4232 Background: Phosphorous 32 microparticle ( 32 P) brachytherapy delivered by echoendoscopy (EUS) represents an innovative therapy in pancreatic cancer (PC). The device to implant it is approved in unresectable locally advanced PC in combination with gemcitabine-based chemotherapy. Our aim is to present the preliminary efficacy and safety results of a series that brings together the experience of thirteen centres in Spain. Methods: After being assessed by a multidisciplinary committee, patients signed consent to receive intratumoural 32 P by EUS. Complications associated with intratumoural 32P injection via EUS, associated adverse events (AEs) and preliminary efficacy results (progression-free survival [PFS], distant and locoregional, and overall survival [OS]) were analysed. Results: Fifty one patients (32 females and 19 males; age 65.5 years [range 48, 84]; 36 ECOG 1 and 14 ECOG 0) with unresectable locally advanced PC (30 in head, 5 in uncinate, 5 in neck and 11 in body; tumour size 30.8 mm [range 12, 60]) were included. The median time from tumour diagnosis to procedure was 5.9 months [0, 28.9]. Twenty-four patients (47 %) had received at least one previous line of treatment; four had received two prior lines. Fifty patients (98%) received gemcitabine-based chemotherapy concomitant with intratumoural 32P (42 gemcitabine plus nabpaclitaxel; 8 gemcitabine monotherapy. There were two AEs related to 32P injection by EUS: G1 epigastric pain (1 patient) and G2 asthenia (1 patient). A total of 30 patients (58.8%) had chemotherapy-related AEs, with 8 cases of G3 neutropenia (1 febrile neutropenia) and/or G3 thrombopenia; 22 had G1-2 toxicities: neurotoxicity (5), asthenia (4), neutropenia (3), thrombopenia (2), anaemia (4), nausea (2), diarrhoea (2), anorexia (1), onycholysis (1), mucositis (1), and constipation (1). Seven patients (13,7%) underwent surgery after intratumoural treatment (5 R0 and 2 R1). With a median follow-up of 8.7 months after injection (range: 1.02 months to 40.77 months), 25 patients (49.2 %) have progressed, 19 of them distantly, and nine also locoregionally. The median PFS since 32P injection is 8.5 months (95% CI 5.3, 17). 33 patients are alive at the end of follow-up (64.7%) with a median OS since 32P injection of 15.6 months 95% CI [10.2, 26.9]. Conclusions: Our experience suggests that intratumoural 32P associated with gemcitabine-based chemotherapy is safe. Patients after 32P injection achieve long overall survival. Surgical rescue was achieved in a high percentages of initially unresectable cases.

Unresectable locally advanced pancreatic cancer (LAPC) is managed with first-line chemotherapy or induction chemotherapy with consolidative chemoradiotherapy. Phosphorus-32 (32P) microparticles serve as a brachytherapy device, approved for use in LAPC, that has the advantage of delivering radiation directly to the tumour while reducing the risk of damage to nearby tissue or organs. The case of a 72-year-old woman with an unresectable pancreatic adenocarcinoma in the head of the pancreas with long-term survival following downstaging to resection with 32P microparticles is presented here. The patient received first-line gemcitabine+nab-paclitaxel chemotherapy, with a partial response occurring during the first three cycles of chemotherapy; however, the tumour remained unresectable and subsequently increased in size after a justified delay in chemotherapy. 32P microparticle implantation was conducted as planned at the end of cycle 4, and no device- or procedure-related adverse events were observed. Gemcitabine+nab-paclitaxel chemotherapy was continued, and computed tomography (CT) imaging during cycle 6 (6.8 months after diagnosis) revealed stabilisation of tumour size and a slight decrease in the density of the pancreatic mass. The surgical team determined that surgery could be feasible at this stage. Surgical resection by an open Whipple procedure was successfully completed 7.9 months after diagnosis. As of January 2026, the patient remains alive without evidence of disease 50 months after diagnosis and 42 months post-resection. This case study shows that the addition of 32P microparticles to first-line gemcitabine+nab-paclitaxel chemotherapy, in a patient with unresectable LAPC, is associated with not only disease stabilisation but also conversion to surgical resection, with no associated radiation-related adverse events.

Supplementary Table 2. Representativeness of Study Participants

Supplementary Table 3. Genetic variant detected in the custom gene panel through whole exome sequencing.

