tbuckley/cabot-search huggingface dataset:
Leading the way: How leading Chinese institutions drive MDT excellence in hepatocellular carcinoma.
Authors: Jiaping Li, Huang Zhiyong, Xiaoping Chen, Jizhou Wang, Wenzhe Fan, Erlei Zhang, Qian Chen, Bichai Yin, Binghao Jia, Poka Yingjing Cui, Zhihao Huang, Si Sun, Yufang Dong, Zoe (Zheng) Su, Pablo Azcue, Lucy Turner, Maria Teresa Campos Partera, Lianxin Liu
Journal: Journal of Clinical Oncology (2025)

563 Background: HCC MDTs involve specialists collaborating on patient cases to create personalized treatment plans. Implementing MDTs can be challenging in countries with limited resources and high disease burdens. In China, there were 368,000 new liver cancer cases in 2022 representative of 40% of global cases. Therefore, evaluating MDT practices at leading hospitals in China may offer valuable insights that could help improve HCC MDT practices worldwide. Methods: This study selected hospitals with distinct MDT models: one for all new patients and one for complex cases. Hospitals handling over 1,000 HCC cases annually were chosen. Desk research and virtual interviews with MDT members from three leading Chinese hospitals—The First Affiliated Hospital of USTC, The First Affiliated Hospital of SYSU, and Tongji Hospital—were conducted to analyze their MDTs and determine key best practices. Results: We identified 6 key best practice in HCC MDTs at these leading Chinese hospitals. 1) Quality Control on MDT process: Leading hospitals ensure the MDT’s efficient execution and effective outcomes. E.g., USTC established a quality control team to audit the MDT process. 2) Real-World Evidence: Leading hospitals prioritize the construction of real-world databases linked to MDT-care to inform impact on outcomes. E.g., SYSU's preliminary data shows impact of MDT care on survival rates (From 2006 to 2010, 5,627 patients who underwent radical liver cancer resection with MDT care saw their five-year survival rate reach 60%, a notable improvement over historical averages) 3) Comprehensive Teams: These hospitals typically have robust teams, involving around 10 specialties. E.g., Tongji Hospital’s MDTs involve ~10 specialties for holistic care. 4) Patient Journey Coverage: MDTs manage patients from diagnosis to rehabilitation, providing a holistic approach to patient management. 5) Guideline-based treatment decisions: They follow latest guidelines coupled with access to approved therapies to make treatment decisions 6) Training: Young physicians are invited to actively participate in MDT consultations (e.g., through case preparation and presentation, etc.). Conclusions: Evaluation of MDT practices at leading China institutes highlights key best practices that could be adopted to enhance care quality for patients with HCC. The ongoing efforts and successes of these institutions provide a model for broader adoption and standardization of MDT practices across the country.
Proto-oncogene HRAS transcript level and overall survival in stage II and III colorectal cancer.
Authors: Donghyun Kim, Saima Sharif, Juan Antonio Raygoza Garay, Michelle L. Churchman, Robert J. Rounbehler, Avinash S. Bhakta, Patrick M Boland, Michael J. Cavnar, Hassan Hatoum, Lyen C. Huang, Joseph Kim, Richard D. Kim, Robert William Lentz, Sarbajit Mukherjee, Mary O'Donnell, Benjamin Quartey, Matthew Reilley, Bodour Salhia, Bryan P. Schneider, Carlos H.F. Chan
Journal: Journal of Clinical Oncology (2025)

231 Background: Mutational landscape is prognostic in colorectal cancer (CRC). Driver mutations in the RAS proto-oncogenes such as KRAS and NRAS portend poor survival outcomes, whereas HRAS mutations are extremely rare and their prognostic value remains uncertain. The prognostic implication of RAS gene activity at the transcript level is also obscure. Here, we retrospectively review stage II and III CRC tumor RNA-Seq data and demonstrate that high transcript levels of HRAS are associated with superior overall survival (OS). Methods: Tumor RNA-Seq of 734 stage II and III CRC cases and their associated clinical data were retrieved from the ORIEN AVATAR database (Aster Insights). Transcript level was determined by batch-corrected TPM (transcripts per million) of each gene, and cohort median was used as a reference to determine “high” versus “low” in subgroup analyses. The p-value and hazard ratio (HR) derived from Kaplan-Meier survival analysis are log-rank. Results: The 4-year HR for death in patients with “very high” HRAS transcript level (top 5%) was 0.15 (95% CI 0.07-0.34, p=0.03) compared to the rest, and this superior OS was independent from TNM stage or peri-operative 5-FU treatment history. In subgroup analyses, “high” HRAS expression was associated with superior OS only in patients with concomitant “low” KRAS expression in the absence of pathologic KRAS mutations in codons 12, 13 and 61 – the 5-year HR in “low” KRAS group was 0.42 (95% CI 0.18-0.96, p=0.03) compared to “high” KRAS group. NRAS transcript level did not influence OS. When further sub-grouped based on primary disease location, this superior OS was present only in the right-sided primary disease group with 5-year HR of “low” KRAS group at 0.17 (95% CI 0.03-0.99, p=0.06) compared “high” KRAS group. Conclusions: Contrary to the notion that RAS family genes are proto-oncogenic, we demonstrate that high HRAS transcript levels are associated with superior OS in stage II and III CRC. The high HRAS-associated OS benefit was most pronounced in patients with right-sided primary expressing low KRAS transcript levels in the absence of pathologic KRAS mutations. We speculate that when expressed at high levels, HRAS may counteract proto-oncogene KRAS but not oncogene KRAS at the transcript level. The potential of HRAS as a prognostic biomarker should be explored further.
