BACKGROUND:As the liver is the most common site of metastasis in colorectal cancer (CRC), and metastatic recurrence frequently occurs after resection of colorectal liver metastases (CRLM), hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment approach. This study investigates the feasibility, safety, and efficacy of postoperative HAIC with oxaliplatin following curative-intent resection of CRLM. METHODS:A retrospective analysis was conducted on all patients with resected CRLM who received postoperative HAIC with oxaliplatin between 2008 and 2022 at a tertiary cancer center. The primary study endpoint were disease-free-survival (DFS) and overall survival (OS). RESULTS:Overall, 119 patients (median age, 56 years; synchronous metastatic disease, 82%) received postoperative HAIC with oxaliplatin after complete resection of their CRLM (median number of metastases resected, 7). They received a median number of 6 HAIC cycles (range, 1-12), mostly combined with intravenous chemotherapy with 5-fluorouracil/leucovorin (n = 118, 99%) and irinotecan (n = 41, 34%). The median DFS was 10.2 months (95% CI 9-12.4) and the median intrahepatic DFS was 18.4 months (95% CI 12.4-29.7,12 months DFS rate, 60%). The median OS reached 55.5 months (95% CI, 50.0-86.6; 5-year OS rate, 46%). Grade 3-4 toxicities occurred in 45% of patients (neutropenia, 38%; peripheral neuropathy, 9%); 54% of patients experienced pain (mostly mild to moderate) during oxaliplatin infusion. HAI catheter-related complications included extrahepatic perfusion (30%) and catheter occlusion (11%). CONCLUSIONS:HAIC with oxaliplatin is an effective, safe and feasible treatment option after resection/ablation of CRLM. These findings support the therapeutic relevance of postoperative HAIC in liver-limited metastatic CRC.

BACKGROUND:A better prognosis is suggested for lung-only metastases patients with pancreatic ductal adenocarcinoma (PDAC), yet biological/clinical underpinnings of organotropism in PDAC remain unclear. Study objective was to compare PDAC patients depending on their metastatic site with a special focus on "lung-only" metastases patients. METHODS:A retrospective analysis included all patients with metastatic PDAC between 2010 and 2022 in an academic-center. Lung-only patients were defined as patients with only lung metastases at diagnosis of metastases. RESULTS:Among 1012 patients, 109 (11 %) presented lung-only metastases, 506 patients (50 %) liver-only, 94 (9 %) peritoneal-only and 303 (30 %) other or multiple sites. Compared with others, lung-only patients were more frequently female (63 % vs. 46 %), older at metastatic diagnosis (median 66 vs. 63 years, p = 0.01), and less likely to have synchronous metastases (42 % vs. 69 %, p < 0.001). ctDNA detection was lower in the lung-only group with less KRAS mutations and TP53 mutations detected with liquid biopsy (but no difference was observed using tumor tissue). Median OS was higher in the lung-only group with 28.7 months (95 %CI [23.3-38.6]) vs 13.5 months (95 %CI [12.4-14.6]) for liver-only group, 11.5 months (95 %CI [9.6-16.9]) for peritoneal-only group and 11.3 months (95 %CI [10.0-13.8]) for other patients (p < 0.0001). Among lung-only patients, local treatments (n = 15) had a positive prognostic impact. CONCLUSIONS:Patients with lung-only metastases had a better OS than others, were more often women, and harbored less KRAS mutations. Our results argue in favor of PDAC with specific characteristics, especially a better prognosis, possibly further enhanced by the possibility to perform local treatments, and less detection of ctDNA.

