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Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers.
Oncologist 2017; 22(2):152-157O

Abstract

BACKGROUND

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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 Oncologist 2017;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+Show Affiliations

Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA.Foundation Medicine Inc, Cambridge, Massachusetts, USA.Department of Pathology, University of California Irvine, Orange, California, USA.Division of Hematology-Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, California, USA.Division of Gynecologic Oncology, University of California Irvine, Orange, California, USA.Division of Gynecologic Oncology, University of California Irvine, Orange, California, USA.Department of Pathology, George Washington University School of Medicine and Health Sciences, Washington, D.C., USA.Foundation Medicine Inc, Cambridge, Massachusetts, USA.Foundation Medicine Inc, Cambridge, Massachusetts, USA.Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, D.C., USA.The Angeles Clinic and Research Institute, Los Angeles, California, USA sklempner@theangelesclinic.org. Cedars-Sinai Medical Center, Los Angeles, California, USA.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

28193735

Citation

Weinberg, Benjamin A., et al. "Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence From Second Primary Cancers." The Oncologist, vol. 22, no. 2, 2017, pp. 152-157.
Weinberg BA, Gowen K, Lee TK, et al. Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers. Oncologist. 2017;22(2):152-157.
Weinberg, B. A., Gowen, K., Lee, T. K., Ou, S. I., Bristow, R., Krill, L., ... Klempner, S. J. (2017). Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers. The Oncologist, 22(2), pp. 152-157. doi:10.1634/theoncologist.2015-0511.
Weinberg BA, et al. Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence From Second Primary Cancers. Oncologist. 2017;22(2):152-157. PubMed PMID: 28193735.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comprehensive Genomic Profiling Aids in Distinguishing Metastatic Recurrence from Second Primary Cancers. AU - Weinberg,Benjamin A, AU - Gowen,Kyle, AU - Lee,Thomas K, AU - Ou,Sai-Hong Ignatius, AU - Bristow,Robert, AU - Krill,Lauren, AU - Almira-Suarez,M Isabel, AU - Ali,Siraj M, AU - Miller,Vincent A, AU - Liu,Stephen V, AU - Klempner,Samuel J, Y1 - 2017/02/13/ PY - 2015/12/14/received PY - 2016/09/19/accepted PY - 2017/2/15/pubmed PY - 2018/1/30/medline PY - 2017/2/15/entrez KW - Genomic profiling KW - Metastatic KW - NSCLC KW - Next‐generation sequencing KW - Recurrence KW - Second primary SP - 152 EP - 157 JF - The oncologist JO - Oncologist VL - 22 IS - 2 N2 - BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 Oncologist 2017;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. SN - 1549-490X UR - https://www.unboundmedicine.com/medline/citation/28193735/Comprehensive_Genomic_Profiling_Aids_in_Distinguishing_Metastatic_Recurrence_from_Second_Primary_Cancers_ L2 - https://doi.org/10.1634/theoncologist.2015-0511 DB - PRIME DP - Unbound Medicine ER -