tbuckley/cabot-search huggingface dataset:
Prognostic value of tumor regression grade (TRG) in patients with gastric/gastroesophageal junction cancer treated by peri-operative chemotherapy and surgery: A single-center experience (Institut Mutualiste Montsouris, Paris, France).
Authors: Antoine Lefèvre, Marine Lefevre, Stéphane Bonnet, Emilie Soularue, Raphael Colle, Jean-Marc Ferraz, Mostefa Bennamoun, Marie-Liesse Joulia, David Malka, Olivier Soubrane, Dewi Vernerey, Julie Henriques, Christophe Louvet
Journal: Journal of Clinical Oncology (2025)

486 Background: Management of locally advanced gastric and gastroesophageal junction (GOJ) cancer relies on peri-operative chemotherapy and radical surgery. Response to neoadjuvant chemotherapy can be evaluated by Mandard Tumor Regression Grade (TRG) performed on the removed specimens. The aim of this study was to investigate the prognostic value of TRG, in terms of post-surgical disease-free survival (DFS) and overall survival (OS). Methods: Retrospective analysis of all consecutive patients (Jan 2010 to Dec 2021) who underwent oncological gastrectomy for gastric or GOJ adenocarcinoma after neoadjuvant chemotherapy was performed. TRG was evaluated according to Mandard classification, ranging from 1 (complete pathological response) to 5 (absence of response), TRG 1-2 being considered as “good responders” and TRG 3-5 as “bad responders”. Univariate and multivariate analysis were performed for DFS and OS. Results: One hundred and ninety-nine patients were included, 157 treated with FOLFOX and 42 with FOLFOX + Taxanes (either FLOT or FOLFOX + Abraxane). TRG 1-2 was observed in 30% in patients (pts) treated with FOLFOX and 24% in pts treated with FOLFOX + Taxanes. With a median follow-up over 5 years (yrs), median DFS and OS were not reached (DFS rates at 3, 5 and 10yrs of 66.5%, 64.1% and 55.7%, respectively; OS rates at 3, 5 and 10yrs of 75.6%, 66.8% and 60.4%, respectively). In univariate analysis, TRG 1-2 was significantly associated with favorable outcome compared to TRG 3-5 in terms of DFS (HR 2.4, p-value 0.0056) and OS (HR 2.6, p-value 0.0061), as well as ECOG at diagnosis (0 vs. 1), ypT stage (yp T0-2 vs. yp T3-4), ypN stage (ypN- vs. ypN+), tumor localization (antrum + body vs. cardia + esophagus), and lymphatic, vascular and peri nervous embolisms (negative vs. positive) for both DFS and OS. However, in multivariate analysis (selection backward Cox-model), only ypT stage and vascular embolisms for DFS, and ypT and ypN stages for OS were found to be independent prognostic factors. Conclusions: Although TRG is a prognostic factor in patients with gastric or GOJ cancer, it does not appear as an independent factor for DFS and OS in this series of 199 pts. These results raise the issue of “good responder” definition, especially for TRG 3. Prognostic impact of TRG needs to be investigated for patients treated with combination of immune checkpoint inhibitors and chemotherapy in neoadjuvant regimens.
Histopathological growth patterns of gastric cancer liver metastasis and their association with patient prognosis.
