Resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAb) is common in metastatic colorectal cancer (mCRC) and reliable predictive biomarkers remain lacking. The identification of new predictive biomarkers is therefore necessary to assess the efficacy of anti-EGFR mAb, in order to optimize the therapeutic strategy for mCRC. Micro-RNAs (miR) are small non-coding RNAs that primarily regulate gene expression, and whose dysregulation in anti-EGFR resistance has been widely reported in CRC. Following a previous analysis using a miRnome strategy, the present study focused on NGS (next-generation sequencing) to investigate a broader range of miRNAs. We identified several miR resistance signatures as well as potential target genes and associated pathways following exposure to different doses of cetuximab or panitumumab in colorectal cancer cells. In the context of the search for useful biomarkers for this cancer, this could help optimize the design of in vivo experiments or future prospective clinical trials.

Background Patients with advanced pancreatic ductal adenocarcinoma (aPDAC) often experience general health decline at diagnosis due to a high-symptom burden. The optimal management of symptoms and/or poor performance status (PS) in these patients remains an unmet medical need. Patients and Methods In this multicenter study, patients with PS≥2 and pathologically confirmed or imaging-suspected aPDAC were included at first oncology visit in a personalized 14-day emergency integrative supportive care program (14-EISCP) to manage pain, nutrition, diagnostics, and stenting procedures. The primary endpoint was the 14-EISCP success in feasibility of planned procedures and clinical benefit defined as post-EISCP PS≤1, ≥5 points improvement in fatigue, pain, global health-related quality of life (HRQoL) scores (EORTC QLQ-C15-PAL), or chemotherapy initiation within 30 days. Results A total of 106 patients were included; 93 evaluable patients considered for primary endpoint analysis (median age: 76 years [68-80], PS3: 20.9%, metastases: 61.3%). The median overall survival was 4.1 months (IC95% 2.6-5.6). The 14-EISCP was successful in 59.1% (n=55) of patients, meeting the primary objective (clinically relevant). The 14-EISCP feasibility was achieved in 70.9% of cases. Post-EISCP clinical benefit was observed in 79.6% of patients, with PS improvement to 0/1 in 13.2%, HRQoL improvement in 23.9%, and chemotherapy initiation ≤30 days in 73.1%. Among evaluable patients, 17.2% received mFOLFIRINOX or gemcitabine-nab-paclitaxel, 35.4% received FOLFOX, 25.3% had gemcitabine or 5-fluorouracil alone, and 22.2% received best supportive care. In patients with PS2 at baseline, the administration of doublet/triplet chemotherapy was associated with improved overall survival compared to single-agent. Discussion These results offer a promising framework for improving outcomes in aPDAC patients, bridging the gap between symptom management and systemic therapy administration. Conclusions In patients with PS≥2 and aPDAC, the personalized 14-EISCP was feasible and lead to meaningful clinical benefit, allowing doublet or triplet chemotherapy in half the patients.

Background: Colorectal cancer (CRC) is a major health burden, the third most common cancer and the second leading cause of cancer-related death worldwide. The development of biomarkers for screening, diagnosis, prognosis and prediction is crucial for early management and treatment of CRC. Despite existing biomarkers, particularly tests targeting alterations in DNA, proteins other than hemoglobin or other molecules in biological samples, there is a need for new, comprehensive and minimally invasive assays that reflect neoplastic biology. Methodology: This study proposes a novel approach combining Mid InfraRed (MIR) spectroscopy and targeted metabolomics to identify novel biomarkers of CRC. Here we present an original statistical pipeline developed in R, which integrates spectroscopic and metabolomic data to identify biomarkers and their associated biological pathways through automated searches of HMDB and KEGG databases. The pipeline is validated by two studies. The first study aims to extract relevant biomarkers to identify the population subgroup more likely to have CRC or advanced precursor lesions in colorectal screening strategy for average-risk adults starting at age 50. It seeks to distinguish between low-risk and high-risk patients for CRC among those undergoing colonoscopy screening. The second study involved a preclinical model of xenografts of CRC cell lines to demonstrate the portability of the pipeline. Results: Our results indicate that this integrated approach may provide a relevant, inexpensive, and accurate method for screening, diagnosing, and understanding CRC pathology. Conclusion: This innovative tool could improve patient management by enhancing the risk assessment of CRC and providing a better understanding of the underlying biological processes. The application of this methodology could extend beyond CRC to other diseases, providing improved screening, diagnosis and treatment strategies in oncology.