dMMR/MSI tumour occurrence during follow-up of patients with Lynch syndrome treated with immune checkpoint inhibitors for a metastatic digestive cancer between 2015 and 2024: A retrospective monocentric cohort.
Authors: Anna Pellat, Camille Loisel, Antoine Dardenne, Thierry Andre
Journal: Journal of Clinical Oncology (2025)

96 Background: Immune check point inhibitor(s) (ICIs) transformed the prognosis of patients with metastatic dMMR/MSI cancers especially for patients with Lynch syndrome (LS). The aim of our study was to describe a population of LS carrier patients treated with ICI(s) for metastatic digestive cancer, specifically assessing the risk of developing metachronous cancer. Methods: We collected data of 93 patients with LS, treated by ICI(s) for a metastatic digestive tumour. These patients were selected from the “immunoMSI” patient cohort, which included all patients presenting with a MSI and/or dMMR digestive cancer treated with ICI(s) between February 2015 and April 2024 in the medical oncology department of Saint-Antoine Hospital (Paris, France). Our primary outcome was the cumulative risk of metachronous MSI/dMMR cancer; secondary outcomes included cumulative risk and time to de novo colorectal polyps, as well as PFS and OS under ICI(s). We performed a cox model to assess the association of predefined variables with OS and PFS under ICI(s). Results: Patients most frequently carried a germline pathogenic variant on the MSH2 (or EPCAM ) gene (47%) or on the MLH1 gene (30%). The majority presented with colorectal cancer (CRC) as their primary cancer (83%), followed by small intestine tumours (6%), stomach and pancreatic cancers (4%) and bile duct cancer (1%). Median age at cancer index was 62 years-old (26-77). A total of 12 out of 93 patients presented metachronous cancers during or after treatment with ICI(s). Ten of these metachronous cancers were dMMR or within the LS spectrum (urothelial n=4, CRC n=2, bilio-pancreatic n=1 and 3 skin cancers including 2 kerato-acanthomas). All patients who developed a metachronous cancer had a complete or partial response under ICI(s) for the index cancer. During a median follow-up of 47.8 months, 44 patients had colonoscopies and a total of 17 patients (39,5 %) developed pre neoplastic colorectal polyps. In multivariate analysis, PS ≥ 2 and age ≥ 70 years were associated with poorer OS with HRs of 6.3 (95% CI [1.5-25.9], p=0.01) and 5.5 (95% CI [1.6-18.9], p=0.006) respectively. Conclusions: Our results show that ICI(s) for patients with LS treated for an MSI/dMMR metastatic digestive cancer can still develop metachronous cancers and pre neoplastic polyps, which underlines the importance of maintaining dedicated follow-up after ICI(s) treatment in this population.
Impact of next-generation sequencing in advanced gastrointestinal cancer.
