ArticleESMO open2025
Impact of whole genome sequencing on the care pathway for patients with cancer of unknown primary.
Article in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with metastatic disease and no identifiable primary tumor, thus diagnosed with cancer of unknown primary (CUP), typically have a poor prognosis. Tumor DNA sequencing has recently shown promise in identifying the molecular tissue of origin. This study evaluated the value of whole genome sequencing (WGS) in the CUP care pathway, by comparing patient outcomes with a historical control cohort. Also, the value of whole transcriptome sequencing (WTS) was explored. PATIENTS AND
methodsA prospective intervention cohort was established of provisional CUP patients (≥18 years of age) who had WGS carried out on metastatic tissue between August 2021 and August 2023. A control cohort was established of CUP patients (≥18 years of age) diagnosed between December 2016 and April 2021 without the availability of WGS. The CUP predicting algorithm was applied to WGS data, and data on definitive diagnosis, molecular actionable alterations [ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) tier 1-3], therapy, diagnostic timelines, and overall survival (OS) were captured.
resultsA total of 159 provisional CUP patients (n = 54 intervention cohort, n = 105 control cohort) were included. WGS and WTS were successfully carried out in 46 (85%) and 27 patients (50%). A primary tumor diagnosis was established in 76% of the intervention cohort compared with 16% of the control cohort (P < 0.001). WGS contributed to a primary tumor diagnosis in 34 patients (63%) and identified an actionable alteration in 34 patients (63%). WTS contributed to a primary tumor diagnosis in three patients (6%). Following WGS, treatment recommendations could be made for 38 patients (70%), of whom 22 started the recommended therapies (58%). The median OS was 11 and 9 months in the intervention and control cohorts, respectively (P = 0.345).
conclusionIncorporation of WGS into the CUP care pathway is of significant value for diagnosing a primary tumor of origin and contributed to the identification of actionable alterations in the majority of patients.
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