SEPTEMBER 4, 2015—Having to tell cancer patients there are no more treatments available for their conditions is one of the worst situations a doctor can face. However, improvements in precision medicine are helping doctors find effective therapies for even the most deadly cancers. By participating in a Virtual Molecular Tumor Board, Georgetown Lombardi is helping physicians take advantage of the latest advances in precision medicine to treat cancer and save lives.
Precision medicine refers to the targeting of cancer treatment based on underlying traits unique to each person and each cancer. It allows doctors to analyze patients’ environment and biology, including their lifestyle and genomic profiles, to determine how such factors might be contributing to their health. This is especially relevant to cancer, which has historically been treated through broad, hit-or-miss drug regimens designed for the average patient.
Under the traditional approach doctors administer drugs that attack the broad hallmarks of cancer, such as tumor growth, and hope they prove effective. Unfortunately, these drugs can often have toxic side effects, and once the physician has exhausted the typical options, there are limited places to turn.
The Virtal Molecular Tumor Board helps evaluate potential treatments for cancer patients by interpreting information gleaned from tumor profiling. In the profiling process, scientists examine a cancerous tumor to determine if it possesses any genetic mutations or biomarkers. If it tests positive, they comb through the scientific literature in an attempt to identify drugs that have shown past success against tumors with such biomarkers. Based on this analysis, researchers can theoretically predict which treatments will produce the best outcomes for different individuals.
“The aim of precision medicine is to find the root cause of a person’s cancer and use this knowledge to design a customized treatment plan,” says Louis Weiner, MD, Director of Georgetown Lombardi. “It’s quite exciting for our cancer center to be involved in what I believe is the future of cancer treatment, and the cutting-edge discussions of the tumor board lead to treatment opportunities that can accelerate the pace of progress towards that goal.”
“Molecular profiling provides us with a treasure trove of data that can be used to construct a complete genomic profile of our patient populations,” Weiner continues. “We hope this will allow us to determine which tumor mutations or related genetic properties are clinically actionable, so that we know which ones to target when treating patients in the future.”
OPENING UP NEW RESEARCH
In addition to expanding potential treatment options, tumor profiling also enables a greater breadth of research at the cancer center.
“Having access to this technology enables Georgetown Lombardi to compete for and ultimately conduct more quality clinical trials,” says John Marshall, MD, chief of the hematology and oncology division and director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancers. “We will often profile our patients’ tumors ahead of time, so if a trial emerges that focuses on their specific mutation, we can match them with that opportunity even more quickly. It benefits our researchers, who are able to study underexplored aspects of cancer, and it potentially benefits patients who have rare, understudied mutations.”
Marshall is one of the doctors leading the charge into this uncharted field. Earlier this year, he was designated chairman of the Caris Centers of Excellence for Precision Medicine Network, a national collaborative effort dedicated to establishing standards for the use of tumor profiling. In his role, Marshall helps develop these guidelines and facilitates knowledge-sharing among physicians.
The Virtual Molecular Tumor Board, which is facilitated by Caris and hosted by a different institution for each session, is a prime example of the power such knowledge-sharing can have. Other participating institutions include Fox Chase Cancer Center in Pennsylvania, Levine Cancer Institute in North Carolina, Barbara Ann Karmanos Cancer Institute in Michigan and West Cancer Center in Tennessee.
By including oncologists from a range of cancer centers and disciplines, the group allows them to draw on each other’s expertise when interpreting profiling results and tackling tough case studies. Though separated by hundreds of miles, members communicate as if they are sitting in the same room. Marshall credits MedStar Georgetown University Hospital for investing in the technology necessary for the meetings.
Georgetown is not alone in seeing the promise of this approach. In his most recent State of the Union Address, President Barack Obama announced the launch of a new federal Precision Medicine Initiative. The initiative allocates $215 million toward investigating and implementing personalized treatments, including $70 million for the National Cancer Institute to increase gene-focused clinical trials and establish a nationwide “cancer knowledge network.”
With physicians from eight different institutions, the Virtual Molecular Tumor Board meets on Monday afternoons to discuss the best treatment options for its patients. Most doctors never meet the patients they discuss and the patients reviewed by the tumor board remain anonymous, but there are very real people whose lives have been changed by precision medicine.
Susan is one such person. Last year, she returned from a trip abroad and visited a physician to ask about her gastrointestinal problems. She was shocked by the diagnosis: inoperable pancreatic cancer.
“I just cried,” Susan says. “Pancreatic cancer is traditionally a death sentence and mine had spread to my liver and lungs. I did some reading and discovered that I was facing some very tough odds so I needed to seek out some non-standard treatment options. In my case, that meant a clinical trial.
With the help of her oncologist, Georgetown Lombardi’s Michael Pishvaian, MD, PhD, Susan had her tumor profiled. Based on the results, she was enrolled in a trial tailored to treat her tumor type. In addition to receiving FDA-approved chemotherapy, she also took an experimental drug that inhibited the cancer from repairing itself. Within nine months, her lesions had shrunk and ultimately disappeared.
Susan believes that tumor profiling had an instrumental role in putting her cancer into remission. “I know I’m here today because I entered this study. I am grateful to be alive and that there was a clinical trial that was right for me. I take it day by day, one moment at a time. I am happy, healthy and I plan to be here tomorrow.”
Marshall says that patients who benefit from precision medicine are still in the minority. However, he hopes that the Caris collaboration and the government’s increased attention on personalized treatment will have positive implications for patients like Susan.
“Gastrointestinal cancer is one of the most common, and unfortunately fatal, kinds of cancer. Despite the widespread impact of this set of deadly diseases, researchers have not yet been able to identify the key molecular drivers that can be therapeutically targeted. This has reduced opportunities to conduct high-impact clinical research. My work in the world of tumor profiling has been my way of advocating for infrastructure that will better allow us to make progress in treating this disease,” Marshall says.
QUESTIONS STILL REMAIN
On paper, the implementation of precision medicine and tumor profiling seems fairly straightforward. When doctors send a patient’s tumor away for molecular analysis, they get back a list of genes expressing mutations, accompanied by a list of drugs. Some drugs, those with “potential benefit,” are put in a green box, while the others are relegated to a red box labeled “therapies with potential lack of benefit.” One might think that choosing a treatment requires a simple check of each box. But what happens when the profiling recommendations clash with a doctor’s own experience?
At one session of the Virtual Molecular Tumor Board, the members debated the proper action to take when a drug they would typically prescribe a patient was highlighted in the red box. The consensus was that going against their own intuition would require robust evidence, something hard to come by in a newly emerging field.
“We can do genetic testing and get an answer, but we don’t always know what to do with the answer,” says Marshall. “Our question then becomes whether such tests can help us reliably predict outcomes. The only way to answer that is through more research.”
Ultimately, Marshall says, achieving medical progress that can be passed along to patients may require baby steps. “We’re in the infancy of molecular profiling. Our goal now is to keep learning, keep working together, so that soon we can at least say we’ve reached adolescence.”