Authors: Aarushi Grover, Neeharika Srivastava Makani
Journal: Journal of Clinical Oncology (2025)

814 Background: Next-generation sequencing (NGS) is a cutting-edge technology that allows for rapid DNA and RNA sequencing, identifying key mutations in cancer patients. It provides both diagnostic and predictive data for treatment decisions. Approximately 75.6% of US oncologists use NGS testing for patients with advanced solid tumors.This study retrospectively evaluates the impact of NGS testing on treatment outcomes for advanced GI cancer patients at a community-based cancer center in Florida. Methods: Between March 2019 and September 2023, 267 patients with stage 3 or 4 solid malignancies underwent NGS testing. Of these, 77 patients with advanced GI cancer were included in the study. Nearly half (48%) of the patients were diagnosed with advanced-stage colon cancer.NGS testing was performed using tissue samples (79.22%), blood samples (16.88%), or both (3.90%). Demographic and clinical outcomes, including time to diagnosis, treatment initiation, and survival, were collected and analyzed. Results: The median age of the study population was 70, with 88.31% of patients insured through Medicare. The cohort was composed of 61.04% males. Targetable mutations were identified in 59.74% of patients, leading to FDA-approved targeted therapies for 44.16%, and clinical trial eligibility for 79.22%. 52 patients were alive at the time of this analysis; those with biomarkers identified through NGS testing had a median treatment duration of 11 months regardless of whether testing impacted choice of therapy; whereas, patients without identified biomarkers had a median duration of 7.5 months. NGS testing impacted first-line therapy in only 6.49% of all patients; however, 80% of those patients were alive at the time of this analysis with a median duration of response of 5 months. Conclusions: NGS testing has become a cornerstone of oncologic care for advanced solid tumors; however, in this cohort of advanced GI malignancies, NGS results influenced first-line treatment decisions in only 6.49% of cases. Although the study included a small sample size, it reflects a real-world community setting where access to therapies and insurance coverage varies. For example, though patients may have targetable novel therapies available for their disease, the indications for such therapies may not be in the first line setting or covered by insurance. Advancements in NGS targeted therapies has greatly impacted the care of other solid malignancies such as non-small cell lung cancer; however, this study highlights that in the field of GI oncology, there is a large clinically unmet need of identifying newer biomarkers that are clinically relevant and impactful in earlier lines of oncologic care.
Real world characteristics and outcomes of patients with BRAFV600E-mutant metastatic colorectal cancer in Australia: The COALA project.
Authors: Nadia Hitchen, Hui-Li Wong, Rachel Wong, Jeremy David Shapiro, Matthew E. Burge, Louise M. Nott, Belinda Lee, Stephanie Hui-Su Lim, Shu Fen Wong, Susan Caird, Vanessa Wong, Natalie Heather Rainey, Adnan Khattak, Hiren A. Mandaliya, Theresa M. Hayes, Javier Torres, Azim Jalali, Angus Campbell, Peter Gibbs, Jeanne Tie
Journal: Journal of Clinical Oncology (2025)

70 Background: BRAFV600E-mutant metastatic colorectal cancer (mCRC) represents a unique molecular subset with poor prognosis and less responsiveness to chemotherapy. The BEACON CRC study demonstrated that encorafenib plus cetuximab (EC) significantly improved overall survival (OS) compared to FOLFIRI plus cetuximab in BRAF-mutant mCRC as 2 nd or 3 rd line therapy. This combination was reimbursed in Australia from January 2022. Methods: We analysed data from the Australian TRACC mCRC clinical registry, encompassing patients (pts) with BRAF-mutant mCRC diagnosed in Australia from 2009 to 2024 at 31 hospitals. We assessed baseline demographics, uptake of EC following reimbursement and efficacy analysis of progression-free survival (PFS) and OS for pts that received EC and those who did not. Pts receiving EC on a clinical trial were excluded. Results: Among 2,800 pts with known BRAF mutation status, 365 (13%) were BRAF mutated. The BRAF mutant cohort had a median age of 63 years, with a significantly higher mutation rate in the 20-39 age group than other age groups (age 20-39, 25.5%; age 40-59, 10%; age 60+, 13.2%; P&lt;0.001); 54.5% were female, 58% right-sided tumours, 64% with synchronous metastatic disease and 21.7% deficient mismatch repair (dMMR). Overall, 314 (86%) pts with BRAF mutant tumours and 2,079 (85%) BRAF wild-type (WT) tumours received 1 st line treatment, and 156 (43%) BRAF mutant and 1,144 (47%) BRAF WT pts received 2 nd line therapy. The median OS from diagnosis was 17.3 months for BRAF mutant pts versus 34.7 months for BRAF WT pts (p &lt; 0.0001). All dMMR BRAF mutant pts received 1 st line pembrolizumab since its reimbursement in August 2021. Among 41 BRAF mutant pts progressing on 1 st line therapy since January 2022,(32 pMMR, 9 dMMR), 33 (80%) were subsequently treated with EC, and 4 (10%) did not receive further treatment. OS from the start of 2 nd line therapy was 9.6 months (95% CI: 7.2-12.5) for pts who received EC and 7.1 months (95% CI: 6.4-8.6) for those who received other systemic treatment. Median PFS for pts receiving EC was 4.6 months (95% CI: 3.4-5.8) and 3.3 months (95% CI: 2.5-5.3) for other 2 nd line treatments. Conclusions: mCRC pts younger than 40 have a high rate of BRAF mutation, where 1 in 4 tumours harbour the mutation. BRAF mutant mCRC has a poorer outcome than BRAF WT despite a similar proportion receiving 1 st and 2 nd line treatment. The majority of eligible BRAF mutant mCRC pts received EC following reimbursement in Australia, with PFS and OS outcomes consistent with the BEACON CRC trial.