Supplementary Table 4. Preclinical model recommendation

PURPOSE:Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options. We compared the efficacy of comprehensive precision medicine against that of the conventional treatment in PDAC. PATIENTS AND METHODS:We report a phase III trial of advanced PDAC in which patients were randomized (1:2) to a conventional treatment treated at physician's discretion (arm A) or to precision medicine (arm B). Subjects randomized to arm B underwent a tumor biopsy for whole-exome sequencing and to generate avatar mouse models and patient-derived organoids for phenotypic drug screening, with final treatment recommended by the molecular tumor board. The primary objective was median overall survival (OS). RESULTS:A total of 137 patients were enrolled with 125 randomized, 44 to arm A and 81 to arm B. Whole-exome sequencing was performed in 80.3% (65/81) patients of arm B, with potentially actionable mutations detected in 21.5% (14/65). Experimental models were generated in 16/81 patients (19.8%). Second-line treatment was administered to 39 patients in the experimental arm, but only four (10.2%) received personalized treatment, whereas 35 could not receive matched therapy because of rapid clinical deterioration, delays in obtaining study results, or the absence of actionable targets. The median OS was 8.7 and 8.6 months (P = 0.849) and the median progression-free survival was 3.8 and 4.3 months (P = 0.563) for the conventional and experimental arms, respectively. Notably, the four patients who received personalized treatment had a median OS of 19.3 months. CONCLUSIONS:Personalized medicine was challenging to implement in most patients with PDAC, limiting the interpretation of intention-to-treat analysis. Survival was improved in the subset of patients who did receive matched therapy.

Supplementary Table 5. Complete Efficacy Data

Supplementary Table 1. Custom virtual gene panel included in the whole exome sequencing analysis

e16358 Background: 32P brachytherapy delivered by echoendoscopy (EUS) represents an innovative therapy in locally advanced pancreatic cancer (LAPC). The device to implant it is approved in unresectable LAPC in combination with gemcitabine-based chemotherapy. Our aim is to present the preliminary efficacy and safety results of a series that brings together the experience of seven centres in Spain. Methods: After being assessed by a multidisciplinary committee and meeting eligibility criteria (Table 1), patients signed consent to receive intratumoural 32P by EUS within the international observational registry OSPREY (March 2022-February 2024). Complications associated with intratumoural 32P injection via EUS, associated adverse events (AEs) and preliminary efficacy results (progression-free survival [PFS], distant and locoregional, and overall survival [OS]) were analysed. Results: Thirteen patients (7 females; age 65 years [range 48, 79]; 10 ECOG 1) with unresectable LAPC (7 in head, 3 in uncinate and 3 in body; tumour size 36.8 mm [range 25, 60]) were included. The median time from tumour diagnosis to procedure was 5 months [1.4, 28.9]. Only 4 patients (30 %) had received a previous line of treatment. Eleven patients (85%) received gemcitabine-based chemotherapy concomitant with intratumoural 32P (8 gemcitabine plus nabpaclitaxel; 3 gemcitabine monotherapy). There were no complications or AEs related to 32P injection or EUS. A total of 7 patients (54%) had chemotherapy-related AEs, with 2 cases of G3 neutropenia; 6 had G1-2 toxicities: neutropenia (1), thrombopenia (2), anaemia (1), nausea (1), asthenia (1), diarrhoea (1) and constipation (1). Two patients underwent surgery after intratumoural treatment. With a median follow-up of 17.3 months after injection, 8 patients (61.5 %) have progressed, all of them distantly, and three also locoregionally. The median PFS since 32P injection is 8.4 months (95% CI 2.7, NR). Six patients are alive at the end of follow-up (46.2 %) with a median OS since 32P injection of 13.8 months 95% CI [10, NR]. At data cut-off, five patients remain on-treatment. Conclusions: Our initial experience suggests that intratumoural 32P associated with gemcitabine-based chemotherapy is safe. Patients after 32P injection achieve long overall survival. Our ongoing prospective registry will allow evaluation of the oncological outcomes of this therapy at longer follow-up times. [Table: see text]

