Retrospective Cohort Study of Pediatric and Young Adult Patients Receiving Radiotherapy for Non-Malignant Vascular Anomalies

Abstract

Non-malignant vascular anomalies (VA) comprise a heterogeneous spectrum of conditions characterized by aberrant growth or development of blood and/or lymphatic vessels. Depending on the location, non-malignant VA can cause significant morbidity, including pain, bleeding, and neurologic deficits. Little is known about outcomes after radiotherapy (RT) in pediatric and young adult (YA) patients with non-malignant VA. Clinical and treatment characteristics were recorded for 30 patients diagnosed with non-malignant VA who were evaluated at a Children’s Hospital Vascular Anomalies Center and treated with RT before 30 years of age between 1945-2017. Median age at diagnosis and at first RT was 0.1 years (range: 0-24) and 15 years (0.2-27), respectively. Median follow-up (FU) from diagnosis and completion of first RT was 16.5 years (range: 0.6-73.4) and 9.8 years (range: 0.02-67.4), respectively. Most patients (76.7%) received RT after 1990. The most common diagnoses were lymphatic malformations (33.3%), kaposiform hemangioendothelioma (KHE) (16.7%), and venous malformations (VMs) (16.7%). Most patients presented with skin or palpable lesions (73.3%) and pain (23.3%). Surgery (46.7%) and sclerotherapy/embolization (26.7%) were the most common treatments before RT. The most common indication for first RT was progression despite standard therapy and/or urgent palliation for symptoms (56.7%). Location of lesions treated with RT included thorax (33.3%), face/skull (30.0%), and back/spine (20.0%). Median dose was 38 Gy (range: 5-58). After first RT, 13 patients (43.3%) had a complete response or partial response (PR), defined as any decrease in size of treated lesion or improvement in symptoms. Four of five patients with KHE had PR after RT, and a patient with spinal cord compression from an epidural VM had improvement in neurologic deficits after RT. One patient is without recurrence with 17.6 years of FU after adjuvant RT for epithelioid hemangioma. After first RT, 27 (90.0%) ultimately required additional treatment, including surgery (40.0%) and sclerotherapy/embolization (26.7%), for progression or recurrence. Long-term complications included telangiectasias, fibrosis, xerophthalmia, radiation pneumonitis, ovarian failure, and central hypothyroidism. No patient developed secondary malignancies. At last FU, three patients (10.0%) were without evidence of disease, 26 (86.7%) with disease, and one died of complications (3.3%). A small group of pediatric and YA patients with non-malignant high-risk VA had clinical benefit from RT with expected toxicity; however, most patients experienced progression after RT. Future prospective studies are needed to characterize indications for RT among pediatric and YA patients with non-malignant VA, particularly in the era of mTOR inhibitors.