BACKGROUND & AIMS:Biliary tract cancers (BTCs) are rare, heterogeneous tumors associated with a poor prognosis, even after curative-intent surgery. Adjuvant capecitabine is currently the standard of care; however, real-world data on its efficacy and tolerance are lacking. PATIENTS AND METHODS:This French, retrospective, multicentre study, nested within the ACABi-PRONOBIL observational cohort, assessed adjuvant capecitabine efficacy in patients, with resected intrahepatic, perihilar, distal cholangiocarcinoma, or gallbladder carcinoma. who had not received prior systemic therapy. Patients treated with adjuvant capecitabine after 2017 were compared with patients diagnosed before 2017 and managed with surveillance only. The primary endpoint was overall survival (OS), secondary endpoints were recurrence-free survival (RFS) and toxicity. Inverse probability of treatment weighting (IPTW) in Cox regressions was used to adjust for measured confounding, imbalanced factors between groups. RESULTS:A total of 320 patients were included (197 in the capecitabine group and 123 in the surveillance group). In IPTW analysis, adjuvant capecitabine was not significantly associated with improved RFS (IPTW HR, 0.81, CI 95%, 0.54-1.21; p = 0.304), or OS (IPTW HR, 0.94, CI 95%, 0.58-1.52; p = 0.798). The point estimate for RFS was consistent with the ITT analysis of the BILCAP trial. In the capecitabine group, 49% of patients required at least one dose reduction, and 35.7% discontinued treatment due to mainly grade 3/4 gastrointestinal (13.4%) and cutaneous (25.8%) toxicities. CONCLUSIONS:In this real-world cohort, adjuvant capecitabine was not significantly associated with improved RFS or OS in patients undergoing curative-intent resection for BTC, although a numerical trend in favor of capecitabine for RFS. These findings support the need for refined patient selection strategies and for prospective evaluation of novel adjuvant approaches. CLINICAL TRIAL REGISTRATION:NCT04935853 IMPACT AND IMPLICATIONS: This multicentre real-world study - BILCAP real study provides important complementary evidence to randomized trials by evaluating the effectiveness and tolerability of adjuvant capecitabine for resected biliary tract cancers in routine clinical practice.Although no statistically significant survival benefit was observed, the consistency of the recurrence-free survival estimate with the intention-to-treat results of the BILCAP trial and the observed toxicity profile provide clinically relevant information for physicians, patients, and multidisciplinary teams involved in postoperative treatment decisions.These findings support shared decision-making by helping clinicians balance the potential benefit of delaying recurrence against the risk of treatment-related toxicity, while emphasizing the need for careful patient selection and toxicity management in daily practice.Given the retrospective design and the possibility of residual confounding despite propensity-score adjustment, these results should be interpreted cautiously and primarily serve to inform the design of future biomarker-driven and prospective adjuvant studies rather than to change current clinical practice.

BACKGROUND AND AIMS:Cancer-related cachexia alters body composition (BC) and organ function, potentially affecting drug pharmacokinetics (PK).This ancillary study of the FFCD0904 phase I/II trial, which evaluated panitumumab -based radiochemotherapy in localized squamous cell carcinoma (SCC) of the anus, explored association between panitumumab PK, BC and its effects. METHODS:Panitumumab PK parameters were estimated using a population PK approach. Pre-treatment CT scans at L3 were used to assess BC. Skin toxicity and efficacy data (tumor response, survival) were analyzed in relation to BC and PK parameters. RESULTS:Among 54 patients, 35 had panitumumab PK measurements, 42 had baseline CT scans, and 36 had skin toxicity data. In 25 patients with complete BC and PK data, AUC0-14 and clearance (CL)tended to be positively correlated with body weight (BW, p = 0.0025 and 0.031), fat mass (FM, p = 0.027 and 0.033), and fat-free mass (FFM, p = 0.059 and 0.049),).Non-sarcopenic patients tended to show higher AUC0-14 than sarcopenic patients (p = 0.0016). Lower albumin appeared to be associated with reduced clearance (p = 0.015). Despite these PK associations, neither BC nor panitumumab exposure seems correlated with tumor response, survival, or early skin toxicity. CONCLUSION:This exploratory analysis suggests that BW and BC may influence panitumumab PK, with patients who had lower BW, FM and FFM might have reduced exposure and clearance. Interpretation should be cautious due to the small sample size, confounding effect between BC and BW and potential disease-related effects. Larger studies with longitudinal BC and PK assessments are needed to clarify these relationships and guide dosing strategies.

