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

TitleThe Exceptional Responders Initiative: Feasibility of a National Cancer Institute Pilot Study.
Publication TypeJournal Article
Year of Publication2021
AuthorsConley, BA, Staudt, L, Takebe, N, Wheeler, DA, Wang, L, Cardenas, MF, Korchina, V, Zenklusen, JClaude, McShane, LM, Tricoli, JV, Williams, PM, Lubensky, I, O'Sullivan-Coyne, G, Kohn, E, Little, RF, White, J, Malik, S, Harris, LN, Mann, B, Weil, C, Tarnuzzer, R, Karlovich, C, Rodgers, B, Shankar, L, Jacobs, PM, Nolan, T, Berryman, SM, Gastier-Foster, J, Bowen, J, Leraas, K, Shen, H, Laird, PW, Esteller, M, Miller, V, Johnson, A, Edmondson, EF, Giordano, TJ, Kim, B, S Ivy, P
JournalJ Natl Cancer Inst
Date Published2021 Jan 04
KeywordsAdult, Aged, Aged, 80 and over, Exome Sequencing, Feasibility Studies, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Mutation, National Cancer Institute (U.S.), Neoplasms, Pilot Projects, Precision Medicine, Retrospective Studies, Sequence Analysis, RNA, Transcriptome, United States

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.

Alternate JournalJ Natl Cancer Inst
PubMed ID32339229
PubMed Central IDPMC7781457
Grant ListU24 CA210969 / CA / NCI NIH HHS / United States
U24 CA264023 / CA / NCI NIH HHS / United States

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