A Review of Ongoing Trials of Stereotactic Ablative Radiotherapy for Oligometastatic Cancers: Where Will the Evidence Lead?

Abstract

Purpose: The oligometastatic state is a proposed entity between localized cancer and widely metastatic disease, comprising an intermediate subset of metastatic cancer patients. Most data to support locally-directed treatment, such as stereotactic ablative radiotherapy (SABR), for oligometastases are from retrospective institutional reports. Following the success of a recently completed and reported phase II trial demonstrating important clinical outcomes, herein we review the current landscape of ongoing clinical trials in this context. Materials and methods: A review of currently activated and registered clinical trials was performed using the clinicaltrials.gov database from inception to February 2019. A search of actively recruiting trials, using the key words oligometastases, SABR, and various related terms was performed. Search results were independently reviewed by two investigators, with discrepancies settled by a third. Data abstracted from identified studies included study type, primary disease site, oncologic endpoints, and inclusion/exclusion criteria. Results: Of the initial 216 entries identified, 64 met our review eligibility criteria after full-text review. The most common study type was a phase II clinical trial ( n = 35, 55%) with other study designs ranging from observational registry trials to phase III randomized controlled trials (RCTs). A minority of trials were randomized in design ( n = 17, 27%). While most studies allowed for metastases from multiple primary disease sites ( n = 22, 34%), the most common was prostate ( n = 13, 15%), followed by breast, gastrointestinal, non-small cell lung cancer (NSCLC), and renal ( n = 6, 9% each). In studies with a solitary target site, the most common was liver ( n = 6, 9%) followed by lung ( n = 3, 5%). The most common primary endpoints were progression-free survival (PFS) ( n = 20, 31%) and toxicity ( n = 10, 16%). A combined strategy of systemic therapy and SABR was an emerging theme ( n = 23, 36%), with more recent studies specifically evaluating SABR and immunotherapy ( n = 9, 14%). Conclusion: The safety and efficacy of SABR as oligometastasis-directed treatment is increasingly being evaluated within prospective clinical trials. These data are awaited to compliment the abundance of existing observational studies and to guide clinical decision-making.

Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis

“…18 Ultimately, disease-specific phase 3 RCTs are needed and ongoing. 19 As recently highlighted by the European Society for Radiotherapy and Oncology and European…”

Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document

“…Although randomised phase III evidence is lacking, recent randomised phase II trials have shown the potential of SBRT to improve survival of patients with OMD [9,10,12] and multiple randomized trials are expected in the next few years. A recent review reports 64 ongoing trials studying ablation of OMD, activated and accruing through February 2019 [102]. Over half were phase II (n = 35), however, 17 randomized controlled trials were noted.…”

“…Others such as oligorecurrence, -progression and -persistence are plausible scenarios where clinically evident disease may represent the true disease state as opposed to impending wide spread disease. Based on ongoing trials it is clear that further complexity will be added regarding the use of concurrent systemic therapy or immunotherapy [102]. It is therefore critical that authors and editors are explicit about inclusion criteria and definitions, endpoints and toxicity, while continuing to generate evidence on this complex and evolving clinical indication.…”

Stereotactic body radiotherapy (SBRT) for adrenal metastases of oligometastatic or oligoprogressive tumor patients

“…With the widespread use of regularly performed staging with CT or positron-emission-tomography (PET)-CT, and the growing recognition of the oligometastatic or oligoprogressive state in different tumor entities, the number of patients presenting with asymptomatic adrenal metastases has increased [32][33][34]. For these patients, surgical resection remains the gold standard, however, many patients are medically unfit for surgery, or their tumors are not technically resectable, and alternative local treatment approaches are required [4,16,35].…”