BACKGROUND AND AIMS:Pretherapeutic evaluation of ampullary carcinomas (ACs) is important to choose the optimal therapeutic strategy. We aimed to assess the ability of EUS and CT to predict the pathologic tumor node metastasis stage of resected AC. METHODS:We analyzed data collected in the Fédération Française de Cancérologie Digestive AC cohort, a French multicentric prospective cohort of patients with resected AC. Our main outcome was the diagnostic performance of EUS to predict pathologic tumor (pT) and pathologic node (pN) and CT to predict pN. RESULTS:Among the 389 patients included in the cohort, data for ultrasound tumor staging, ultrasound node staging, and CT node staging, along with pathology results, were available for 143, 160, and 185 patients, respectively. For pT1 prediction, values for sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) were 68%, 87%, 53%, and 93%, respectively, for EUS, with an accuracy of 84%. For pT2 prediction, values were 58%, 75%, 56%, and 75%, respectively, with an accuracy of 68%. For pT3-T4 prediction, values were 62%, 79%, 71%, and 71%, respectively, with an accuracy of 71%. For pN0 prediction, values for Se, Sp, PPV, NPV, and accuracy were 88%, 38%, 60%, 75%, and 64%, respectively, for EUS, and 94%, 39%, 63%, 85%, and 68%, respectively, for CT. CONCLUSIONS:Although the overall performance of both modalities was low, we found that both EUS and CT had good NPV for the prediction of pN0, and EUS had a good NPV for predicting pT1.

BACKGROUND:Management of low locally advanced rectal cancer (LARC) requires balancing oncologic radicality, sphincter preservation, postoperative function, and long-term stoma acceptability. These challenges are amplified in settings where socioeconomic and cultural factors influence treatment decisions. This study aimed to provide a descriptive comparison of surgical and reconstructive pathways for LARC in France and Morocco. METHODS:This retrospective bicentric study included patients operated on between January 2017 and December 2024 for low LARC (cT3/T4 and/or node-positive adenocarcinoma within 5 cm of the anal verge). Outcomes were compared between Tours University Hospital, France (LARC-Fr), and the National Institute of Oncology, Rabat, Morocco (LARC-Mo). RESULTS:A total of 224 patients were included (80 LARC-Fr; 144 LARC-Mo). French patients were older (68 vs 57 years, p < 0.001) and had higher ASA III-IV scores (26.3% vs 2.1%, p < 0.001), whereas cT4 tumors were more frequent in Morocco (22.9% vs 7.5%, p = 0.003). Sphincter-preserving procedures, including intersphincteric resection (35.0% vs 0%, p < 0.001) and TaTME (35.0% vs 2.8%, p < 0.001), were more common in France, while abdominoperineal resection (APR) predominated in Morocco (79.2% vs 48.8%, p < 0.001). Among Moroccan patients with a definitive stoma, pseudocontinent perineal colostomy (PCPC) was performed in 64.1%. Major postoperative morbidity and reoperation rates did not differ significantly between cohorts. Complete mesorectal excision and R1 resection rates did not differ significantly. Three-year disease-free survival was 74.5% versus 73.2% (p = 0.075), and overall survival was 85.0% versus 71.9% (p = 0.279), respectively. CONCLUSIONS:This bicentric retrospective study describes distinct surgical and reconstructive pathways for low rectal cancer in France and Morocco. In the Moroccan cohort, PCPC was used after abdominoperineal resection as an alternative to a conventional permanent abdominal colostomy when sphincter preservation was not considered appropriate.

