Concurrent Circulating Tumor DNA and Tissue Genotyping—Ready for Prime Time?
Menée à l'aide de données cliniques et moléculaires portant sur 3 209 patients atteints d'une tumeur solide (âge médian au diagnostic : 65,3 ans), cette étude évalue l'intérêt, du point de vue du taux de détection de mutations, d'ajouter un séquençage ciblé de l'ADN tumoral circulant à un séquençage ciblé de l'ADN des tissus tumoraux
Molecularly directed targeted therapies have become a key component of caring for patients with metastatic solid tumors, both alongside and instead of conventional chemotherapy and immunotherapy. Treatment options for patients with advanced cancer have expanded dramatically over the past decade, with the development of a wide variety of targeted therapies for oncogene-addicted tumors and the demonstration of efficacy of immune checkpoint inhibitors for many cancer types. Cell-free circulating tumor DNA (ctDNA) is shed by tumor cells into the systemic circulation and, thanks to advancements in next-generation sequencing (NGS) technologies, affords the opportunity to noninvasively detect cancer-specific somatic variants. The use of ctDNA-based molecular genotyping for tumor profiling and identification of patients eligible for targeted therapies has been integrated into clinical practice for a variety of tumor types. The prime example of this is in non–small cell lung cancer (NSCLC), where identifying actionable variants via genomic profiling is essential to determining the appropriate standard of care for patients. The National Comprehensive Cancer Network recommends that all patients with metastatic NSCLC undergo molecular genotyping, and the European Society for Medical Oncology mandates testing for oncogenic drivers for which there are approved drugs. Earlier approaches supported by the International Association for the Study of Lung Cancer prioritized tissue-based NGS at time of diagnosis, with ctDNA-based molecular genotyping relegated to the identification of resistance variants after progression on targeted therapy. However, practical considerations, including faster resulting time, lower potential for sample inadequacy, and elimination of the need for invasive and, in some situations, prohibitively hazardous tissue sampling have led to the increased utilization of ctDNA molecular genotyping at diagnosis.
JAMA Network Open , éditorial, 2023