TY - JOUR
T1 - The exceptional responders initiative
T2 - Feasibility of a National Cancer Institute pilot study
AU - Conley, Barbara A.
AU - Staudt, Lou
AU - Takebe, Naoko
AU - Wheeler, David A.
AU - Wang, Linghua
AU - Cardenas, Maria F.
AU - Korchina, Viktoriya
AU - Zenklusen, Jean Claude
AU - McShane, Lisa M.
AU - Tricoli, James V.
AU - Williams, Paul M.
AU - Lubensky, Irina
AU - O’Sullivan-Coyne, Geraldine
AU - Kohn, Elise
AU - Little, Richard F.
AU - White, Jeffrey
AU - Malik, Shakun
AU - Harris, Lyndsay N.
AU - Mann, Bhupinder
AU - Weil, Carol
AU - Tarnuzzer, Roy
AU - Karlovich, Chris
AU - Rodgers, Brian
AU - Shankar, Lalitha
AU - Jacobs, Paula M.
AU - Nolan, Tracy
AU - Berryman, Sean M.
AU - Gastier-Foster, Julie
AU - Bowen, Jay
AU - Leraas, Kristen
AU - Shen, Hui
AU - Laird, Peter W.
AU - Esteller, Manel
AU - Miller, Vincent
AU - Johnson, Adrienne
AU - Edmondson, Elijah F.
AU - Giordano, Thomas J.
AU - Kim, Benjamin
AU - Percy Ivy, S.
N1 - Publisher Copyright:
© 2021 Oxford University Press. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
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U2 - 10.1093/JNCI/DJAA061
DO - 10.1093/JNCI/DJAA061
M3 - Article
C2 - 32339229
AN - SCOPUS:85099332282
SN - 0027-8874
VL - 113
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 1
M1 - DJAA061
ER -