The Duke Molecular Tumor Board (DMTB) is a collaboration between the Duke Pathology Department and the Duke Cancer Institute (DCI). It was developed to foster precision medicine within the DCI. The goal of this effort is to match the most effective and safest therapy to each patient in real-time.
The field of precision cancer medicine is rapidly evolving, with an ever-growing list of targeted therapies approved for use in advanced cancer patients harboring specific genetic alterations. The Molecular Tumor Board is a robust and rapidly expanding clinical tumor sequencing program, which offers our patients the highest quality and most comprehensive genomic profiling test available.
In addition, the Duke Molecular Tumor Board provides molecular decision-making support to advance biomarker-based clinical research and to foster precision cancer medicine within the Duke Cancer Institute. Its members meet weekly and include a diverse group of pathologists, oncologists, scientists, medical geneticists, and clinical trial teams.
The Duke Molecular Tumor Board analyzes the results of clinical next-generation sequencing (NGS) tests and shares its insights with the patient’s care team. Discussions include clinical best practices, clinical recommendations based on specific mutational profiles, clinical trial matching, and referrals to medical genetics.
Molecular profiling data is kept in a secure registry maintained by the Duke Molecular Tumor Board, and updated recommendations are disseminated to patient care teams as clinical best practices evolve and novel therapeutic options emerge.
part of a Special Report by Duke Cancer Institute & the Department of Pathology, Duke University School of Medicine — as featured in the 2021-22 Department of Pathology Annual Report (pdf)
Oncologists today have a wider range of anti-cancer drugs to reach for, many of which target the molecular alterations believed to contribute to the cancer’s development.
Comprehensive genomic profiling, also known as next-generation sequencing (NGS), is used to identify these molecular alterations. Duke Cancer Institute (DCI) oncologists partner with Duke University Health System (DUHS) Clinical Labs and private diagnostics companies to test patients at diagnosis and/or after the cancer grows or spreads.
While it can vary across cancer types, increasingly, targeted therapies that can save patients from needing toxic chemotherapy are becoming available at multiple points in a patient’s cancer treatment, from first line standard of care to subsequent treatment after progression on conventional therapies.
Test results are entered into a Molecular Registry of Tumors known as Frameshift MRT. This centralized informatics tool — designed, built, and coded at Duke byMichael Datto, MD, PhD, (currently the medical director of DUHS Clinical Labs and vice chair for Clinical Pathology) and Christopher Hubbard (DUHS clinical informatics architect) — helps oncologists identify if anything in their patient’s mutational profile, even extremely rare targets, can be treated with any existing targeted therapies or immunotherapies.
Duke Cancer Institute has been offering its patients NGS testing since 2014. Developing Frameshift MRT three years later to organize and optimize the growing volume and complexity of data, and the subsequent formation, in early 2018, of a weekly multidisciplinary Molecular Tumor Board to review complex patient cases was a perfectly timed great leap forward.
The Precision Cancer Medicine Initiative — launched in 2017 by DCI, the BioRepository & Precision Pathology Center (BRPC), and the Clinical Labs — was the critical push behind it.
“It had become increasingly clear that the needs of sophisticated cancer researchers were changing across all cancer types; moving away from generic, archived, cancer-tissue samples, to fresh samples, to samples with a specific molecular abnormality,” explains Shannon McCall, MD, director of the BRPC, a DCI and Duke University School of Medicine Shared Resource housed in the Department of Pathology. “This coincided with clinical advances. Providers, including at DCI, were utilizing these broad molecular profiling assays to direct the care of cancer patients. There was a need to harness all this molecular profiling data to support both cancer research and treatment. I was totally on fire to get this started. We have so many big thinkers at Duke who said, ‘Let’s think about data and what’s possible.’”
