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Whole Genome Sequencing Is Feasible in Clinical Practice

Findings from the WIDE study
19 Sep 2020
Translational research

Findings from the first 800 patients with biopsies that were assessed by clinical-grade whole genome sequencing (cWGS) revealed that cWGS had good turn-around times, a low error rate, and uncovered novel treatment options for many of these patients. Findings from the WIDE study (WGS Implementation in standard cancer Diagnostics for Every cancer patient) were reported by Kim Monkhorst of the Pathology Department, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital in Amsterdam, Netherlands at the ESMO Virtual Congress 2020.

Dr. Monkhorst and colleagues performed cWGS, as well as standard-of-care (SOC) molecular diagnostics using patient biopsy samples; the results of the cWGS and molecular diagnostics were compared and discussed in a dedicated tumour board. Initial discordances were further evaluated by additional tests.

The primary endpoints of this study were feasibility and clinical validity.

Whole-Genome-Sequencing-Is-Feasible-in-Clinical-Practice-1189O

Implementation of Whole genome sequencing in clinical practice. Primary endpoints: Feasibility (turnaround time), Clinical validation (concordance WGS and SOC molecular analysis); Secondary endpoints: Added clinical value, Health technology assessment.

© Kim Monkhorst.

The investigators performed cWGS in 570 of 867 biopsy procedures (66%), translating to a 71% success rate on patient level. Inability to obtain cWGS results was primarily due to an insufficient number (<20%) of tumour cells in the received biopsy (83%; 227/273). The median turn-around-time for cWGS was 14 days, which decreased incrementally as continuous improvements to the clinical procedure and cWGS pipeline were made.

A routine molecular diagnostic assay was performed in 402 of the 800 (50%) patients. This resulted in a total of 645 genomic biomarkers for clinical validation that were identified by SOC molecular diagnostics.

Error rates were low with both procedures, the respective error rates with cWGS and molecular diagnostics were 2.9% (19/645) and 0.9% (6/645). Most (19 of 20) of the biomarkers that were not reported by cWGS were present in the raw data but not reliably identified due to very low variant allele frequencies. Improvements to further increase the sensitivity are currently being implemented with an anticipated reduction of the cWGS error rate to 2%.

Clinically relevant actionable targets were detected by cWGS that were not detected by molecular diagnostics

Overall, cWGS identified a clinically actionable (routine practice and experimental) biomarker in 394/ 566 (70%) of all patients tested.

Compared to SOC molecular diagnostics, cWGS identified one or more additional treatment options in 203 of 402 (50%) patients. In addition, actionable variants were identified by cWGS in 80 of 160 (50%) patients that were not tested by SOC molecular diagnostics.

Conclusions

Based upon data from the first 800 patients in the WIDE study, the authors found that cWGS was clinically feasible in routine molecular diagnostics in a comprehensive cancer centre setting and has added value by providing additional treatment options for half of patients.

This study was sponsored by the Netherlands Organisation for Health Research and Care innovation (ZonMW) and Hartwig Medical Foundation.

Reference

1189O - Monkhorst K, Samsom K, Schipper L, et al. Validation of whole genome sequencing in routine clinical practice. ESMO Virtual Congress 2020.

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