Inclusion Criteria:
* Histologically and/or cytologically proven locally advanced pancreatic adenocarcinoma
* Target lesion is technically amenable for Alpha DaRT sources implantation.
* Measurable lesion per RECIST (version 1.1) criteria
* Stable disease or tumor response per RECIST (version 1.1) criteria compared to before initiation of mFOLFIRINOX
* Lesion size ≤ 5 cm in the longest diameter
* Interstitial radiation indication validated by a multidisciplinary team which includes an oncologist, a radiation oncologist, radiologist, gastroenterologist and a surgeon specialized in pancreatic oncology in the case that a surgical emergency occurs during the procedure
* Patients have received 8 - 12 cycles of mFOLFIRINOX
* ECOG Performance Status Scale 0 - 1
* Life expectancy is more than 6 months
* WBC ≥ 3500/µl, granulocyte ≥ 1500/µl
* Platelet count ≥60,000/µl
* Creatinine ≤1.9 mg/dL
* AST and ALT ≤ 2.5 X upper limit of normal (ULN)
* INR \< 1.4 for patients not on Warfarin
* Age ≥18 years old
* Subjects are willing and able to sign an informed consent form
* Women of childbearing potential (WOCBP) will have evidence of negative pregnancy test before the Ra-224 implantation and are required to use an acceptable contraceptive method to prevent pregnancy for 3 months after initiation of Alpha DaRT therapy
* Patients must agree to use adequate contraception (vasectomy or barrier method of birth control) prior to study entry, for the duration of study participation and for 3 months after DaRT insertion.
Exclusion Criteria:
* Concomitant immunotherapy within the past 4 weeks.
* Patients with metastatic disease
* Borderline unresectable pancreatic cancer, and/or cases fit for surgical exploration unless patient refuses surgery.
* Known hypersensitivity to any of the components of the treatment.
* Patients undergoing systemic immunosuppressive therapy excepting intermittent, brief use of systemic corticosteroids.
* Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months.
* Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial or interfere with the study endpoints.
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, low risk prostate cancer, or in situ cervical cancer.
* Patient requires treatment not specified in this protocol which may conflict with the endpoints of this study including evaluation of response or toxicity of DaRT.
* Patients do not agree to use adequate contraception (vasectomy or barrier method of birth control) prior to study entry, for the duration of study participation and for 3 months after discontinuing therapy.
* Volunteers participating in another interventional study in the past 30 days which might conflict with the endpoints of this study or the evaluation of response or toxicity of DaRT.
* High probability of protocol non-compliance (in opinion of investigator).
* Breastfeeding women or women of childbearing potential unwilling or unable to use an acceptable contraceptive method to prevent pregnancy for 3 months after RT.