728 Background: Oligometastatic disease (OMD) in pancreatic ductal adenocarcinoma (PDAC) is an emerging clinical entity. The limited extension of the disease prompt to explore the role of metastases-directed therapies (MDT); however, their actual survival and clinical benefits remain uncertain. Additional studies with larger effectives are needed to clarify the role of MDT in clinical practice. Methods: We conducted a retrospective multicenter, observational French-Belgian study to evaluate the impact of MDT on event-free survival (EFS) and overall survival (OS) in patients with OMD-PDAC. OMD was defined as metastases (mets) involving no more than 2 organ and ≤5 mets (Leonhardt CS. ESMO Open 2023). Eligible patients were adults with histologically confirmed PDAC who underwent a resection of the primary tumor, with concurrent or subsequent MDT of MDT. OS was defined as the delay from MDT to death from any cause; EFS was calculated from the date of MDT until radiologically confirmed disease progression, recurrence or death. The ALTOPANC score—based on known prognostic factors (CA 19-9 >90 U/mL, > 1 met, and non-pulmonary mets)—was correlated with OS and EFS. Results: Between 01/2011 and 12/2024, 155 patients with OMD-PDAC were included; 138 had metachronous metastases. Sites of mets included liver (n=71, 45%), lung (n=61, 39%), periaortic lymph nodes (n=13, 8%) and peritoneum (n=5, 3%). At time of the met's diagnosis, 107 patients (71%) had a single met, and 25 (17%) patients had presented two mets. After a median follow-up of 4.42 years, median EFS and median OS in the entire population were of 0.8 and 3,4 years respectively. MDT modalities consisted in surgery (n=69, 45%), radiotherapy (n=50, 32%), and thermoablation (n=36, 23%). In the multivariate Cox model, higher CA 19-9 level (HR = 1.29, 95% CI: 1.13–1.48, p = 0.0002) and the presence of 2 (HR = 2.54, 95% CI: 1.32–4.88, p <0.0001) or ≥3 treated mets (HR = 4.39, 95% CI: 2.18–8.84, p <0.0001) were independent adverse prognostic factors for OS. Thermoablation was independently associated with an improved OS compared to other technics (HR=0.51, 95%CI: 0.27–0.96, p =0.0127). The ALTOPANC score was significantly associated with EFS :2-year EFS rates were 53.1%, 23.8%, 8.3%, and 0% in patients with scores of 0, 1, 2, and 3, respectively (p < 0.001). A similar trend was observed for OS. Conclusions: 1) This real-world, study shows promising results of MDT in patients with OMD-PDAC, particularly thermoablation ; 2) among patients with favorable prognostic profile (low ALTOPANC score) may have the higher benefit. A prospective randomized study is warranted to confirm these results.

PURPOSE The choice of adjuvant chemotherapy in pancreatic ductal adenocarcinoma (PDAC) is mainly guided by patients' general condition. We hypothesized that tumor morphology may predict differential treatment benefit and tested whether deep learning applied to histology images could derive a biomarker of relative benefit from gemcitabine (GEM) versus modified FOLFIRINOX (mFOLFIRINOX) in resected PDAC. PATIENTS AND METHODS Standard whole-slide images from a retrospective multicentric series of 231 patients who underwent curative-intent pancreatectomy and received adjuvant mFOLFIRINOX (n = 54) or GEM (n = 177) were used to train regimen-specific histology models on disease-free survival (DFS), which were then combined into PANCprAId, a biomarker estimating personalized relative benefit from adjuvant GEM versus mFOLFIRINOX. External validation was performed in the randomized PRODIGE-24/CCTG PA6 trial (n = 313). RESULTS In PRODIGE-24/CCTG PA6, the treatment-specific histology scores used to construct PANCprAId stratified outcomes among patients treated with GEM (hazard ratio [HR], 1.69 [95% CI, 1.04 to 2.73]; P = .03) and mFOLFIRINOX (HR, 2.02 [95% CI, 1.4 to 3.0]; P < .001). When combined into PANCprAId, the biomarker identified subgroups with differential relative benefit from adjuvant GEM versus mFOLFIRINOX, with significant treatment interactions for DFS (interaction P = .003) and cancer-specific survival (interaction P = .001). Predicted sensitivity to each regimen was associated with distinct epithelial and stromal features. CONCLUSION Histology-based deep learning can derive a predictive biomarker of relative benefit from adjuvant GEM versus mFOLFIRINOX in resected PDAC.

