Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Center for Genomic Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Acta Oncol. 2023 Dec;62(12):1831-1839. doi: 10.1080/0284186X.2023.2272293. Epub 2023 Nov 25.
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).
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.
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 ( = .024). No significant correlation between tumor size and heterogeneity ( = .7) was observed.
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.
基因组分析越来越多地用于治疗决策和作为靶向治疗试验的纳入标准。然而，肿瘤的不同区域的突变景观可能不同，肿瘤内异质性将挑战基于单一肿瘤活检的治疗或临床决策。本研究的目的是使用 ESMO 分子靶向治疗临床可操作性量表（ESCAT）评估头颈部鳞状细胞癌（HNSCC）中遗传肿瘤内异质性的临床相关性。
这项前瞻性研究纳入了 28 例原发性或复发性 HNSCC 患者的 33 个全肿瘤标本，这些患者被转诊接受手术治疗。从中央、半外围和外围位置选择了三个肿瘤块，模拟了三个不同位置的活检。使用 Oncoscan 对三个活检进行体细胞拷贝数改变（SCNAs）的基因分析，重点关注 45 个预先选择的 HNSCC 相关基因。使用 ESCAT 评分评估临床相关性，以研究是否以及如何根据同一肿瘤的三个活检来改变治疗决策。
在来自同一肿瘤的三个肿瘤活检中鉴定出的 45 个预先选择基因中的 SCNAs 显示出明显的变化。如果只使用一个肿瘤活检，这些检测到的差异可能会影响 36%的患者的治疗方法或临床决策。复发性肿瘤的 SCNAs 变化明显高于原发性肿瘤（ = .024）。肿瘤大小与异质性之间无显著相关性（ = .7）。
在 36%的诊断为 HNSCC 的患者中，观察到具有临床意义的肿瘤内异质性，这可能对患者管理产生影响。这一发现证实了未来需要专门研究与肿瘤内异质性相关的临床意义的研究。
