein kinase CK2 expression are associated with different cancer clinical characteristics as well as cancer-specific mutations and signaling pathways.
Can an alteration of the gut microbiome increase risk of gastrointestinal malignancies? Insights from the National Inpatient Sample.
Authors: Sweta Lohani, Suriya Baskar, Chaula Desai, Fiqe Khan, Rajiv Midha, Udhaya Baskar, Anush Vasikaran
Journal: Journal of Clinical Oncology (2025)

841 Background: The gut microbiome is composed of trillions of microorganisms, inhabiting the lining of the gastrointestinal (GI) tract. The gut microbiome plays multiple roles in upholding human health including maintaining metabolism and regulating immune homeostasis. Dysregulation of the gut flora is known as gut dysbiosis. Studies have shown that gut dysbiosis is linked to the development of malignancies such as colorectal cancer. The purpose of this study is to assess the correlation between an altered gut flora and development of GI malignancies. Methods: The National Inpatient Sample was queried between 2016-2020 for all adult patients with altered gut flora, defined by history of gastrointestinal/bariatric surgeries, history of clostridium difficile infection, long-term antibiotic use, and inflammatory bowel disease. Rates of various cancers were compared between this cohort and all other patients utilizing chi-squared tests. Binary logistic regressions were utilized to calculate odds ratios of developing the various cancers, adjusted for age, sex, Charlson Comorbidity Index (CCI), and smoking status. Results: A total of 7,758,168 hospitalizations with altered gut flora were identified. Esophageal cancer (aOR 3.16, 95% CI 3.08 - 3.24) and colorectal cancer (aOR 3.15, 95% CI 3.11 - 3.18) were observed to have the highest odds of occurring in patients with altered gut flora. Gastric, hepatobiliary, pancreatic, and neuroendocrine cancers also all had significantly higher odds of occurring in patients with altered gut flora. Conclusions: Our study shows that conditions altering the gut flora are associated with increased odds of malignancies of the GI tract. This suggests that the gut microbiome may play an intricate role in regulation of tumor cell proliferation. Optimization of gut health and restoration of gut flora may prove beneficial to patients at high risk for malignancies of the GI tract. Altered Gut Flora (%) Intact Gut Flora (%) Adjusted Odds Ratio (CI) p-value Esophageal 0.4 0.1 3.16 (3.08 - 3.24) &lt;.001 Gastric 0.3 0.1 1.67 (1.64-1.69) &lt;.001 Colorectal 2.5 0.6 3.15 (3.11 - 3.18) &lt;.001 Hepatobiliary 0.4 0.3 1.04 (1.02 - 1.07) &lt;.001 Pancreatic 0.6 0.3 1.34 (1.31 - 1.37) &lt;.001 Neuroendocrine 0.2 0.1 1.38 (1.33 - 1.44) &lt;.001
Comparing outcomes for early and late drainage of malignant ascites.