Biological and therapeutic impact of tumor mutational burden in microsatellite instability/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC) treated with immune checkpoint inhibitors (ICI).
Authors: Sarah Blanchet Deverly, Balthazar Raffy, Toky Ratovomanana, Remy Nicolle, Paula Nay, Thierry Andre, Alex Duval, Romain Cohen
Journal: Journal of Clinical Oncology (2025)

272 Background: Microsatellite instability (MSI) is linked to hypermutability and response to ICI(s), especially in colorectal cancer. The predictive impact of tumor mutational burden (TMB) in ICI-treated MSI/dMMR metastatic colorectal cancer remains controversial, with some studies suggesting low TMB as a potential biomarker of resistance to ICI(s). We aimed to investigate the biological relevance of TMB in MSI/dMMR mCRC and its impact on survival outcomes in ICI(s)-treated patients (pts). Methods: MSI/dMMR mCRC pts treated with ICI(s) from the NIPICOL trial (NCT03350126) and the immunoMSI prospective monocentric cohort with available data from whole exome sequencing (WES) and RNA-sequencing (RNA-seq) were included. All cases were centrally assessed for MSI and dMMR status. TMB was calculated as described (Dupain et al., BMC, 2024). The search for a cutpoint able to optimize the difference in survival between 2 groups of patients with low and high-TMB was applied. The main endpoint was progression free survival (PFS) by iRECIST criteria. The cohort (NIPICOL, immunoMSI) was included as a covariate in the analysis of differential gene expression and pathway enrichment, with various tumor mutational burden (TMB) thresholds evaluated, specifically 10 and 30 mutations per megabase (mut/Mb). Results: A total of 99 pts were analyzed, with 4 (4%) excluded after central MSI/dMMR status review. Of these, 52 received anti-PD1 plus anti-CTLA4 therapy, while 43 received anti-PD1 alone. Median follow-up was 25 months. Median TMB was 51.8 mut/Mb (IQR: 35.9-74.9). TMB was not predictive of patient PFS, whatever the TMB threshold applied, including cutpoints already reported in the literature, the 2-year PFS rates being 80% versus 80% for TMB ≤ 10 and &gt; 10 mut/Mb, and 79% versus 82% for TMB ≤ 30 and &gt; 30 mut/Mb, respectively. Multivariate analysis including treatment type confirmed no association between TMB and PFS (HR 1.00, 95% CI [0.97–1.04]). TMB levels were not linked with specific signalling pathways related to immune checkpoints or antigen presentation as evaluated by RNA-seq with Gene Set Enrichment Analysis (GSEA) at a TMB threshold of 10 or 30 mut/Mb. However pathways involved in cell proliferation (e.g., “cell cycle”, “DNA replication”) were increased in TMB high (adjusted p-value &lt;0.05). RNA-seq signature quantification and deconvolution analysis revealed similar cell populations (e.g., fibroblasts, B cells, T cells) between high and low TMB groups at a TMB threshold of 10 and 30 mut/Mb. Conclusions: TMB has no survival impact for patients with ICI(s)-treated dMMR/MSI mCRC and does not discriminate two biologically distinct subpopulations. Other biomarkers should be developed for personalized medicine amongst these patients.
