Efficacy of pharmacological interventions in alveolar soft part sarcoma: A network meta-analysis.

Abstract

e23563 Background: Alveolar soft part sarcoma (ASPS) is a very rare sarcoma of uncertain histogenesis, first described in 1952 by Christopherson, then a fellow in surgical pathology, as a ‘malignant myoblastoma’ or ‘granular-cell myoblastoma’. It is histologically characterized by uniform, organoid cell nests arranged in an alveolar pattern, separated by fibrovascular septa containing sinusoidal vascular channels lined by flattened endothelium with characteristic intracytoplasmic rod-shaped crystals. It accounts for < 1% of all soft-tissue sarcomas and belongs to a newly defined category of ultra-rare. It is most commonly seen in patients 15-35 years of age, with a well-documented female predominance. It primarily affects the deep soft tissues of the lower limbs but can also involve the buttocks, trunk, internal organs, and head and neck regions. Initial course of ASPS may seem indolent, but the overall prognosis is poor, characterized by late metastases, which often occur ten years after diagnosis. Although refractory to conventional cytotoxic chemotherapy, recent reports have discussed the possible benefits of targeted therapy, such as antiangiogenic drugs and immune-stimulating therapy. This network meta-analysis (NMA) aims to systematically evaluate the comparative efficacy of various such pharmacotherapies. Methods: A systematic search of PubMed/ MEDLINE, Cochrane, EMBASE, Scopus, and ClinicalTrials.gov identified clinical trials that evaluated the efficacy of pharmacological interventions in ASPS up to October 2024. A frequentist network meta-analysis was conducted to compare treatments for Progression Free Survival (PFS) in ASPS using odds ratios (ORs) and 95% confidence intervals. Results: The analysis included 3 studies involving 156 patients, 10 pairwise comparisons, and 6 treatments. For PFS in ASPS, none of the treatments demonstrated a significant advantage compared to placebo. Cediranib (1.20, 0.34–4.21) and Cediranib followed by Sunitinib (1.20, 0.13–11.29) showed modest trends toward improved PFS but with wide confidence intervals. Crizotinib (0.46, 0.13–1.65), Sunitinib (0.72, 0.12–4.24), and Sunitinib followed by Cediranib (0.72, 0.09–5.85) indicated non-significant reductions in PFS. Heterogeneity was minimal (I² = 0%), with no inconsistency observed across designs. Conclusions: Cediranib and Cediranib followed by Sunitinib showed modest trends toward improved PFS, but wide confidence intervals limit certainty. Minimal heterogeneity (I² = 0%) and consistent study designs support the robustness of findings. In conclusion, this NMA showed no significant PFS benefit for any treatment compared to placebo. Future clinical trials with larger sample sizes need to be conducted to warrant better evaluation of these interventions in ASPS.