Authors: Dan Sha, Qingchun Zhuang, Liguang Wang, Frank A. Sinicrope, Haiyan Jing, Chunfang Tian, Shuo Zhang, Qian Yang, Jing Sun, Jinshen Wang, Wei Song
Journal: Journal of Clinical Oncology (2025)

484 Background: The histopathological growth patterns (HGPs) of liver metastasis reflect the complicated and varied interactions between tumor cells and the host microenvironment. We studied HGPs of gastric cancer liver metastasis (GCLM) and sought to predict them using radiomic and clinical variables. Methods: Hepatectomy was performed in 62 patients with GCLM at our university hospital between 2011 and 2021. HGPs were evaluated according to international consensus guidelines, and were classified as either desmoplastic HGP (dHGP) or non-dHGP. CD4, CD8, VEGF and CD31 were analyzed by immunohistochemistry. Eight hundred and fifty-one radiomics features were extracted from CT portal venous phase images and the optimal radiomics signature was determined by univariate analysis and LASSO regression. Multivariable regression analyses and ROC curves were used to assess the predictive performance of HGPs with a radiomic and clinical combined model. Results: Among 62 patients, 14 were categorized as dHGP, and 48 as non-dHGP. Non-dHGP vs. d-HGP was associated with higher tumor N stage and CEA level, and with decreased CD8 + T cells, and lower VEGF and CD31 expression. HGP status was independently associated with patient cancer-specific survival (CSS) (P＜0.05) multivariately.Analysis of percent relative contribution revealed that HGP ranked first for CSS (35.9%), ahead of T (28.9%) and N (28.9%) stage. A model with combined radiomic and clinical features demonstrated robust performance with area under the curve (AUC) values of 0.993 and 0.933 in the training and validation sets, respectively. Conclusions: Non-invasive determination of radiomic and clinical features was shown to predict HGPs types. Compared to dHGP, GCLM with non-dHGP exhibited significantly lower immune cell infiltration and decreased angiogenesis. Among features examined in GCLM, HGP was the most robust for prognostication. Univariate and multivariate analysis of prognostic factors for cancer-specific survival. Characteristics Univariate analysis Multivariate rergression analysis HR (95%CI) P HR (95%CI) P Gender ( Women vs Men ) 1.13(0.61-2.09) 0.71 Age ( &gt;60years vs ≤60years) 1.08(0.60-1.70) 0.98 HGP ( non-desmoplastic HGP vs desmoplastic HGP ) 3.63(1.78-7.41) 0.00 3.48(1.37-8.88) 0.01 T stage ( T3-T4 vs T1-T2 ) 2.03(1.08-3.80) 0.03 2.29(1.15-4.58) 0.02 N stage ( N1-N3 vs N0 ) 3.46(1.66-7.23) 0.00 2.54(1.17-5.56) 0.02 CEA ( &gt;5ng/ml vs ≤5ng/ml ) 2.37(1.25-4.48) 0.01 1.56(0.70-3.48) 0.27
Molecular and clinical profiling of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs): An analysis of the Oncology Research Information Exchange Network database.
Authors: Benjamin Edward Ueberroth, Hannah Ruth Robinson, S. Lindsey Davis, Christopher Hanyoung Lieu, Nicole Baranda Balmaceda, Alexander Hayden, Alexis Diane Leal, Sunnie S. Kim, Robert William Lentz, Wells A. Messersmith, Emily Baiyee Toegel
Journal: Journal of Clinical Oncology (2025)

669 Background: The incidence of neuroendocrine tumors (NETs) is approximately 7 per 100,000 persons and rising. By location, tumors in the gastroenteropancreatic (GEP) region, particularly midgut NETs, are most common. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling, providing opportunities to identify novel associations between molecular features and clinical outcomes in GEP-NETs. Methods: Survival analyses were performed using the log-rank testing, and clinical features were evaluated using Wilcoxon and chi-squared tests. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test. Transcriptomic analyses utilized a student’s t-test. We reviewed 240 samples from 226 patients, with 124 of pancreatic origin, 90 small bowel, 16 gastric, and 10 colorectal. All specimens were well-differentiated; further grading information was unavailable on the ORIEN platform. A p-value &lt;0.05 was considered significant. Results: Patients with metastatic disease were significantly younger at diagnosis (58 vs. 61 years, p=0.0242) and had significantly higher tumor mutational burden (TMB) (0.48 vs. 0.32 mut/Mb, p=0.001). Among the 100 most common alterations across the entire cohort, BPTF (p=0.03) and PRKCA (p=0.007) mutations were more prevalent in pancreatic NETs than in other primary sites. The most frequently mutated genes identified included TTN (27.7%), MUC16 (25.1%), CCDC168 (22.1%), KIR3DL1 (20%), TGIF2LX (20%), MUC17 (19.1%). TTN mutation was significantly associated with higher TMB (p&lt;0.0001). The most common copy number alteration was MUC3a amplification (7q22.1) in 61.5% of samples. This amplification was associated with more prolonged overall survival (OS) with a significance of p=0.0501. Patients with NETs harboring a mutation in CSNK2A2 (p=0.0149), WDR74 (p=0.0386), or NCMAP (p=0.0248) experienced significantly shorter OS compared to the cohort as a whole. Conclusions: We report the first clinical, genomic, and transcriptomic analysis of ORIEN GEP-NET cases. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of well-differentiated NETs. Most prevalent mutations in GEP-NETs from ORIEN database. Mutation Prevalence (Percentage of Samples) TTN 27.7% MUC16 25.1% CCDC168 22.1% KIR3DL1 20.0% TGIF2LX 20.0% MUC17 19.1%
Spatial transcriptomics and lethality-associated stromal remodeling of colorectal cancer.
