PURPOSE Pamrevlumab demonstrated favorable safety and therapeutic potential in locally advanced pancreatic cancer (LAPC) in phase I/II trials (ClinicalTrials.gov identifiers: NCT01181245 ; NCT02210559 ). LAPIS (phase III; ClinicalTrials.gov identifier: NCT03941093 ) evaluated the efficacy and safety of adding pamrevlumab versus placebo to chemotherapy for patients with LAPC. METHODS Eligible patients (randomly assigned 1:1) received investigator's choice of chemotherapy (gemcitabine plus nab-paclitaxel or folinic acid, fluorouracil, irinotecan, and oxaliplatin per the standard protocol) with either pamrevlumab (35 mg/kg every 2 weeks on days 1 and 15 before chemotherapy; additional dose on day 8 of cycle 1; arm A) or placebo (arm B) for up to six cycles. Patients were assessed for surgical eligibility based on a composite of biomarkers (carbohydrate antigen 19-9, fluorodeoxyglucose positron emission tomography [FDG-PET] imaging, RECIST v1.1 response criteria, and resectability status), guided by an independent surgical review panel. The primary end point was overall survival (OS). Treatment-emergent adverse events were monitored to evaluate safety. RESULTS Of 284 patients, 143 and 141 were randomly assigned to arms A and B, respectively (median [range] age, 65.0 [31-90] years; 53.2% male). The median OS was 17.3 versus 17.9 months for arms A and B, respectively, and the primary end point was not met (hazard ratio [95% CI], 1.08 [0.83 to 1.41]; P = .5487). No appreciable increase in toxicity was noted in the pamrevlumab arm. One pamrevlumab-related death occurred in arm A. CONCLUSION LAPIS did not meet its primary end point in this large, phase III trial featuring a design including FDG-PET imaging for response assessment, defined surgical eligibility criteria, an independent surgical review panel, and a composite event-free survival end point, collectively enhancing assessment rigor and clinical applicability and potentially establishing future standards for LAPC trials.

BACKGROUND:Current therapies offer limited benefit for patients with previously treated metastatic pancreatic ductal adenocarcinoma (mPDAC). Aberrant activation of the RAS pathway is the key driver of PDAC, with oncogenic RAS mutations present in more than 90% of cases. Daraxonrasib is an oral RAS(ON) multiselective, tri-complex inhibitor of the active guanosine triphosphate-bound state of mutant and wild-type RAS. METHODS:In this phase 3, international, open-label, randomized trial, we randomly assigned patients with previously treated mPDAC to receive daraxonrasib or chemotherapy of the investigator's choice. The dual primary end points were overall survival and progression-free survival in the subpopulation of patients with RAS G12 mutations (the RAS G12 population). Key secondary end points included overall survival and progression-free survival in the overall population (which included patients with RAS G12, G13, or Q61 mutations or with no RAS mutation identified) and objective response and patient-reported quality of life in the RAS G12 and overall populations. Safety was also assessed. RESULTS:A total of 500 patients, including 91.8% with RAS G12 mutations, were randomly assigned to receive daraxonrasib (248 patients) or chemotherapy (252 patients). The median overall survival in the RAS G12 population was 13.2 months with daraxonrasib and 6.6 months with chemotherapy, and the median overall survival in the overall population was 13.2 months and 6.7 months, respectively; the hazard ratio was 0.40 in both populations (P<0.001). The median progression-free survival in the RAS G12 population was 7.3 months with daraxonrasib and 3.5 months with chemotherapy, and that in the overall population was 7.2 months and 3.6 months, respectively; the hazard ratios were 0.45 and 0.49, respectively (P<0.001 for both comparisons). Adverse events that occurred after the start of treatment were reported in all the patients in the daraxonrasib group and in 97.7% of those in the chemotherapy group; the incidence of adverse events of grade 3 or higher was 61.8% and 69.6%, respectively. Treatment-related adverse events that led to treatment discontinuation occurred in 1.2% of the patients in the daraxonrasib group and in 11.2% of those in the chemotherapy group. CONCLUSIONS:Among patients with previously treated mPDAC, treatment with daraxonrasib led to significantly longer overall survival and progression-free survival than chemotherapy. (Funded by Revolution Medicines; RASolute 302 ClinicalTrials.gov number, NCT06625320.).

