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Summarizing discussion and future perspectives1116Despite demonstrating the feasibility of this treatment and the observed relatively favorable PFS and OS, this phase I study was not succeeded by a phase II study. Meanwhile the standard chemotherapy with gemcitabine changed to multiagent FOLFIRINOX after the PRODIGE-4 trial conducted by Conroy et al. in which FOLFIRINOX demonstrated an enhanced response rate (RR) and improved OS compared to gemcitabine monotherapy for patients with metastatic PDAC (13). The current guideline recommends induction chemotherapy with FOLFIRINOX as initial treatment also for patients with LAPC followed by an additional resection in selected patients. FOLFIRINOX for LAPC is associated with a median OS of approximately 12 months in a multicenter cohort study (14) and extends to 16-24 months in clinical trials (15, 16). Novel local therapies such as radiofrequency ablation (RFA) and irreversible electroporation (IRE; a nonthermal ablative technique using direct current) are used and studied extensively for the treatment of LAPC (17). Randomized studies in which local therapy is compared with systemic therapy are important to determine the most favorable treatment strategy. The efficacy of the addition of RFA to FOLFIRINOX chemotherapy is being investigated in the Pelican study (ClinicalTrials.gov Identifier: NCT03690323). The CROSSFIRE Trial compares FOLFIRINOX followed by IRE with FOLFIRINOX followed by stereotactic ablative radiotherapy (SABR) (ClinicalTrials.gov Identifier: NCT02791503). The results of these randomized studies are awaited for further treatment optimization. The concept of CRT with gemcitabine remains an interesting treatment option for future trials, particularly given the positive results of the PREOPANC trial. The addition of an EGFR inhibitor such as panitumumab to CRT may be explored in future trials considering the feasibility data of the phase I study described in chapter 2. Current guidelines advise combination chemotherapy with FOLFIRINOX in patients with metastatic PDAC in a good clinical condition based on the PRODIGE-4 trial (13). Nab-paclitaxel plus gemcitabine can also be considered as initial systemic treatment, based on the results of the MPACT trial (median OS 8.5 vs. 6.7 months for gemcitabine monotherapy) in patients with metastatic PDAC (18). Nab-paclitaxel plus gemcitabine is often recommended for patients in a moderate condition or older age (>75 years) based on the eligibility criteria of these trials. First-line modified FOLFIRINOX and nab-paclitaxel plus gemcitabine regimens were recently compared in the planned interim analysis of 527 patients in the multicenter, randomized, open-label, phase II/III JCOG1611-GENERATE trial, as presented at the ESMO congress (October 2023, abstract 1616O) (19). The authors recommend nab