BACKGROUND:Tumor volumetry and liquid biopsy are emerging tools reflecting tumor burden and enhancing prognostic assessment in advanced pancreatic ductal adenocarcinoma (PDAC). METHODS:This retrospective monocentric study of 102 advanced PDAC patients assessed the prognostic value of total tumor volume (TTV), measured on CT-scans, and circulating tumor fraction (TF) at diagnosis. Liquid biopsy provided the TF and variant allele frequency (VAF) of mutations. All cutoff values were determined by maximizing Youden's index. Overall survival (OS) was analyzed using Kaplan-Meier and Cox models. Patients were stratified into high and low TTV groups according to the TTV threshold; the same approach was applied to TF. A composite prognostic score integrating TTV and TF categories stratified patients into high- and low-risk OS groups. Pearson and Spearman coefficients assessed correlations between TTV, TF, and VAFs. RESULTS:Among 102 patients (7927 lesions manually annotated), patients in high TTV group had a significantly shorter OS than those in low TTV group (cutoff ≥ 211 cm3, HR=1.78, p = 0.02). Similarly, patients in high TF group had a significantly shorter OS than those in low TF group (cutoff ≥ 5%, HR=1.84, p = 0.01). The combined TTV-TF score showed the strongest prognostic value (HR=2.09, p < 0.005). Furthermore, TTV correlated with TF (Spearman r = 0.70), TP53 VAF (Pearson R2=0.49) and KRAS VAF (Spearman r = 0.54). CONCLUSIONS:Early integration of tumor volumetry and ctDNA profiling refines advanced PDAC prognosis. The combined TTV-TF score offers greater prognostic value than either parameter alone, to be validated in a larger prospective cohort.

Background & Aims: The incidence of biliary tract cancers (BTC) among young individuals (≤50 years) is currently rising. We aimed to investigate the clinical, therapeutic and molecular characteristics and outcomes of young-onset BTC (YO-BTC). Methods: Patients with histologically confirmed BTC treated at Gustave Roussy (France) and Vall d’Hebron Institute of Oncology (Spain) were categorized as YO-BTC (≤50 years old), average-onset (AO-BTC; 51-69 years old), and late-onset (LO-BTC; ≥70 years old). The primary endpoint was overall survival (OS). The secondary endpoint was the growth modulation index (GMI), e.g., the ratio of progression-free survival (PFS) with the targeted therapy line to the PFS of the n-1 line. Results: Among 1,023 patients with BTC, 184 (18%) had YO-BTC, 561 (54.8%) had AO-BTC, and 278 (27.2%) had LO-BTC. Median OS in metastatic patients was longer in the YO group (22 months; 95% CI 18–26) than in the AO group (18 months; 95% CI 17–20; p = 0.010) or LO group (15 months; 95% CI 13–17; p <0.001), despite a higher tumor burden in YO-BTC. FGFR2 fusions were more frequent in YO-BTC (12% vs. 5.7% AO and 4.3% LO; p = 0.038). Patients with YO-BTC received more targeted therapies as second or later lines (48%, 37%, and 29% for YO, AO, and LO; p = 0.020). Among patients receiving molecular-matched treatments, GMI >1.33 was more frequent in YO-BTC (61.1%, 39.2%, and 33.3% for YO, AO, and LO; p = 0.044), although no differences in PFS or OS were observed. Conclusion: Patients with YO-BTC have improved outcomes in the metastatic setting. The YO-BTC group is enriched for FGFR2 fusions, highlighting opportunities for precision oncology-based approaches. Impact and implications: The study underscores the scientific justification for investigating age-related differences in biliary tract cancers, revealing that patients with young-onset biliary tract cancer have improved survival outcomes and a higher prevalence of actionable molecular alterations, particularly FGFR2 fusions. Physicians can apply these results by incorporating molecular profiling and targeted therapies earlier in the treatment plan for younger patients, potentially improving their prognosis and quality of life. However, it is crucial to consider the study's limitations, such as the retrospective design and potential selection bias, to avoid overgeneralization and ensure appropriate application of the findings in clinical practice and future research.

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.

