Fueling cancer research efforts with patient biospecimen collection & big data

Immuno-Oncology Insights 2023; 4(2), 47–53

DOI: 10.18609/ioi.2023.008

Published: 14 May 2023
Interview
Ronan Kelly


Abi Pinchbeck, Assistant Editor, BioInsights, speaks to Ronan Kelly, MB BCh, Director of Oncology, Baylor Scott & White Charles A Sammons Cancer Center at Baylor University Medical Center in Dallas & Chief of Oncology, North Texas Division, Baylor Scott & White Health

In this interview, we discuss Dr Ronan Kelly's work with the Baylor Scott & White Research Institute developing the Texas Immuno-Oncology Biorepository, a research initiative that collects, catalogs and stores biological samples with matching well annotated clinical data in order to improve our understanding of cancer.



What are you working on right now?

RK: Baylor Scott & White Health is the largest not-for-profit healthcare system in Texas. Across our cancer system, we have 13 cancer centers throughout the state from Dallas over to Fort Worth, down through Central Texas, and into the Austin market (Figure 1Baylor Scott & White Health has the largest network of hospital-based cancer programs in Texas and the 3rd largest hospital-based network of cancer centers accredited by the Commission on Cancer (COC) in the United States.) . This represents the third largest hospital-based network of cancer centers accredited by the Commission on Cancer in the United States.

When I arrived in Texas, one of the things I wanted to put in place was a state-wide clinical informatics and biospecimen collection system to learn from the over 150,000 cancer patients that we treat in the Baylor Scott & White healthcare system each year. Essentially, we wanted to develop a program to engage interested patients within our existing cancer programs to gain a more comprehensive understanding of how their immune systems are continually evolving and adapting to keep up with an ever-changing tumor.

We know one of the keys to this understanding is learning from a diverse population. Currently, 95% of patients enrolling in clinical trials nationally are White. There is great opportunity to engage Black, Hispanic, Asian and other non-White patients. Clinical trial deserts exist across the US, and we do not have enough patients from rural backgrounds enrolling in novel studies.

The Texas Immuno-Oncology Biorepository (TIOB) was created with the central vision of treating every patient, while also learning from every patient, regardless of social, racial, or economic background.

Through the TIOB, we consent patients who are receiving standard-of-care immune checkpoint inhibitors every day, for a wide range of tumors. We are looking to collect, catalog, process, store, and analyze well-defined and well-annotated serial biospecimens of tissue, blood, urine, stool, and saliva, as well as pathologic and radiological images, from tens of thousands of patients. This has evolved from a focus solely on metastatic cancer to including early-stage operable malignancies where several US Food and Drug Administration (FDA) approvals for immune checkpoint inhibitors have come in the neoadjuvant and adjuvant space and to patients at high risk of developing cancer as part of our population medicine initiative.

In Dallas, physicians on the medical staff at Baylor University Medical Center (Figure 2Charles A Sammons Cancer Center at Baylor University Medical Center Dallas Texas.) were responsible for two out of the first three FDA approvals for immune checkpoint inhibitors in early-stage malignancies. My colleague, Dr Joyce O’Shaughnessy, was the senior author of the KeyNote-522 study that resulted in the approval of pembrolizumab in early-stage triple-negative breast cancer. I was the lead author and the principal investigator on the CheckMate 577 study which resulted in the approval of adjuvant nivolumab in operable esophageal cancer. Our teams were cognizant of the fact that we had a leading role to play to help improve our understanding of the differences in the immune system between patients with metastatic disease and early-stage disease, which is why Baylor Scott & White launched the TIOB.

What are the key aims and findings of the TIOB project? 

RK: There are several aims for the TIOB. Number one is to gain a more comprehensive understanding of the human immune system and the changes that occur longitudinally over a patient’s entire journey with cancer. A challenge we face is that the vast majority of clinical trials are sponsored by pharmaceutical companies and they are understandably most interested in the period of time when a patient is on their particular drug. If a patient comes off their drug or off their study, we have not had a way of following that patient and understanding the impact of certain interventions on one’s immune system and how that may help or hinder a patient’s response to subsequent therapeutics. Through the TIOB, we want to understand how a patient’s immune system evolves and changes over many years. We need to understand the multiple ways that a tumor is evolving and adapting for us to be able to identify new targets and new ways to defeat cancer cells.