Authors: Suriya Baskar, Anuj Sharma, Davin Turku, Chaula Desai, Anush Vasikaran
Journal: Journal of Clinical Oncology (2025)

842 Background: Malignant ascites (MA) is a common sequela of peritoneal carcinomatosis resulting in significant morbidity and poses substantial management challenges for clinicians. Large volume paracentesis remains the gold standard treatment. The impact of time to drainage of MA is poorly studied. The purpose of this study was to compare clinical outcomes of hospitalized patients with MA that had drainage performed within 48 hours of admission and after 48 hours of admission. Methods: The NIS was queried between the years 2016 and 2020 to identify all adult patients hospitalized with malignant ascites (ICD-10 code R18.0) and had a drainage procedure performed (ICD-10 Procedure code 0W9Gx). These patients were then stratified into an early cohort (&lt;48 hours after admission) and late cohort (&gt;48 hours after admission). Baseline characteristics and clinical outcomes were collected and analyzed using chi squared tests, independent sample t-tests, and binary logistic regression (adjusted for age, gender, and Charlson comorbidity index or CCI). Adjusted Odds ratios (aOR) are presented with 95% Confidence intervals (CI). Results: A total of 129,040 patients were analyzed, with 89,905 (69.7%) hospitalizations in the early cohort and 39,135 (30.3%) in the late cohort. Baseline characteristics were similar between the groups, with no significant differences in age (63.8 vs 63.6, p = .06) or gender distribution (63.6% vs 63.1%, p = .09). However, patients in the early paracentesis group exhibited a lower CCI (9.8 vs 10.2, p&lt;.001). Notably, early paracentesis was associated with significantly improved outcomes, including lower mortality (aOR 0.67, 95% CI 0.64–0.69), reduced incidence of sepsis (aOR 0.67, 95% CI 0.65–0.69), decreased need for transfusions (aOR 0.69, 95% CI 0.66–0.71), lower rates of mechanical ventilation (aOR 0.44, 95% CI 0.42–0.47) and vasopressor use (aOR 0.79, 95% CI 0.73–0.87). Conclusions: Early paracentesis in patients with malignant ascites was found to be associated with significantly improved clinical outcomes, independent of comorbidity burden. These findings underscore the importance of timely intervention to mitigate complications and enhance quality of life. Late ParacentesisN=39,135 EarlyN=89,905 p-value Age (years) 63.6 ± 13.1 63.8 ± 13.0 .06 Gender (% female) 24665 (63.1%) 57120 (63.6%) .09 CCI 10.2 ± 3.1 9.8 ± 3.2 &lt;.001 Mortality 5720 (14.6%) 9030 (10.0%)aOR .67 (.64 - .69) &lt;.001 Sepsis 7675 (19.6%) 12525 (13.9%)aOR .67 (.65 - .69) &lt;.001 Transfusion 5275 (13.5%) 8605 (9.6%)aOR .69 (.66 - .71) &lt;.001 Ventilation 2130 (5.4%) 2190 (2.4%)aOR .44 (.42 - .47) &lt;.001 Vasopressor 770 (2.0%) 1385 (1.5%)aOR .79 (.73 - .87) &lt;.001
Evaluation of event-free survival (EFS) as a surrogate for overall survival (OS) in patients with locally advanced esophageal carcinoma (LA EC) receiving definitive chemoradiotherapy (dCRT).
Authors: Manish A. Shah, Weiguang Xue, Karthik Ramakrishnan, Jenny Zhou, Yan Meng, Sonal Bordia, Adriana Valderrama
Journal: Journal of Clinical Oncology (2025)

412 Background: Drug development in esophageal cancer is rapidly evolving, and identifying surrogates for patient outcomes to accelerate clinical drug development remains an important unmet medical need. Although early clinical endpoints such as EFS, disease free survival (DFS) are proven to be valid surrogates for overall survival (OS) in early esophageal (Ajani JA et al. 2022), gastric (Oba K et al. 2013; Wainberg ZA et al. 2023), and gastroesophageal junction tumors (Ronellenfitsch U. et al. 2013) after disease resection, there are no such surrogacy data evaluating patients who underwent non-operative management. Specifically, there has been no prior systemic evaluation of the predictive value of EFS as a surrogate for OS among LA EC patients treated with dCRT. This study evaluated the trial-level correlation between EFS and OS in unresectable LA EC patients receiving dCRT. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of dCRT interventions in unresectable LA EC (search cutoff date: April 2023). Studies reporting EFS (or similar outcomes such as progression free survival (PFS), defined as time from randomization to local, regional, or distant recurrence, or death) and OS were included. EFS and OS hazard ratios (HRs) of each treatment comparison were extracted. Correlation between the log(HR) of EFS and OS was assessed using weighted linear regression (WLR). The coefficient of determination (R 2 ) was used to evaluate the strength of the correlation. A good surrogate was defined as an R 2 ≥ 0.65 (Ciani et al . 2017) or an R 2 ≥ 0.75 (Lassere et al . 2008). Leave-one-out cross-validations and sensitivity analyses were conducted to assess the robustness of the WLR model and correlation analyses, respectively. Results: The final analysis included 14 between-treatment comparisons from 11 RCTs (total number of patients = 2,812). We found a strong statistical correlation between EFS and OS, with an estimated slope coefficient of 0.91 ( p &lt; 0.001) and R 2 of 0.80 (95% confidence interval [CI]: 0.38, 0.96). In the leave-one-out cross validation, 71.4% of observed OS HRs fell within the predicted 95% CIs. Sensitivity analyses showed R 2 of 0.75 among studies conducted in China and R 2 of 0.73 after including studies that did not report EFS definition. Conclusions: In a pooled analysis of 11 clinical trials corresponding to over 2800 patients, we observed a strong statistical correlation between EFS and OS outcomes. This analysis supports the utility of EFS as a valid surrogate of OS in patients with unresectable LA EC receiving dCRT.