In this study, we aim to assess the impact of tumor height on surgical strategy, oncological outcomes, and long-term function in locally advanced rectal cancer. This retrospective cohort study included patients with cT3–T4 and/or N+ rectal cancer treated between 2017 and 2024. Tumors were classified as low locally advanced rectal cancer (LARC; 0 to < 5 cm) or middle locally advanced rectal cancer (MARC; ≥ 5 to < 10 cm). All patients underwent total mesorectal excision (TME) following multimodal therapy. Outcomes included perioperative variables, overall survival (OS), disease-free survival (DFS), and functional results assessed using Wexner, low anterior resection syndrome (LARS), the 36-Item Short-Form health survey (SF-36), and Five-Item International Index of Erectile Function (IIEF-5) scores. Predictors of permanent stoma were analyzed using multivariable regression. A total of 164 patients were included (MARC n = 84; LARC n = 80). Sphincter-sacrificing procedures were significantly more frequent in LARC (abdominoperineal resection [APR]: 48.8

EC-cell familial small intestine neuroendocrine tumors (EC-cell F-SINET) are a recently described but poorly characterized entity. We aimed to describe their clinical and pathological features, and to compare them to patients with a sporadic form (EC-cell S-SINET). We constituted a nationwide cohort including (retrospectively patients diagnosed before 2012 and prospectively from 2012 to 2022) all patients with F-SINET (histologically proven SINET in ≥ 2 first or second-degree relatives) managed in the French GTE-RENATEN network. Clinical and pathological data were described and compared to the GTE-RENATEN population-based cohort including 2460 patients with EC-cell S-SINET using multivariable logistic regression. The survival impact of EC-cell F-SINET was explored using Cox proportional hazard analyses. We included 92 patients with EC-cell F-SINET from 47 families. Median age at diagnosis was 60.4 years. Among these patients, 22

OBJECTIVES:To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP1-RA) use and all-cause mortality in patients with type 2 diabetes treated for colorectal cancer, using a real-world health database. METHODS:This retrospective cohort study was conducted using the TriNetX global health records network. Adult patients with type 2 diabetes diagnosed with colorectal cancer between 2010 and 2025 were included. Patients were divided into two cohorts based on GLP1-RA exposure versus other oral antidiabetic drugs. Propensity score matching was applied to balance covariates. Overall survival (primary outcome) and metastasis-free survival (secondary outcome) were analysed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS:After propensity score matching, each cohort included 751 patients. Median follow-up period was 731 days in the GLP1-RA cohort and 779 days in the non-GLP1-RA cohort. GLP1-RA users had a significantly reduced all-cause mortality rate (11.5%) compared with non-users a (20.4%), with a hazard ratio of 0.58 (95%CI: 0.45-0.76; P < 0.001). Metastasis-free survival rate were 5.3% in the GLP1-RA cohort versus 8.9% in the matched non-user cohort, with a hazard ratio of 0.60 (95%CI: 0.40-0.87; P = 0.01). The incidence of major adverse cardiovascular events (MACE) did not differ significantly between cohorts, with a hazard ratio of 0.84 (95%CI: 0.66-1.06; P = 0.16). CONCLUSIONS:In this real-world cohort of diabetic patients treated for colorectal cancer, GLP1-RA therapy was associated with a significant improvement in overall survival. These findings support the continued use of GLP1-RA agents in this population and may provide reassurance to clinicians and patients regarding the safety and potential benefit of these agents following a colorectal cancer diagnosis.

