A Study of High Dose Radiation Therapy for Locally Advanced Pancreatic Cancer That Responded to Initial Chemotherapy Treatment

The goal of this clinical trial is to test the effect of high-dose radiation therapy after initial chemotherapy in patients with locally advanced pancreatic cancer. The main question it aims to answer is:

• For patients with locally advanced pancreatic cancer that responded to initial chemotherapy (stayed stable or decreased in size), will high-dose RT (radiation therapy) contribute to improving treatment outcomes, enhancing quality of life, or increasing overall survival rates?

Participants will:

* Undergo an optional tumor biopsy.
* Be treated with high dose radiation therapy.
* Complete quality of life questionnaires.
* Donate research blood samples.


Eligibility Criteria:
Inclusion Criteria:

* Have a histological or cytological diagnosis of LAPC.
* Have pancreatic tumour \<8.0 cm in greatest axial dimension at the time of treatment planning but final determination of eligibility will be based upon satisfying the radiation normal tissue constraints.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Karnofsky ≥70%).
* Life expectancy of greater than 6 months, as judged by the investigator.
* Patients must have had prior first-line chemotherapy for this cancer for at least 16 weeks without clinical or radiographic progression. There should be a washout of at least 2 weeks from first-line chemotherapy and start of therapy on clinical trial.
* Ability to understand and willing to sign a written informed consent document.
* Women must not be pregnant or breast-feeding. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 4 weeks prior to registration. All breastfeeding women should discontinue breastfeeding prior to study registration.

Exclusion Criteria:

* Metastatic disease at the time of registration
* Age\<18.
* Patients who have had prior systemic treatment (chemotherapy or any other anti-cancer agent) in the metastatic setting.
* Prior radiotherapy to the upper abdomen region that would result in overlap of RT volume for the current study.
* Patients who are currently on anti-cancer treatment including chemotherapy.
* Uncontrolled inter-current illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant and breastfeeding women.
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
* Individuals with a history of a different malignancy except if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
* Individuals with diseases precluding high dose ablative RT (e.g. scleroderma, gastric or bowel ulceration or perforation within the planned irradiated volume)
* Patient should NOT be treated with MR-Linac if they have any contraindications for MRI, including presence of a heart pacemaker, (ferrous) metallic foreign bodies, and severe claustrophobia. Patients will be screened and excluded from the study if they have previous anaphylactic reactions to gadolinium and severe kidney disease (glomerular filtration rate \< 30mL/min/1.73m2) or acute kidney disease.