Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Conley BA

PROVIDER: S-EPMC7781457 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Conley Barbara A BA Staudt Lou L Takebe Naoko N Wheeler David A DA Wang Linghua L Cardenas Maria F MF Korchina Viktoriya V Zenklusen Jean Claude JC McShane Lisa M LM Tricoli James V JV Williams Paul M PM Lubensky Irina I O'Sullivan-Coyne Geraldine G Kohn Elise E Little Richard F RF White Jeffrey J Malik Shakun S Harris Lyndsay N LN Mann Bhupinder B Weil Carol C Tarnuzzer Roy R Karlovich Chris C Rodgers Brian B Shankar Lalitha L Jacobs Paula M PM Nolan Tracy T Berryman Sean M SM Gastier-Foster Julie J Bowen Jay J Leraas Kristen K Shen Hui H Laird Peter W PW Esteller Manel M Miller Vincent V Johnson Adrienne A Edmondson Elijah F EF Giordano Thomas J TJ Kim Benjamin B Ivy S Percy SP

Journal of the National Cancer Institute 20210101 1

<h4>Background</h4>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.<h4>Methods</h4>Exceptional r ...[more]

PMID: 32339229

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Project description:ObjectiveTo evaluate the extent to which the inter-institutional, inter-disciplinary mobilisation of data and skills in the Farr Institute contributed to establishing the emerging field of data science for health in the UK.Design and outcome measuresWe evaluated evidence of six domains characterising a new field of science:defining central scientific challenges,demonstrating how the central challenges might be solved,creating novel interactions among groups of scientists,training new types of experts,re-organising universities,demonstrating impacts in society.We carried out citation, network and time trend analyses of publications, and a narrative review of infrastructure, methods and tools.SettingFour UK centres in London, North England, Scotland and Wales (23 university partners), 2013-2018.Results1. The Farr Institute helped define a central scientific challenge publishing a research corpus, demonstrating insights from electronic health record (EHR) and administrative data at each stage of the translational cycle in 593 papers with at least one Farr Institute author affiliation on PubMed. 2. The Farr Institute offered some demonstrations of how these scientific challenges might be solved: it established the first four ISO27001 certified trusted research environments in the UK, and approved more than 1000 research users, published on 102 unique EHR and administrative data sources, although there was no clear evidence of an increase in novel, sustained record linkages. The Farr Institute established open platforms for the EHR phenotyping algorithms and validations (>70 diseases, CALIBER). Sample sizes showed some evidence of increase but remained less than 10% of the UK population in primary care-hospital care linked studies. 3.The Farr Institute created novel interactions among researchers: the co-author publication network expanded from 944 unique co-authors (based on 67 publications in the first 30 months) to 3839 unique co-authors (545 papers in the final 30 months). 4. Training expanded substantially with 3 new masters courses, training >400 people at masters, short-course and leadership level and 48 PhD students. 5. Universities reorganised with 4/5 Centres established 27 new faculty (tenured) positions, 3 new university institutes. 6. Emerging evidence of impacts included: > 3200 citations for the 10 most cited papers and Farr research informed eight practice-changing clinical guidelines and policies relevant to the health of millions of UK citizens.ConclusionThe Farr Institute played a major role in establishing and growing the field of data science for health in the UK, with some initial evidence of benefits for health and healthcare. The Farr Institute has now expanded into Health Data Research (HDR) UK but key challenges remain including, how to network such activities internationally.

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Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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