‘Precision oncology’ can ensure the best suitable treatment at the right time by tailoring treatment towards individual patient and comprehensive tumour characteristics. In current molecular pathology, diagnostic tests which are part of the standard of care (SOC) only cover a limited part of the spectrum of genomic changes, and often are performed in an iterative way. This occurs at the expense of valuable patient time, available tissue sample, and interferes with ‘first time right’ treatment decisions. Whole Genome Sequencing (WGS) captures a near complete view of genomic characteristics of a tumour in a single test. Moreover, WGS facilitates faster implementation of new treatment relevant biomarkers. At present, WGS mainly has been applied in study settings, but its performance in a routine diagnostic setting remains to be evaluated. The WIDE study aims to investigate the feasibility and validity of WGS-based diagnostics in clinical practice. 1200 consecutive patients in a single comprehensive cancer centre with (suspicion of) a metastasized solid tumour will be enrolled with the intention to analyse tumour tissue with WGS, in parallel to SOC diagnostics. Primary endpoints are (1) feasibility of implementation of WGS-based diagnostics into routine clinical care and (2) clinical validation of WGS by comparing identification of treatment-relevant variants between WGS and SOC molecular diagnostics. Secondary endpoints entail (1) added clinical value in terms of additional treatment options and (2) cost-effectiveness of WGS compared to SOC diagnostics through a Health Technology Assessment (HTA) analysis. Furthermore, the (3) perceived impact of WGS-based diagnostics on clinical decision making will be evaluated through questionnaires. The number of patients included in (experimental) therapies initiated based on SOC or WGS diagnostics will be reported with at least 3 months follow-up. The clinical efficacy is beyond the scope of WIDE. Key performance indicators will be evaluated after every 200 patients enrolled, and procedures optimized accordingly, to continuously improve the diagnostic performance of WGS in a routine clinical setting. WIDE will yield the optimal conditions under which WGS can be implemented in a routine molecular diagnostics setting and establish the position of WGS compared to SOC diagnostics in routine clinical care.

中文翻译：

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研究方案：全基因组测序在每位癌症患者的标准诊断中的实施（WIDE）


“精准肿瘤学”可以根据个体患者和综合肿瘤特征制定治疗方案，确保在正确的时间提供最合适的治疗。在当前的分子病理学中，作为护理标准（SOC）一部分的诊断测试仅涵盖基因组变化范围的有限部分，并且通常以迭代方式进行。这种情况的发生是以牺牲患者宝贵的时间和可用的组织样本为代价的，并且会干扰“一次正确”的治疗决策。全基因组测序 (WGS) 在一次测试中捕获了肿瘤基因组特征的近乎完整的视图。此外，WGS 有助于更快地实施新的治疗相关生物标志物。目前，WGS 主要应用于研究环境，但其在常规诊断环境中的表现仍有待评估。 WIDE 研究旨在调查基于 WGS 的诊断在临床实践中的可行性和有效性。单一综合癌症中心的 1200 名连续患有（疑似）实体瘤转移的患者将被纳入研究，目的是在 SOC 诊断的同时，利用 WGS 分析肿瘤组织。主要终点是 (1) 将基于 WGS 的诊断实施到常规临床护理中的可行性，以及 (2) 通过比较 WGS 和 SOC 分子诊断之间治疗相关变异的识别来对 WGS 进行临床验证。次要终点包括 (1) 在额外治疗选择方面增加临床价值，以及 (2) 通过健康技术评估 (HTA) 分析，与 SOC 诊断相比，WGS 的成本效益。此外，(3) 基于 WGS 的诊断对临床决策的感知影响将通过问卷进行评估。 根据 SOC 或 WGS 诊断启动（实验）治疗的患者人数将在至少 3 个月的随访后报告。临床疗效超出了WIDE的范围。每入组 200 名患者后将评估关键绩效指标，并相应优化流程，以不断提高全基因组测序在常规临床环境中的诊断性能。 WIDE 将产生在常规分子诊断环境中实施 WGS 的最佳条件，并确立 WGS 与 SOC 诊断相比在常规临床护理中的地位。