tbuckley/cabot-search huggingface dataset:
Evaluation of CSF1R as a potential prognostic biomarker in colorectal cancer (Alliance).
Authors: Sandra Algaze, Yan Yang, Joshua Millstein, Francesca Battaglin, Shivani Soni, Pooja Mittal, Priya Jayachandran, Karam Ashouri, Hiroyuki Arai, Lesly Torres-Gonzalez, Wu Zhang, Fang-Shu Ou, Alan P. Venook, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2025)

285 Background: Immune checkpoint inhibitors (ICIs) have shown limited efficacy in colorectal cancer (CRC) outside of mismatch repair (MMR) deficient/microsatellite instability-high (MSI-H) tumors. Most CRC cases are MMR proficient /microsatellite stable and demonstrate resistance to ICIs, attributed to the tumor microenvironment. Colony Stimulating Factor 1 Receptor (CSF1R), a regulator of tumor-associated macrophages, has emerged as a potential target due to its association with poor prognosis in CRC. Methods: Data from 433 metastatic CRC (mCRC) patients in the CALGB/SWOG 80405 trial were analyzed. CSF1R RNA was extracted from formalin-fixed, paraffin-embedded tumor samples and sequenced. Patients were divided into tertiles of CSF1R expression (high, medium, low). Progression-free survival (PFS) and overall survival (OS) were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. Subgroup analyses were conducted based on liver metastases, treatment type (Bevacizumab, Cetuximab, FOLFOX, FOLFIRI), and MSI status. Results: Low CSF1R expression (CSF1R-L) was associated with significantly better survival outcomes. Median PFS was 12.9 months for CSF1R-L, compared to 11.2 and 9.2 months for CSF1R-M and CSF1R-H (p = 0.003). Median OS was 35.8 months for CSF1R-L versus 32.5 and 24.4 months for CSF1R-M and CSF1R-H (p = 0.00086). Stratification by liver metastases showed that CSF1R-L remained a strong prognostic factor only in patients with liver metastases. There were no significant survival differences based on CSF1R expression in bevacizumab-treated patients. However, in cetuximab-treated patients, CSF1R-L tumors had significantly longer PFS (12.9 vs 8.8 months, p = 0.037) and OS (35.8 vs 21.4 months, p = 0.002) than CSF1R-H tumors. Similarly, in FOLFOX-treated patients, CSF1R-L tumors showed longer PFS and OS (p = 0.018 and p = 0.013, respectively), and in FOLFIRI-treated patients, OS was significantly longer for CSF1R-L tumors (42.2 vs 24.7 months, p = 0.022) than CSF1R-H tumors. Conclusions: Our data suggests that CSF1R expression may serve as a prognostic biomarker in CRC, with lower expression potentially linked to improved survival, particularly in patients with liver metastases. These findings warrant further investigation of CSF1R as a possible prognostic and predictive biomarker, as well as a potential therapeutic target in CRC. Clinical trial information: NCT00265850 .
Effect of tRF-28-ZJ47D112Z4DZ on the pathogenesis of gastric cancer through targeting cyclin D1/CDK4 and its early diagnostic value.
Authors: Xiuchong Yu
Journal: Journal of Clinical Oncology (2025)

475 Background: Gastric cancer exhibits high incidence and mortality rates worldwide. Current research on gastric cancer aims to discover stable and effective early diagnostic markers, as well as uncover the disease's pathogenesis. tRNA-derived fragment (tRF) is a newly discovered regulatory non-coding RNA, which plays an important role in tumor diagnosis and treatment. Methods: This study, through transcriptome sequencing and MINTBase v2.0 database, screened out a new molecule tRF-28-ZJ47D112Z4DZ (tRF-28) related to gastric cancer. An absolute quantitative method was established to quantify the level of tRF-28 in plasma. ROC curve, survival curve, Cox regression model were constructed, and clinicopathological factors were collected to analyze the diagnostic value of tRF-28. "Overexpression" and "knockdown" tRF-28 gastric cancer cell models and xenograft tumor models were established to study the effects of tRF-28 on cell proliferation. Using bioinformatics, qRT-PCR, Western blot, dual luciferase reporter gene, fluorescence in situ hybridization, RNA binding protein immunoprecipitation assay, rescue experiment and immunohistochemistry to study the regulatory role of tRF-28 by binding to the 3'UTR of CCND1. Results: This study clarified the tRF-28 levels in the plasma of healthy individuals, and gastric benign and malignant lesions, providing a new candidate biomarker for the early diagnosis of gastric cancer. Through upregulating and downregulating the level of tRF-28 in gastric cancer cells, it was revealed that tRF-28 inhibits the proliferation of gastric cancer cells in vivo and in vitro by regulating key proteins such as Cyclin D1, CDK4, Rb, and p-Rb. In studying specific molecular mechanisms, tRF-28 and CCND1 were co-located in the cytoplasm. tRF-28 combines with Ago2 protein to form a complex and plays a role in silencing the target gene CCND1 in the cytoplasm. The rescue experiments revealed that silencing the target gene CCND1 can reverse the carcinogenesis effect of tRF-28 inhibitors, clarifying the biological functions of tRF-28 by regulating CCND1. Conclusions: Based on a series of research findings, we elucidated that tRF-28 form a complex with Ago2 protein, binding to the 3' UTR of CCND1 to downregulate Cyclin D1, CDK4, and other critical proteins, thereby inhibiting the proliferation of gastric cancer cells. Our study aims to offer new insights into identifying potential early diagnostic markers and therapeutic targets for gastric cancer.