The secondary objective is to establish the differences between early-stage malignancies and late-stage malignancies in terms of how the immune system is working to fight cancer. The TIOB is divided up into three sections: patients with metastatic disease, patients with operable disease, and patients who are at high risk for cancer.

The final piece is that the TIOB has now evolved into a resource to allow for pan-omics studies, involving novel artificial intelligence (AI)-powered platforms. We have the potential to enhance immunologic characterization and improve, for example, tissue phenotyping by launching novel pathology studies, in addition to leveraging radiology and deep-learning algorithms from digital images to allow us to participate in the burgeoning field of radiomics. Additional specimens we are collecting allow us to participate in large-scale proteomic and genomic studies. We have numerous studies opening that will utilize circulating tumor (ct) DNA for minimal residual disease detection post-operatively using blood, urine, and saliva, and others investigating the utility of extracellular vesicles analysis to help with early diagnosis and recurrence post-surgical resection.

Baylor Scott & White also has an award-winning health app: MyBSWHealth. This is an innovative app that over 2.6 million Texans have downloaded to use as part of their healthcare interactions with our system. On a day-to-day level, those patients are looking at blood results, radiological results, and even paying their bills. We hope to use the MyBSWHealth app as a mechanism to perform population medicine research where we can interact with patients in the comfort of their own homes.

How can the data collected and stored in the TIOB be used? 

RK: One of the designs of the TIOB is that we collaborate with outside industry or academic centers to answer a wide variety of questions. We have developed standard operating procedures to collect and process specimens at the highest quality and match this with well annotated clinical data across the largest not for profit health system in Texas.

The hope is that the TIOB will be a cancer resource for generations to come. We are available to work with multiple collaborators to answer the most salient oncology questions of our time. We are excited by the relaunch of the cancer moonshot program and what this means for cancer care, and we hope to play an important role in improving the outcome for all cancer patients.

How can TIOB be used to improve patient outcomes? And what are the goals for the TIOB over the coming years?

RK: Firstly, we are enrolling patients from minority and rural backgrounds. Right now, our enrollment is made up of about 25% of patients who are either of Black or Hispanic descent and we hope to expand that further to other under-represented populations. We do not see that type of enrollment in clinical trials across the US. This is a real-world biorepository with real patients treated throughout our health system. This will be extremely informative moving forward.

Secondly, the technologies used will continue to evolve and adapt over time. Right now, the whole world is beginning to develop an understanding of how impactful AI programming and deep learning algorithms can be. Those types of studies can be done using TIOB specimens and data to help us understand how the human immune system evolves and adapts, or how we can diagnose cancer using a range of omics technologies.

The final piece is we hope to contribute to advancements in making cancer care more accessible for all, meeting patients where they are. As researchers, we need to make things as easy as possible for our patients and remove the barriers to care that have developed over time. The TIOB now allows us to envision engaging with patients in new ways, leaning on the infrastructure of our MyBSWhealth app.

When a patient is diagnosed with cancer, their world is turned upside down. They are scared and nervous, and they need someone to walk them through the whole process. Our team of navigators are able to interact with patients in a variety of ways to be able to answer the most important questions that patients have. If they need a genetics consultation, we can do that through telemedicine consult. If we need them to speak to a nurse navigator, we can do a virtual follow-up or a traditional phone call. All of this complements the traditional doctor/patient face-to-face clinic appointments.

What do you see as the biggest limitations in current eligibility criteria and trial design?

RK: Limitation number one is the lack of enrollment of a diverse patient population. One of the reasons we created the TIOB was the lack of diversity in clinical trials. We saw an opportunity to improve our understanding of how cancers are evolving over diverse racial, social, and ethnic backgrounds. This means enrolling patients not just from large urban areas but also from smaller rural centers, including patients that have never been able to participate in any type of clinical research or translational research before.