BACKGROUND:Curative R0-R1 resection is not always feasible in patients with extensive bilobar colorectal liver metastases (CRLM). When unresectatility is confirmed, the standard of care is palliative chemotherapy or more recently liver transplantation (LT) with very restrictive eligibility criteria. This exploratory study evaluated cytoreductive surgery as an alternative to chemotherapy alone in patients with initially unresectable CRLM responding well to systemic chemotherapy but ineligible to LT. METHODS:This prospective study (January 2017-January 2024) included patients with permanently unresectable CRLM involving >6 segments, with or without limited extrahepatic metastases. Those achieving a sustained partial response on RECIST criteria after ≥3 months of chemotherapy and not amenable to LT, underwent cytoreductive surgery defined as resecting or ablating all visible residual lesions while leaving disappearing liver metastases (DLMs) untreated-The primary endpoint was 5-year overall survival (OS); secondary endpoints included disease-free survival (DFS) and time to surgical failure (TSF). RESULTS:Of 330 patients undergoing CRLM resection, 33 were eligible, and 28 underwent cytoreductive surgery (18 major, 10 limited hepatectomies, frequently with ablation). Grade ≥ III complications at 3 months occurred in 4 patients (14%), including one mortality (3.6%). At 57- month median follow-up, 5-year OS was 47% (whole cohort) and 64% (operated patients), respectively. Liver recurrence occurred in 22 patients (79%), with a 5-year DFS of 17%. Recurrences were frequently managed with repeat hepatectomy and/or ablation, including second (n = 15) and third (n = 7) hepatectomies, resulting in a 5-year TSF rate of 36%. CONCLUSIONS:Cytoreductive surgery combined with chemotherapy is a strategy that may improve long-term survival in selected patients with unresectable CRLM. This favorable outcome is likely driven by highly selected tumor biology, by sustained response to chemotherapy and by the feasibility of repeat surgical resections for recurrences, rather than by the initial surgery alone.

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.

Currently, no consensus exists regarding the definition of oligometastatic pancreatic ductal adenocarcinoma, its necessary diagnostic measures, and potential treatment approaches. To address these knowledge gaps, the OligoPanc project brought together an interdisciplinary group of experts to establish consensus using a modified Delphi process and clinical vignettes. Participants agreed that the number of metastatic lesions and the number of affected organs are key elements in defining oligometastatic pancreatic ductal adenocarcinoma. Specifically, up to three lesions in a single organ, either the liver or the lung, define oligometastatic pancreatic ductal adenocarcinoma and could be either synchronous or metachronous. Necessary diagnostics include a triple-phase contrast-enhanced CT scan of the chest and abdomen and MRI of the liver with a hepatocyte-specific contrast agent. In unclear cases, [18F]fluorodeoxyglucose-PET CT or MRI can be considered. A multidisciplinary tumour board is essential. Patient-intrinsic factors, including age, do not define oligometastatic disease but should be considered for any treatment decision. Systemic treatment before any local consolidative treatment, including surgery, stereotactic ablative radiotherapy, or other locally ablative techniques, is mandatory. The proposed definition should be incorporated into future trials to improve comparability and enable validation.

Circadian disruption of telemonitored rest-activity rhythm was an early warning signal of Emergency Admission (EA) and hematologic toxicity of standard cancer chemotherapy in 52 patients with advanced pancreatic cancer. It also predicted for limited antitumor efficacy. Patients carried a telecommunicating actimetry wearable linked to a digital platform whilst receiving chemotherapy. Circadian disruption was defined by a dichotomy index (I < O) ≤ 96%, which was automatically computed in real time. In this multicentre longitudinal interventional trial, sustained circadian disruption preceded EA by 8 days, and severe neutropenia by 5.5 days [IQR, 3.5 to 8]. The trial hypothesis of < 15% EAs for adverse events was validated, with a rate of 3.8% [95% CL, 1.1%-13%]. The drop of I < O≤ 96% after cycle 2 and 3 was significantly associated with a three-fold reduction in the chances of achieving tumor response. Telemonitored circadian rhythms are promising biomarkers toward jointly improving treatment efficacy and tolerability in individual patients.

