Stereotactic Ablative Radiation Therapy to All Lesions in Patients With Oligometastatic Cancers: A Phase 1 Dose-Escalation Trial

Abstract

Increasing evidence suggests that patients with a limited number of metastases benefit from SABR to all lesions. However, the optimal dose and fractionation remain unknown. This is particularly true for bone and lymph node metastases. Therefore, a prospective, single-center, dose-escalation trial was initiated. Methods: Dose-Escalation trial of STereotactic ablative body RadiOtherapY for non-spine bone and lymph node metastases (DESTROY) was an open-label phase 1 trial evaluating SABR to nonspine bone and lymph node lesions in patients with up to 3 metastases. Patients with European Cooperative Oncology Group performance status 1, an estimated life expectancy of at least 6 months, and histologically confirmed nonhematological malignancy were eligible. Three SABR fractionation regimens, ie, 5 fractions of 7.0 Gy versus 3 fractions of 10.0 Gy versus a single fraction of 20.0 Gy, were applied in 3 consecutive patient cohorts. The rate of !grade 3 toxicity, scored according to the Common Toxicity Criteria for Adverse Events v. 4.03, up to 6 months after SABR, was the primary endpoint. The trial was registered on clinicaltrials.gov (NCT03486431). Results: Between July 2017 and December 2018, 90 patients were enrolled. In total 101 metastases were treated. No !grade 3 toxicity was observed in any of the enrolled patients (95% CI 0.0%-12.3% for the first cohort with 28 analyzable patients; 95% CI 0.0%-11.6% for the second and third cohort with 30 analyzable patients each). Treatment-related grade 2 toxicities occurred in 4 out of 30 versus 2 out of 30 versus 2 out of 30 patients for the 5, 3 and 1 fraction schedule, respectively. Actuarial local control rate at 12 months was 94.5%. Conclusion: All 3 treatment schedules were feasible and effective with remarkably low toxicity rates and high local control rates. From a patient and resource point of view, the single-fraction schedule is undoubtedly most convenient.

Toxicity and Efficacy of Local Ablative, Image-guided Radiotherapy in Gallium-68 Prostate-specific Membrane Antigen Targeted Positron Emission Tomography–staged, Castration-sensitive Oligometastatic Prostate Cancer: The OLI-P Phase 2 Clinical Trial

“…The strengths of this prospective study include consistent and predefined patient selection, use of the state-ofthe-art gallium-68-PSMA-PET hybrid imaging as an initial staging procedure, consistent use of two predefined treatment schedules, and relatively long followup. Meanwhile, several clinical trials have been able to show safety and low risk for late complications of high-dose local aRT; nevertheless, there are also reports of serious side effects leading to death after aRT in oligometastatic patients [5,20,21]. Although the majority of patients in our trial had previously been irradiated, and some METs in 73% of patients were marginally or completely overlapping with the initial radiotherapy treatment volume, observed longterm toxicity was mild.…”

Evaluation of 5 Fraction Stereotactic Body Radiation Therapy (SBRT) for Osseous Renal Cell Carcinoma Metastases

“…Multiple recently published studies have demonstrated the significant benefit of localized therapy for oligometastatic RCC using ablative-intent SBRT in the treatment of metastases with improvements in overall survival, progression-free survival (PFS), and LC in the setting of acceptable treatment toxicity. [8][9][10][11] Furthermore, when specifically discussing treatment for oligometastatic RCC, studies suggest the benefit of ablative SBRT with improved outcomes. 12,13 In oligometastatic RCC patients who have prolonged survival, the importance of LC and decreasing morbidity of disease progression is even more pronounced.…”