A multi‐institutional phase 2 trial of stereotactic body radiotherapy in the treatment of bone metastases in pediatric and young adult patients with sarcoma

Abstract

Background Metastasectomy is standard of care for pediatric patients with metastatic sarcoma with limited disease. For patients with unresectable disease, stereotactic body radiotherapy (SBRT) may serve as an alternative. Herein, the authors report the results of a prospective, multi‐institutional phase 2 trial of SBRT in children and young adults with metastatic sarcoma. Methods Patients aged >3 years and ≤40 years with unresected, osseous metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone were eligible. Patients received SBRT to a dose of 40 Gray (Gy) in 5 fractions. Local control (LC), progression‐free survival (PFS), and overall survival (OS) were calculated using the Kaplan‐Meier method. Results Fourteen patients with a median age of 17 years (range, 4‐25 years) were treated to 37 distinct metastatic lesions. With a median follow‐up of 6.8 months (30.5 months in surviving patients), the Kaplan‐Meier patient‐specific and lesion‐specific LC rates at 6 months were 89% and 95%, respectively. The median PFS was 6 months and the median OS was 24 months. In a post hoc analysis, PFS (median, 9.3 months vs 3.7 months; log‐rank P = .03) and OS (median not reached vs 12.7 months; log‐rank P = .02) were improved when all known sites of metastatic disease were consolidated with SBRT compared with partial consolidation. SBRT was well tolerated, with 2 patients experiencing grade 3 toxicities. Conclusions SBRT achieved high rates of LC in pediatric patients with inoperable metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone. These results suggest that the ability to achieve total consolidation of metastatic disease with SBRT is associated with improved PFS and OS.

Palliative radiotherapy for children: Symptom response and treatment‐associated toxicity according to radiation therapy dose and fractionation

“…In this series, SBRT was used in only a small minority of cases ( n = 15, 3%) and represented only 4% (3/72) of cases treated with five or lesser fractions evaluable for pain response. SBRT is an attractive method of delivering palliative RT, particularly for less radiation‐sensitive histologies, such as sarcoma, where it has been demonstrated to be safe and effective in children 18–20 . Though SBRT does deliver a higher BED, it is a highly conformal treatment with minimal normal tissue exposure, and BED was not associated with treatment toxicity on multivariable analysis in this report.…”

The Evolving Role of Radiotherapy for Pediatric Cancers With Advancements in Molecular Tumor Characterization and Targeted Therapies

“…The prospective phase II study by Elledge et al. importantly suggested that survival outcomes may be improved with consolidation of all known metastatic sites with SBRT ( 90 ), consistent with data from the EURO-EWING trial indicating improved EFS with local therapy to primary and metastatic sites ( 92 ). Current COG trial AEWS1221 is evaluating SBRT for treatment of osseous metastatic sites, to a dose of 40 Gy in 5 fractions [NCT02306161].…”

“…Thus, SBRT may become increasingly relevant with effective targeted systemic therapies. Several retrospective and early phase prospective studies (summarized in Table 3) have evaluated SBRT for metastatic and recurrent sarcomas (88)(89)(90)(91). These have generally shown good local control outcomes, but increased toxicity when given with concurrent systemic therapy or in the re-irradiation setting.…”

Radiation Therapy in Metastatic Soft Tissue Sarcoma: From Palliation to Ablation

“…The 6-month lesion-specific control rate was excellent at 95%. In post-hoc analysis, patients who underwent consolidation of all sites had improved progression free survival (median, 9.3 months vs. 3.7 months; p = 0.03) and overall survival (median not reached vs. 12.7 months; p = 0.02) compared to patients who underwent partial consolidation [ 56 ].…”