Pancreatic ductal adenocarcinoma shows early dissemination, stromal remodeling, and therapy resistance, but how tumor programs co-evolve with immune and stromal changes across stages remains unclear. We built a stage-resolved transcriptomic atlas using bulk RNA sequencing of FFPE samples from 443 untreated tumors spanning resectable, locally advanced, primary metastatic, and liver metastatic disease. Integrative modeling identified ten transcriptional programs with monotonic dynamics during progression. Early stages were enriched for epithelial differentiation and immune-stimulatory signals. Advanced stages showed increased cytoskeletal remodeling, vesicular trafficking, oxidative stress responses, and mitochondrial metabolism. Pathway analysis revealed enhanced PI3K-AKT-mTOR signaling and MYC target engagement in metastatic disease. Immune deconvolution showed loss of CD8+ T cells, dendritic cells, and M1 macrophages. Compact gene signatures stratified stage and survival and generalized to TCGA and ICGC cohorts. Functional assays confirmed greater invasiveness, altered redox balance, and mitochondrial dependence in advanced disease, suggesting stage-associated metabolic vulnerabilities.

PURPOSEIn 2023, the G7 Cancer Initiative was launched by Australia, Canada, France, Germany, Japan, the United Kingdom, and the United States with the aim of enhancing global cancer control, and with poor-prognosis cancers as a priority. To facilitate effective collaboration among G7 Cancer, we aimed to address the lack of standardized definitions and coordinated initiatives across countries.METHODSWe examined how the G7 Cancer Initiative countries defined poor-prognosis cancers, objectively classified them, quantified their burden, and assessed national response strategies. A review of national cancer plans was conducted together with an expert email survey to evaluate definitions and classifications. Poor-prognosis cancers were identified based on 5-year net survival (NS) below 30% and a mortality-to-incidence (M/I) ratio over 0.75 using CONCORD-3 and Global Cancer Observatory 2022 data.RESULTSPancreatic cancer was consistently categorized as a poor-prognosis cancer, while some countries also included liver, esophageal, stomach, and some brain cancers. For lung cancer, classification varied depending on the definition used. These six cancers accounted for a major share of cancer deaths, with lung (18%-23%) and pancreatic (6%-10%) cancers contributing the most. National strategies differed, with Australia, France, and Japan implementing specific policies for poor-prognosis cancers, while others addressed them indirectly or not at all.CONCLUSIONTo enhance cancer outcomes for poor-prognosis cancers, the G7 Cancer Initiative should coordinate efforts through joint programs focused on early detection, treatment, and policy alignment. Standardized definitions and collaborative action are essential to strengthening the global poor-prognosis cancer response.

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.

PURPOSE:Predicting recurrence of pancreatic cancer after surgery could inform clinical decision making, including adjuvant therapies and follow-up. This study aimed to develop and validate a deep learning model using digitized whole-slide images (WSI) of histopathology. METHODS:Publicly available WSI of pancreatic ductal adenocarcinoma resections from three cohorts were used for training. The model consisted of a pan-cancer foundation model to generate embeddings, mean-pooling across tissue patches, and then a fully connected neural network. Model predictions were compared with human-labeled histopathologic features and genomic alterations. The model was externally validated in a meta-analysis of a single-center cohort from Princess Margaret Cancer Centre, a multicenter cohort from France, and the PRODIGE 24 trial of adjuvant chemotherapy. RESULTS:The deep learning model was trained on 12,594 tissue patches from 257 patients. High-risk classifications were associated with squamous morphology, reactive stroma, tumor cellularity, and necrosis, whereas low-risk classifications were associated with tubulopapillary and conventional morphologies, as well as deserted stroma. High-risk cancers were enriched for basal-like gene expression profiles and distinct oncogenic pathways. In a meta-analysis of the external cohorts, the hazard ratio (HR) for death comparing high-versus low-risk cancers was 1.49 (95% CI, 1.25 to 1.79, P < .001), whereas the HR for recurrence or death was 1.41 (95% CI, 1.19 to 1.68, P < .001). The classifications remained prognostic among moderately differentiated cancers. CONCLUSION:An open-source deep learning model using WSI from pancreatic cancer resections generated risk classifications that correlated with histopathologic and genomic features. Classifications were externally validated in a meta-analysis of three cohorts. This model could be applied to WSI to provide individualized prognostic information for patients.

