Clinical implication of genetic intratumor heterogeneity for targeted therapy in head and neck cancer.

Autor: Gram SB; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Alosi D; Center for Genomic Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Bagger FO; Center for Genomic Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Østrup O; Center for Genomic Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., von Buchwald C; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Friborg J; Department of Oncology, Section of Radiotherapy, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Wessel I; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Vogelius IR; Department of Oncology, Section of Radiotherapy, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Rohrberg K; Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Rasmussen JH; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Acta oncologica (Stockholm, Sweden) [Acta Oncol] 2023 Dec; Vol. 62 (12), pp. 1831-1839. Date of Electronic Publication: 2023 Nov 25.
DOI: 10.1080/0284186X.2023.2272293
Abstrakt: Background: Genomic profiling is increasingly used both in therapeutic decision-making and as inclusion criteria for trials testing targeted therapies. However, the mutational landscape may vary across different areas of a tumor and intratumor heterogeneity will challenge treatments or clinical decisions based on single tumor biopsies. The purpose of this study was to assess the clinical relevance of genetic intratumor heterogeneity in head and neck squamous cell carcinomas (HNSCC) using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT).
Materials and Methods: This prospective study included 33 whole tumor specimens from 28 patients with primary or recurrent HNSCC referred for surgery. Three tumor blocks were selected from central, semi-peripheral, and peripheral positions, mimicking biopsies in three different locations. Genetic analysis of somatic copy number alterations (SCNAs) was performed on the three biopsies using Oncoscan, focusing on 45 preselected HNSCC genes of interest. Clinical relevance was assessed using the ESCAT score to investigate whether and how treatment decisions would change based on the three biopsies from the same tumor.
Results: The SCNAs identified among 45 preselected genes within the three tumor biopsies derived from the same tumor revealed distinct variations. The detected discrepancies could potentially influence treatment approaches or clinical decisions in 36% of the patients if only one tumor biopsy was used. Recurrent tumors exhibited significantly higher variation in SCNAs than primary tumors ( p  = .024). No significant correlation between tumor size and heterogeneity ( p  = .7) was observed.
Conclusion: In 36% of patients diagnosed with HNSCC, clinically significant intratumor heterogeneity was observed which may have implications for patient management. This finding substantiates the need for future studies that specifically investigate the clinical implications associated with intratumor heterogeneity.
Databáze: MEDLINE
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