Abstract
BackgroundPatients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. Stereotactic ablative radiotherapy (SABR) has shown promise in the treatment of oligometastatic disease, but the utility of SABR in treating all sites of polymetastatic disease has yet to be evaluated. This study aims to evaluate the maximally tolerated dose (MTD) of SABR in patients with polymetastatic disease.MethodsUp to 48 patients with polymetastatic cancer (> 10 sites) will be enrolled on this phase I, modified 3 + 3 design trial. Eligible patients will have exhausted (or refused) standard systemic therapy options. SABR will be delivered as an escalating number of weekly fractions of 6 Gy, starting at 6 Gy × 2 weekly fractions (dose level 1). The highest dose level (dose level 4) will be 6 Gy × 5 weekly fractions. Feasibility and safety of SABR will be evaluated 6 weeks following treatment using a composite endpoint of successfully completing treatment as well as toxicity outcomes.DiscussionThis study will be the first to explore delivering SABR in patients with polymetastatic disease. SABR will be planned using the guiding principles of: strict adherence to dose constraints, minimization of treatment burden, and minimization of toxicity. As this represents a novel use of radiotherapy, our phase I study will allow for careful selection of the MTD for exploration in future studies.Trial registrationThis trial was prospectively registered in ClinicalTrials.gov as NCT04530513 on August 28, 2020.
Highlights
Patients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease
While systemic radiotherapy in the form of therapeutic radiopharmaceuticals are available or emerging as treatment for some polymetastatic cancers [3], in most cases this treatment has been limited to the palliation of bone disease with bone seeking radiopharmaceuticals [4]
The traditional role of radiotherapy in patients who have metastatic cancer has been for palliation of symptomatic metastases where systemic therapy does not penetrate [5], or targetable sites of disease causing symptoms such as pain, obstruction and/ or bleeding [6,7,8]
Summary
Patients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. The traditional role of radiotherapy in patients who have metastatic cancer has been for palliation of symptomatic metastases where systemic therapy does not penetrate (i.e. brain metastases) [5], or targetable sites of disease causing symptoms such as pain, obstruction and/ or bleeding [6,7,8]. Recent studies have examined a subset of patients with metastatic cancer who have a limited burden of metastatic disease, known as oligometastatic cancer. The oligometastatic state is best defined as a stage of disease where a cancer has spread beyond the primary tumour to a limited number of sites, but is not yet widely metastatic [9]. While definitions of oligometastatic cancer vary, most would consider the oligometastatic state to represent 1–3 or 1–5 metastatic lesions [10, 11]
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