Ultrathin bronchoscopy-guided small airway biopsy for diagnosing sarcoidosis: A prospective study
Authors: Rocco Trisolini, Giovanni Sotgiu, Alessandra Cancellieri, Giuliana Pasciuto, Vanina Livi, Maria Chiara Flore, Marta Viscuso, Daniele Magnini, Fausto Leoncini, QuianQuian Zhang, Mariangela Puci, Luca Richeldi
Journal: Pulmonology (2024)

New ultrathin bronchoscopes (UTBs) enable the inspection and biopsy of small airways, potentially offering diagnostic advantages in sarcoidosis. In this prospective study, patients with suspected sarcoidosis underwent airway inspection with a UTB. Observed airway abnormalities were categorised into six predefined patterns. UTB-directed small airway biopsies (SABs) were collected from the upper lobes following a standardised procedure. We evaluated the prevalence and patterns of SAAs, as well as the diagnostic yield of UTB-directed SAB. Among 79 participants, 65 (82.3%) were diagnosed with sarcoidosis. Small airway abnormalities were identified in 26/65 (40%) patients, predominantly in those with parenchymal involvement on CT compared to those with lymphadenopathy only (58.1% VS. 23.5%, P = 0.005). The diagnostic yield of SABs for detecting granulomas was significantly higher in patients with SAAs than in those without (65.4% VS. 23.1%, P = 0.001) and in patients with parenchymal disease on CT compared to those without (54.8% VS. 26.5%, P = 0.02). Notably, random biopsies taken under direct visualisation from small airway carinas revealed peribronchiolar parenchyma in 23% of the patients. Small airway abnormalities are prevalent in sarcoidosis patients with parenchymal involvement, and biopsying these abnormalities yields a high rate of granuloma detection.
AGITG ASCEND: Randomised, double-blind phase II study of certepetide or placebo added to gemcitabine plus nab-paclitaxel in patients with untreated metastatic pancreatic ductal adenocarcinoma: Initial results.
Authors: Andrew Peter Dean, Katrin Sjoquist, Val Gebski, Christos Stelios Karapetis, Chris Lomma, Matthew E. Burge, Christopher B. Steer, Niall C Tebbutt, Belinda Lee, Christopher G. C. A. Jackson, Fiona Day, Shamsudheen Padinharakam, James Murray, Sonia Yip, Jan Mumford, Derrick HW Siu, Joanna Lee, Yan Ru Gao, Marion Harris, Timothy Jay Price
Journal: Journal of Clinical Oncology (2025)

728 Background: Gemcitabine (GEM) plus nab-paclitaxel (NAB-PAC) is a standard first-line chemotherapy regimen for advanced/metastatic pancreatic ductal adenocarcinoma (PDAC), with median Progression Free Survival (mPFS) and Overall Survival (mOS) of 5.5 &amp; 8.7 in the MPACT trial and 5.6 &amp; 9.2 months (mo) in the NAPOLI 3 trial, respectively. Certepetide (formerly LSTA1 or CEND-1) is a novel cyclic peptide that improves targeted penetration of co-administered drugs into tumor and stroma, leading to potentially increased anti-neoplastic activity. ASCEND is a randomized phase II trial designed to investigate the impact of adding certepetide to GEM/NAB-PAC. (NCT05042128). Methods: Eligible participants (pts) with histologically confirmed advanced PDAC and ECOG 0-1 were randomized 2:1 to receive GEM/NAB-PAC plus certepetide (3.2 mg/kg) or placebo (PLA) on days 1, 8, &amp; 15 of a 28-day cycle. Stratification was by age (&lt;65/≥65 years), ECOG (0/1), presence of liver metastasis (Y/N) and trial site. The primary objective was to determine the effect of adding certepetide to GEM/NAB-PAC on PFS. Objective tumor response rate (OTRR), safety and OS were secondary objectives. This non-comparative phase II design targeted a PFS increase of 17% at 6 mo from 47% to 63%. A sample size of 65 patients in the certepetide arm was expected to have 80% power, with 95% confidence to exclude an uninteresting 6-mo PFS rate of 47%. Results: 95 pts (66 certepetide, 29 PLA) were enrolled between May 2022 to December 2023. 6-mo PFS in the certepetide and PLA groups was 49.0% (95% CI 36.4%, 60.5%) and 40.8 (95% CI 22.6%, 58.3%) respectively, with mPFS of 5.5 mo in both groups. mOS was 12.42 mo for the certepetide and 9.72 mo for the PLA. An OTRR of 38.3% (certepetide) and 26.9% (PLA) was observed. Of note, 4 complete responses were observed in the certepetide group vs. 0 in PLA group. In subjects with ECOG 0, 6 mo PFS was 68.1% (95% CI 48.7%, 81.4%) in the certepetide compared to 36.4% (95% CI 11.2%, 62.7%) in the PLA. Grade ≥3 toxicities were similar in both groups at 16% (certepetide) and 15% (PLA). Conclusions: The addition of certepetide is safe and despite showing no improvement in 6-mo PFS, a possible signal of benefit in OS and OTRR, including the 4 complete responses was observed, warranting further investigation. A further cohort of the ASCEND study evaluating the addition of a second dose of certepetide is ongoing. Clinical trial information: NCT05042128 .