Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 113, Issue 1, Pages 27-37Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djaa061
Keywords
-
Categories
Funding
- NCI, National Institutes of Health
- LEIDOS [HHSN261200800001E/17X184TO1]
- Nationwide Children's Hospital on LEIDOS [HHSN261200800001E/14X242TO1]
- NCI [HHSN261201700005I/TO1]
- IMS on NCI [HHSN26120150002B/TO10]
- University of Chicago (Genomic Data Center) [HHSN261200800001E/17X147TO2]
- [5U24CA143843]
Ask authors/readers for more resources
Tumor molecular profiling from exceptional responders to systemic therapy can provide insights into cancer biology. This pilot study evaluated the feasibility of identifying these responders retrospectively and analyzing their pre-treatment tumor tissues with molecular tools. Results suggest that standard and investigational treatments can lead to exceptional responses, with potential actionable targets identified in molecular analyses.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available