In mid-2018, Executive Director of DCI Michael Kastan, MD, PhD, a noted cancer biologist, and Chair of the Department of Pathology Jiaoti Huang, MD, PhD, a prostate cancer researcher, signed a memorandum of understanding to co-fund the staffing necessary to further support the Molecular Tumor Board — co-directed by oncologists John Strickler, MD (for solid tumor cancers), and Matthew McKinney, MD (for blood cancers) — and to manage the Frameshift MRT database. This included hiring a bioinformatician/ data analyst (Jonathan Bell, PhD) and a savvy genetics scientist (Michelle Green, PhD).
Green, fresh from a position in the molecular diagnostic testing industry, joined the Duke Pathology (with salary support from DCI) in the spring of 2019 as senior research program leader of the Molecular Tumor Board and main user and manager of Frameshift MRT. She tracks promising clinical trials and new FDA drug approvals and has configured Frameshift MRT to automatically send therapy alerts to providers when their patients' molecular profiles match any known anti-cancer drug(s). This match could include drugs that are already FDA-approved, drugs that are “emerging” with strong clinical evidence, drugs that are being tested in clinical trials, or drugs that are approved or being trialed in another cancer type.
Over the course of the COVID-19 pandemic, Green has made several significant changes to Frameshift MRT that make it more user-friendly, interactive, and accessible for clinicians and researchers, who can access the Frameshift MRT dashboard when logged into the Duke VPN. Green is available to train and advise.
TheDuke Cancer Institute (DCI) and the Duke University School of Medicine commit to a five-year, $3 million investment in a new Duke BioRepository & Precision Pathology Center (BRPC) — a clinical research and discovery entity with its administrative home in the Department of Pathology. Michael Datto, MD, PhD, is named director.
Shannon McCall, MD, takes over as director of the BRPC and the BRPC receives CAP accreditation as a tissue, blood, and fluid biorepository, tissue procurement service, and research support core laboratory.
The BRPC becomes an approved Duke University School of Medicine Service Center (also known as a Core Research Facility) and a DCI Shared Resource.
Duke Cancer Institute begins partnering with leading private diagnostics companies and the Duke University Health System Clinical Labs to screen the DNA of cancer cells in tumor tissue and blood for hundreds of potentially "druggable" (targetable with anti-cancer drugs) molecular alterations.
Jiaoti Huang, MD, PhD, is named chair of the Department of Pathology.
The BRPC absorbs the Pathology Department’s Research Histology Laboratory (then led by Alan Proia, MD, PhD) and adds Histology and Immunohistochemistry services; laser capture microdissection tech; and a tissue microarrayer device.
North Carolina Biotechnology Center infrastructure grant is awarded to Shannon McCall, MD, BRPC director, which allows for the addition of a Leica AT2 whole slide imager, dedicated image handling software, and the Visiopharm Oncotopix research image analysis software platform.
The BRPC leadership team expands with the addition of an associate director — Xiaoyin (Sara) Jiang, MD. (Jiang serves in that role throughout 2018 and early 2019 before becoming chief of the Head and Neck Pathology Service)
In-house Molecular Registry of Tumors called Frameshift MRT — the backbone of the Precision Cancer Medicine Initiative — is developed, designed, and programmed by Michael Datto, MD, PhD, with the assistance of Chris Hubbard and input from Shannon McCall, MD, at minimal cost (covered by Pathology). No outside software contracts or private programming services are required.
The first multidisciplinary Molecular Tumor Board (MTB) meeting — co-led by DCI oncologists John Strickler, MD (a medical oncologist with solid tumor expertise) and Matthew McKinney, MD (a medical oncologist who specializes in hematologic malignancies) — is held on Jan. 29. The MTB meets weekly to discuss comprehensive genomic profiling results and promote the adoption of precision oncology at DCI.
Executive Director of DCI Michael Kastan, MD, and Chair of the Department of Pathology, Jiaoti Huang, MD, PhD, sign a memorandum of understanding to fund the positions necessary to support the growing Duke Precision Cancer Medicine Initiative.