Background Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second deadliest cancer in Europe by 2030. Given the underlying differences in embryogenesis, the objectives of this study were to describe the clinical and molecular features and outcomes of PDAC based on the primary tumor location [head (H) or body/tail (B/T)]. Patients and methods A retrospective single-center study included patients with a histologically confirmed PDAC and known tumor location from 2012 to 2024. The molecular panels included in-house panel on tumor tissue, FoundationMedicine® (tumor tissue) or FoundationOne Liquid CDx® (liquid biopsy) panels. HR and P value were computed via Cox regression between H versus B/T tumors. Results A total of 1011 patients were included, among them 520 patients (51%) with H-tumor. Molecular alterations were available for 373 patients. Most common genes altered were KRAS (78%), TP53 (69%), CDKN2A (24%), and SMAD4 (12%), without significant differences between the two groups. Median overall survival (OS) from diagnosis was 20.6 months [95% confidence interval (CI) 19.2-22.6 months] in H tumors compared with 16.2 months in B/T tumors (95% CI 14.2-17.8 months, P = 0.00057). Median OS from metastatic diagnosis was 14.4 months in H tumors (95% CI 13.4-16.7 months) versus 12.9 months in B/T tumors (95% CI 11.0-14.9 months, P = 0.033). In multivariable analysis, operated patients [hazard ratio (HR) 0.36, P < 0.001], lung-only metastases (HR 0.55, P = 0.003) and low neutrophil/lymphocyte ratio (HR 0.56, P < 0.001) were associated with a longer OS while liver metastases (HR 1.25, P = 0.02) and B/T primary tumor site (HR 1.23, P = 0.03) worsened the prognosis. Conclusions In a large retrospective cohort, H-PDAC was found to have a longer median OS than B/T-PDAC from initial and metastatic diagnosis.

Background: Total tumor volume (TTV), derived from imaging data, has emerged as a potential prognostic biomarker in various cancers. This study aimed to evaluate the impact of TTV on outcomes in advanced pancreatic ductal adenocarcinoma (PDAC) and to validate a survival prediction model combining TTV with baseline clinico-biological markers. Materials and Methods: We conducted a retrospective analysis of 150 patients with locally advanced or metastatic PDAC treated with first-line FOLFIRINOX from 2010 to 2021. TTV was calculated by manually segmenting all visible lesions on baseline CT scans. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. A cut-off value for TTV predicting 6-month PFS was determined in 140 patients using AUC and Youden's Index and then applied to OS analysis. A multivariate Cox regression model incorporating TTV, CA 19-9, and neutrophil-to-lymphocyte ratio (NLR) was developed in 94 patients to establish a survival risk score. Results: 12,028 lesions were annotated. OS was slightly but significantly different between TTV above and below the median value of 69.60 cm3 (12.4 vs. 13.5 months, p = 0.0269). A cut-off of 400 cm3 distinguished two groups: patients with TTV > 400 cm3 had significantly shorter OS (9.4 months) compared to those with TTV ≤ 400 cm3 (13.0 months, p = 0.0056). A similar trend was observed for PFS, though not statistically significant (7.4 months for TTV > 400 cm3 vs. 8.2 months for TTV ≤ 400 cm3, p = 0.0735). The combined model achieved a mean c-index of 0.62 for PFS and 0.64 for OS. Based on the risk score, high-risk patients had significantly worse median PFS (5.5 vs. 9.2 months, p = 0.0008) and median OS (7.2 vs. 13.5 months, p < 0.0001). Conclusions: TTV is a valuable prognostic marker in advanced PDAC. A model integrating TTV with biological markers enhances survival prediction and supports risk stratification in clinical practice.

