Multimodal Combination Treatment in a Patient-Centered Approach is Associated with Improved Outcome in Relapsed/Refractory Sarcomas in Children: A Comparative Single-Institution Real-World Analysis.

INTRODUCTION

Targeted treatment in children, especially with sarcomas, has limited utility due to small numbers of patients with driving mutations. Multimodal combination treatment and patient-centered approach combine treatment modalities administered based on comprehensive biological and empirical factors. Together, they extend precision oncology beyond a single molecular target.

METHODS

This is a single-institution real-world study of children and young adults diagnosed between 2004 and 2021, with relapsed/refractory and/or primary metastasizing high-risk solid tumors who underwent molecular tumor board. Patients underwent comprehensive biological examination of the tumor. A treatment recommendation was made subsequently combining empirical and biological data. All progressive/recurrent events during disease follow-up were analyzed using a hierarchical survival modeling approach combining individual patient time series in a meta-analytic framework for comparative analysis of treatment effects.

RESULTS

A total of 93 patients were included in the analysis who experienced 189 events. Overall survival was 7.5 years. A comparative analysis utilizing event-free survival (EFS) ratio was possible in an ultra-high-risk subset of 66 patients with relapsed/progressive disease. Effectiveness was demonstrated in the treatment of sarcomas by empirical treatment (HR 0.57, p = 0.005), which consisted mainly of orally administered cyclophosphamide, vinblastine, and celecoxib, and by sunitinib or pazopanib (HR = 0.66, p = 0.032) in biologically guided administration.

CONCLUSIONS

This study demonstrates that individualized treatment offers effective treatment options to a wide range of patients with high-risk cancers even for tumors without known high-level evidence molecular targets. We have shown that an alternative analytical approach based on the n-of-1-inspired framework is needed and applicable to demonstrate the effectiveness.