Background Liquid biopsies and the dynamic tracking of somatic mutations within circulating tumour DNA (ctDNA) can provide insight into the dynamics of cancer evolution and the intra-tumour heterogeneity that fuels treatment resistance. However, identifying and tracking dynamic changes in somatic copy number alterations (SCNAs), which have been associated with poor outcome and metastasis, using ctDNA is challenging. Pancreatic adenocarcinoma is a disease which has been considered to harbour early punctuated events in its evolution, leading to an early fitness peak, with minimal further subclonal evolution. Methods To interrogate the role of SCNAs in pancreatic adenocarcinoma cancer evolution, we applied whole-exome sequencing of 55 longitudinal cell-free DNA (cfDNA) samples taken from 24 patients (including 8 from whom a patient-derived xenograft (PDX) was derived) with metastatic disease prospectively recruited into a clinical trial. We developed a method, Aneuploidy in Circulating Tumour DNA (ACT-Discover), that leverages haplotype phasing of paired tumour biopsies or PDXs to identify SCNAs in cfDNA with greater sensitivity. Results SCNAs were observed within 28 of 47 evaluable cfDNA samples. Of these events, 30% could only be identified by harnessing the haplotype-aware approach leveraged in ACT-Discover. The exceptional purity of PDX tumours enabled near-complete phasing of genomic regions in allelic imbalance, highlighting an important auxiliary function of PDXs. Finally, although the classical model of pancreatic cancer evolution emphasises the importance of early, homogenous somatic events as a key requirement for cancer development, ACT-Discover identified substantial heterogeneity of SCNAs, including parallel focal and arm-level events, affecting different parental alleles within individual tumours. Indeed, ongoing acquisition of SCNAs was identified within tumours throughout the disease course, including within an untreated metastatic tumour. Conclusions This work demonstrates the power of haplotype phasing to study genomic variation in cfDNA samples and reveals undiscovered intra-tumour heterogeneity with important scientific and clinical implications. Implementation of ACT-Discover could lead to important insights from existing cohorts or underpin future prospective studies seeking to characterise the landscape of tumour evolution through liquid biopsy.

Background: Pancreatic adenocarcinoma (PDAC) remains one of the most lethal cancers. This study aimed to compare the efficacy of a comprehensive approach to precision medicine, including genomic and bio-informatic analysis of tumor biopsies, as well as modeling of the disease in Avatar Mouse Models and Patient Derived Organoids (PDO) to conventional treatment. Method: We conducted a prospective, randomized, multicenter clinical trial in which, patients with newly diagnosed advanced PDAC were randomized to either a personalized medicine approach or to a conventional treatment in a 2:1 ratio. Patients randomized to the conventional arm were treated with standard of care therapy. Patients randomized to the experimental arm underwent a tumor biopsy to determine their genetic status through whole exome sequencing (WES) and to generate an Avatar and PDO model. Personalized treatment was based on the targets identified by genetic and bioinformatic analysis, as well as by phenotypic screening of 40 anticancer agents in the patient derived models after discussion in a molecular committee. Results: A total 129 PDAC patients with a median age of 62 years old, were enrolled and 122 were included in the analysis. Seventy-eight patients were randomized to the experimental arm and 44 to the conventional one. WES has been performed in 66 patients and in 56 of them potentially actionable pathogenic variants were detected. Experimental models were successfully generated in 28 patients and screened. However, only 4 patients were treated with selected agents. The remaining 52 patients could not be treated according to the results of the study: 73% of them because of premature clinical deterioration, 8% because of delaying in obtaining results due to technical matters and 19% because the recommended treatment was not felt to have adequate data support by the molecular committee. The median overall survival (from the date of randomization until the date of death) was 8,7 months for patients from conventional arm and 8,8 months for patients from experimental arm (not statistically different). The median overall survival (from the date of randomization until the date of death) for the four patients treated according to the results of the study was 19,5 months. Conclusions: In our study, a full personalized medicine approach did not improve the overall survival of patients with PDAC. Failure to obtain genomic data and models, lack of actionable genetic alterations and targeted agents in living models, and the rapid course of PDAC limited the implementation of precision medicine treatments. Outcome was improved in the 6% of patients in whom a personalized treatment was administered. Citation Format: Manuel Hidalgo, Francesca Sarno, Laura Medina, Roberto Pazo, Ignacio Juez, Rocío García-Carbonero, Carmen Guillén-Ponce, Jaime Feliú, Carolina Alonso, Jair Tenorio_Castano, Pablo Lapunzina. A randomized trial of integrated genomics, organoids and avatar mouse models for personalized treatment of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT225.