BACKGROUND:Peritoneal mesothelioma is a rare disease treated with curative approach- cytoreductive surgery and hyperthermic intraperitoneal chemotherapy -when resectable.In case of inoperable disease or extra-peritoneal involvement, the standard of care is based primarily on systemic chemotherapy. Platinum-based chemotherapy is used in the first-line setting, but no standard exists for subsequent lines.Peritoneal mesothelioma harbors a pro-inflammatory tumor microenvironment, making it potentially sensitive to immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS:We included inoperable patients with peritoneal mesothelioma treated between 2017 and 2024 at two institutions in France, using ICIs-based treatments (immunotherapy with or without anti-angiogenic agents).The primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS:A total of 22 patients with peritoneal mesothelioma were included.The median age at diagnosis was 57 years (IQR: 50-66);the majority had epithelioid histology (n = 17; 77 %).After a median follow-up of 13.76 months (95 % CI: 6.40-22.49),median Progression free survival(PFS) was 10.22 months (95 % CI: 4.82-15.87),median Overall Survival(OS) was 16.8 months (95 % CI: 6.46-37.73) No significant differences in PFS (p = 0.73) or OS (p = 0.16) were observed between BAP1-positive and BAP1-negative tumors.Among evaluable patients (n = 13, 62 %), the objective response rate was 30 % (95 % CI: 22 %-50 %).The disease control rate at 6 and 12 months for the entire cohort was:55 % (95 % CI: 33 %-74.5 %) at 6 months and 41 % (95 % CI: 21.9 %-63.04 %) at 12 months.Grade 3 toxicity occurred in 3 patients; no grade 4 toxicity was reported. CONCLUSION:The benefit of ICI-based treatment was confirmed in this European real-world cohort and should be considered as a treatment option in this rare setting.

Retroperitoneal lymph node metastases (RLNMs) of colorectal cancer (CRC) have a low incidence, and the optimal treatment strategy remains unclear due to limited evidence. This study aimed to analyze morbidity and long-term oncologic outcomes associated with different multimodal approaches including systemic chemotherapy, surgery with or without preoperative radiotherapy. This retrospective, single-center study included consecutive patients treated from 2000 to 2023 for sub-renal RLNM from CRC. After induction chemotherapy, the patients were divided into two groups: those receiving radio(chemo)therapy (RCT) followed by surgery (RCT-surgery group; n = 30) and those undergoing upfront surgery (surgery-alone group; n = 24). The study analyzed treatment methods, perioperative data, morbidity, mortality, overall survival (OS), and recurrence-free survival (RFS). The study included 54 patients (32 males, 22 females, age 51 years). Presentation of RLNM was synchronous in 48.1

INTRODUCTION:FOLFIRINOX, a primary chemotherapy for metastatic pancreatic cancer, often causes severe toxicity, necessitating hospitalization and dose adjustments. This study aims to identify predictors of FOLFIRINOX toxicity, focusing on biological, clinical, and anthropometric factors. MATERIAL & METHODS:This retrospective study analyzes pancreatic adenocarcinoma patients on FOLFIRINOX, assessing pre-treatment biological, clinical, and anthropometric traits. Hospitalizations and tolerance during the first chemotherapy month were evaluated using CTCAE v5.0 grading, with early toxicity assessed via anthropometric factors using Anthropometer3DNet software from pre-treatment scans. RESULTS:In 152 pancreatic cancer patients (median age: 62), FOLFIRINOX was administered in metastatic (81%), locally advanced (14%), and adjuvant/neoadjuvant (5%) settings. Performance Status was zero (49%), one (41%) and ≥ 2 (10%). Median follow-up was 62.5 months, with median overall survival of 13.7 months and progression-free survival of 8.9 months. First-cycle dose reduction occurred in 14% of patients. Within the first month, 48% experienced toxicity leading to hospitalization and/or dose reduction, with 28% requiring a median 8-day hospitalization. Low muscle body mass (MBM) significantly correlated with dose reduction (AUC 0.63; p = 0.005). An NLR ratio less than 4 was significantly associated with longer OS (p = 0.001). CONCLUSION:Low MBM is linked to FOLFIRINOX toxicity, suggesting MBM assessment could allow better selection of patients to avoid these toxicities, warranting further confirmation in larger cohorts.

