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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
114
Precise radiation therapy delivered in a single session using magnetic resonance imaging for guidance.
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
RECRUITINGLocal control (LC) of treated target lesion compared to high dose MR-guided stereotactic single-fraction radiation.
The primary endpoint is LC defined as time from randomization to local failure of the treated target lesion. The LC will be estimated by cumulative incidence function with death and/or progression outside the treated target lesion (without local failure) as competing risk factors.
Time frame: 5 years
Overall survival (OS)
Endpoints related to patterns of failure, disease control, and survival will be determined by study investigators using standard-of-care imaging and clinical surveillance.
Time frame: 5 years
Progression free survival (PFS)
Endpoints related to patterns of failure, disease control, and survival will be determined by study investigators using standard-of-care imaging and clinical surveillance.
Time frame: 5 years
Intra-hepatic progression
Endpoints related to patterns of failure, disease control, and survival will be determined by study investigators using standard-of-care imaging and clinical surveillance.
Time frame: 5 years
Widespread progression.
Endpoints related to patterns of failure, disease control, and survival will be determined by study investigators using standard-of-care imaging and clinical surveillance.
Time frame: 5 years
Physician-assessed toxicities: National Cancer Institute (NCI) Common Terminology Criteria of Adverse Events (CTCAE) V.5.
Acute and late toxicities of treatment will be evaluated by CTCAE V5.0. The cumulative proportions of patients with at least one moderate to severe (grade 3-5) acute or late RT-related toxicity, measured by CTCAE (v5.0), will be compared between arms.
Time frame: 5 years
Patients-reported toxicity: Patient Reported Outcomes - Common Terminology Criteria of Adverse Events (PRO CTCAE) V.1.
Acute and late toxicities of treatment will be evaluated by PRO CTCAE (v1.0). The cumulative proportions of patients with at least one moderate to severe (grade 3-5) acute or late RT-related toxicity, measured by PRO CTCAE (v1.0), will be compared between arms.
Time frame: 5 years
Quality of life (QOL): European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, Core 15 for Palliative Care (EORTC QLQ-C15-PAL)
Acute and late toxicities of treatment will be evaluated by QOL (for English-speaking eligible patients) will be measured using the EORTC QLQ-C15-PAL, which will be administered before and after treatment. Scores of all domains of the EORTC questionnaires for each treatment arm will be evaluated before and after treatment.
Time frame: Prior to treatment and after treatment up to 5 years.
Quality of life (QOL): European Organization for Research and Treatment of Cancer Quality of Life Questionnaires, liver metastases (EORTC QOQ-LM21).
Acute and late toxicities of treatment will be evaluated by QOL (for English-speaking eligible patients) will be measured using the EORTC QOQ-LM21, which will be administered before and after treatment. Scores of all domains of the EORTC questionnaires for each treatment arm will be evaluated before and after treatment.
Time frame: Prior to treatment and after treatment up to 5 years.
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