Soft Tissue Sarcoma: Is Molecular Profiling Worth It?
"Unlocking the potential of NGS in personalized sarcoma treatment."
Over the last few decades, cancer treatments have improved significantly, leading to better outcomes for many patients. Discoveries in chemotherapy and the development of multimodal therapies have dramatically increased cure rates for childhood cancers. Similarly, survival rates for testicular and breast cancer have also seen substantial improvements.
Unfortunately, progress in treating soft-tissue sarcomas (STS) has been slow. These rare tumors, which include over 70 different subtypes, present unique challenges. STS affects both children and adults, with 5% of cases occurring in those under 20, and 30% in those over 75 years old.
Many STS subtypes have unique oncogenesis mechanisms, making them potentially responsive to targeted systemic treatments. Identifying new therapies for STS patients is crucial, as 40% to 50% of patients develop metastatic disease. Once metastasis occurs, treatment options are limited, primarily involving palliative chemotherapy with a median survival of only 12 to 20 months.
Targeting Sarcomas with Next-Generation Sequencing
While whole-genome sequencing is valuable for discovery-based research, targeted gene panel sequencing is a cost-effective approach for identifying targetable alterations in cancer patients. By focusing on specific genes or regions, sequencing can be performed at a much higher depth than with whole-genome or whole-exome approaches.
- Level 1: Alterations associated with approved anti-cancer drugs in sarcomas.
- Level 2: Standard care biomarker predictive of response to drugs not approved for sarcoma management.
- Level 3: Alterations associated with compelling clinical evidence of predictive value, but neither biomarker nor drug is standard of care.
- Level 4: Alterations associated with compelling biological evidence, but neither biomarker nor drug is standard of care.
The Future of Sarcoma Treatment: NGS and Personalized Medicine
The MULTISARC trial, launched in early 2018, aims to demonstrate that NGS implementation can improve overall survival in advanced STS patients. This prospective randomized study randomizes patients with advanced STS to either NGS-informed management or conventional treatment. The trial integrates comprehensive clinical and molecular data, creating a unique resource for the scientific community.
Recent years have seen rapid advancements in sequencing technology, enabling quick and efficient tumor tissue analysis to identify actionable mutations and provide personalized therapies. Studies have shown promise, and it is believed that this technology will become even more beneficial in the future.
High-quality randomized trials and prospective studies are necessary to provide level I evidence supporting NGS implementation in the routine management of advanced STS. As technology advances and more data becomes available, personalized treatment strategies based on molecular profiling hold the potential to significantly improve outcomes for sarcoma patients.