tbuckley/cabot-search huggingface dataset:
Does chemotherapy regimen matter for first-line immunochemotherapy in low programmed cell death ligand 1 (PD-L1)-expressing esophageal squamous cell carcinoma (ESCC)? A systemic review and meta-analysis.
Authors: Jhe-Cyuan Guo, Pei-Shan Lin, Wen-Yi Shau, Yu-Yun Shao, Chi-Ling Chen, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2025)

395 Background: Anti-programmed death 1 (PD-1) therapy plus chemotherapy has become standard first-line therapy for patients with high PD-L1-expressing advanced ESCC. The benefit for patients with low PD-L1-expressing ESCC remains debatable. Methods: Eligible studies were phase III trials investigating anti-PD-1/PD-L1 therapy plus chemotherapy (immunochemotherapy) vs chemotherapy as first-line therapy of advanced ESCC. Study-level pooled analyses of hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) with corresponding 95% confidence intervals (CI), were used to compare the different groups in random-effects model. PD-L1 expression levels with tumor proportion score (TPS) ≥ 1% vs &lt; 1%, tumor area positivity (TAP) ≥ 10% vs &lt; 10%, and combined positive score (CPS) ≥ 10 vs &lt; 10 were collectively categorized as high vs low PD-L1 expression. The impact of two different chemotherapy regimens, TP (paclitaxel plus platinum) and PF (platinum pus fluoropyrimidine), stratified by PD-L1 expression levels, on the survival benefit of immunochemotherapy vs chemotherapy was investigated. Results: Eight randomized controlled trials including 4733 subjects were enrolled. Immunochemotherapy vs chemotherapy was associated with significantly improved PFS and OS irrespective of PD-L1 expression levels or chemotherapy regimens (Table). The PFS and OS benefits were more pronounced in high PD-L1 group than low PD-L1 group. In patients with high PD-L1 expression, the PFS and OS benefits were not significantly different between two chemotherapy regimen subgroups. However, in patients with low PD-L1 expression, the PFS benefit was more significant in TP subgroup than PF subgroup, and OS benefit trended to be in favor of TP subgroup. Conclusions: The addition of anti-PD-1/PD-L1 therapy to TP chemotherapy may associate with more significant survival benefit than to PF chemotherapy in advanced ESCC with low PD-L1 expression. Population PFS (immunochemotherapy vs chemotherapy) OS (immunochemotherapy vs chemotherapy) HR(95% CI) P value(subgroup differences) HR(95% CI) P value(subgroup differences) All patients 0.63 (0.57-0.69) 0.69 (0.64-0.74) High PD-L1 group 0.54 (0.49-0.60) P &lt; 0.01 0.60 (0.53-0.67) P &lt; 0.01 Low PD-L1 group 0.71 (0.62-0.81) 0.78 (0.70-0.87) TP group 0.56 (0.50-0.62) P &lt; 0.01 0.66 (0.59-0.74) P = 0.32 PF group 0.68 (0.62-0.75) 0.72 (0.65-0.79) Among high PD-L1 patients TP subgroup 0.56 (0.45-0.69) P = 0.75 0.60 (0.46-0.78) P = 0.90 PF subgroup 0.53 (0.45-0.62) 0.59 (0.50-0.69) Among low PD-L1 patients TP subgroup 0.59 (0.48-0.74) P = 0.01 0.72 (0.55-0.93) P = 0.32 PF subgroup 0.82 (0.72-0.94) 0.84 (0.72-0.97)
The effect of renin-angiotensin system inhibitors on patients with pancreatic cancer receiving systemic treatment: A retrospective cohort study from TriNetX US collaborative networks.
