Bryce
PATIENT CASE
Stage IV Metastatic Prostate Cancer
We invite all scientists, researchers and medical professionals with intermediate to advanced experience to participate in Bryce's case. Research to the People's cases are Open Participation, Open Data and Open Results. Submitted analysis will be presented to Bryce and his medical team and will remain accessible through this site.
Bryce introduction and welcome video - December 2020
SUMMARY
Bryce is a 50-year-old Portland-based tech executive with Intel corporation, a single dad of a 12-year old girl, and an internationally known patient advocate for genomics guided precision medicine with deep connections in the industry. His story was recently profiled in Wired. He was diagnosed with advanced aggressive metastatic prostate cancer in 2014. In additional to a radical prostatectomy in 2014, a thoracic corpectomy and spinal fusion in 2020, and several stereotactic high beam radiation (SBRT) therapies, Bryce has burned through 7 lines of treatment over the last ~7 years including standard of care chemotherapy (Docetaxel), hormone therapy (Lupron, Eligard, and Abiraterone w/Prednisone), and a prostate cancer immunotherapy (Provenge) along with multiple clinical trial targeted therapies (PI3k Inhibitors, and cabozantinib w/atezolizumab that he is currently on). Bryce is probably one of the most genomic profiled prostate cancer patients on the planet, with multiple genomic cancer panel tests and other genomic research data from Tempus, Foundation Medicine, Guardant, TGEN, UCSD, and OHSU in Portland, Oregon that have profiled his blood, primary tumor and four metastatic bone metastases. Though his current clinical trial has kept new metastases from forming, it hasn’t stopped existing metastasis and he was close to suffering a spinal cord compression this summer before intervening with emergency spinal surgery. It is inevitable that his current clinical trial will stop working and his next steps are unclear.
We have a golden opportunity to bring together experts that can combine Bryce’s data with other patient / research data to potentially find new patterns and insights in that data, and ideally a breakthrough therapy for him. We will look for the best IO/vaccine/experimental options to pursue which can be repositioned (ie off label for prostate cancer) or given to him as an N of 1 therapy. We are exploring other targeted + IO therapies, other early phase clinical trial drugs, off label standard of care drugs, experimental combinations, and potentially novel drug development. His primary oncologist is Dr. Rana McKay at UCSD.
STRUCTURE
BIOINFORMATICS
CLINICAL
GOALS
The following approaches have been proposed for Bryce. Our goal is to provide insight and analysis on which path(s) will be most effective.
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PSMA radiopharmaceutical (ie Lu-177) or potentially PSMA bispecific T-cell engager (new PSMA PET scan currently being ordered to highlight current PSMA+ disease.
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EZH2 inhibitor w/ anti-CTLA4: (Wanting to see where Bryce’s cancer DNA/RNA levels sit relative to other metastatic prostate cancer patients on clinically relevant Neuroendocrine4/Rb functional signature.)
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PI3k/AKT/MTOR inhibitor with AR inhibition (Wanting to see where Bryce’s cancer DNA/RNA levels sit relative to other metastatic prostate cancer patients on clinically relevant Pi3k-AKT pathway alterations, PTEN Loss and Pi3k pathway activation. Also of strong interest is determining which Pi3k/AKT/Mtor inhibitors and AR inhibitors to best select based on his tumor genomics and other insights from Roche perhaps.)
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Other potential targeted drugs or chemotherapies (ie A. FGFR inhibitor if FGFR pathway activation or low AR or low RB signature, B. Carboplatin if 2 of 3 tumor suppressor genes RB, TP53 or PTEN loss, FANC alterations, HRD signature or Basal signature, C. CDK4/6/9 inhibitors if amplification of those genes in the absence of Rb/CDKN1b loss.
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Other potential immuno-oncology approaches: A. Nivo-Ipi if Bryce is MSI-H, TMB-high or with CDK12 mutations and has high immune/T-effector. B. If through tumor bone marrow aspirates or some other technique we can recapitulate the tumor microenvironment and use that as guide.
DATA
Data Available:
xT sequencing + RNA sequencing + PD-L1 IHC from August 2020
xF sequencing from July 2020
xT sequencing from September 2019
PD-L1 and MMR IHC only from May 2019
File Types Available:
(The data will be accompanied with a manifest and data dictionary for each file type/table.)
Sequencing files:
FastQ
BAM
VCF (for DNA)
Fusions/Structural variants (CSVs from DNA and RNA)
Tabular data:
Copy number variants
RNA Expression
Tumor immune infiltration (Composition of immune cell types present in the tumor predicted from RNA)
Predicted neoepitopes (from DNA and RNA, if available)
Tumor mutational burden scores (this will match what is on your reports)
MSI statuses (these will also exactly match what is on your reports)
High-Res Images (Whole slide scans):
H&E
PD-L1
MMR Stains (MLH1, MSH2, MSH6, PMS2)
TIMELINE & AGENDA
Bryce's case is launching December 2020 and will be an ongoing effort.
Pre-Launch
December 23rd @ 9am PST
Opening meeting for invited partners and collaborators
Watch the pre-launch video: research2people.org/bryce-launch-video
Data Generation Meeting
December 29th @9am PST
Note: This meeting was more of a group discussion than Data Generation focused (Recorded)
Watch: (Coming)
COMMUNICATIONS
Communications for this case will be hosted on Slack. Slack is the fastest way to reach anyone associated with organizing or partnering on this case. The following Slack channels have been created and more to come:
PEOPLE
Over 100 people have already been involved in consulting, organizing, connecting and promoting Bryce's case! We're working on representing all contributors and partners below.
