背景：基因组分析越来越多地用于治疗决策和靶向治疗试验的纳入标准。然而，肿瘤不同区域的突变情况可能有所不同，肿瘤内异质性将挑战基于单个肿瘤活检的治疗或临床决策。本研究的目的是使用 ESMO 分子靶标临床可操作性量表 (ESCAT) 评估头颈鳞状细胞癌 (HNSCC) 肿瘤内遗传异质性的临床相关性。 材料和方法：这项前瞻性研究包括 33 个完整肿瘤标本取自 28 名转诊接受手术的原发性或复发性 HNSCC 患者。从中央、半周边和周边位置选择三个肿瘤块，模拟三个不同位置的活检。使用 Oncoscan 对三个活检组织进行体细胞拷贝数改变 (SCNA) 的遗传分析，重点关注 45 个预选的感兴趣的 HNSCC 基因。使用 ESCAT 评分评估临床相关性，以调查治疗决策是否以及如何根据来自同一肿瘤的三个活检进行改变。结果：在来自同一肿瘤的三个肿瘤活检中的 45 个预选基因中识别出的 SCNA 显示出明显的变化。如果仅使用一次肿瘤活检，检测到的差异可能会影响 36% 患者的治疗方法或临床决策。复发性肿瘤的 SCNA 变异显着高于原发性肿瘤 (p = .024)。未观察到肿瘤大小和异质性之间存在显着相关性 (p = .7)。结论：在 36% 诊断为 HNSCC 的患者中，观察到临床上显着的肿瘤内异质性，这可能对患者管理具有影响。这一发现证实了未来研究的必要性，专门调查与肿瘤内异质性相关的临床意义。

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.