Implementing precision oncology for sarcoma patients: the CCCLMUmolecular tumor board experience

Abstract

Purpose Due to poor outcomes and limited treatment options, patients with advanced bone and soft tissue sarcomas (BS/STS) may undergo comprehensive molecular profiling of tumor samples to identify possible therapeutic targets. The aim of this study was to determine the impact of routine molecular profiling in the setting of a dedicated precision oncology program in patients with BS/STS in a German large-volume sarcoma center. Methods 92 BS/STS patients who received comprehensive genomic profiling (CGP) and were subsequently discussed in our molecular tumor board (MTB) between 2016 and 2022 were included. Patient records were retrospectively reviewed, and the clinical impact of NGS-related findings was analyzed. Results 89.1% of patients had received at least one treatment line before NGS testing. At least one molecular alteration was found in 71 patients (82.6%). The most common alterations were mutations in TP53 (23.3% of patients), followed by PIK3CA and MDM2 mutations (9.3% each). Druggable alterations were identified, and treatment recommended in 32 patients (37.2%). Of those patients with actionable alterations, ten patients (31.2%) received personalized treatment and six patients did benefit from molecular-based therapy in terms of a progression-free survival ratio (PFSr) > 1.3. Conclusion Our single-center experience shows an increasing uptake of next-generation sequencing (NGS) and highlights current challenges of implementing precision oncology in the management of patients with BS/STS. A relevant number of patients were diagnosed with clinically actionable alterations. Our results highlight the potential benefit of NGS in patients with rare cancers and currently limited therapeutic options.

Current challenges and practical aspects of molecular pathology for bone and soft tissue tumors

“…Central to this collaboration is the multidisciplinary tumor board, where diverse specialists come together to discuss and design the optimal treatment plan for patients. Molecular pathologists play a pivotal role in these boards, as their detailed molecular insights can dictate the direction of treatment [ 38 ]. For instance, if a molecular pathologist identifies a specific genetic mutation that makes a particular sarcoma subtype responsive to a targeted therapy, this information must be communicated in an accessible and understandable manner.…”

Palbociclib in Patients With Soft Tissue Sarcoma With CDK4 Amplifications: Results From the Targeted Agent and Profiling Utilization Registry Study

“…2 However, because of the rare nature, and pathologic and molecular heterogeneity of STS, determining the optimal treatment strategy is challenging and depends on an accurate pathologic diagnosis that may be supported by tumor genomic profiling. 3,4 Approximately 25%-30% of STS contain alterations in genes regulating cell cycle progression. 5,6 Alterations in cyclin-dependent kinase 4 (CDK4), a kinase that regulates cell cycle progression, have been reported in up to 12% of sarcomas.…”