PURPOSE:Modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX/mFFX) is the standard adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC), offering survival benefits over gemcitabine (GEM). However, the contribution of molecular biomarkers to treatment selection remains unclear. Here, we characterize the molecular landscape of tumors from the PRODIGE-24/CCTG PA6 trial and assess the clinical impact of genomic alterations and molecular subtypes. PATIENTS AND METHODS:Tumor DNA sequencing was successfully performed in 317/350 tumors (168 mFFX; 149 GEM), complemented by transcriptomic subtyping using the PurIST classifier. Mutational status of four key PDAC driver genes and 24 homologous recombination repair (HRR)-associated genes was analyzed, alongside single-base substitution (SBS) mutational signatures. Primary and secondary end points were disease-free survival (DFS) and cancer-specific survival (CSS), respectively. RESULTS:In the mFFX group, the PurIST subtype was prognostic, with classical tumors showing superior DFS compared with basal-like tumors (stratified hazard ratio [sHR], 0.48 [95% CI, 0.31 to 0.77]). Among KRAS-mutated patients, mFFX significantly improved DFS compared with GEM (sHR, 0.60 [95% CI, 0.45 to 0.79]; P < .001), while no benefit was observed in KRAS wild-type tumors (interaction test, Pint. = 0.010). HRR and BRCA status were not predictive (Pint. = .568 and Pint. = .785, respectively). The benefit of mFFX was consistent across SBS-positive and SBS-negative subgroups. CONCLUSION:Overall, these results do not support a change in current adjuvant treatment strategies. mFFX remains the standard adjuvant regimen in PDAC, and the observed lack of benefit in KRAS wild-type tumors should be considered hypothesis-generating and warrants further investigation.

LBA5 Background: Available 2L therapies offer limited clinical benefit in mPDAC with reported mPFS of 3–4 mo and mOS of 6–7 mo. Aberrant RAS pathway activation is the key driver of PDAC, with oncogenic RAS mutations (mut) identified in >90% of cases, most commonly at codon G12. Daraxonrasib is an oral, RAS(ON) multi-selective, tri-complex inhibitor of the active, GTP-bound state of mutant and wild type RAS. Methods: RASolute 302 (NCT06625320) is a global, randomized, open-label, Ph 3 study in pts with 2L mPDAC and ECOG PS 0-1. Pts were randomized 1:1 to receive daraxonrasib 300 mg PO QD or investigator’s choice of SOC cytotoxic chemo. Dual primary endpoints were OS and PFS by BICR in the RAS G12 mutant (RAS G12) population. Key secondary endpoints included OS and PFS by BICR in the overall population, ORR by BICR in RAS G12 and overall populations. Results: 248 pts were randomized to daraxonrasib and 252 to chemo. Baseline characteristics were balanced between arms. At data cutoff (Feb 10, 2026; mFU: 8.5 mo), all primary and key secondary endpoints were met. Statistically significant, clinically meaningful improvements in OS and PFS were observed with daraxonrasib vs chemo in the RAS G12 and overall populations (Table). Gr ≥3 TRAEs occurred in 43.6% of pts receiving daraxonrasib vs 57.5% receiving chemo. The most common (≥10%) Gr ≥3 TRAEs were rash (13.7%) and stomatitis (12.0%) for daraxonrasib; neutrophil decrease (18.2%) and anemia (16.4%) for chemo. TRSAEs occurred in 10.8% of pts receiving daraxonrasib vs 18.7% receiving chemo. Discontinuation due to TRAEs occurred in 1.2% of pts for daraxonrasib vs 11.2% for chemo. Median/mean daraxonrasib dose intensity was 93.1%/84.7%. Conclusions: Daraxonrasib demonstrated unprecedented improvements in OS and PFS vs chemo in pts with 2L mPDAC with or without an identified tumor RAS mut. Daraxonrasib was generally well tolerated, with a manageable safety profile and with no new safety signals. Results support daraxonrasib as the new SOC for 2L mPDAC. Clinical trial information: NCT06625320 . RAS G12 Overall b Daraxonrasibn=228 Chemo n=231 Daraxonrasib n=248 Chemo n=252 OS Median; mos(95% CI) 13.2(10.0–NE) 6.6(5.4–8.2) 13.2(10.0–NE) 6.7(5.8–8.0) HR(95% CI)P-value 0.40(0.30-0.54)<0.0001 0.40(0.30-0.53)<0.0001 PFS a Median; mos(95% CI) 7.3(6.3–8.1) 3.5(2.9–3.8) 7.2(5.7–7.5) 3.6(2.9–4.2) HR(95% CI)P-value 0.45(0.34-0.59)<0.0001 0.49(0.38-0.64)<0.0001 ORR a %(95% CI) 33.2(27.0–39.9) 11.8(7.8–16.8) 31.6(25.8–38.0) 11.2(7.5–15.9) a By BICR. b RAS G12, G13 or Q61 mut or no RAS mut identified.