Patient-reported outcomes in GI cancer: Leading change to meet the needs of the gastrointestinal cancer community.
Authors: Martha Raymond, Margaret-Ann Simonetta
Journal: Journal of Clinical Oncology (2025)

813 Background: According to the World Health Organization International Agency for Research on Cancer, globally gastrointestinal (GI) cancers account for 1 in 4 cancer cases and 1 in 3 cancer deaths, with an estimated 4.8 million new cases and 3.4 million GI cancer deaths reported annually. Understanding the global burden of GI cancers and the importance of understanding the real-world impact of a GI cancer diagnosis, the GI Cancers Alliance (GICA) conducted a 12-month patient-reported outcomes (PRO) research initiative that included a workshop at the 2023 American Society of Clinical Oncology (ASCO) annual meeting. In addition, our PRO research was published in the Journal of Clinical Oncology (J Clin Oncol 42, 2024 suppl 3; abstr 731) with a poster presented at the 2024 ASCO Gastrointestinal Cancers Symposium. Methods: Based on our 2022-2023 PRO research of 1,122 patients highlighting the unmet needs and critical gaps in services of the GI cancers community, we developed a series of follow-up initiatives. Nutrition education 17%, biomarker/precision medicine education 19%, patient-centered care education 11% and caregiver support 16% were four of the highest levels of unmet need based on our global research. Subsequently, in 2023 we created the ‘GI Cancers Patient &amp; Caregiver Advisory Board’ representing all GI cancers. The board hosts educational forums supporting patients and caregivers throughout the care continuum. Our pilot nutrition program launched at the 2024 ASCO annual meeting, consisting of in-person and online video components, and an extensive nutrition guide with recipes tailored for GI cancer patients. In 2024, we partnered with our gastric cancer advocates to develop ‘Test Your Biomarkers’ enhancing education and awareness of biomarker testing and precision medicine. Results: Implementing direct patient feedback from our published research, we are creating actionable solutions to unmet needs and gaps in services. Our ‘Patient &amp; Caregiver Advisory Board’ continues to amplify the patient and caregiver voice participating in global engagement opportunities. GICA provided 10,000 nutrition guides to community oncology centers, and our online messaging reached 250,000 individuals across digital platforms and partner websites in the first three months from launch. In the first six months of the ‘Test Your Biomarkers’ campaign our messaging reached 1.7 million individuals across all digital platforms, campaign, and partner websites. Conclusions: Our PRO research provides the roadmap for new initiatives and programming to meet the needs of our GI cancer community. The GI Cancers Alliance will proceed to collaborate with our 100+ partner organizations to activate change by targeting the needs of our patient community while eliminating critical gaps in services. By doing so, we will continue to provide greater patient impact through the amplification of the patient voice.
The efficacy of anti-EGFR therapy across different lines of treatment in <i>RAS</i> wild-type left-sided metastatic colorectal cancer.