Authors: Cheng-Wei Chou, Jun-Fu Lin, Ching-Heng Lin
Journal: Journal of Clinical Oncology (2025)

734 Background: This study aimed to assess the impact of renin-angiotensin system inhibitors, including angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs), on patients with pancreatic cancer undergoing systemic chemotherapy. Methods: We conducted a global, retrospective collaborative network analysis using TriNetX data from January 1, 2014, to December 31, 2023, to explore this question. The study captured data on pancreatic cancer diagnoses, comorbidities, medications, and survival outcomes. Propensity score matching (PSM) was used to create 1:1 matched groups. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated to assess survival outcomes, while the Kaplan–Meier method was employed to evaluate survival probabilities. Subgroup analyses were performed based on sex, age, surgery, race, and comorbidities. Results: The study included 1,861 patients who were on ARBs/ACEIs and 4,875 patients who were not on these medications at baseline. After 1:1 propensity score matching, both groups were well-balanced with 1,627 patients each. Compared to the non-ARBs/ACEIs group, patients receiving ARBs/ACEIs demonstrated significantly better overall survival (HR: 0.846, 95% CI: 0.753–0.949). Subgroup analyses revealed significantly improved survival outcomes in patients on ARBs/ACEIs, including those without surgery (HR: 0.846, 95% CI: 0.749–0.956), males (HR: 0.762, 95% CI: 0.640–0.908), patients aged 65 years and older (HR: 0.801, 95% CI: 0.709–0.906), and White patients (HR: 0.806, 95% CI: 0.704–0.924). Notably, similar survival benefits were observed in patients with comorbidities such as diabetes, ischemic heart disease, dyslipidemia, and hypertension. Conclusions: In the largest TriNetX matched cohort study on pancreatic cancer, the use of ARBs/ACEIs was associated with a reduced risk of overall mortality. However, prospective studies are needed to further evaluate the effects of concomitant ARB/ACEI use in patients with pancreatic cancer undergoing systemic treatment.
The effect of TU-100 on hepatocarcinogenesis and colorectal liver metastasis in MASH model.
Authors: Shinichiro Yamada, Yuji Morine, Tetsuya Ikemoto, Yu Saito, Hiroki Teraoku, Katsuki Miyazaki, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2025)

577 Background: TU-100 is most commonly used herbal medicine in clinical setting. We have already reported that TU-100 suppressed dysbiosis (J Med Invest, 2013), bacterial translocation (Surg Today, 2017) and hepatic fibrosis (Surgery, 2016). This time we investigate the effect of TU-100 on hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in MASH model. Methods: 1: Effect on HCC: Seven-week-old Tsumura Suzuki obese diabetes mice, a model that shows the spontaneous onset of MASH and HCC, were used. They were divided into a TU-100 treated group and a control group. Mice were sacrificed at 24 and 48 weeks to evaluate hepatic steatosis, fibrosis, carcinogenesis, cytokine expression, and microbiome abundance. 2: Effect on CRLM: Six-week-old male C57BL/6J mice were used. They were divided into the western diet (WD) group and the WD+TU-100 group. MC38 colon cancer cells were injected into the spleen at 16 weeks, and mice were killed at 2 weeks after injection to evaluate hepatic steatosis, fibrosis and mRNA expression in the liver. Results: 1: Effect on HCC: At 24 weeks, the TU-100 group showed significantly lower expression of IL6, IL1B, and ACTA2 mRNA in the liver (P&lt;0.05). At 48 weeks, the TU-100 group showed a lower rate of MASH than the control group (28% vs 72%; P=0.1). Tumor diameter was significantly smaller in the TU-100 group compared with that in the control group (P&lt;0.05). Regarding the intestinal microbiome, the genera Blautia and Ruminococcus were increased in the TU-100 group (P&lt;0.05), whereas Dorea and Erysipelotrichaceae were decreased in the TU-100 group (P&lt;0.05). 2: Effect on CRLM: Steatosis of the WD+TU-100 group was significantly suppressed compared with the WD group (p&lt;0.05). The WD+TU-100 group showed significantly smaller tumor diameter than the WD group (p&lt;0.05). In the WD+TU-100 group, expression of SAA1 and TIMP1 mRNA in the liver was significantly lower than in the WD group (p&lt;0.05). Conclusions: TU-100 regulates the intestinal microbiome and may suppress hepatic steatosis and subsequent hepatocarcinogenesis in the MASH model. Furthermore, TU-100 may have effect on CRLM via suppression of SAA1/TIMP1.
A multicenter, prospective phase II trial of second-line aflibercept plus FOLFIRI in patients with metastatic colorectal cancer refractory to anti-EGFR agents (HGCSG1801): Updated analyses.
