Surgical resection is the only potentially curative treatment for patients with pancreatic cancer with the aim of curative R0 resection and related improvement of survival. As a standard, surgery is usually followed by adjuvant therapy that improves survival but neoadjuvant therapy (NAT) is a rapidly emerging concept that needs to be explored and validated in terms of therapeutic options in borderline resectable pancreatic tumors. In this setting, preoperative FFX seems to be feasible and can be prolonged by radiation therapy. However, the exact and best therapeutic sequence is not yet known and the additional role of adding isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT) to chemotherapy requires validation in randomised trials. We propose to evaluate the impact and efficacy of adding iHD-SBRT to preoperative neoadjuvant mFFX or Gem-NabP in patients with borderline resectable pancreatic adenocarcinoma.
Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinated process or body or tail. Diagnosis should be verified by local pathologist
cTNM stage: T1-4N0-2M0
Confirmation of clinical and radiographic stage as borderline resectable (CT scan and/or MRI scan with contrast according to the NCCN criteria) by a multidisciplinary board, composed by a dedicated oncological surgeon, radiologist and GI oncologist)
Age > 18 years old
Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI or PET scan), histologically proven or at laparoscopy, including distal nodal involvement beyond the peripancreatic tissues (including non-regional lymph node involvement, ie: proven involvement of precaval lumbar lymphadenopathy(ies) and/or distant metastases
Locally advanced disease as defined by the NCCN criteria (version 2.2021) ie > 180° arterial encasement (SMA and CA) unreconstructible venous encasement (SMV/PV) due to tumor involvement or occlusion of a long segment.
CA 19.9 > 2500 kU/l (baseline and absence of cholestasis)
Contraindication of surgery (general)
Parallel
mFOLFIRINOX or Gemcitabine nab-paclitaxel
Drugoxaliplatin IV, irinotecan IV, leucovorin IV and 5-FU IV OR Gemcitabine IV Nab paclitaxel
Isotoxic High-Dose (iHD)-SBRT
RadiationRadiation therapy
Surgery
Procedure/SurgerySurgery
Disease free survival
Defined as time from randomisation to the first documentation of event where events considered are 1) disease progression, per RECIST, prior to surgery, 2) discovery of hepatic or peritoneal carcinomatosis during surgical exploration, 3) recurrent disease following R0-R1 surgery, or 4) death due to any cause.
R0 Resection rate
Defined as the proportion of eligible randomised patients in whom a R0 resection was achieved during surgery after neoadjuvant treatment with FOLFIRINOX +/- iHD-SBRT. R0 resection indicates a microscopically margin-negative resection (\>1 mm) from the inked margins (pancreatic transection, vascular and posterior circumferential resection margins).
Resection rate
defined as the percentage of eligible randomised patients that underwent a curative-intent resection
Pathologic complete/major response (pCR)
Defined as the proportion of patients in whom a pCR or a major (\<10% of residual tumour cells) was confirmed by histopathologic review of the surgical specimen.
Complete feasibility of the therapeutic sequence
Defined as the proportion of patient who performed completely the neoadjuvant therapeutic sequence with mFFX (or Gem-Nab-P) +/- iHD-SBRT until surgery (abdominal exploration with or without pancreatectomy). The therapeutic sequence will not be considered as feasible if less than 60% of patients do not complete it until surgery.
Overall survival (OS)
Defined as the time interval between randomisation and death. 95% confidence interval will be estimated based on standard method.
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Erasme University Hospital
Lead sponsor
Jules Bordet Institute
Collaborator
Belgian Group of Digestive Oncology
Collaborator
University Hospital St Luc, Brussels
Collaborator