Authors: Anita Archwamety, Charuwan Akewanlop, Krittiya Korphaisarn
Journal: Journal of Clinical Oncology (2025)

86 Background: Anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs) are recommended as a first-line treatment in RAS wild-type (RASwt ) left-sided metastatic colorectal cancer (mCRC). However, the efficacy of these therapies across different treatment lines remains unclear. This study aims to evaluate the efficacy of anti-EGFR mAb across first, second, third, and later-line treatments. Methods: We conducted a retrospective analysis of patients diagnosed with RASwt mCRC who received anti-EGFR mAb in all treatment lines at Siriraj Hospital between 2008 and 2023. The impact of anti-EGFR mAb treatment line on progression-free survival (PFS) and overall survival (OS) was determined using the Kaplan-Meier method and compared with the log-rank test. Results: Of the 350 patients with RASwt mCRC receiving anti-EGFR mAb, 33% (115 of 350) were treated in the first-line, while 16%, 45% and 6% were treated in the second-, third- and later-line settings, respectively. Eighty-six percent of patients had left-sided tumors, and anti-vascular growth factors were used in 34% of patients. The median follow-up time was 30.4 months (mo). Among patients with left-sided tumors, those receiving first-line anti-EGFR mAb treatment exhibited a significantly longer mPFS (11.9 mo, 95% CI 7.4-16.3, p&lt;0.001). The mPFS in the second-, third- and later-line settings were 6.1 mo (95% CI 4.6-7.5), 4.9 mo (95% CI 3.8-6.0), and 5.1 mo (95% CI 2.3-7.9), respectively. There were no significant differences in terms of OS across treatment lines (p=0.27). Conclusions: Although first-line treatment with anti-EGFR mAb had the longest mPFS in left-sided mCRC, OS did not significantly differ among treatment lines. Therefore, anti-EGFR mAb can be incorporated as a part of therapy at any line of treatment.
Personalised use of repurposed non-anticancer drugs in colorectal cancer based on up-regulated signalling pathways: A real world cohort feasibility study.
Authors: Andrew M. Gaya, Darshana Patil, Vineet Datta, Navin Srivastava, Sachin Apurwa, Dadasaheb B Akolkar, Aditya V. Shreenivas
Journal: Journal of Clinical Oncology (2025)

833 Background: Targeting signaling pathways in colorectal cancers is a common therapeutic strategy. In addition to targeted drugs, non- anticancer drugs approved for use in other health conditions can inhibit key pathways. De novo tumor transcriptome analysis can identify patient-specific up- and down-regulated transcripts, based on which the corresponding repurposed drugs can be used in synergistic combinations with standard of care (SoC) regimens. Methods: This retrospective study was conducted on a real-world cohort of 459 colorectal cancer cases (218 females, 241 males; median age 56 years) who had taken Exacta multi-omics tumor profiling for selection of personalized treatments. Transcriptome analysis was performed as part of the evaluations to determine up and down-regulated gene transcripts for selecting targeted, endocrine, and cytotoxic anticancer agents as well as non-anticancer (repurposed) drugs and phytochemicals that could be used for tandem targeting of the dysregulated signaling pathways, as indicated in the table below. Results: Transcriptome analysis of this cohort revealed dysregulation of ≥1 pathway in 391 patients (85.2%). MAPKs (n = 244, 53.2%) and MMPs (n = 210, 45.8%) were most frequently upregulated. Celecoxib (n = 292, 63.6%), Atorvastatin (n = 255, 55.6%), and Doxycycline (n = 208, 45.3%) were the most frequently indicated repurposed drugs for targeting the identified dysregulated pathways. Potential indications for ≥1 repurposed drugs were seen in 353 patients (76.9%). Conclusions: Several cellular signaling pathways are known or potential therapeutic targets in cancers. The present study indicates that it may be possible to use multi-omics analyses to create personalized treatment strategies using a synergistic combination of repurposed drugs to potentiate the action of SoC systemic anticancer agents in colorectal cancer. Biomarkers for non anti-cancer drugs selection. Drug Biomarker/Gene Expression Aspirin PTGS2 (COX2) Atorvastatin HMGCR, MAPK Bromelain PTGS2 (COX2) Celecoxib PTGS2 (COX2), FZD, WNT, ΜΑΡΚ Chloroquine HMGB1 Curcumin MMP, BIRC5, BCL2 Doxycycline MMP Metformin MMP, BCL2, ΜΑΡΚ Quercetin FZD, WNT Resveratrol MMP, BCL2, PCNA, PTGS2 (COX2) Vitamin C SLC2A1 (GLUT1) Artesunate FZD, WNT, MMP, BCL2 Cannabidiol MMP Epigallocatechin gallate MMP, MAPK Mebendazole XIAP, MMP, MAPK
Fruquintinib plus camrelizumab combined with paclitaxel liposome and nedaplatin as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, phase II clinical trial.
