The Exceptional Responders Initiative: Feasibility of a National Cancer Institute Pilot Study
| Autor: | Maria F. Cardenas, Kristen M. Leraas, Lalitha K. Shankar, Adrienne Johnson, Benjamin Kim, Jean C. Zenklusen, Thomas J. Giordano, Vincent A. Miller, Julie M. Gastier-Foster, Linghua Wang, Paula M. Jacobs, Brian Rodgers, Irina A. Lubensky, Tracy S. Nolan, Elise C. Kohn, Bhupinder Singh Mann, Richard F. Little, Shakun Malik, Elijah F. Edmondson, Viktoriya Korchina, Lou Staudt, Barbara A. Conley, Manel Esteller, Hui Shen, James V. Tricoli, Sean M Berryman, Carol J. Weil, Geraldine O'Sullivan-Coyne, Jay Bowen, David A. Wheeler, S. Percy Ivy, Lyndsay Harris, Naoko Takebe, Roy Tarnuzzer, Jeffrey White, Paul Williams, Lisa M. McShane, Peter W. Laird, Chris Karlovich |
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| Rok vydání: | 2020 |
| Předmět: |
Oncology
0303 health sciences Cancer Research medicine.medical_specialty education.field_of_study business.industry Population MEDLINE Exceptional Response Disease Systemic therapy Deep sequencing 03 medical and health sciences 0302 clinical medicine Germline mutation 030220 oncology & carcinogenesis Internal medicine medicine education business Exome sequencing 030304 developmental biology |
| Zdroj: | JNCI: Journal of the National Cancer Institute. 113:27-37 |
| ISSN: | 1460-2105 0027-8874 |
| DOI: | 10.1093/jnci/djaa061 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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