Phase II study of mFOLFIRINOX efficacy as first and subsequent lines of advanced gastrointestinal neuroendocrine tumors G3 and neuroendocrine carcinomas therapy.
Authors: Yaroslav Zhulikov, Ekaterina Evdokimova, Vera Gorbunova, Galina Emelianova, Alla Anatolievna Markovich, Abidat Kachmasova, Vera Delektorskaya, Elena Kovalenko, Kizler Gadzhieva, Elena Artamonova
Journal: Journal of Clinical Oncology (2025)

659 Background: Gastrointestinal (GI) neuroendocrine carcinomas (NEC) are rare tumors and account for 3% of all NECs. Despite the differences in genetic characteristics, treatment principles of GI NECs are extrapolated from lung NECs. The standard first-line therapy is platinum and etoposide-containing regimens, which allow to achieve a median PFS of 5-6 months. A small retrospective study demonstrated the potential effectiveness of the mFOLFIRINOX regimen with a median PFS of 5.4 months, despite that the majority of patients (pts) received this regimen as second or subsequent lines. The aim of this study is to evaluate mFOLFIRINOX +/- somatostatin analogues (SA) efficacy in GI NEC subgroup. Methods: This prospective, single center phase II study used a two-stage Simon design. The primary endpoint is disease control rate (DCR) ≥ 6 months. Statistical hypothesis: investigated therapy improves DCR compared with historical control from 50 to 70%. Secondary endpoints are progression-free survival (PFS), overall survival (OS), objective response. At the first stage, enrollment of 16 pts was planned (α=0.05, power 80%). If a disease control ≥ 6 months was achieved in at least 9 of the 16 pts, it was planned to continue enrollment up to 39 pts. Here we present results of the first stage of this study. Inclusion criteria: pts ≥18 y.o. with histologically confirmed advanced GI NEC or neuroendocrine tumor (NET) G3 ki67≥55%; ECOG 0-2. Recruitment of pts was carried from 2019 to February 2024. Results: The study included 16 pts, 12 male and 4 female. The most common sites of primary tumor are stomach (N=8, 50%) and pancreas (N=5, 31.3%). 10 (62.5%) pts had large cell carcinoma, 1 – small cell carcinoma (6.3%), 5 (31.3%) – NET G3. The median ki-67 was 70% (40-95%). 15 pts (93.7%) had IV stage, 1 (6.3%) – III. The most common site of metastases is liver – 11 (68.8%), more than half of pts have isolated metastases in liver (N=9, 56.3%). ECOG status was evaluated as 0-1 in 15 (93.7%) cases. Majority of pts (N=14, 87.5%) received mFOLFIRINOX as first line therapy. 7 pts (46.7%) had positive expression of SSTR-2A or -5 and received concurrent treatment with SA. ORR was 62.5% (N=10/16), stable disease – 37.5% (N=6/16). DCR ≥ 6 months was 93.7% (N=15). With a median follow-up of 13.2 months, median PFS was 10.8 months (95% CI 7.57-14.1). One pts had serious adverse event - myocardial infarction, no grade 5 toxicity was observed. Conclusions: Chemotherapy with mFOLFIRINOX showed promising results in GI NECs or NETs G3 ki67≥55% treatment. Primary endpoint was met, enrollment of patients in the study continues.