Authors: Yanhong Gu, Tianzhu Qiu, Lu Mingjie, Yuwen Dong
Journal: Journal of Clinical Oncology (2025)

445 Background: Camrelizumab in combination with chemotherapy has become a standard of care for the first-line treatment of advanced ESCC. Previous studies have indicated synergistic effect of fruquintinib in combination with chemotherapy or immunotherapy. Hence, we conducted a phase II trial to evaluate the efficacy and safety of fruquintinib plus camrelizumab, paclitaxel liposome, and nedaplatin as a first-line therapy for advanced ESCC. Methods: This is a single-arm, phase II study consisting of a dose-finding and a dose-expansion phase. A total of 33~36 patients aged 18~80 years with previously untreated advanced ESCC and an ECOG PS of 0-2 were planned to be enrolled. The dose-finding phase followed a 3+3 approach in order to determine the recommended phase II dose (RP2D) of fruquintinib for dose expansion. Patients received fruquintinib (3 mg, 4 mg, and 5 mg once daily on days 1-14, starting at 4 mg) orally, plus intravenous camrelizumab 200 mg d1, paclitaxel liposome 135 mg/m 2 d1, and nedaplatin 70 mg/m 2 d1, 21 days as one cycle. A maximum of 6 cycles was conducted, followed by maintenance therapy with fruquintinib in combination with camrelizumab. The primary endpoint was objective response rate (ORR, RECIST 1.1). Secondary endpoints included RP2D, disease control rate (DCR), progression-free survival (PFS), and adverse events (AEs). Results: As of August 24, 2024, 11 patients (9 males) were enrolled with a median age of 66 years (range 50-76). All patients had distant metastases, and the median number of sites of metastasis was 2 (range 1-5). In the dose-finding phase, 3 patients were treated with 4 mg of fruquintinib, and 6 patients were treated with 5 mg of fruquintinib. No dose-limiting toxicities (DLTs) were observed. Thus, the RP2D of fruquintinib was established as 5 mg once daily on days 1-14, 21 days as one cycle. Of the 7 evaluable patients, 6 achieved partial response, and 1 had stable disease. The ORR was 85.7% (95% CI 42.1%-99.6%), and the DCR was 100.0% (95% CI: 59.0%-100.0%). The median PFS was not reached. The most common treatment-related adverse events (TRAEs) were anemia (7/11), hypercholesterolemia (6/11), hypoalbuminemia (5/11), oral mucositis (5/11), hematuria (4/11), hypertension (4/11), fatigue (4/11), constipation (3/11), and neutropenia (3/11). Grade 3 TRAEs were identified in 2 patients, including oral mucositis (2/11), and anemia (1/11). No treatment-related serious adverse events (SAEs) or deaths occurred. Conclusions: The combination of fruquintinib, camrelizumab, paclitaxel liposome, and nedaplatin demonstrated significant efficacy and manageable toxicity profiles as a first-line treatment for advanced ESCC, suggesting a potential new treatment strategy. Clinical trial information: NCT06010212 .
Trends in surgery and overall survival in non-metastatic anal cancer: A population-based analysis.
