Huizi Chen, MD, PhD, did not plan to become intimately familiar with an autopsy suite. "The idea of autopsies struck me as somewhat morbid," said the advanced medical oncology fellow at the Comprehensive Cancer Center of the The Ohio State University Wexner Medical Center. But when her research mentor Sameek Roychowdhury, MD, PhD, approached her about starting a research autopsy program, she agreed to take up the charge.
"About 2 years ago, we spent 5 months developing the logistics and goals for the program together with the director and staff of the OSU Regional Autopsy Center. My role along with that of others from the Roychowdhury lab is to actually collect tissues at the autopsies to be taken back to the lab and studied. At that point, I also generate data with help from the bioinformatics group, examine and analyze that data, come to conclusions about our findings, and write papers and grants," Chen detailed. OSU is now one of less than a dozen U.S. institutions with a program in research autopsy, sometimes called "rapid research autopsy."
"The true purpose of the program, with its success contingent upon collaboration and teamwork, is to understand the biology of cancers refractory to treatment," said Chen. "Patients, all of whom have widely metastatic cancer that have stopped responding to treatment, consent to donate their bodies after death to cancer research.
"We really need to understand the complex biology of such cancers by studying their genomes. Through this process, we hope to identify important mutations in cancer cells that lead to treatment resistance, for instance, and determine if we are able to develop therapies against those mutations."
Chen told Oncology Times that research autopsy allows her to collect an extensive amount of tumor tissue samples with which to work, something that is not possible when biopsying a living patient.
"Through research autopsy, we can study how cancer in one area or organ in the body is different from cancer in another part of the body," she explained. "This is a big problem clinically because we now know that cancer is not only different from person to person, but also very different from one area to the next in the same person. We know cancers evolve over time.
"This presents a great challenge because, in the patient who is alive, we can't go in and biopsy every single site of disease. It simply is not feasible," she continued. "To understand cancer evolution and treatment resistance, we have to get those tissue samples in a post-mortem setting like this."
Following a Dual Path
A native of Southwest China and daughter of a father with a PhD in biochemistry and a physician mother who practiced endocrinology in China, it is not surprising that Chen decided to take a dual MD/PhD path.
"I think it was partially innate," said Chen of her interest in both research and patient care. "I have an intellectual curiosity about how cancer develops and what we can do to treat it. And treating patients-interacting with them and their families-is very satisfying for me.
"But some cancers are not curable, and patients will die no matter what we do. So, we need to understand why cancer is resistant to therapy to really move the field forward and develop new therapies. That must happen in the lab and the science end of things. I just couldn't give either one up."
To combine both interests, Chen entered a physician scientist training program at OSU after graduating from Cornell University. Her parents had settled in Columbus, Ohio, by then "... so OSU was a 'coming home,'" she revealed.
She has found the work in research autopsies extremely satisfying, in more than one way. Beyond the excitement of emerging findings, Chen also finds a special privilege in working with patients who ultimately are willing to donate their bodies to science.
"It is a unique opportunity to study cancer in a human body setting. But before that can happen, I first have to approach a patient and their loved ones and talk about death, and what will happen during the autopsy," she said. "It is surprising how many patients are willing to consent to doing this-and moreover actually want to do this. They understand that they will eventually die from their disease and they resolve to do everything they can to help other patients in the future and accelerate the development of novel treatments. Seeing their involvement and actual gratitude has been the most gratifying part of my experience so far."
The first autopsy within the program was performed in 2016; 26 were completed in the first 2 years. "We have one later today-someone died this morning who was willing to do the study, so this will be number 27," remarked Chen. "We try to do autopsies as soon as we can because we want to get tissue that is as viable as possible, which means getting it as close to post-mortem as possible.
"We look through the entire body, although we usually have an idea which organs we want to examine based on previous imaging studies," she explained. "But again, the purpose is to collect tissue to be studied after the fact. Once tissue is removed from the body, it is cryopreserved and can be kept for a long time."
Small Cell Lung Cancer
Chen recently received an award from the ASCO Conquer Cancer Foundation for a project in which she hopes to understand, through research autopsy of patients with relapsed small cell lung cancer, why their cancers come back by identifying the important genetic mutations that occur after first-line chemotherapy.
"Small cell lung cancer is a bad cancer-as bad as pancreatic cancer. There have been no new treatments approved for it in the last several decades," said Chen. "You hear about immunotherapy and CAR T-cell therapy for other cancer types, but there is really nothing like that for small cell lung cancer. I think this is partly because of its stigma as a 'smoker's cancer'-99.9 percent of those who develop small cell lung cancer are smokers.
"Patients typically get chemotherapy and initially respond, but this cancer tends to come back with a vengeance. And once it returns there is really nothing we can offer these patients to prolong their survival. They usually die very quickly. I am trying to find out what makes them so resistant to subsequent therapies. Studying and gaining an understanding of the mechanisms may lead us to develop more effective therapies."
Actively involved in that work, Chen explained, "We have five patients with metastatic treatment-refractory small cell lung cancer that we have autopsied. We are looking at their data right now and hope to make sense of it in the next 3 or 4 months. Looking forward, we hope to have more patients and do this on a much bigger scale."
It's a bit odd, admitted Chen, to be talking about patients who, in the context of this work, necessarily have to be dead. It is the emotional hoop she must jump through to be successful in the tasks at hand. "I knew I would see patients die; that is simply part of oncology. I don't have any aversion to death itself. But what is most difficult for me is just initiating and having that consent conversation with patients and their families. Everything else afterward is comparatively easy."
After a pause, Chen amended the latter statement. "Actually, it is difficult when you have had relationships with patients for a long time, know their fears and hopes, know their families, and then you see them on an autopsy table. You knew them in life and now you know them in death."
Upon further reflection, Chen said her work with research autopsies has also opened a new way for her clinical physician persona to interact with families. "We've had families of [deceased] patients come into the lab and sit through scientific presentations about what we have learned from their loved ones. That is incredibly meaningful for them. And for me to see that, and know that caring for a patient, then losing that patient, wasn't all in vain is so powerful.
"The care-these relationships-continues beyond death. It has become apparent how people are looking for ways to get involved to help each other. I am grateful and humbled to be a part of that."
Valerie Neff Newitt is a contributing writer.
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