This international multi-centre phase 3 randomized control trial investigates whether giving a very high dose of radiation in a single treatment session (ultra-high dose: experimental) using advanced technology called MR-Linac is more effective than a high dose (control) for treating liver tumors that have spread from other parts of the body (liver metastases). This study also aims to identify predictors of treatment response and side effects by analyzing various factors such as imaging markers and genetic profiles.

Liver metastases are common in several cancers, but surgery is often not feasible for many patients. Stereotactic body radiotherapy (SBRT), which delivers focused radiation to tumors, is an alternative treatment option. Previous studies have shown promising results with SBRT, but the optimal radiation dose for liver metastases is still uncertain.

This study will look at patients with specific types of primary cancers known to respond well to SBRT. Treatment effectiveness will be assessed by monitoring tumor control, overall survival, and quality of life.

By comparing ultra-high dose SBRT with standard high dose, the study aims to determine if the former can provide better tumor control with fewer side effects. If successful, this approach could offer a significant advancement in the treatment of liver metastases, potentially improving outcomes and quality of life for patients.

Inclusion Criteria:

• Histologically confirmed malignancy (colorectal adenocarcinoma, pancreatic adenocarcinoma, head and neck SCC, cervix SCC, skin SCC and NSCLC) with metastatic liver disease detected on imaging. Biopsy of metastasis is preferred, but not mandatory.
• One, two or three liver metastases "target lesion", ≥ 2 cm from luminal and biliary structures
• Target lesions(s) that can receive high/ultra-high dose SBRT: Maximum number: 3, Maximum diameter of each target lesion: 6cm
• Non-target lesion(s) can be treated with 3- or 5-fraction SBRT for non-target liver metastases
• Patients must be Child-Pugh score A within one month prior to study entry.
• Must be ≥ 18 years of age.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Expected life expectancy > 6 months.
• Suitable for MR-linac treatment (e.g., ability to lie on the treatment couch for at least one hour)
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
• Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in English. The baseline assessment must be completed within required timelines, prior to treatment start. Inability (lack of comprehension in English, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study.
• Women of child bearing potential must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 6 months after the last day of RT. Sexually active males must use an accepted and effective method of contraception and/or abstain from sexual intercourse while on protocol treatment and for at least 6 months after SBRT.
• 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:

• Liver metastases from primary cancer other than listed in the eligibility criteria (i.e., tumor with low α/β ratio).
• Target lesion "planned for high/ultra-high dose SBRT" in proximity (<2cm) to luminal or biliary structures.
• Evidence of > 5 liver metastases (exception is in cases of oligoprogression, patients may have more than 5 liver metastases, but SBRT for target lesions will be required for 1, 2, or 3 liver metastases only).
• Any previous RT to the abdomino-pelvic region that would result in significant overlap of RT volume for the current study.
• Previous liver-directed transarterial radioembolization (note that previous transarterial chemoembolization, microwave ablation, or radiofrequency ablation are permitted).
• Individuals with severe, active co-morbidity including any of the following:
• Chronic obstructive pulmonary disease or other pulmonary illness requiring hospitalization within 30 days of study registration
• Unstable angina and/or congestive heart failure requiring hospitalization within the 30 days of study registration
• Acute myocardial infarction within 30 days of study registration
• Diseases precluding RT (e.g., active scleroderma, lupus or inflammatory bowel disease)
• Contraindications to MR imaging (e.g. implanted metallic prostheses, defibrillators, stimulators, pacemakers, or neurotransmitters) per institutional policy on management of patients with internal and external medical devices.
• History of claustrophobia
• The total length of treatment volume is beyond the capacity of MRL machine
• Participants must not be receiving any other standard anti-cancer therapy or experimental agent concurrently with SBRT (≥1 week break of systemic therapy prior to SBRT is required).