Prevention of Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy by Preoperative Radiotherapy : a Phase 2 Trial

• Stereotactic radiotherapy / pancreaticoduodenectomy (Other): A dose of 20 Gy delivered in 2 fractions of 10 Gy, 1 day apart, of preoperative stereotactic radiotherapy Surgery : pancreaticoduodenectomy

Primary outcomes

• Number of patients at W22 (within 90 days from surgery) without grade B/C postoperative pancreatic fistula (POPF) [Week 22]: Postoperative fistula grade B and C is defined according to the last ISGPS classification of 2016 and will be adjudicated by independant experts.

Secondary outcomes

• To assess overall surgical complication rate at W22 (90 days after surgery) [Week 22]: defined as a grade 1 to 5 according to the Dindo-Clavien classification complications occurring within 3 month from surgery
• To assess severe surgical complication rate at W22 (90 days after surgery) [Week 22]: defined as a grade 3 to 5 according to the Dindo-Clavien classification complications occurring within 3 month from surgery
• To assess, during surgery (W10), the hardness of pancreas texture on the specimen after resection with a durometer [Week 10]: determined intraoperatively by Durometer measurement of the radiated and irradiated pancreatic tissue in Shore OO
• To assess, during surgery (W10), the hardness of pancreas texture on the specimen after resection by the surgeon [Week 10]: Determined intraoperatively by the pancreatic surgeon. Texture is scaled as soft/intermediate/hard at W10
• To assess, during surgery (W10), technical difficulties added by radiotherapy, according to the surgeon [Day of surgery- Week 10]: Determined by 2 questions * To what extent was the surgery complicated by the radiotherapy? (Answers: 1 - not complicated; 2 - slightly complicated; 3 - clearly complicated; 4 - severely complicated; 5 - impossible) * Did you have to adapt the surgical plan due to the administration of radiotherapy? (Answers: Yes/No)
• To assess on a pathological point of view the resected specimen at W14 [Day of surgery-week 14]: determined by the pathologist by evaluation of macroscopic differences between radiated and irradiated pancreatic tissue. \- The extent and distribution of fibrosis and fat infiltration were evaluated using the score established by Rebours et al. in intra- and extralobular locations
• To assess on a pathological point of view the resected specimen at W14 [Day of surgery-week 14]: determined by the pathologist by evaluation of macroscopic differences between radiated and irradiated pancreatic tissue. \- Fibrosis quantification was also assessed by determining the area of collagen using Sirius red staining (as performed in FIBROPANC trial)
• Pancreatic functionnal outcomes at W22 (de novo diabetes) [Week 22]: Determined by \- De novo diabetes : In accordance with French and European recommendations, diabetes is diagnosed if fasting blood glucose is greater than or equal to 1.26 g/L on two occasions, or greater than or equal to 2 g/L at any time of the day, or if HbA1c is greater than 6.5%
• Pancreatic functionnal outcomes at W22 (exocrine pancreatic insufficiency) [Week 22]: Determined by \- Exocrine pancreatic insufficiency: A fecal elastase level < 100 mg/g stool is commonly accepted for diagnosing severe exocrine pancreatic insufficiency, a fecal elastase level between 100 and 200 mg/g indicates moderate exocrine pancreatic insufficiency, and a level > 200 mg/g stool rules out exocrine pancreatic insufficiency
• To assess mortality rate at W22 [Week 22]
• To assess overall length of hospital stay after surgery [Up to Week 34]: Length of hospital stay between the operation and the day of discharge from hospital
• To assess readmission rate at W22 [Week 22]: Proportion of readmission at W22, whatever the cause
• To assess radiation-induced complications rate, overall and by grade at W9, W10, W14, W22, W34 [Week 9, Week 10, Week 14, Week 22 and Week 34]: to CTCAE classification (Common Terminology Criteria for Adverse Events), overall and by grade (grade 1 to 5)
• To assess safety of radiotherapy at W9, and W34 [Week 9 and Week 34]: Proportion of patients at W9 and W34 who underwent at least one side effects of radiotherapy among gastritis or gastric bleeding

Sex: All, ages: 45 Years to any

Inclusion Criteria:

* Aged ≥ 45 years old
* Candidate for pancreaticoduodenectomy by laparotomy
* Body mass index (BMI) ≥ 25kg/m2
* Diameter of main pancreatic duct (MPD) < 3 mm on preoperative CT scan or MRI at the isthmus of the pancreas (future pancreatic section area)
* Affiliation to a social security system (AME excepted)
* Signed informed consent

Exclusion Criteria:

* Surgery indication : Chronic pancreatitis
* Surgery indication : Pancreatic ductal adenocarcinoma
* History of syndromic or hereditary pancreatic tumor
* Contraindication to pancreaticoduodenectomy
* Planned multivisceral resection involving organs or parts of organs not normally involved in pancreatico-duodenectomy
* Planned external drainage of the main pancreatic duct at the end of the surgery
* Neoadjuvant treatment planned or performed by chemotherapy or radiotherapy
* History of chronic hepatitis (F3) or cirrhosis (F4)
* Contraindication to radiotherapy
* Previous history of abdominal radiotherapy
* Extended pancreatic resection on the left beyond the radiotherapy area (left of the pancreatic isthmus)
* History of complicated peptic ulcer
* Patient treated for less than 4 weeks for an ulcer
* History of pancreatic surgery
* Ongoing pregnancy (confirmed by a test beta-HCG) or breast feeding or absence of birth control
* Patients with a active pathology or history that may interfere with the study in progress or the interpretation of its results according to the investigator
* Patients with a history or suspicion of non-compliance with medical regimens or will be unable to complete the entire study
* Treatment with systemic corticosteroids (excluding inhaled corticosteroids)
* Participation in another interventional clinical study (RIPH1, clinical investigation or clinical trial) or exclusion period set after the study
* Protected persons under legal guardianship or conservatorship