4204 Background: Severe Adverse Events (SAEs) requiring emergency admissions (EAs) alter quality of life and treatment efficacy, and increase health costs. Toxicities, EAs, and reduced survival have been linked to the disruption of circadian rhythms, whose relevance is tested here in a multicentre, prospective, longitudinal, single-arm interventional trial. Methods: Continuous telemonitoring and automatic analyses of circadian rhythms and daily body weight and ePROs over 50 days (d) aim to reduce EAs in PDAC pts receiving the first 3 cycles of mFOLFIRINOX. The hypothesis (H 0 ) is that EAs involve <15% of the pts, rather than a historical rate of 15-30%. Pts data were collected through telecommunicating chest sensor, balance and tablet connected to a multidimensional digital platform. The main circadian parameter was (IResults: 28 males and 24 females had a median age of 65 years (33-82), and WHO performance status of 0-1 in 92% of them. PDAC was metastatic in 69% of cases, including liver in 50%. An EA occurred in 2 pts (3.8% [95% CL, 1.1-13%]), thus validating H 0 . SAEs in both EA pts were grade (Gr) 3 febrile neutropenia and diarrhea; and Gr 3 leuco-neutropenia and hypokaliemia respectively. Symptom-free circadian disruption preceded EA by 8 d in both pts. Circadian disruption occurred at least once in 65-75% of the pts on treatment, and lasted > 20 d in 27 pts (52%). Severe fatigue and anorexia were self-reported by 62% and 58% of the treated pts respectively. Main Grade 3-4 toxicity was neutropenia in 17% of the pts [95% CL, 9-30]. Disease control rate at 2 months was 75% [53-100]. Multidom revealed (i) a high level of pt engagement supported both by data compliance rates of 84-92% for circadian rhythms, 93-100% for body weight, and 86-100% for ePROs; and by median duration of platform use of 46 d (IQR, 38-50]; (ii) 1881 medical type e-alerts for circadian disruption (43%), MDASI symptoms (25%), and body weight loss (12%); (iii) 883 categorized responses to medical e-alerts, and (iv) highest global score of self-rated pt experience of participation (median, 5/5 (4 to 5). Conclusions: Combining telemonitoring of circadian rhythms, body weight and symptoms in remote PDAC pts on mFOLFIRINOX revealed potential benefit on pts real life through informed proactive telecare, and likely improved treatment safety. Actual benefits from such telemonitoring-telecare platform with circadian metrics need further confirmation in trials involving pts at risk of SAEs. Clinical trial information: NCT04263948 .