Introduction: The risk of colorectal cancer (CRC) is increased in first-degree relatives of patients with CRC or advanced adenoma, for whom targeted screening by colonoscopy is recommended. The rate of completion of this examination is insufficient. The main hypothesis is that patients are not sufficiently aware of the familial implications of their disease or have difficulty informing their relatives. This study is part of the development of a personalized prevention education (PE) program based on sessions inspired by motivational interviewing. The aim of index-case education was to encourage participants to engage with their relatives to promote CRC screening among them. Aim of the study: This ancillary study, which complemented a cluster-randomized trial, aimed to qualitatively measure the performance of this PE. Methods: Based on a qualitative methodology, semi-structured interviews were conducted with14 index-case patients and three trainers (FTs) who delivered PE to them. A thematic content analysis followed by a textual analysis, and then a cross-analysis of these two methods, were performed. Results: The patients' discourse is shaped by their experience of the disease, family relationships, and interactions with healthcare providers. The linear biographical approach allows them to "re-situate" the PE, butfew precise methodological elements are reported. Nevertheless, both analyses highlight a predominantly positive experience of the PE. A majority of the trainers' discourse focuses on the reception of the patients' accounts of their experiences, and the methodology is unclear. The trainers report that the training and PE sessions are too short and that there is a lack of clarity about their role and stance, preventing them from fulfilling the objective. Conclusions: Despite patients' generally positive experience of the PE, this study did not clearly establish its relevance and methodological coherence. While not fundamentally called into question, this methodology likely requires revision and improvement

BACKGROUND:Small bowel adenocarcinoma (SBA) is a rare malignancy with poor prognosis. In metastatic disease, evidence regarding the efficacy of chemotherapy (CT) combined with bevacizumab or anti-EGFR agents is limited to small studies. This study aimed to assess, in real-world practice, the effectiveness of first-line CT combined with targeted therapies (TT)-either antiangiogenic (AA) or anti-EGFR-compared with CT alone in patients with metastatic SBA (mSBA) and proficient mismatch repair/microsatellite stable (pMMR/MSS) status. PATIENTS AND METHODS:This retrospective multicentre study included all patients receiving at least one cycle of CT with or without TT for mSBA. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Analyses used inverse probability of treatment weighting (IPTW) in univariable Cox models to account for potential confounding factors that were unbalanced between groups. RESULTS:A total of 255 patients were included: 153 received CT alone, 45 CT+AA, and 16 CT+anti-EGFR as first-line therapy. Median PFS was 8.0 months with CT alone versus 11.9 months with CT+AA (IPTW HR=0.38; 95% CI: 0.29-0.49; p < 0.0001). Median OS was 15.9 versus 23.1 months (IPTW HR=0.38; 95% CI: 0.28-0.51; p < 0.0001). ORR did not differ significantly (33.8% vs 43.2%; p = 0.26). Among 78 patients with RAS wild-type tumours, outcomes did not significantly differ between CT alone and CT+anti-EGFR groups. CONCLUSION:Adding antiangiogenic therapy to CT significantly improved PFS and OS in first-line treatment of mSBA, warranting confirmation through prospective randomized trials.

Introduction&amp;#160;: The risk of colorectal cancer (CRC) is increased in first-degree relatives of patients with CRC or advanced adenoma, for whom targeted screening by colonoscopy is recommended. The rate of completion of this examination is insufficient. The main hypothesis is that patients are not sufficiently aware of the familial implications of their disease or have difficulty informing their relatives. This study is part of the development of a personalized prevention education (PE) program based on sessions inspired by motivational interviewing. The aim of index-case education was to encourage participants to engage with their relatives to promote CRC screening among them. Aim of the study&amp;#160;: This ancillary study, which complemented a cluster-randomized trial, aimed to qualitatively measure the performance of this PE. Methods&amp;#160;: Based on a qualitative methodology, semi-structured interviews were conducted with14 index-case patients and three trainers (FTs) who delivered PE to them. A thematic content analysis followed by a textual analysis, and then a cross-analysis of these two methods, were performed. Results&amp;#160;: The patients&amp;#8217; discourse is shaped by their experience of the disease, family relationships, and interactions with healthcare providers. The linear biographical approach allows them to &amp;#8220;re-situate&amp;#8221; the PE, but few precise methodological elements are reported. Nevertheless, both analyses highlight a predominantly positive experience of the PE. A majority of the trainers&amp;#8217; discourse focuses on the reception of the patients&amp;#8217; accounts of their experiences, and the methodology is unclear. The trainers report that the training and PE sessions are too short and that there is a lack of clarity about their role and stance, preventing them from fulfilling the objective. Conclusions&amp;#160;: Despite patients&amp;#8217; generally positive experience of the PE, this study did not clearly establish its relevance and methodological coherence. While not fundamentally called into question, this methodology likely requires revision and improvement.

