The Exceptional Responders Initiative: Feasibility of a National Cancer Institute Pilot Study.

Autor:	Conley BA; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Staudt L; Center for Cancer Genomics, National Cancer Institute, Bethesda, MD, USA., Takebe N; Developmental Therapeutics Clinic, National Cancer Institute, Bethesda, MD, USA., Wheeler DA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Wang L; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Cardenas MF; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Korchina V; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA., Zenklusen JC; Center for Cancer Genomics, National Cancer Institute, Bethesda, MD, USA., McShane LM; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Tricoli JV; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Williams PM; Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Lubensky I; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., O'Sullivan-Coyne G; Developmental Therapeutics Clinic, National Cancer Institute, Bethesda, MD, USA., Kohn E; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Little RF; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., White J; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Malik S; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Harris LN; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Mann B; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Weil C; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Tarnuzzer R; Center for Cancer Genomics, National Cancer Institute, Bethesda, MD, USA., Karlovich C; Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Rodgers B; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Shankar L; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Jacobs PM; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Nolan T; Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Berryman SM; Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Gastier-Foster J; Nationwide Children's Hospital, Columbus, OH, USA; Van Andel Research Institute, Grand Rapids, MI, USA., Bowen J; Nationwide Children's Hospital, Columbus, OH, USA; Van Andel Research Institute, Grand Rapids, MI, USA., Leraas K; Nationwide Children's Hospital, Columbus, OH, USA; Van Andel Research Institute, Grand Rapids, MI, USA., Shen H; Van Andel Research Institute, Grand Rapids, MI, USA., Laird PW; Van Andel Research Institute, Grand Rapids, MI, USA., Esteller M; Josep Carreras Leukaemia Research Institute, Badalona, Barcelona, Catalonia, Spain., Miller V; Foundation Medicine Inc, Cambridge, MA, USA., Johnson A; Foundation Medicine Inc, Cambridge, MA, USA., Edmondson EF; Pathology and Histology Laboratory, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Giordano TJ; Department of Pathology, University of Michigan, Ann Arbor, MI, USA., Kim B; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA., Ivy SP; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2021 Jan 04; Vol. 113 (1), pp. 27-37.
DOI:	10.1093/jnci/djaa061
Abstrakt:	Background: Tumor molecular profiling from patients experiencing exceptional responses to systemic therapy may provide insights into cancer biology and improve treatment tailoring. This pilot study evaluates the feasibility of identifying exceptional responders retrospectively, obtaining pre-exceptional response treatment tumor tissues, and analyzing them with state-of-the-art molecular analysis tools to identify potential molecular explanations for responses. Methods: Exceptional response was defined as partial (PR) or complete (CR) response to a systemic treatment with population PR or CR rate less than 10% or an unusually long response (eg, duration >3 times published median). Cases proposed by patients' clinicians were reviewed by clinical and translational experts. Tumor and normal tissue (if possible) were profiled with whole exome sequencing and, if possible, targeted deep sequencing, RNA sequencing, methylation arrays, and immunohistochemistry. Potential germline mutations were tracked for relevance to disease. Results: Cases reflected a variety of tumors and standard and investigational treatments. Of 520 cases, 476 (91.5%) were accepted for further review, and 222 of 476 (46.6%) proposed cases met requirements as exceptional responders. Clinical data were obtained from 168 of 222 cases (75.7%). Tumor was provided from 130 of 168 cases (77.4%). Of 117 of the 130 (90.0%) cases with sufficient nucleic acids, 109 (93.2%) were successfully analyzed; 6 patients had potentially actionable germline mutations. Conclusion: Exceptional responses occur with standard and investigational treatment. Retrospective identification of exceptional responders, accessioning, and sequencing of pretreatment archived tissue is feasible. Data from molecular analyses of tumors, particularly when combining results from patients who received similar treatments, may elucidate molecular bases for exceptional responses. (Published by Oxford University Press 2020. This work is written by US Government employees and is in the public domain in the US.)
Databáze:	MEDLINE
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