Authors: Hiroshi Nakatsumi, Kazuaki Harada, Satoshi Yuki, Atsushi Ishiguro, Kentaro Sawada, Susumu Sogabe, Takayuki Ando, Yusuke Sasaki, Ayumu Yoshikawa, Michio Nakamura, Masayoshi Dazai, Miki Tateyama, Osamu Muto, Masahito Kotaka, Tamotsu Sagawa, Tetsuhito Muranaka, Kazuteru Hatanaka, Ryo Takagi, Yuh Sakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2025)

147 Background: The HGCSG1801 trial evaluated the treatment outcomes of aflibercept (AFL) plus FOLFIRI for patients(pts) with metastatic colorectal cancer (mCRC) refractory to an oxaliplatin-based regimen combined with an anti-EGFR agent. Here we report results of the updated efficacy, safety, and a biomarker analysis. Methods: This was a prospective open-label phase II trial. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m 2 , leucovorin 200 mg/m 2 iv, bolus 5-fluorouracil [5-FU] 400 mg/m 2 , and infusional 5-FU 2400 mg/m 2 /46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was 6-month progression-free survival (PFS) rate, and the secondary endpoints included overall survival (OS), PFS, overall response rate (ORR), disease control rate (DCR), and adverse events. Angiogenic factors were analyzed in plasma sample using a Luminex multiplex assay using the Cox proportional hazards model. This study was sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and supported by a grant from Sanofi. Results: Forty-three pts were enrolled between November 2019 and October 2022. The data cut-off date was April 30, 2024. The 6-month PFS rate was 59.0% (90% confidence interval [CI], 45.8–72.1%). Median PFS and OS were 7.3 months (95% CI, 5.5–11.0 months) and 18.8 months (95% CI, 12.9–26.6 months), respectively. The ORR was 20.9% (95% CI, 10.0–36.0%) and DCR was 88.4% (95% CI, 74.9–96.1%). No deaths and no new safety signals with a causal relation to the study treatment were observed. A biomarker analysis using pretreatment plasma samples showed a trend toward better PFS in pts with low VEGF-A (hazard ratio [HR] 0.40 [95% CI, 0.18-0.91]), TSP-2 (HR 0.40 [95% CI, 0.18-0.88]) or IL-8 levels (HR 0.43 [95% CI, 0.20-0.93]). There was also a trend toward better OS in pts with low levels of TSP-2 (HR 0.30 [95% CI, 0.11-0.81]) or TIMP-1 (HR 0.20 [95% CI, 0.06-0.69]). Conclusions: These updated data further support the activity and manageable safety profile of AFL plus FOLFIRI for pts with mCRC who failed an oxaliplatin-based regimen combined with an anti-EGFR agent. It was suggested the association between some angiogenic factors in plasma samples and the activity of AFL plus FOLFIRI in mCRC. Clinical trial information: jRCTs011190006 .
Dual versus single immune checkpoint blockade for patients with metastatic colorectal cancer harboring microsatellite instability: The Saint-Antoine immunoMSI score.
Authors: Léa Jehanno, Romain Cohen, Camille Loisel, Thomas Samaille, Baptiste Cervantes, Raphael Colle, Julie Henriques, Dewi Vernerey, Thierry Andre
Journal: Journal of Clinical Oncology (2025)

168 Background: Anti-PD1 monotherapy (mono) and anti-PD1 plus anti-CTLA4 therapies (combo) are validated for metastatic colorectal cancer (mCRC) harboring microsatellite instability and/or mismatch repair deficiency (MSI/dMMR). We aimed at assessing the efficacy of combined anti-CTLA4 and anti-PD1 blockade versus anti-PD1 monotherapy and identifying which subgroups benefit more from the combo. Methods: All patients (pts) with MSI/dMMR mCRC treated by anti-PD1 ± anti-CTLA4 included in the prospective monocenter immunoMSI cohort were analyzed. The choice between monotherapy or combination therapy varied according to open studies and regulatory approvals, without taking pt characteristics into account. Datalock date was April 23, 2024. Main endpoints were progression-free survival (PFS) per iRECIST and overall survival (OS) estimated with the Kaplan-Meier method. Univariate Cox proportional hazards models were used to estimate hazard ratios with CI. The interactions between studied subgroups and the treatment group were modelized by adding in a single Cox model the studied subgroups, the treatment group parameters, and their interaction term. Results: Among 210 pts, 97 were treated combo and 113 with mono. Baseline characteristics were similar in both groups. 25% and 17% were in first line, respectively. Median follow-up was 4.4 years: 4.1 years for combo and 5.4 years for mono. Combo was associated with better PFS (HR=0.48; 95%CI 0.31-0.76) and OS (HR=0.49; 0.29-0.84). Best observed response rates were: 78% of objective responses, 17% of stable diseases and 5% disease progressions with combo versus 60%, 25% and 15% with mono. Subgroup analyses showed significant differential effect of the treatment group for gender (PFS HR=0.21 vs 0.87 for females and males, P-interaction: 0.0067), liver metastases (PFS HR=0.30 vs 0.79 for pts without liver mets and those with liver mets, P-interaction: 0.0479) and sidedness (PFS HR=0.27 vs 0.64 for left-sided and right-sided mCRC, P-interaction=0.0922), but not RAS / RAF mutations. We computed a predictive score based on gender (female: 2 points), no liver met (1 point) and left side (1 point). PFS HR was 0.1 (0.03-0.33) for the group ≥3 points (N=67), 0.66 (0.36-1.23) for the group with 1-2 points (N=113) and 1.54 (0.50-4.70) for the group with 0 point (N=30). Conclusions: Combined CTLA4 and PD1 blockade is associated with improved PFS and OS compared to anti-PD1 alone in MSI/dMMR mCRC. The subgroup deriving the highest benefit of the combo seems to be female pts with left sided tumor and no liver met. Data from the randomization between nivolumab versus nivolumab + ipilumumab in the CheckMate-8HW phase III study are expected.
