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Harvard initiative aims to determine why certain patients are ’exceptional responders’
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A Harvard Medical School project will mine multiple data sources to try to determine why some patients are more likely to have exceptional responses to cancer treatments.
A national registry of “exceptional responders” — patients with cancer who beat overwhelming odds and respond remarkably well to treatments that most others fail — could provide a deeper understanding of population-wide differences and identify physiological alterations that could serve as novel therapeutic targets.
“Across many different cancer types, there may be signals that might otherwise be missed if we did not gather data on these patients together as a group in one registry,” Isaac Kohane, MD, cofounder of the new network and chair of the department of biomedical informatics at Harvard Medical School, said during an interview.
HemOnc Today spoke with Kohane about the benefits of this registry, the timeline for when actionable information may be available and the knowledge gaps this effort may fill.
Question: How did this registry come about?
Answer: My colleague and I witnessed how successful we were building the Undiagnosed Diseases Network, a research study backed by the NIH Common Fund that seeks to provide answers for patients and families affected by mysterious conditions. We wrote an article in Science Translational Medicine published in 2016 in which we asked the question: What if we viewed patients who are exceptional responders to cancer therapies as essentially the mirror image of undiagnosed patients?
Q: How many people have been included so far and how many do you hope to include?
A: We hoped to include around 100 patients. Through word-of-mouth, we were able to gather about five patient applicants initially. Then a story that described this network was picked up by NPR, and we went from five applicants to 160 applicants. However, we do not yet know how many of these applicants are exceptional responders because we have to go through every case and identify each patient’s cancer type, the stage and prognosis.
Q: What are the eligibility criteria?
A: The eligibility criteria are measures of how unusual a patient is for a specific case. For example, not all stage IV breast cancers are the same. So, what we have to do is consult with the literature and with experts to come up with what would constitute an outlier in terms of survival.
Q: What types of data will be analyzed?
A: We are casting a wide net as we do not yet know where the signal will be. We are looking into obtaining germline genomes as well as somatic genomics of the cancer, and we will obtain the health records of each patient using a variety of different methods. For some patients, we will obtain expression profiles of the tumor. We also will have an extensive number of questionnaires for patients, which will include questions about exercise patterns, spiritual beliefs, DNA and environment.
Q: What do you hope to learn from the analysis?
A: Just as has been our experience with undiagnosed patients, it is hard to know in advance. I suspect we will have several unique cases where the mechanism for exceptional response is different from all others, as well as collections of cases with shared mechanism — for example, a shared downregulation and disruption of an oncogenic signally pathway. But, again, it is hard to know in advance.
Q: Wh en may actionable information be available?
A: I would be surprised if within 2 years we have not found something interesting and relevant to improve survival in at least a subset of patients. In these cases, these individuals are doing well, they are healthy and there is no specific action to take. The actionable part is whether we get insight that will allow us to treat other patients so they respond better to treatment. Patients do not sign up to do this because they need help. They do so because something terrible happened to them and now they are doing well, but they want to understand why this happened to them and what meaning it has. One way it can have meaning is by helping others.
Q: What makes this initiative unique?
A: There are other efforts like this, but this different due to scope and process. First, patients are able to immediately re-donate their formatted data to any organization of their choice. Second, we have partnered with industry for support, for patients and for collaborative studies. Third, we have chosen to be agnostic about which cancers to study because we have learned humility from our previous efforts in prematurely focusing on a single mechanism.
Q: What knowledge gaps could this effort fill?
A: As we thought about building this network, we explored where the patients are. We saw these exceptional responders are studied 10 or 20 at a time, if that. The gap we are trying to fill is across cancer types and across institutions. The hypothesis is that, because a lot of these patients are categorized either by cancer type or by institution, there are some patterns that would not otherwise be noticed if we did not aggregate patients across these different categories and bring them together. It has been heartwarming that these patients stepped forward to cross those boundaries, and we are beginning to see real interest by pharmaceutical companies that are now looking at these protocols to enter patients into this network. – by Jennifer Southall
Reference:
Perakslis ED and Kohane IS. Sci Transl Med. 2016;doi:10.1126/scitranslmed.aaf6146.
For more information:
Isaac Kohane, MD, can be reached at Harvard Medical School, 25 Shattuck St., Boston, MA 02115; email: isaac_kohane@harvard.edu.
Disclosure: Kohane reports no relevant financial disclosures.