The Duke Cancer Institute is invited to join a national consortium of institutions pooling their de-identified genomic data into a national molecular registry of tumors for the global good of cancer research and care [PROJECT GENIE (Genomics, Evidence, Neoplasia, Information, Exchange).
Shannon McCall, MD, Duke site PI, and her team of BRPC experts in histopathologic and molecular data annotation, partner with Michael Datto, MD, PhD, Chris Hubbard, computer programmers Jeremy Gresham and Michael Fox, and Kouros Owzar, PhD (director of the DCI Bioinformatics Shared Resource), prepare the first annual batch of 500 (de-identified) NGS test records from Frameshift MRT for upload into the GENIE system.
A bioinformatician/data analyst (Jonathan Bell, PhD) — split-funded by DCI and the Pathology Department — is hired to support the Duke Precision Cancer Medicine Initiative.
The Duke University AI Health Initiative invests in a Leica GT450 whole slide imager and image server for the BRPC.
Genetics scientist Michelle Green, PhD, is hired by the Department of Pathology to serve as Senior Research Program Leader for the Molecular Tumor Board and main user of Frameshift MRT.
Three new sub-specialized associate director roles are created in the Department of Pathology: William Jeck, MD, PhD (for the Artificial Intelligence & Computational Pathology Service); Avani Pendse, MD, PhD (for the Immunohistochemistry Service and the Proteomics Service); and Jadee Neff, MD, PhD (for the Genomics Service and for the Digital Spatial Profiling Service).
A new BRPC position — liaison to the Autopsy Service — is created. This role is filled by Carolyn Glass, MD, PhD.
The BRPC, with Shannon McCall, MD, as principal investigator, is named the new site of the Southern Division of the National Cancer Institute-supported Cooperative Human Tissue Network (CHTN).
The Duke University School of Medicine invests in a Nanostring GeoMx Digital Spatial Profiler for the BRPC service center, making spatially-resolved transcriptomics (a type of technology named 2020 "Method of the Year" by the journal Nature Methods) available to Duke researchers.
The V-Foundation awards a grant to a DCI clinical team led by Duke Cancer Network medical director Linda Sutton, MD — “Advancing Cancer Care in the Rural Southeast: Enhancing Precision Medicine and Institutional Collaboration in Community Cancer Centers.” The funding is used to train Duke Cancer Network providers in North Carolina on how to access and utilize next-generation sequencing (NGS) testing to expand treatment and clinical trial options for their patients and to educate patients about these tests.
The V-Foundation awards a grant — “Implementing Evidence-Based Interventions to Enhance Equity in Oncology Genomic Testing” — to Tomi Akinyemiju, PhD, MS, DCI social and molecular cancer epidemiologist and associate director, DCI Community Outreach, Engagement, and Equity (COEE). Linking Frameshift MRT data with Tumor Registry data and interviewing oncologists and patients, she begins to assess differences in NGS testing use among cancer patients at DCI, the Duke Cancer Network, and other cancer clinics by race and cancer type, and to examine key socio-demographic, healthcare access-related and clinical drivers of potential disparities. (Preliminary results confirm that Black patients are less likely to receive genomic testing and associated targeted therapies)
Carolyn Glass, MD, PhD, is named BRPC liaison to the National Cancer Institute-Designated DCI Immuno-Oncology Research Program.
Shannon McCall, MD, and John Strickler, MD are named as co-leaders of the National Cancer Institute-designated DCI Precision Cancer Medicine & Investigational Therapeutics Research Program (together with Dorothy Sipkins, MD, PhD, director of the Sipkins Lab)
Duke Cancer Institute and the BRPC lay the groundwork for the expansion of NGS testing access, integration of test results into the Frameshift MRT database, and Molecular Tumor Board support, to Duke Cancer Network clinic sites in rural North Carolina and beyond. A team led by Michael Datto, MD, PhD, builds the software infrastructure, and two-year precision oncology fellow Bennett Caughey, MD, is brought on to help facilitate the workflow that this will require. Hereditary genetics counselor Nicholette T. Sloat, CGC, MA, MS, also joins the project team.
