Pancreatic Fistula, Pancreaticoduodenectomy
Conditions
Keywords
Pancreatic fistula, Surgery, pancreaticoduodenectomy, Radiotherapy
Brief summary
Design of the study Prospective, single arm, multicentric, phase II open trial Number of participating sites 14 French centers of HPB Surgery departments associated with 14 Radiation Oncology Departments. Implementation of the study A screening of eligible patients will be made locally by the referring surgeon of each centre based on patient medical records. * Inclusion visit at the first surgical consultation (W-3 to D1) (V0) The inclusion visit will be done by the surgeon within 3 weeks before the first radiation oncologist visit * D1 (V1): first radiation oncologist visit * W2 (+/- 3D) and W4 (+/- 3D) (V2 et V3): Preoperative simulation process and treatment delivery * A first visit at W+2 (+/- 3 D) will be mandatory to validate the positioning of the target volume by CBCT with IV constrast or MRI * Then to start of the administration of radiotherapy at W+4 (+/- 3 D): Radiotherapy with 20 Gy, in 2 fraction of 10Gy with a one-day gap, so over a total period of 3 W9 ( +/- 1W) (V4): post-radiotherapy follow-up \- Preoperative visit Day-1 before PD (V5) W10 (+/- 1W) (V6): * Pancreaticoduodenectomy and post operative hospitalisation W14 (+/- 1W) (V7): follow up with surgeon (30 days after pancreaticoduodenectomy) * W22 (+/-1W) (V8): follow up with surgeon (90 days after pancreaticoduodenectomy) * W34 (+/-1W) (V9): Last study visit (radiation oncologist) (6 months after pancreaticoduodenectomy) Medical follow-up by radiation oncologist at 6 months after surgery to assess the occurrence of potential late toxicities due to radiotherapy
Interventions
OTHERStereotactic radiotherapy / pancreaticoduodenectomy
A dose of 20 Gy delivered in 2 fractions of 10 Gy, 1 day apart, of preoperative stereotactic radiotherapy Surgery : pancreaticoduodenectomy
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
France
Contacts
CONTACTSébastien GAUJOUX, PU/PH
CONTACTCharles DE PONTHAUD, PU/PH
Outcome results
None listed