For pediatric patients, conventional radiation therapy to treat tumors presents major difficulties: they are exposed to multiple doses of radiation that can cause side effects such as headaches and nausea, and may have reduced late effects that can interfere with normal development; the treatment time frame also disrupts their school schedule and everyday activities.
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In recent years, targeted high-dose radiotherapy has been an effective alternative for pediatric patients. Since this treatment is aimed “tight to the target,” it can use higher doses, requiring only one to five sessions (fractions), which minimizes disruption to a young patient’s daily routine. This type of radiotherapy spares normal tissue, increases biologic effectiveness, and minimizes radiation exposure and potential side effects. The high doses of radiation also have the potential to activate the patient’s immune system and chemotherapy can be started sooner.
Cleveland Clinic has been using stereotactic radiosurgery (SRS) in pediatric patients to treat brain disease – benign and metastatic tumors, including pilocytic astrocytoma and arteriovenous malformation (AVM) — with positive outcomes. Building on Cleveland Clinic’s extensive experience using SRS to treat adult spine metastases, SRS use was extended to treat spine metastases—Ewing sarcoma and osteosarcoma—in adolescents and young adults. Since sarcoma is considered to be a radioresistant histology, it makes sense to treat it with a dose intensive radiation therapy.
More recently, Cleveland Clinic has used stereotactic body radiation therapy (SBRT) to treat metastatic and recurrent Ewing sarcomas and osteosarcomas in the lungs and non-spine bones. Using tumor site specific imaging, the treatment target is localized and separated from critical organs at risk. SBRT is performed with linear accelerators equipped with image-guidance technology and the capability to deliver a high radiation dose.
“Since children with metastatic disease can have extended survival with more systemic therapy options, we use an aggressive approach to try to cure all sites of disease. We can treat multiple sites on the same day and get these treatments done quickly with less impact on the child’s quality of life. It’s exciting to have another approach to offer these patients,” says Erin Murphy, MD, Director of Pediatric Radiation at Cleveland Clinic.
Regarding impact on the immune system, “we understand that radiation affects lymphocyte count, which may correlate with overall survival. There may be benefits to having a shorter course of radiation therapy in patients treated with immunotherapy. This is an area that is under investigation,” says Dr. Murphy.
Evidence shows positive outcomes
Cleveland Clinic studied early oncologic outcomes and toxicity in patients treated with SBRT for metastatic sarcomas. Using data from an institutional-review board registry, researchers identified 23 patients (median age 16.2 at the time of treatment) who received SBRT from 2015 – 2019. The patients had 63 lesions with the following diagnoses: Ewing sarcoma (8), osteosarcoma (10), rhabdomyosarcoma (2) small round blue cell sarcoma (1), clear cell sarcoma (1) and synovial sarcoma.
Prior to treatment with SBRT, all patients had systemic therapy. The median time from the development of local recurrence or metastatic disease to starting SBRT was 16.3 months.
The median radiation dose was 30 Gy in five fractions; the median follow-up time was 9.6 months. The six-month and 12-month local control rates were 88% and 78%, respectively. Overall, the treatment was well tolerated. No patients developed acute grade 3 or greater toxicities; five developed acute grade 2 toxicities. Two patients developed late grade 3 or higher toxicity; one patient developed late grade 2 pain and two patients developed grade 2 radiation recall reactions. The 12-month overall survival rate was 44.2%.
The study will be presented at the American Society of Radiation Oncology (ASTRO) annual meeting in September 2019.
“With young patients whose tissues are growing and developing, you need to be thoughtful about protecting normal tissue to avoid or reduce late toxicities. Patients tolerate SBRT well when you are careful about concurrent therapies. It’s a new modality for pediatric patients and we are learning how to integrate it into their overall treatment plan,” says Dr. Murphy.
Prospective studies are needed to establish guidelines for indications, identify optimal doses and technique, better understand the role of systemic therapies and reduce toxicity.