Background:Biliary tract cancers (BTC) are often diagnosed after the age of 70, when comorbidities and compromised performance status (PS) are more prevalent. Objectives:This study compared clinical and disease characteristics and outcomes in BTC patients aged ⩽70 and >70 years. Design and methods:PRONOBIL-ACABI is a cohort study including 1256 BTC patients treated across 16 French centers from January 2003 to June 2021. We analyzed demographics, clinical characteristics, treatment modalities, molecular profiles, overall survival (OS) as the primary endpoint, and progression-free survival (PFS). Results:Among the 1256 BTC patients (53% male; median age: 64.5), 31% were aged >70. Patients >70 exhibited poorer PS (PS ⩾2, 17% vs 8%; p < 0.0001), a higher rate of comorbidities (⩾1, 89% vs 78%; p < 0.0001), and were less often proposed a molecular profile (43% vs 65%; p < 0.0001) than those ⩽70. Patients with unresectable BTC aged >70 had significantly shorter OS compared to younger patients (median OS: 14.6 vs 17.4 months, p < 0.0001), despite similar PFS (median PFS: 6.6 vs 5.8 months, p = 0.61). They were also less likely to receive first-line chemotherapy (87% vs 97%, p < 0.0001). In resected BTC, survival outcomes were comparable across age groups, with a median OS of 47.0 months in patients >70 vs 48.8 months in those ⩽70. Conclusion:Patients aged >70 years with unresectable BTC had a significantly shorter OS compared to those aged ⩽70, despite similar first-line PFS. In resected BTC, elderly patients achieved OS and PFS outcomes comparable to those aged ⩽70.

Bevacizumab shows inter-individual pharmacokinetic variability, with an exposure-response relationship in metastatic colorectal cancer (mCRC) patients. This study explores whether a double dose of bevacizumab, compared to a standard dose, increases efficacy in mCRC patients treated with bevacizumab-based chemotherapy as first-line therapy and who have a low initial trough concentration of bevacizumab. PHARBEVACOL is a multicenter, randomized, double-blind, two-parallel group trial. All patients will receive first-line bi-weekly 5 mg/kg bevacizumab-based chemotherapy and those with low initial bevacizumab concentrations (≤15.5 mg/L) will be randomized to either continue the standard dose (5 mg/kg every 14 days) or receive a double dose (10 mg/kg every 14 days). The primary objective is to evaluate the effect of doubling dose on progression-free survival (PFS). During a screening phase, the first serum trough concentration will be measured on day 14, before the second infusion of bevacizumab. We hypothesize a 40 % PFS in the control group at 9 months versus 60 % in the study group, corresponding to a hazard ratio of 0.56. With 80 % power, a 5 % two-sided type I error, and a minimum 12-month follow-up, 116 patients need to be included. Since only 50 % of screened patients will be eligible for randomization, approximately 244 patients will be screened. Recruitment is scheduled to begin in February 2025.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.dld.2025.05.009. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal

BACKGROUND:Hepatocellular carcinoma (HCC) frequently develops in underlying cirrhosis. Liver dysfunction impacts survival and may influence treatment results. About a quarter of patients with advanced HCC present with Child-Pugh B liver functions. All recent phase 3 trials validating standard of care limited inclusion to patients with Child-Pugh A liver function. Results of immunotherapy is less described in patients with altered liver function. We previously showed that the ALBI grade might be able to better select patients with Child-Pugh B liver functions who could benefit from sorafenib. Single-agent anti-PD-(L)1 antibodies might have a more favorable safety profile than standard of care combinations. METHODS:We thus launched a study, the HESTIA trial, testing tislelizumab, an anti-PD-1 antibody that was demonstrated as non-inferior to sorafenib as first-line treatment, in the population of patients with advanced HCC, Child-Pugh B and ALBI grade 1 or 2 liver function. RESULTS:In this article, we present the design of the study and first safety results. This is a single-arm phase 2 study. Fifty patients will be included. The primary endpoint is objective response rate. The first safety analysis showed no signal of increased toxicity of the drugs. However, this population is at high risk for liver-related adverse events. CONCLUSION:The study is currently pursuing accrual.