Jeffrey van Putten, Petur Snaebjornsson, Linda J.W. Bosch, Roelof Koster, Paul Roepman, Joseph Usset, Mirjam C. Boelens, Tom van Wezel, Efraim H. Rosenberg, Serena Marchetti, Marieke A. Vollebergh, Doenja M. J. Lambregts, Lizet E. van der Kolk, Edwin Cuppen, Hilde H. Nienhuis, Kim Monkhorst
Molecular testing is essential in precision oncology. Whole-genome sequencing (WGS) provides a tumor-agnostic solution for detecting an increasingly complex range of DNA-based biomarkers. Here we present real-world data from 888 patients to demonstrate the clinical utility of routine, paired tumor-normal WGS diagnostics for solid cancers in a comprehensive cancer center. WGS succeeded in 89% of cases with a median turnaround time of 6 working days. Potentially actionable biomarkers were identified in 73% of patients, including biomarkers for reimbursed (27%) and experimental (63%) therapies. Within 1 year, 40% and 19% of patients, respectively, started biomarker-informed treatment, which was associated with a 31% longer median overall survival (+96 days) compared with patients not receiving such therapy. Among patients without prior systemic therapy, biomarker-informed treatment yielded significantly longer overall survival (median not reached) than non-biomarker-informed therapy (427 days) or no systemic therapy (214 days). In cancers of unknown primary (n = 123), WGS contributed to diagnostic solution or detected biomarker-driven reimbursed treatment options in 67%, with 68% starting tumor-type-specific therapy. Clinically relevant pathogenic germline variants were identified in 6.5% of patients. Overall, WGS-based diagnostics had clinical consequences for 41% of tested patients, providing a versatile tool for routine clinical practice in solid oncology.