Phase I/II Study of Stereotactic Body Radiation Therapy for Pulmonary Metastases in Pediatric Patients
Pulmonary metastases are common in many pediatric solid tumors; however, little is known about safety and efficacy of lung stereotactic body radiation therapy (SBRT) for pediatric patients. We conducted a phase I/II study to investigate the minimum effective dose level of SBRT with an acceptable safety profile in pediatric patients. Patients with sarcoma and metastatic pulmonary lesions ≤3 cm in diameter and ≤21 years of age were enrolled. Dose levels 1, 2, and 3 were 24, 30, and 36 Gy in 3 fractions, respectively. Enrolled patients with metastases from primary renal tumors and sarcoma histologies were to begin at dose level 1 and 2, respectively. Exclusion criteria included receipt of whole-lung/hemi-thorax irradiation >12 Gy within 6 months of consent. Primary endpoints were tolerability and safety per Common Terminology Criteria for Adverse Events grading and disease response at 6 weeks post-SBRT per response evaluation criteria in solid tumors (RECIST) 1.1 criteria. Secondary endpoints included rates of local control and distant failure within the lung, but outside of the treatment volume. Five patients with median age of 13 years (range, 7-21) received SBRT at dose level 2. Primary tumor histologies included Ewing sarcoma (n = 3), anaplastic chordoma (n = 1), and osteosarcoma (n = 1). No grade ≥3 adverse events were observed. At 6 weeks after SBRT, 7/8 (87.5%) lesions achieved partial response. With median follow-up of 2.1 years (range, 1.4-2.5), 2-year local control and distant failure-free survival were 60% (n = 8) and 40% (n = 5), respectively. One patient developed widespread metastases and succumbed to disease 1.4 years after SBRT. SBRT for pulmonary metastases produces responses in pediatric patients with sarcoma at 6 weeks with acceptable toxicity; however, patients remain at risk of local and distant failure within the lung. Future prospective studies are needed to investigate whether higher doses of SBRT, possibly in combination with other therapies, are safe and provide more durable response.