Abstract
Introduction: Alveolar Soft Part Sarcoma (ASPS) is an extremely rare sarcoma, accounting for 1% of soft tissue tumors that predominantly affects adolescents and young adults between 15 and 35 years of age (Brohl et al., 2021; Chang et al., 2021). ASPS often presents as a mass in the head and neck region in pediatric patients and in the thigh and buttocks in adults (Chang et al., 2021; Jaber et al., 2015). This disease process is characterized by the ASPSCR1-TFE3 fusion derived from an unbalanced translocation between chromosome 17 and the X chromosome (Schuetz & Jones, 2024). The standard of care for localized disease is primary surgical resection as conventional chemotherapies and radiation lack significant clinical benefit (Chang et al., 2021; Genevois et al., 2024). However, current research has identified tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) as potential new treatments that target unique features of ASPS tumor cells.
Case Report: Our patient is a 14-year-old male presented to the Oncology clinic with a soft tissue mass of his posterior left thigh. His staging evaluation further identified bilateral lung masses. Core biopsies of the thigh and a lung mass were consistent with a diagnosis of metastatic ASPS. Additional analyses identified an unbalanced translocation associated with the ASPSCR1-TFE3 fusion and increased molecular expression of PD-L1. Informed by prior pediatric ASPS studies, his initial treatment regimen consisted of axitinib and pembrolizumab, a TKI and ICI respectively. He continued on this regimen for nearly one year with relative disease stabilization and minimal side effects. He subsequently developed a persistent dry cough with imaging confirming progression of his lung masses but continued stable thigh disease. In the setting of worsening disease/evolving mixed response, the patient was transitioned to a similar regimen of atezolizumab and cabozantinib. He has favorably responded to this regimen with significant improvement to all sites of disease as monitored by interval PET/CT imaging with minimal side effects.
Conclusions: Amid emerging research on alternative ASPS treatments, this case report demonstrates the positive impact of immunotherapy on the progression and outcomes of pediatrics ASPS. By analyzing this patient's unique ASPS tumor characteristics, it became possible to develop a targeted and effective treatment approach. Overall, this case supports the synergistic effect of TKIs and ICIs on ASPS while highlighting their limited side effect profile, suggesting an opportunity for future studies on combinations of immunotherapies.
