Background On the basis of historical data, patients with cancer of unknown primary (CUP) are generally assumed to have a dismal prognosis with overall survival of less than 1 year. Treatment is typically cytotoxic chemotherapy guided by histologic features and the pattern of metastatic spread. The purpose of this study was to provide a clinical and pathologic description of patients with CUP in the modern era, to define the frequency of clinically actionable molecular alterations in this population, to determine how molecular testing can alter therapeutic decisions, and to investigate novel uses of next-generation sequencing in the evaluation and treatment of patients with CUP. Patients and methods Under Institutional Review Board approval, we identified all CUP patients evaluated at our institution over a recent 2-year period. We documented demographic information, clinical outcomes, pathologic evaluations, next-generation sequencing of available tumor tissue, use of targeted therapies, and clinical trial enrollment. Results We identified 333 patients with a diagnosis of CUP evaluated at our institution from 1 January 2014 through 30 June 2016. Of these patients, 150 had targeted next-generation sequencing carried out on available tissue. Median overall survival in this cohort was 13 months. Forty-five of 150 (30%) patients had potentially targetable genomic alterations identified by tumor molecular profiling, and 15 of 150 (10%) received targeted therapies. Dominant mutation signatures were identified in 21 of 150 (14%), largely implicating exogenous mutagen exposures such as ultraviolet radiation and tobacco. Conclusions Patients with CUP represent a heterogeneous population, harboring a variety of potentially targetable alterations. Next-generation sequencing may provide an opportunity for CUP patients to benefit from novel personalized therapies.

中文翻译：

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现代未知原发性癌症患者的临床和分子特征。

背景 根据历史数据，原发性不明癌症 (CUP) 患者通常被认为预后不佳，总生存期不到 1 年。治疗通常是由组织学特征和转移扩散模式指导的细胞毒性化学疗法。本研究的目的是提供现代 CUP 患者的临床和病理学描述，确定该人群中临床可操作分子改变的频率，确定分子检测如何改变治疗决策，并研究新用途下一代测序在 CUP 患者评估和治疗中的应用 患者和方法 在机构审查委员会的批准下，我们确定了最近 2 年在我们机构评估的所有 CUP 患者。我们记录了人口统计信息、临床结果、病理学评估、可用肿瘤组织的下一代测序、靶向治疗的使用和临床试验登记。结果 我们确定了 2014 年 1 月 1 日至 2016 年 6 月 30 日期间在我们机构评估的 333 名诊断为 CUP 的患者。在这些患者中，150 名在可用组织上进行了靶向下一代测序。该队列的中位总生存期为 13 个月。150 名患者中有 45 名 (30%) 具有通过肿瘤分子分析确定的潜在可靶向基因组改变，150 名患者中有 15 名 (10%) 接受了靶向治疗。在 150 个中的 21 个 (14%) 中确定了显性突变特征，主要涉及外源性诱变剂暴露，例如紫外线辐射和烟草。结论 CUP 患者代表异质人群，具有多种潜在的靶向改变。下一代测序可能为 CUP 患者提供从新型个性化治疗中受益的机会。