Weinberg Benjamin A, Gowen Kyle, Lee Thomas K, Ou Sai-Hong Ignatius, Bristow Robert, Krill Lauren, Almira-Suarez M Isabel, Ali Siraj M, Miller Vincent A, Liu Stephen V, Klempner Samuel J
Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA.
Foundation Medicine Inc, Cambridge, Massachusetts, USA.
Oncologist. 2017 Feb;22(2):152-157. doi: 10.1634/theoncologist.2015-0511. Epub 2017 Feb 13.
Metastatic recurrence after treatment for locoregional cancer is a major cause of morbidity and cancer-specific mortality. Distinguishing metastatic recurrence from the development of a second primary cancer has important prognostic and therapeutic value and represents a difficult clinical scenario. Advances beyond histopathological comparison are needed. We sought to interrogate the ability of comprehensive genomic profiling (CGP) to aid in distinguishing between these clinical scenarios.
We identified three prospective cases of recurrent tumors in patients previously treated for localized cancers in which histologic analyses suggested subsequent development of a distinct second primary. Paired samples from the original primary and recurrent tumor were subjected to hybrid capture next-generation sequencing-based CGP to identify base pair substitutions, insertions, deletions, copy number alterations (CNA), and chromosomal rearrangements. Genomic profiles between paired samples were compared using previously established statistical clonality assessment software to gauge relatedness beyond global CGP similarities.
A high degree of similarity was observed among genomic profiles from morphologically distinct primary and recurrent tumors. Genomic information suggested reclassification as recurrent metastatic disease, and patients received therapy for metastatic disease based on the molecular determination.
Our cases demonstrate an important adjunct role for CGP technologies in separating metastatic recurrence from development of a second primary cancer. Larger series are needed to confirm our observations, but comparative CGP may be considered in patients for whom distinguishing metastatic recurrence from a second primary would alter the therapeutic approach. 2017;22:152-157 Distinguishing a metastatic recurrence from a second primary cancer can represent a difficult clinicopathologic problem but has important prognostic and therapeutic implications. Approaches to aid histologic analysis may improve clinician and pathologist confidence in this increasingly common clinical scenario. Our series provides early support for incorporating paired comprehensive genomic profiling in clinical situations in which determination of metastatic recurrence versus a distinct second primary cancer would influence patient management.
局部区域性癌症治疗后的转移性复发是发病和癌症特异性死亡的主要原因。区分转移性复发与第二原发性癌症的发生具有重要的预后和治疗价值，且是一个困难的临床情况。需要超越组织病理学比较的进展。我们试图探究综合基因组分析（CGP）在区分这些临床情况方面的能力。
我们确定了3例先前接受局部癌症治疗的患者复发性肿瘤的前瞻性病例，其中组织学分析提示随后出现了一种不同的第二原发性肿瘤。对来自原始原发性肿瘤和复发性肿瘤的配对样本进行基于杂交捕获二代测序的CGP，以识别碱基对替换、插入、缺失、拷贝数改变（CNA）和染色体重排。使用先前建立的统计克隆性评估软件比较配对样本之间的基因组图谱，以评估超越整体CGP相似性的相关性。
在形态学上不同的原发性肿瘤和复发性肿瘤的基因组图谱之间观察到高度相似性。基因组信息提示重新分类为复发性转移性疾病，患者基于分子测定接受了转移性疾病的治疗。
我们的病例证明了CGP技术在区分转移性复发与第二原发性癌症发生方面的重要辅助作用。需要更大规模的系列研究来证实我们的观察结果，但对于区分转移性复发与第二原发性癌症会改变治疗方法的患者，可考虑进行比较性CGP。2017；22：152 - 157 区分转移性复发与第二原发性癌症可能是一个困难的临床病理问题，但具有重要的预后和治疗意义。辅助组织学分析的方法可能会提高临床医生和病理学家在这种日益常见的临床情况下的信心。我们的系列研究为在确定转移性复发与明显的第二原发性癌症会影响患者管理的临床情况下纳入配对综合基因组分析提供了早期支持。