Anal squamous cell carcinoma (aSCC) is a rare, predominantly HPV-driven cancer with limited treatment options. This study aimed to define its genomic landscape, identify actionable targets (AT), and highlight the clinical value of molecular profiling—especially liquid biopsy (LB)—based on Gustave Roussy’s (GR) experience. In this retrospective analysis, 1844 patients from the U.S. and France underwent tissue biopsy (TB, n = 1733) and/or LB (n = 140), analyzed using the FoundationOne®CDx or FoundationOne® Liquid CDx assays both comprehensive genomic profiling assays for solid tumors covering 324 genes. Twenty-nine patients had paired TB/LB, and 44 LB patients formed the clinically annotated GR subgroup. HPV was detected in 86.6

BACKGROUND:Metastatic pancreatic adenocarcinoma (mPDAC) has a poor prognosis. FOLFIRINOX (FFX) and gemcitabine nab-paclitaxel (GN) are the preferred first line (L1) regimens. We evaluated real-world outcomes of L1 therapies. METHODS:Retrospective analysis of all patients who received L1 chemotherapy for mPDAC between 2010 and 2024 at a single academic comprehensive cancer center. RESULTS:A total of 1012 patients were included: 48 % women, median age 63 years, 91 % ECOG 0-1. Synchronous metastases occurred in 66 % of patients. Liver (67 %), lung (20 %) and peritoneum (20 %) were the most frequent sites of metastasis. L1 regimens were FFX (n = 621, 61 %), gemcitabine (Gem) (141, 14 %), GN (78, 8 %), and others (n = 172, 17 %). Compared with GN, FFX recipients were younger (61 vs 65 years, p < 0.0001) with better ECOG (≥ 2 in 4 % vs 13 %, p < 0.0001). Median OS was 14.5 months (95 %CI [13.3-15.8]) with FFX, 12.4 [9.4-21.9] with GN, 7.9 [6.5-10.7] with Gem and 9.2 [7.2-13.1] with others (p < 0.0001). Respective median PFS were 7.0 months [95 %CI: 6.5-7.9], 5.4 [4.0-8.3], 4.9 [3.6-6.0] and 5.6 [3.6-7.0] (p < 0.05). CONCLUSIONS:In this large real-world cohort, FFX was associated with superior response rate, PFS, and OS compared with other L1 regimens, supporting its use as standard first-line therapy for mPDAC.

Second opinions are increasingly sought by patients, particularly in complex and life-altering conditions such as gastrointestinal (GI) cancers, to ensure confidence in their diagnosis and treatment plans or to seek therapeutic trials. This retrospective study analyzed second-opinion requests handled by the GI oncology team in our institution between January and March 2024, examining the types of questions raised, patient characteristics, and their impact on clinical decision-making. Of 261 eligible patients, 259 were included in this analysis. Most patients had metastatic disease (86

INTRODUCTION:In the HERIZON BTC 01 trial for patients with HER2-positive biliary tract cancer (BTC) previously treated with systemic therapy, zanidatamab improved the objective response rate, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). However, real-world data are needed to assess its efficacy and safety outside clinical trials. PATIENTS & METHODS:We conducted an investigator initiated national multicenter retrospective study of most patients with BTC treated with zanidatamab in France as part of a compassionate access. The primary endpoint was PFS. RESULTS:Our study included 20 patients with metastatic BTC enrolled between September 2022 and November 2024. The median age at diagnosis was 61.5 (interquartile range: 55-69) years and the majority of patients had gallbladder cancer (n = 12, 60 %). After a median follow-up of 8.5 (95 % confidence interval [CI]: 3.3-11.8) months, the median PFS was 6.7 (95 % CI 1.3-11.8) months, with an estimated OS at 1 year of 79.1 % (95 % CI: 53.2-91.6 %). The DCR was 65 %, with 40 % confirmed partial responses and a median duration of response of 7.3 (95 % CI: 2.06-16) months. Patients with immunohistochemistry (IHC) 3 + HER2 scores had a better PFS [8 (95 % CI: 1.5-18.4) months] than those with 2 + HER2 scores obtained by IHC followed by fluorescence in situ hybridization amplification or next-generation sequencing [1.4 (95 % CI: 1.1-6.8) months] (P = 0.02). No statistical difference in 1-year estimated OS rates was observed (P = 0.39). There were no grade 3 or 4 treatment-related adverse events or cardiac toxicities. CONCLUSION:The benefits of in patients with HER2-positive BTC were confirmed. Zanidatamab should be considered for patients with this condition.