Multimodal Combination Treatment in a Patient-Centered Approach is Associated with Improved Outcome in...

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.

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.

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.

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.