Phase I/II Study of Stereotactic Body Radiation Therapy for Pulmonary Metastases in Pediatric Patients

Abstract

Purpose 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. Methods and Materials 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. Results 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. Conclusions 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.

Pediatric radiotherapy for thoracic and abdominal targets: Organ motion, reported margin sizes, and delineation variations – A systematic review

“…Most commonly reported margins types were GTV-CTV and CTV-PTV margins for thoracic [44, (Fig. 2A), abdominal [15,18,30,41,45,[50][51][52][53][54][55][56]60,[62][63][64]66,70,73,74,[76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94] (Fig. 2B), spinal [43,46,48,63,82, (Fig.…”

“…Other margin types for spinal treatment included PTV margins of 5 mm [99,130,131], and a GTV-PTV margin range of 7 to 10 mm [128]. Furthermore, one study reported a security margin of 3 mm for the spine [78], and in one study a 5 mm margin was reported but no margin type was specified [132].…”

Efficacy and Safety of Stereotactic Body Radiation Therapy for Pediatric Malignancies: The LITE-SABR Systematic Review and Meta-Analysis

“… 7 Although a number of prospective and retrospective experiences have reported on the use of SBRT for pediatric and AYA patients, each is limited by number of patients and lesions treated with larger multi-institutional trials pending analysis. 8 , 9 , 10 As such, we aimed to perform a systematic review and study-level meta-analysis of available data in the literature to characterize both the safety and efficacy of SBRT for the pediatric and AYA population.…”

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

“…In that group, primary tumor histologies included Ewing sarcoma ( n = 3), anaplastic chordoma ( n = 1), and osteosarcoma ( n = 1). At 6 weeks, 7/8 treated lesions had a response, but two-year local control was only 60% [ 57 ].…”