656 Background: Randomized clinical trials have established new chemotherapeutic standards of care for metastatic pancreatic cancer, namely FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GNP) after demonstrating a significant and relevant increase of overall survival. However, there are some important uncertainties regarding how many patients are candidate to each of the two new regimens in the real life and how is the pattern of use in the elderly population. Methods: This is a retrospective study. Departments of Pharmacy of 7 Spanish hospitals generated the listings of patients (pts) treated in first line with these new regimens (FFX or GNP). Non-metastatic patients were excluded. An exploratory analysis was performed in the elderly population. Results: From Jan 2012 to Dec 2017, a total of 119 pts (M/F 58/42 %) were treated. Med age 63 y (38-83 y), 99% adenocarcinoma. 40% located in the head of pancreas. ECOG 87% 0-1. 89% had liver mets. In the 1st line 49.6% were treated with FFX and 50.4% with GNP. 53% of the pts could receive a 2nd line (82% after FFX 75% after GNP). The median OS was 12 months with no statistically significant differences between both regimens (12,7m for FFX vs 10,2 m for GNP). Elevated Ca 19.9 levels and Neutrophil-Lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70 yo. 13 (41%) were treated with FFX and 19 (59%) with GNP. The median OS for patients older than 70 was 9.5m versus 12.3m for patients younger than 70. Conclusions: In our setting the use of FFX and GNP for treating metastatic pancreatic cancer is quite similar. Superiority could not be demonstrated for any of the schemes in first-line. Overall survival was determined by basal Ca 19.9 and NLR. Patients receiving both regimens (FFX or GNP) in first/second line whichever the sequence, exhibited the best survival rates. In our series elderly patients had poor survival rates.

To determine the efficacy and safety data of aflibercept + FOLFIRI in wt RAS mCRC patients after progression to standard chemotherapy + anti-EGFR treatment. Retrospective, observational study in real life conducted in wt RAS mCRC patients treated with FOLFIRI-aflibercept after progression to standard first line chemotherapy + anti-EGFR treatment. A total of 120 patients from 12 Spanish hospitals were enrolled. Median age is 60 years (62.5%/37.5%male/female). Primary tumor site is 24.1%/75.9% right/left-side colon, and 40.8% of patients had a prior resection. All patients had wild-type RAS tumors including 5% of patients with BRAF mutations and received anti-EGFR treatment. At the time aflibercept was initiated, ECOG PS is 0/1 in 96% of patients. Median number of FOLFIRI-aflibercept cycles is 12. Efficacy results: Overall response rate is 33%; progression-free survival (PFS) is 6.9 months (95%CI: 6.1–7.8). Primary tumor resection was the only significant variable related to PFS in the multivariate analysis. Median overall survival (OS) is 14.5 months (95%CI: 9.7–19.3). ECOG and number of metastatic sites were related to OS in multivariate analysis. About 54.1% of patients received a third-line therapy including TAS-102 (23%), regorafenib (18.5%), and capecitabine (9.2%). Toxicity: Grade 3–4 toxicities were observed in 37.5% of the patients (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Aflibercept dose was reduced in 18.3% of patients. The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.

Primary objective of the study was to assess the relative weighting between benefit in survival time (SV), benefit in quality of life (QoL) and willingness to experience adverse events (AEs), in patient preferences for chemotherapy treatment. We included cancer patients with current or past systemic treatment of cancer (STC) as well as physicians placed as hypothetical patients. Participants filled a choice-based conjoint analysis questionnaire with 19 choices among three STC scenarios with variable amounts of benefit in SV or QoL and different types AEs. One hundred patients (50 on curative and 50 on palliative intention treatment) and 114 physicians (61 oncologists and 53 non-oncologists) were included and asked about their preferred chemotherapy treatment. The relative weighting (sum 100%) of SV–QoL–AEs for making the choice in the 100 patients was SV35%–CV33%–AEs31% what was not significantly different from a random distribution (Goodness of fit Chi square P = 0.91) just as it was not for both subgroups, palliative (SV37%–QoL29%–AEs34%; GoF Chi square P = 0.55) and curative (SV34%–QoL36%–AEs30%; GoF Chi square P = 0.73) treatment. The observed distribution in the group of 114 physicians (SV46%–QoL31%–AEs23%) was significantly different from a random distribution (GoF Chi square P = 0.018) just as it was for both subgroups, medical oncologists (SV48%-QoL29%-AEs23%; GoF Chi square P = 0.006) and non-medical oncologists (SV44%–QoL33%–AEs23%; GoF Chi square P = 0.04). The three attributes (SV, QoL, and AEs) are considered in the same way by cancer patients to make choices on their STC. On the contrary, when placed as hypothetical patients, physicians prefer for themselves those treatments that provide more SV.

