Session Item

To compare toxicity and efficacy of the three most commonly used SBRT (i.e. 5, 3 or single fraction) schedules for bone and lymph node oligometastases.

Patients with ≤ 3 bone and/or lymph node metastases were included in this prospective trial. In the first, second and third cohort of each 30 patients, all metastases were treated to 5 x 7 Gy, 3 x 10 Gy and 1 x 20 Gy, respectively. SBRT could be combined with standard of care (SOC) systemic treatment. Dose constraints for OAR were prioritized over PTV coverage in accordance with the recommendations from the report of the American Association of Physicists in Medicine (AAPM) task group 101. Dose-limiting toxicity, defined as any ≥ grade 3 up to 6 months after SBRT, was the primary endpoint. Secondary endpoints were acute and late toxicity, local response (LR) at 6 months after SBRT, local failure (LF), and progression-free survival (PFS). Toxicity was graded using CTCAE version 4.03. LR was evaluated by RECIST version 1.1 or on functional imaging (PSMA or FDG PET/CT) if available. LF was scored as an event if an irradiated lesion showed an increase in size of ≥ 20% according to RECIST v1.1. Dosimetric evaluation was performed with RayAnalytics.

From July 2017 until December 2018, 90 patients received SBRT to a total of 101 metastases. Seven patients were non-evaluable 6 months after SBRT and left out of the toxicity and LR analysis. Treatment groups were well balanced for patient and tumor characteristics (Table 1). Functional imaging was available in 78% of the lesions.  Median follow-up was 15.0 months (range 6.3-25.6). No dose-limiting toxicity was observed. No ≥ grade 3 acute or late toxicity occurred. Acute toxicity consisted of 3% grade 2 GI toxicity and 3% grade 2 pain flare. Late grade 2 toxicity was seen in 2 patients (1 patient with GI toxicity received 3 x 10 Gy, 1 rib fracture was seen after 1 x 20 Gy). Toxicity was not different between the different fractionation schemes. There was no difference in LR at 6 months between the treatment schedules. LF was seen in 4 patients, with a median time to local failure of 8.5 months (range 6.6-12). Median PFS was 14.8 months (95% CI 10.8-NA), Figure 1. Dosimetric analysis showed a difference in PTV coverage with the prescribed dose between the 3 schedules, with the lowest median coverage being reported for 5 x 7 Gy (p=0.03); however, GTV coverage was sufficient for all treatments. Flow cytometry of peripheral immune cells is being evaluated for the 3 vs 1 fraction groups.

This phase I trial confirms that SBRT to all oligometastatic lesions, combined with SOC systemic treatment when available, is extremely safe and leads to excellent local control as well as promising long-term PFS. 
Since no significant differences in toxicity, local control nor clinically relevant differences in target coverage were observed between the 3 schedules, single-fraction SBRT should probably be preferred, considering both resource-efficiency and patient comfort.