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:Adapted physical activity (APA) is key supportive care in cancer patients. Very few studies have evaluated APA in digestive cancers, and the eligibility and feasibility of an APA program in this population have not been clearly defined. Objectives:Primary objective: to analyze the reasons for failure of an APA program in digestive cancer patients. Secondary objectives: to assess patient eligibility, feasibility of an APA program, and the potential changes in patient quality of life, physical performance, and nutritional status. Design:APACADIG is a pilot, single-center, prospective non-randomized study. Methods:All consecutive patients with digestive cancer seen from January 18, 2021 to February 15, 2021, were proposed a supervised 2-month APA program. Results:Sixty-five consecutive patients (men 69%, median age 69.8 years old, PS 0/1: 78.5%) with mainly colorectal (38%) and pancreaticobiliary (35%) cancers were included. Forty-seven of these patients (72%) were eligible, and 22 (46.8%) accepted the APA program. The latter were more often active women, living in urban areas (59.1%) with higher socioeconomic status (40.9%). The barriers to APA were clinical, the cost of transport, lack of awareness of the benefits of APA, and a sedentary lifestyle before the cancer diagnosis. Withdrawal from APA was mainly due to changes in physical status. APA improved patients' physical performance (6-min walk test) (distance 516.1 m ± 102.7 m vs 414.5 m ± 111.9 m; p = 0.0430). Conclusion:Only one-sixth of the population completed the program, and we identified several barriers to APA.

1650 Background: The disruption of circadian clocks is associated with reduced survival and treatment tolerability in cancer patients (pts). Here, real-time analyses of telemonitored circadian rhythms and electronic Pt-Reported Outcome (ePRO) are integrated within a multidimensional telemonitoring-telecare digital platform that triggers proactive telecare toward improved quality of life (QoL) and treatment safety. Methods: The multicentre, interventional, prospective, longitudinal, single-arm study recruited pts receiving mFOLFIRINOX chemotherapy (CT) q2-weeks for pancreatic ductal adenocarcinoma (PDAC). Early warning signals of circadian disruption, body weight loss, and ePROs severity are extracted from real time analysis and graphical displays of (i) continuously telemonitored rest-activity and chest surface temperature (chestemp) rhythms using a chest sensor, and (ii) daily body weight (e-balance), and (iii) daily self-rating of 23 symptoms using a GPRS tablet (MD Anderson Symptoms Inventory, MDASI). Pts participate for 1 week before (baseline) and 6 weeks after 1 st CT course. Circadian disruption is defined by an (I < O) value < 96%. (I < O) is the % accelerations per min In-Bed that are below median accelerations per min Out-of-Bed for 3 days; (I < O) range in controls, 97-100%). Automatic alerts are sent via internet for decision of proactive intervention by the oncology team, in case of circadian disruption, chestemp increase by 1.5°C, weight loss > 5%, or MDASI symptom ≥ 7. Results: From 6/2021 to 7/2024, 58 pts with advanced PDAC were selected (male, 52%), median age, 58 y.o. (range, 33-82); WHO performance status (PS) 0/1/2, 36%/53%/10% of the pts; metastatic sites 0/1/ > 2, 38%/24%/8%; liver metastases, 50%). Early PDAC-related complications prevented platform use in 5 pts. The platform was used by 53 pts during a median of 45.5 days (IQR, 38-50], with > 85% compliance. At baseline, large between-pts differences in circadian rhythms were found for both rest-activity I < O (median [IQR]), 98.4 accelerations/min [95.8-99.6]); range, 75 to 100), and chestemp circadian amplitude (median, 1.1°C [IQR, 0.7-1.4], range, 0.3°C to 2.7°C). Baseline circadian disruption was larger in male pts (56% vs 31%; p = 0.07) and in those with PS 1-2 (47% vs 14%; p = 0.02). Consistently, median chestemp circadian amplitude was less in males compared to females (0.8°C vs 1.3°C, p < 0.01) and in pts with PS = 1-2 compared to PS = 0 (0.8°C vs 1.3°C; p < 0.01). Maximum toxicities of CT were circadian disruption (100% of the pts), body weight loss > 5% (59%), and MDASI symptom ≥7 (46%), without any influence of baseline pt characteristics. Conclusions: The use of this multidimensional digital platform combining circadian and other physiology metrics with ePROs was feasible and accepted by the pts. Its implementation seemed to be clinically relevant toward improving the care of remote pts at risk of adverse events. Clinical trial information : 04263948.