In early January 2022, the National Comprehensive Cancer Network Oncology Research Program (NCCN-ORP), with support from Eli Lilly and Company, awards a two-year $300,000 grant to John Strickler, MD, co-leader of the Molecular Tumor Board, to “Expand the Duke Molecular Tumor Board to Community Oncology Sites Across the Southeast to Support Adoption of Comprehensive Genomic Profiling and Biomarker Driven Therapy Selection for Lung and Thyroid Cancer Patients.” The grant, which takes effect in November 2022, will give further support to the expansion that's already in progress. The team will track the rate of NGS tests ordered for lung and thyroid cancers compared to peer centers, the frequency at which actionable alterations are detected, and the rate at which patients receive molecularly-targeted therapies compared to peer centers.
Part of a Special Report by Duke Cancer Institute & the Department of Pathology, Duke University School of Medicine — as featured in the 2021-22 Department of Pathology Annual Report.
Part of a Special Report by Duke Cancer Institute the Department of Pathology, Duke University School of Medicine — as featured in the 2021-22 Department of Pathology Annual Report
The Duke BioRepository & Precision Pathology Center (BRPC, a clinical research and discovery Shared Resource with its administrative home in the Department of Pathology, was launched in 2012 with a five-year three-million-dollar investment from Duke Cancer Institute and the Duke University School of Medicine. Spurred by key investments in technology, services, and personnel, the BRPC grew, thrived, and progressively built a national reputation.
“It’s success,” notes BRPC director and DCI pathologist Shannon McCall, MD, “represents the evolution and extension of the Department of Pathology’s support and commitment to cancer research."
The BRPC has served as the biospecimen/pathology core for several U.S. government-funded, multi-institutional, and homegrown studies at Duke Cancer Institute (DCI).
The inclusion of at least one core, McCall notes, and often more than one core, is required for large program-level government grants.
“A strong BRPC, plus a strong Biostatistics Core (another DCI/School of Medicine Shared Resource) and/or the Bioinformatics Core boosts the competitiveness of DCI for these big grants,” notes McCall.
McCall herself is American Board of Pathology-certified in Clinical Informatics as well as Anatomic/Clinical Pathology and General Pathology and is chair of the Biorepository Accreditation Program Committee of the College of American Pathologists. She has been involved in numerous translational cancer research projects that rely on the study of human biological samples and data-driven research. With a research focus on upper GI tract carcinogenesis, she previously served as a member of the data analysis working group for The Cancer Genome Atlas (TCGA) esophageal and pan-GI projects.
Under McCall's leadership,DCI joined a national molecular registry of tumors — the American Association for Cancer Research's PROJECT GENIE (Genomics Evidence Neoplasia Information Exchange) — and became the base for the National Cancer Institute-supported Southern Division of the Cooperative Human Tissue Network.
Leading cancer pathologists with the BRPC, like McCall, have worked and continue to work hand in glove with other DCI investigators on several major cancer research grants, which are described below.
Tissue-Based Research & Precision Cancer Medicine Come of Age
A Special Report by Duke Cancer Institute & the Department of Pathology, Duke University School of Medicine — as featured in the 2021-22 Department of Pathology Annual Report
Duke University Marching Band Kicks Off the DCI 50th Celebration (photo by Drawbridge Media)
On Thursday, April 14, 2022, Duke Cancer Institute clinical providers, researchers, staff, and leadership came together to celebrate the 50th anniversary of the Duke Comprehensive Cancer Center (now called Duke Cancer Institute).
As the DCI 50th kickoff celebration was gearing up on the grassy circle in front of Duke Cancer Center building in Durham, a few patients stopped by the adjacent Seese-Thornton Garden of Tranquility for some respite.