Authors: Colin Wood, Joao Da Silva Filho, Tengyu Zhang, Campbell SD Roxburgh, Paul G. Horgan, Joanne Edwards, Matthias Marti, Colin William Steele, Nigel Balfour Jamieson
Journal: Journal of Clinical Oncology (2025)

227 Background: Colorectal cancer (CRC) is surgically resectable and eminently screenable yet remains a lethal entity with high affinity to metastasise synchronously and metachronously. It has been proposed that cellular and extracellular components of the microenvironment contribute to metastatic potential. Dissociative profiling techniques such as bulk transcriptomic and single-cell RNA sequencing have contributed insight but limited therapeutic progress. Spatial transcriptomic (ST) assessment allows molecular profiling of tissue while preserving tissue architecture. Here we employ ST approaches to interrogate tumor compartments of primary resectable and matched synchronous CRC demonstrating stromal signatures with distinct collagen expression associated with outcome. Methods: 25 patients with primary resectable CRC and 4 patients with matched primary CRC and liver metastasis (CRLM) underwent single-cell spatial transcriptomics using the Nanostring CosMx Spatial Molecular Imager (SMI, 1000plex gene panel) (Discovery cohort). 71681 epithelial and 88806 stromal cells with intact spatial resolution were analysed. The spatial single-cell signatures were reconstituted in 89 patients using the Nanostring GeoMx Digital Spatial Profiler (Validation cohort). 3 GeoMx compartments were analysed: Epithelial (PanCK+); Stroma (aSMA+); Immune (PanCK-aSMA-). Results: CosMx demonstrated 2 distinct collagen signatures: COL1A1,COL1A2,COL3A1 associated with normal fibroblasts; COL9A2 associated with cancer-related stroma and lethal subtypes of epithelial cell. In the GeoMx validation cohort, 42 patients expressed the COL1A1 signature in the aSMA compartment and 47 did not (5 year recurrence free survival: 0.88 vs 0.49, p &lt; 0.005) with different morphological patterns of each distinct aSMA group. In patients with favourable prognosis, chemokine high epithelial subtypes expressed CXCL5 and recruited COL9A2-, IL6+ neutrophils to the surrounding microenvironment. In contrast, epithelial cells in patients with poor prognosis expressed CXCL8 and recruited COL9A2+ neutrophils which were frequently in contact with SPP1+ macrophages. Conclusions: We have used ST approaches to interrogate cellular compartments of CRC demonstrating stromal subtypes that impact outcome. These insights could be used in the clinical setting to quantify COL9A2 expression in aSMA+ cells to prognosticate patients. Targeting of tumor collagen has been proposed to augment existing anti-cancer therapies and this work has demonstrated COL9A2 as a potential target in need of further investigation.