Cetuximab every second week in combination with daily encorafenib in patients with BRAF V600E mutated metastatic colorectal cancer: Interim analysis from NEW BEACON.
Authors: Martina Eriksen, Per Pfeiffer, Kristoffer Staal Rohrberg, Christina Westmose Yde, Lone Nørgård Petersen, Laurids Poulsen, Camilla Qvortrup
Journal: Journal of Clinical Oncology (2025)

153 Background: Weekly administered cetuximab in combination with the BRAF inhibitor encorafenib has improved survival in pre-treated patients (pts) with BRAF V600E mutated (BRAFmut) metastatic colorectal cancer (mCRC), with a median progression free survival (PFS) of 4.3 months in the BEACON study. It is now standard-of-care in the second line treatment. However, a regimen with cetuximab administered every second week may demonstrate comparable efficacy and is more convenient for the pts. Thus, we initiated the NEW BEACON study investigating cetuximab given every second week together with daily encorafenib. Details on the rationale and aims of the study have previously been published (doi: 10.1186/s12885-022-10420-x.). Methods: NEW BEACON is an open-label, single-arm, multicenter, phase II study including pts with pre-treated BRAFmut mCRC. The primary end point is 2 months PFS rate. We report here the result of a pre-specified interim analysis after treatment of the first 19 included pts. We collected fresh tumor tissues for comprehensive molecular profiling in order to explore features associated with response and resistance. Baseline genomic variants will be reported. Results: From February 2021 to February 2024 20 pts were included in the study. 1 patient never started study treatment due to rapid disease progression. At the data cut-off date 19 pts had initiated study treatment. The 2 months PFS rate was 89% (17/19 pts). We had tumor tissue for molecular profiling available from 12 pts. Pathogenic variants in TP53 were the most frequently detected co-mutations at baseline in 83% of pts (10/12 pts). Available preliminary safety, efficacy, and survival data and more extensive genomic data will be presented at the meeting. Conclusions: The preliminary PFS data from pts with BRAFmut mCRC treated with cetuximab every second week together with daily encorafenib is promising demonstrating a 2 months PFS rate of 89%. This is similar to what was reported from the BEACON study (2 months PFS rate of 84%). Loss-of-function mutations in tumor suppressor genes were frequently detected as co-mutations at baseline. Clinical trial information: EudraCT: 2020-003283-10 .
The prevalence of Lynch syndrome and associated clinicopathologic features in patients with mismatch repair deficient gastric cancer.