Thromboembolic disease is the second leading cause of death in cancer patients (mostly, in the first year from diagnosis). The needing for anticoagulation with low molecular weight heparin (LMWH) in patients who are at high risk for complications (risk of bleeding in digestive tumors, brain tumors ...) require us to be more aware of their evolution. In addition, presenting venous thromboembolic disease (VTE) is usually an exclusion criterion in clinical trials so we do not know what happens with the combination of new drugs. Our objective is to study in a sample of 31 patients diagnosed with VTE, whether incidence of complications such as re-thrombosis or bleeding is higher in patients treated with tinzaparin (LMWH) depending on BMI.

First of all, we have to think about the risk of VTE in these patients. There are risk factors according to neoplasia, treatment ant patient. Risk factors related to neoplasia were lung (11/31), breast (4/31), colon (3/31) and 2 ovary and head/neck. Isolated cases of pancreas, stomach, sarcoma, prostate, peritoneum and unknown origin tumor were also described. According to tumor stage, more than 80% were metastatic disease. It is well known that stage IV is more prothrombotic than localized disease. Pathological anatomy is also important because adenocarcinoma is usually the most frequent one within VTE and cancer. So, 16/31 were adenocarcinomas, 5/31 epidermoids 2 serous and ductal, isolated cases of lobular, microcytic and non-small cell. In relation to treatment, the most important risk factor was chemotherapy, especially antiangiogenic (7/31). In addition, gemcitabine, platinum, etoposide, and irinotecan are the chemotherapy agents with the highest thromboembolic risk, indeed, in our sample 29/31 had received them [2]. Risk factors associated with the patient were non-oral contraceptives, recent surgery or the elderly population (12/31 were>65 years). 1/31 mutation carried the prothrombin gene. Comorbidities (Charlson Index) are also important. We reached a puntuation of 10 points; however 8 of 10 points were already for neoplasia and metastasis. Another factors to consider were previous admissions. So, 71% were admitted while 29% were ambulant (mostly Deep Venous Thrombosis).

e15023 Background: Studies in 2L metastatic colorectal cancer (mCRC) have survival ranging around 10-14 months (m). No study has averaged over 10cy. In daily practice, there is a subset of patients (pt) treated with FA with unknown characteristics receiving a number of cy higher than the average numbers of cy from the clinical trials. Chau et al. identified best-responders as those with ECOG0 with any metastatic site (MS) and those with ECOG1 with only one MS, but the number of cy received is unknown. Materials and Methods: Retrospective analysis based on the clinical records of Spanish mCRC pt receiving ≥ 25cy in 2L with FA to identify clinical and pathological features. Analyses were performed with SPSS (Statistical Package for the Social Science) for the progression-free survival (PFS) and overall survival (OS) curves. Results: Eighteen patients (male/female 9/9) were identified. Median age: 56years (39-68). All tumors were located in left colon: rectum 10pt, sigma 6pt, left 2pt. Histologic grade was well or moderately differenciate in 12pt. 7 pts had perineural or vascular invasion. RAS was mutated in 13pt and wild type in 5pt. Disease characteristics in 1L: MS at first diagnostic: 1 in 9pt (liver only 7pt, liver+other 7pt, lung only 1pt, lung+other 2pt). Oxaliplatin based CT was the treatment in 1L. Objective response rate (ORR) 77,8%. Bevacizumab was given in 12pt, anti-EGFR in 4pt. 1L PFS was 16.03m (15.14-16.91). 8 pts were resected from their metastases. Starting 2L: ECOG0 13pt; ECOG1 5pt (all with more than 1 MS). Number of MS: 1 in 6pt. (lung only 4pt, lung+other 8pt, liver+other 4pt). ORR was 61,1%. Median cy administred: CT 30 (12-50), Aflibercept 34 (25-50). Doses modification: CT 14pt, Aflibercept 4pt. OS 2L with 14 pt ongoing: 28.74m (25.85-31.64). Global OS since diagnosis: 46,67m (42,99-50,36). Conclusions: Long treatment duration can be achieved with FA, independently of the ECOG or the number of MS. In this series, all patients had a left-sided tumor and were mostly RAS mutant. The safety is in line with the VELOUR trial. Tumor location should be evaluated as a potential predictive factor. Funded by sanofi

Some rare cases of erysipelas-like or pseudocellulitis have been reported in relation to gemcitabine. This rare adverse event is more frequent in the presence of edema. Here, we report a case of pseudocellulitis after adjuvant treatment for pancreatic cancer. Oncologists should be aware of this infrequent and non-well understood adverse event. They should be especially careful when administering gemcitabine in the presence of lymphedema.