Authors: Cathy Eng, Madison Conces, Kristen Keon Ciombor, Jennifer Anne Dorth, Joshua E. Meyer, Timothy Geiger, Aimal Khan, Jeneth Aquino, Natalie A. Lockney, Anuradha Bapsi Chakravarthy, Al Bowen Benson III, Chan Shen
Journal: Journal of Clinical Oncology (2025)

3 Background: The incidence of anal cancer has recently exceeded &gt; 10,000 patients/year in the United States. For non-metastatic squamous cell carcinoma of the anal canal (SCCA), concurrent chemoradiotherapy (CRT) followed by abdominoperineal resection (APR) as salvage surgery for non-responders is a key treatment approach. Over the past two decades, findings from phase III trials (RTOG 98-11 and ACT II) have increased our knowledge about appropriate treatment approaches. ACT II indicated that delayed assessment of tumor response and consideration of APR up until 26 weeks is appropriate, as many patients demonstrate delayed response to treatment. Our analysis examines whether current evidence has influenced real-world clinical practice by analyzing trends in rates of primary APR and overall survival (OS) outcomes. Methods: We conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) registry, including patients diagnosed with non-metastatic SCCA between 2004 and 2020. Patients with T0 or T1N0 stage disease were excluded. Descriptive statistics were generated, and chi-square tests were used to compare characteristics between patients who underwent surgery and those who did not. Temporal trends in surgery and radiation therapy were analyzed using the Cochrane-Armitage trend test. Multivariable logistic regression was employed to identify factors associated with surgery uptake, while OS trends were analyzed using Kaplan-Meier and Cox proportional hazard models. Results: A total of 16,718 patients were included, with 33.1% requiring salvage APR following CRT. The proportion of patients requiring surgery significantly declined from 46.6% in 2004 to 31.1% in 2020 (p &lt; 0.001). Factors associated with surgery included younger age, male gender, and non-Hispanic Black race (p &lt; 0.001). Kaplan-Meier analysis revealed significant improvements in OS over the study period (log-rank p = 0.0002), with more recent years (2016-2020) associated with significantly better OS compared to earlier periods (2004-2007, HR = 0.77, p &lt; 0.001). Conclusions: The significant decrease in rates of salvage APR for non-metastatic SCCA likely reflects the global impact of recent phase III trials. Meanwhile, OS rates have been steadily improving. These findings suggest improved overall knowledge regarding treatment strategies and highlight the real-world impact of clinical investigation in non-metastatic squamous cell carcinoma of the anal canal.
Exploring predictive factors for detecting KRAS mutations in pancreatic cancer using liquid biopsy.
Authors: Takaaki Furukawa, Ippei Fukada, Naomi Hayashi, Manabu Takamatsu, Yoichiro Sato, Yuri Maegawa, Tatsuki Hirai, Takafumi Mie, Takeshi Okamoto, Tsuyoshi Takeda, Takashi Sasaki, Masato Ozaka, Shunji Takahashi, Naoki Sasahira
Journal: Journal of Clinical Oncology (2025)

782 Background: Liquid biopsy offers an alternative to tissue specimens for comprehensive genetic profiling. However, circulating tumor DNA is sometimes insufficient to detect genomic alterations in pancreatic cancer (PC). The detection rate of KRAS mutations was reportedly increased in PC with liver metastasis. In contrast, the predictive value of CA19-9 levels, the timing of liquid biopsy, or the type of liquid biopsy for detecting KRAS mutations remains unclear. We investigated whether these factors could be predictive of detecting KRAS mutations in PC. Methods: From September 2021 to August 2024, we retrospectively reviewed patients with PC who underwent liquid biopsy. Results: A total of 106 patients were enrolled (median age: 64 years, male: 66). Patient characteristics were as follows: tumor status: locally advanced: 10, metastatic: 90, recurrence: 6; metastatic site: liver: 51, lung: 26, lymph nodes: 20, peritoneum: 38, others: 7; number of metastatic sites: 1: 63, 2: 25, ≥3: 8; treatment line at liquid biopsy: 1: 21, 2: 77, 3:8; median CA19-9 level: 1053.4 U/mL; type of liquid biopsy: FoundationOne Liquid CDx (FL): 75 or Guardant360 (G): 31. The overall rate of KRAS mutations was 47%, with a median variant allele frequency of 0.83 [range:0.1-71.0]. The patterns of KRAS mutations were as follows: G12D: 23, G12V: 18, G12R: 4, and others: 14. The detection rate of KRAS mutations varied by the follows factors: metastatic site: liver: 65%, other organs: 44%; number of metastatic sites: ≥2: 47%, &lt;2: 48%; CA19-9 level: ≥2,000 U/mL: 68%, &lt;2,000: 38%; timing of liquid biopsy: 1st line: 42%, ≥2nd line: 67%; types of liquid biopsy: FL: 49%, G: 42%. In multivariate analysis, liver metastasis and CA19-9 level ≥2,000 U/mL were identified as independent factors associated with improved detection of KRAS mutations. In PC with these two factors, the detection rate of KRAS mutation increased to 76%. Conclusions: Our findings indicate that liver metastasis and CA19-9 levels above 2,000 U/mL are predictive factors for detecting KRAS mutations in PC through liquid biopsy.