Redefining the use of a first-line FOLFIRINOX-like regimen in older patients with metastatic pancreatic cancer.
Authors: Arthur Winer, Dina Ioffe, Karen J Ruth, Eric A. Ross, Katrina Bynum, Eli Mikkelsen, Igor A. Astsaturov, Christopher G Cann, Namrata Vijayvergia, Vanessa Wookey, Timothy Lewis Cannon, Raymond Couric Wadlow, Jasmine Huynh, Yoomi Lee, Efrat Dotan
Journal: Journal of Clinical Oncology (2025)

681 Background: Prospective elderly-specific data for treating pancreatic cancer are scarce. First-line treatment with triplet chemotherapy (e.g., FOLFIRINOX) is often too toxic for older adults (OA). An alternating regimen of FOLFOX and FOLFIRI (aFOLFIRINOX) has demonstrated efficacy and decreased toxicity in patients with colon cancer. This ongoing multicenter phase II trial evaluates the tolerability and efficacy of aFOLFIRINOX in OA with metastatic pancreatic adenocarcinoma (mPDAC). Herein we report the interim safety analysis results. Methods: Eligible patients (goal n=37) ≥65 years old with measurable untreated mPDAC, ECOG PS 0-2, receive standard doses of FOLFOX alternating with FOLFIRI every 2 weeks for up to 6 months. Patients can continue treatment thereafter at the discretion of their physician. The primary endpoint is rate of treatment-limiting grade ≥3 adverse events (TLAE) per CTCAE v5.0 in the first 8 weeks of therapy. These toxicities are defined as treatment-related grade 3 non-hematologic AE persisting &gt; 2 weeks despite best supportive care, grade 3 anemia or thrombocytopenia, grade &gt;3 neuropathy, or any grade &gt; 4 AE. The study is powered to detect a 20% improvement in grade ≥3 TLAE: null vs alternate: 45% vs 65% of patients without TLAE at 8 weeks. Secondary endpoints include progression free &amp; overall survival (PFS &amp; OS) and objective response rate (ORR). FACT-G and PROMIS-10 quality of life (QOL) surveys and geriatric assessments are collected and will be correlated with treatment outcomes. Results: 21 eligible patients were included in the interim safety analysis: 11 male, 10 female; median age:73 (range 65-82); 18 patients had ECOG PS 0-1. 16 (76%) patients did not experience TLAE as defined above. TLAE included neutropenia, thromboembolism, and hypokalemia, and are similar to reported toxicity with FOLFOX and FOLFIRI in this patient population. One patient died of their disease within 8 weeks of treatment initiation and another within 2 weeks due to pulmonary embolism deemed unrelated to treatment. Of the 18 patients evaluable for response, ORR was 11% (partial response: n =2), Disease Control Rate was 89% (stable disease: n =14). 7 patients completed 6 months of treatment on study. Conclusions: The interim safety analysis of this clinical trial fulfilled the predefined futility rule without excess treatment-limiting or unexpected toxicity among OA with mPDAC treated with first-line aFOLFIRINOX, suggesting this may be a reasonable treatment option in this patient population. Trial is ongoing for evaluation of efficacy data of this regimen. Clinical trial information: NCT05360732 .
Gender imbalance in colon cancer screening rates in Texas: A population-based cohort study.