Authors: Sun Mi Lee
Journal: Journal of Clinical Oncology (2025)

380 Background: Approximately 2-4% of patients with primary colorectal cancer are estimated to be associated with Lynch syndrome. However, the prevalence of Lynch syndrome and associated clinicopathologic features in patients with mismatch repair-deficient (dMMR) gastric cancer (GC) is not well understood. In this study, we investigated the frequency of dMMR GCs in unselected GCs and the prevalence of Lynch syndrome, as well as associated clinicopathologic features and molecular alterations in dMMR GCs. Methods: A total of 847 cases of unselected GCs from 2010 to 2012 were collected at Jeju National University Hospital. Immunohistochemistry for mismatch repair proteins (MMR), including MLH1, MSH2, MSH6, and PMS2, and MSI analysis were performed on representative tumor sections of surgically resected specimens. Follow-up genetic counseling and genetic and/or epigenetic alterations of the MMR genes were also investigated. Results: Loss of one or more MMR proteins and microsatellite instability-high were observed in 72 patients; 67 patients showed loss of MLH1/PMS2, 2 patients showed loss of PMS2 alone, and 3 patients with MSH2/MSH6. Genetic counseling demonstrated that ten patients had a family history of LS-associated cancers and nine patients had a history of metasynchronous cancers. Of the 72 patients, 65 revealed hypermethylation of the promoter region of MLH1. The subsequent genetic germline tests demonstrated 2 patients with MLH1 mutation, 3 with MSH2 mutation, and 2 with PMS2 mutation. Conclusions: dMMR tumors were identified in 72 (8.5%) of 847 unselected primary GCs. This study estimated that 0.8% of patients with unselected GC and 9.7% of patients with dMMR GC fulfilled the revised Bethesda criteria and are associated with Lynch syndrome. The detection of dMMR GCs and necessary genetic counseling/tests based on revised Bethesda criteria would help find Lynch syndrome in patients with GC. Clinical and immunophenotypical features of patients with dMMR GC. Age ≤ 50 years 5 (6.9) &gt; 50 years 67 (93.1) Other malignancy history except GAC No 63 (87.5) Yes 9 (12.5) History of metachronous cancers Esophageal cancer 1 (1.4) Maxillary sinus cancer 1 (1.4) Papillary thyroid cancer 1 (1.4) Colorectal cancer 1 (1.4) Pancreatic cancer 1 (1.4) Breast cancer 1 (1.4) Breast cancer and malignant GIST 1 (1.4) Multiple HCCs 2 (2.8) History of Family with LS related cancers No 62 (86.1) Yes 10 (13.9) Fulfillment of the rBG No 63 (87.5) Yes 9 (12.5) MMR proteins Loss of MLH1 and PMS2 67 (93.1) Loss of PMS2 2 (2.8) Loss of MSH2 and MSH6 3 (4.2) Germline mutation test MLH1 mutations 2 (2.8) MSH2 mutations 3 (4.2) PMS2 mutations 2 (2.8)
Differential gut microbiota profiles among normal colorectal mucosa, adenomatous and hyperplastic polyps in healthy volunteers: ColoMAR-1 study.
Authors: Maria Dolores Martos-Morillo, Idoia Sanluis, Jose M Cardenas, Jose Luis Ulla, Paula March, Jorge Lopez, Angel Ayuso, Jesus Rodriguez-Pascual
Journal: Journal of Clinical Oncology (2025)

271 Background: Increasing evidence indicates that the interaction between intestinal microbiota and host cells plays an important role in colorectal cancer oncogenesis through immune, inflammatory and/or metabolic alterations. However, there are no clear evidence in the very early adenoma-carcinoma sequence at which microbiota species influences future steps to colorectal carcinoma. This study aims do find a point in the adenoma-carcinoma sequence ad witch microbiota species suggest the risk of a future tumor to develop less invasive forms of early diagnosis. Methods: In this cross-sectional study, healthy volunteers above 45 years old were selected to participate. Exclusion criteria includes previous colonoscopy performed in the last 5 years. Stool sample were collected before a colonoscopy with biopsy. Samples of normal mucosa were systematically obtained, and all polyps found were removed. In fecal samples, microbiota species were identified using GoodGut test: Bacteroides fragilis, Subdoligranulm variabile, Ruminococcus, Roseburia, Coprococcus , eubacteria, Faecalibacterium prausnitzii and Gemella morbillorum . Number of genomic copies/μL were analyzed using the Wilcoxon test. Results: From February to June 2024, 29 healthy volunteers between 45 and 69 years were recruited. 62% were female. Adenomatous polyps or hyperplastic polyps were found in 9 volunteers. No case of colorectal cancer was found. For species S. variabile, Ruminococcus, Roseburia, Coprococcus and F. prausnitzii , higher counts were found in stool samples from volunteers with adenomatous or hyperplastic polyps than in those from volunteer with a normal colonoscopy, both in the total count and after correction for bacterial load (p&lt;0.001). For B. fragilis , bacterial count was higher in samples from volunteers with adenomatous polyps, but not in the samples from people with hyperplastic polyps compared with those samples from volunteers with a normal colonoscopy. G. morbillorum counts were not related to any type of polyps. None of this counts met the laboratory-designated threshold related to colorectal cancer. Conclusions: The presence of B. fragilis could be related to the differential risk of malignancy of adenomatous compared to hyperplastic polyps. Bacterial count for each sample and specie. Bacteria specie* Normal mucosa Adenoma Hyperplastic B. fragilis 22.13 22.3 20.42 S.variable 6.06 7.29 7.53 Ruminococcus, Roseburia, Coprococcus 6.08 7.29 7.47 F. prausnitzii 4.7 6.28 7.09 G.morbillorum 20.91 20.54 20.84 *Number of genomic copies/μL.