Primary goal:

Improvement of the therapeutic index by reducing the toxicity of treatment and increasing local control of the cancer process while evaluating the possibility of conversion to the surgical status.

Secondary targets:

• Survival rate (OS) assessment in patients treated with mFOLFIRINOX + SBRT
• Assessment of quality of life using questionnaires: EQ-5D, EORTC (QLQ-C30) and pancreatic cancer-specific QLQ PAS module 26
• Early toxicity <3 months after completion of SBRT treatment.
• Percentage of local control (1-year)

STUDY PLAN Patients will receive initial mFOLFIRINOX (6 cycles) chemotherapy, followed by evaluation of the response to the treatment (imaging and laboratory testing) followed by SBRT, followed by mFOLFIRINOX chemotherapy.

In case of exclusion of disease progression after 10 weeks +/- 2 weeks after completion of SBRT, patients will be qualified to surgical treatment to attempt a radical surgical treatment.

Inclusion Criteria:

1. Signing informed consent for treatment.
2. Age> = 18 years.
3. Patients with histopathological diagnosis of adenocarcinoma of the pancreas.
4. Advanced disease referred to as locally advanced definitive non-resetable, non-metastatic pancreatic cancer.
5. No prior systemic treatment due to pancreatic adenocarcinoma
6. No prior radiotherapy in the abdominal area
7. No prior radical surgical treatment due to pancreatic adenocarcinoma (palliative surgical procedures such as bypass surgery or biliary tract surgery are acceptable).
8. ECOG 0 or 1.
9. Expected survival time in excess of 12 weeks.
10. Adequate organ performance based on laboratory blood tests.

Exclusion Criteria:

1. Patients diagnosed with other types of pancreatic cancer than adenocarcinomas (eg neuroendocrine cancer).
2. Advanced disease that allows primary surgical treatment.
3. Borderline pancreatic cancer (BRPC) disease.
4. The presence of metastases.
5. Previous systemic treatment because of pancreatic adenocarcinoma.
6. Preoperative radiotherapy in the abdominal area.
7. Previous radical surgery for pancreatic adenocarcinoma.
8. Large surgical procedure with the exception of diagnostic biopsies within the last 4 weeks after the start of treatment and / or patients who have not fully recovered after surgery.
9. Heart failure (NYHA Class II, III or IV)
10. Hemodynamic instability in the course of coronary and / or valvular heart disease and / or hypertension and / or other clinical conditions (eg uncontrolled diabetes mellitus).
11. Clinically relevant cardiac arrhythmias requiring treatment.
12. Stroke and / or myocardial infarction history within 6 months of inclusion.
13. Respiratory failure associated with other co-morbidities.
14. Serious psychiatric illnesses, which, in the researcher's opinion, could have a significant negative impact on the safety of the treatment.
15. Other serious accompanying illnesses, which, in the researcher's opinion, could seriously adversely affect the safety of the treatment.
16. Transplanted organ transplant including allogeneic bone marrow transplant.
17. Positive diagnosis for HBV or HCV indicating acute or chronic infection (for screening).
18. HIV infection.
19. The period of pregnancy and breastfeeding.
20. Alcoholism or drug abuse.
21. Limited legal capacity.