Chad and Missy Eddy enjoyed a favorite spot of Missy’s grandparents in her home state of West Virginia in Fall 2018. Chad is from upstate New York, but moved to Raleigh after graduating from Liberty University in Virginia. The couple met in a singles class at church. September 20, 2019, marks their fifth wedding anniversary.
Life threw Chad Eddy “a curve ball" when simple back pain escalated into something much bigger. Now, in recovery, he's giving back.
He is all set to join the DCI LUNGe team on September 29 to help raise awareness about lung cancer — and he's the featured speaker.
Chad Eddy, a Raleigh resident from upstate New York was excited for his 40th birthday, March 20, 2019. His wife Missy had promised, “This year we’re going to go big.”
So, the couple, who didn’t travel very often, set off with their families for Orlando, Florida, to chill at the pool, enjoy some beach time, and take in a spring training Yankee game.
There was much to celebrate. Life, no less.
A year before, in the span of a month, Chad had gone from feeling perfectly normal, to experiencing numbness in his leg, increasing pain in his back, and limited mobility.
No abnormalities were found in an x-ray. Neither a cortisone shot nor physical therapy worked.
“Just being an athlete, I’d had injuries, but it wasn’t like I could walk it off, I knew that something needed to be fixed, bad,” recalled Chad. “It got to the point where I had to pull on my leg to move it. It was very scary.”
“He was basically the picture of health,” added his wife Missy. “Then suddenly, he could hardly walk. He was only 39.”
Finally, an MRI revealed a tumor — likely malignant — that had broken his vertebrae. The couple barely had time to process the news, when less than 24 hours later, Chad fell, immobilized by the pain of a severely compressed spinal cord that had weakened his legs. He was rushed by ambulance to Duke University Hospital.
That day, May 16, 2018, he underwent a four-hour spinal surgery that included the removal of a cancerous tumor and the insertion of eight screws and a rod in his spine and a cage in between the vertebral bones.
“The morning after surgery, I wanted to prove to Dr. Goodwin that I could walk so I did,” said Chad. “I took two little steps and he said, “Alright, now rest up some.” On the second or third day I was able to walk down the stairs and was cleared to check out of the hospital. Dr. Goodwin said that I was one of the most positive patients he’s ever had.”
“His ability to go from not walking to walking is a major predictor of his overall survival,” said Duke neurosurgeon Rory Goodwin, MD, PhD, who co-leads the Duke Center for Brain and Spine Metastasis and performed Chad’s spinal surgery.
However, with a diagnosis of stage 4, metastatic, non-small cell lung cancer — lung cancer that had spread to his spine — Chad needed treatment beyond surgery.
The couple was shocked that Chad had cancer at all and that it had advanced so quickly. And how did he get lung cancer? Chad wasn’t even a smoker.
According to Goodwin, the fact that Chad didn’t discover he had lung cancer until it had already spread to the spine, is not uncommon.
Neither is it uncommon for someone who doesn’t smoke to get lung cancer. While smoking is the leading cause of lung cancer, 18 to 20% percent of lung cancer patients, like Chad, have never smoked. Sixty percent, at the time of diagnosis, will have already quit.
Chad said he didn’t dwell too much on the cause. After a successful surgery and brief recovery, he just wanted to know the game plan.
Chad was referred to thoracic oncologist Jeffrey Clarke, MD, who advised genomic testing — a non-invasive “liquid biopsy” of the tumor DNA and tumor cells in his blood — to identify possible treatments. The test revealed that Chad’s cancer was caused by a particular mutation in the EGFR gene which was driving his cancer cells to grow.
Fortunately, a new drug had just been FDA-approved for patients with new diagnosis of lung cancer — osimertinib (brand name: Tagrisso) — that had been shown to bind to the EGFR protein and shut down cancer growth. First, Chad would first undergo 10 radiation sessions with Duke radiation oncologist Jordan Torok, MD.
He started taking osimertinib in June 2018, and toughed out the “hard work” of physical therapy to rebuild his strength. Chad was back at his customer service job part-time, then full-time, within a couple months of surgery.