title: Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers.
abstract: 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.The Oncologist2017;22:152-157Implications for Practice: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.
authors.affiliation: Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Weinberg
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Gowen
authors.affiliation: Department of Pathology, University of California Irvine, Orange, California, USA.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California, USA.
authors.forename: Sai-Hong Ignatius
authors.initials: SI
authors.lastname: Ou
authors.affiliation: Division of Gynecologic Oncology, University of California Irvine, Orange, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bristow
authors.affiliation: Division of Gynecologic Oncology, University of California Irvine, Orange, California, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Krill
authors.affiliation: Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, D.C., USA.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Almira-Suarez
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts, USA.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Foundation Medicine Inc, Cambridge, Massachusetts, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Liu
authors.affiliation: The Angeles Clinic and Research Institute, Los Angeles, California, USA sklempner@theangelesclinic.org.|Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Klempner
mesh_terms: D000368:Aged; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology; D012008:Recurrence
keywords: Genomic profiling; Metastatic; NSCLC; Next‐generation sequencing; Recurrence; Second primary