Authors: Jorge Rodriguez Vazquez, Ahmed Bashir Sukhera, Gloria Erazo, Merry Mathew, Mosffa Ullah, Oboseh John Ogedegbe, Asley Sanchez, John Garza
Journal: Journal of Clinical Oncology (2025)

92 Background: Males have a higher risk of acquiring Colorectal Cancer (CRC) than females. In Texas, males are diagnosed with CRC more than females, regardless of race or ethnicity. Texas CRC screening compliance rates are lower than the national average of 72.2%. It is important to understand the gender trends in screening to apply more specific strategies. Methods: We used the Texas Outpatient Public Use Data File (TOPUDF), a deidentified and publicly available statewide dataset, to conduct a population-based cohort study of outpatient colon cancer screenings of residents age 45 -74 years old at hospitals and ambulatory surgery centers during 2021. Colon cancer screenings were identified using Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes. We queried the National Cancer Institute Surveillance, Epidemiology and End Results Program (SEER) for age grouped populations in 2021 stratified by gender, race, age group, and county of residence. We calculated age-adjusted outpatient colon cancer screening rates per 100,000 population (AASRs) using the direct standardization method based on the age group weights from the 2000 standard US population. Confidence intervals for AASR were derived by estimating the standard error as the AASR divided by square root of number of colon cancer screenings. The statistical significance of the difference between female and male AASR were tested by comparing the intersection of 95% confidence intervals (95% CI) for the individual rates. Subgroup analyses included age group, rural vs urban residence, and race/ethnicity. Results: A total 514,601 outpatient colon cancer screenings were included in the study of which 275, 189 (53.5%) were for female residents. During 2021, 51.1% of state residents age 45-74 years old were female. The overall statewide AASR in 2021 was 6071.5 (95% CI 6054.6 – 6088.4)) with the female AASR (6282.1 [95% CI 6258.1 – 6306.0]) significantly higher than the male AASR (5847.7 [95% CI 5823.9 – 5871.5]). For residents aged ≥ 45 years the statewide AASR was 5580.8 (95% CI 5565.5 – 5596) with the female AASR (5735.2 [95% CI 5715.9 – 5754.4]) significantly higher than the male AASR (5429.8 [95% CI 5410.1 – 5449.6]). Female residents had higher AASR amongst White, Black, and Hispanic race/ethnicity groups with the largest difference observed for Blacks; female AASR 5843.9 (5777.7 - 5910.1) vs male AASR 4733.5 (4668.5 - 4798.5). The difference between male and female outpatient screening rates was significant among both rural and urban residents. Conclusions: Despite a clear relationship between male gender and CRC, females have a higher rate of colon cancer screening. The Black population has the largest gender difference among race/ethnicity groups.
Nivolumab plus ipilimumab in advanced hepatocellular carcinoma with Child-Pugh B: A multicenter retrospective study.
Authors: Jung Sun Kim, Youngun Kim, Beodeul Kang, Chansik An, Ilhwan Kim, Hyeyeong Kim, Chan Kim, Hong Jae Chon
Journal: Journal of Clinical Oncology (2025)

551 Background: The phase 3 CheckMate 9DW trial proposed that nivolumab plus ipilimumab (Nivo/Ipi) significantly improved the survival of patients with advanced hepatocellular carcinoma (aHCC) compared with sorafenib or lenvatinib as first-line treatment, but it only included patients with Child-Pugh A. Given the limited treatment options for patients with poor liver function, we aimed to assess the efficacy and safety of Nivo/Ipi in aHCC patients, stratified by liver function. Methods: This study included patients with aHCC who received Nivo/Ipi treatment at three referral hospitals between March 2020 and September 2023. Patients received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks (four doses), followed by nivolumab (240 mg) every 2 weeks. Results: Of 106 patients treated with Nivo/Ipi, 96 evaluable patients were included in the final analysis. Among them, 76 patients had Child-Pugh A, while 20 had Child-Pugh B. The baseline characteristics were generally comparable between the two groups, except for a significantly higher rate of extrahepatic metastasis in patients with Child-Pugh A (86.8% vs. 65.0%, p = 0.043) and a higher incidence of macrovascular invasion in patients with Child-Pugh B (55.0% vs. 27.6%, p = 0.032). The objective response rate (ORR) was 28.9% (22/76, 4 complete responses [CR] and 18 partial responses [PR]) in the Child-Pugh A group and 10.0% (2/20; 0 CR and 2 PR) in the Child-Pugh B group. Disease control rates were 42.1% in the Child-Pugh A group and 25.0% in the Child-Pugh B group. In a median follow-up duration of 29.3 months (95% confidence interval [CI], 28.8-29.8), the median overall survival (OS) was 8.9 months (95% CI, 5.5-17.6) in the Child-Pugh A group and 3.9 months (95% CI, 2.1-4.8) in the Child-Pugh B group (p &lt; 0.001). The median progression-free survival (PFS) was 1.6 months (95% CI, 1.2-3.5) in the Child-Pugh A group and 1.2 months (95% CI, 0.8-2.1) in the Child-Pugh B group (p = 0.003). Adverse events of any grade occurred at a comparable rate between the two groups, although immune-related adverse events were significantly more frequent in the Child-Pugh A group. Multivariable analysis indicated that Child-Pugh B was consistently associated with a worse PFS and OS, while prior exposure to immune checkpoint inhibitors (ICIs) was associated with a poorer PFS. Notably, both responders with Child-Pugh B were both ICI naïve. Conclusions: While Nivo/Ipi treatment showed reduced efficacy in patients with Child-Pugh B, identifying potential responders beyond the current clinical trial criteria may offer opportunities to improve outcomes in this challenging population.
Efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) vs percutaneous transhepatic biliary drainage (PTBD) for cholangiocarcinoma biliary obstruction: An updated systematic review and meta analysis.
Authors: Alan Ortega-Macias, Oscar Felipe Borja Montes, Tomas Escobar Gil, Erika Maestas
Journal: Journal of Clinical Oncology (2025)

557 Background: Perioperative and/or palliative biliary drainage for the management of cholangiocarcinoma biliary obstruction has been part of the backbone of the multidisciplinary approach that this condition requires. For both intrahepatic and perihilar cholangiocarcinoma, ERCP and PTBD are the two main techniques available. There has yet to be consensus favoring one approach over the other. Methods: Following the PRISMA guidelines, a systematic review and meta-analysis were performed to determine if there was a difference in efficacy and safety of ERCP compared to PTBD for Cholangiocarcinoma Biliary Obstruction. Primary outcomes were successful biliary drainage, mean number of needed procedures, length of stay and overall adverse events rate. Data were analyzed using R version 4.2.2. The risk of bias was assessed by the Robins-I and RoB 2 tool. The quality of evidence was graded using the GRADE scale and Newcastle-Ottawa guidelines. Results: Three randomized clinical trials and two observational studies described the successful biliary drainage rate of ERCP vs PTBD for cholangiocarcinoma associated biliary obstruction, totaling 340 patients. Meta-analysis test for overall effect, showed no statistical difference between groups (RR = 0.88; 95% CI = [0.69; 1.13]; p = 0.23; Fig. 1). Similarly, in terms of the mean number of needed procedures per patient, a total of three randomized clinical trials and two observational studies, totaling 340 patients were included, no statistically significant difference was found (SMD = 0.64; 95% CI = [- 9.36; 10.63]; p = 0.57; Fig. 2). Likewise, one randomized clinical trial and two observational studies showed no statistically significant difference on the length of stay (days) mean between groups (SMD = 0.06; 95% CI = [- 1.57; 1.68]; p = 0.73; Fig. 3). Although, the three clinical trials and three observational studies showed a mild decreased adverse event and death (within 3 months) rate in the ERCP group, after undergoing statistical analysis, meta-analysis test for overall effect, showed no statistical difference (RR = 0.99; 95% CI = [0.55; 1.77]; p = 0.97; Fig. 4 and RR = 0.61; 95% CI = [0.10; 3.87]; p = 0.22; Fig. 5, respectively). The risk of bias was low with moderate-to-high quality of evidence amongst the included studies. Conclusions: Our updated systematic review and meta-analysis demonstrated no statistically significant difference in the successful biliary drainage rate, mean number of needed procedures, length of stay, death within 3 months and adverse event rate between ERCP vs PTBD for management of cholangiocarcinoma biliary obstruction. Further randomized studies are needed to confirm these findings.