Limitation number two is that we only learn what happens to a patient when they are in the study. When a patient comes off a clinical trial, they can live for many years. What happens to their immune system when they get a second or a third treatment? It is important to take longitudinal samples over many years of a patient’s entire journey with cancer to get a full picture of what is happening as tumors evolve and adapt over time. If we continue to only monitor certain moments in time in a patient’s journey, we are going to miss key pieces of information that could be transformative.

Thirdly, one of the reasonings behind creating the TIOB is that we now have multiple FDA approvals for immune checkpoint inhibitors in many tumor types in metastatic and operable settings. We can take specimens from consenting patients who are getting those treatments and learn how and why some patients have great responses and other patients develop resistance. With this information, we can then reverse engineer that knowledge to optimally design the next generation of clinical trials. This will hopefully result in better designed trials and give patients a greater chance of response.

Once a patient progresses on a PD-1 inhibitor, it is not yet clear what the next combination should be. My hope is to gain additional insight so that we can design better trials for the next generation of patients.

What are your goals for your work over the next 12–24 months?

RK: TIOB is a large project – Texas is one of the largest states in the US. Creating this statewide biorepository is a large project in itself. We have spent the last four years making that work. We are now launching innovative trials, which have the potential to be transformative. We are open to collaborating with industry and academia, to understand how the human immune system is evolving.

The TIOB is benchmarked off The Cancer Genome Atlas (TCGA) and worked with some of the original founders of the TCGA to help design the TIOB. The cancer moonshot hopes that as a community we can decrease cancer mortality by 50% in the next 25 years. I hope the TIOB can play a major role in that initiative.

Biography

Dr Ronan Kelly, MB BCh, MBA is the Director of the Charles A. Sammons Cancer Center and the WW Caruth Jr Endowed Chair of Immunology at Baylor University Medical Center in Dallas Texas and the Chief of Oncology for Baylor Scott & White Health, North Texas. Dr Kelly is a Clinical Professor at Texas A&M University and Professor Clinical Science Division at the Translational Genomics Research Institute. He remains an Adjunct Associate Professor at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. He previously served as the Director of the Gastroesophageal Cancer Therapeutics Program at Johns Hopkins and as the Director of Global Oncology for John Hopkins International. Dr Kelly is the co-chair and lead author of the Society for Immunotherapy of Cancer GI committee which has developed some of the most comprehensive immuno-oncology specific guidelines for GI malignancies. Dr Kelly is the Director of the Texas Immuno-Oncology Biorepository (TIOB) which is providing comprehensive, standardized and cutting-edge immune monitoring across thousands of real-world cancer patients throughout Texas to enhance cancer therapy and improve biomarker discovery. The TIOB produces high-quality specimens, suited for employment in a wide array of multi-omic platforms across a diverse community from multiple racial, genomic and social backgrounds. Dr Kelly is author or co-author of more than 200 publications, including peer-reviewed journal articles, abstracts and book chapters.

Affiliation

Ronan Kelly
Director of Oncology,
Baylor Scott & White Charles A Sammons Cancer Center,
Baylor University Medical Center,
Dallas, USA
and;
Chief of Oncology,
North Texas Division, Baylor Scott & White Health

Authorship & conflict of interest

Contributions: The named author takes responsibility for the integrity of the work as a whole, and has given his approval for this version to be published.

Acknowledgements: None.

Disclosure and potential conflicts of interest: Kelly R has an Institutional Grant from Bristol Myers Squibb and an Institutional Grant from Eli Lilly. He also receives consulting fees from BMS, EMD Serono, Novartis, Astra Zeneca, Daicchi Sankyo, Novocure, Merck, Grail, Toray, Astellas, Eisai, Ipsen, Eli Lilly, Takeda, Steris.

Funding declaration: The author received no financial support for the research, authorship and/or publication of this article.

Article & copyright information

Copyright: Published by Immuno-Oncology Insights under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Attribution: Copyright © 2023 Kelly R. Published by Immuno-Oncology Insights under Creative Commons License Deed CC BY NC ND 4.0.

Article source: This article is based on an interview with Ronan Kelly carried out on Feb 21 2023.

Interview held: Feb 21 2023; Revised manuscript received: Mar 21 2023; Publication date: May 15 2023


This article is part of the Clinical development strategy spotlight