Defense Media Network

The VA Targets Cancer

VA flexes its muscle – and leverages its many partnerships – to bring cutting-edge cancer care to a growing number of veterans.

In spring 2017, when they launched their yearslong study of lung cancer treatments, Drew Moghanaki, M.D., MPH, a radiation oncologist at the Hunter Holmes McGuire VA Medical Center in Richmond, Virginia, and Tomer Karas, M.D., FACS, a thoracic and cardiac surgeon at the Miami VA Healthcare System, were attempting something that had been tried before: comparing the effectiveness of radiotherapy to that of surgery, which has long been the standard treatment for early stage lung tumors.

Previous comparison studies of surgery and radiation to treat lung cancer, Moghanaki said, have been historically difficult to complete. There have been insurmountable challenges in recruiting and treating a large enough cohort of patients to truly understand if there are differences between these treatments. Five such trials have been attempted, said Moghanaki, but all were closed because they couldn’t recruit enough participants. “It’s a difficult choice to make,” he said, “to go on a trial that’s going to flip a coin to decide your treatment.” But Moghanaki and Karas have several advantages over their predecessors: First, advances in radiation techniques, over the past 20 years, have led to the discovery of a new form of treatment, known as stereotactic radiotherapy, that may be just as good as or even better than surgery for controlling lung cancer. But, as Moghanaki cautions, “While there’s reason for enthusiasm that most patients can avoid surgery, there still isn’t any convincing evidence that this is the case.”

Large multisite studies such as the VALOR and CONFIRM trials, Moghanaki said, allow the VA to directly address some of the most important clinical questions facing practitioners.

A second advantage is the VA’s track record in completing difficult randomized trials. “Our veterans have always been willing to serve our nation,” said Moghanaki, “and the history of successfully completed clinical trials in the VA is a testament to their willingness to help others with similar health problems.”

The study being conducted by Moghanaki and Karas, known as the VALOR trial, benefits from the capacity of the Veterans Health Administration (VHA) – the largest integrated health care system in the United States – and the VA Cooperative Studies Program, which has been coordinating large, multicenter clinical trials since the 1970s. One such study, the CONFIRM trial, is the largest clinical trial ever sponsored by the VA, evaluating the two most common types of colorectal cancer screening among 50,000 veterans.

Video-assisted cancer surgery

Lt. Col. (Dr.) B. Zane Atkins, center, 60th Surgical Operations Squadron chief of cardiothoracic surgery, performs video-assisted thoracoscopic surgery on a patient with lung cancer at David Grant USAF Medical Center. U.S. Air Force photo by Staff Sgt. Lilana Moreno

Large multisite studies such as the VALOR and CONFIRM trials, Moghanaki said, allow the VA to directly address some of the most important clinical questions facing practitioners. He sees his own study – which he and Karas hope will include 670 veterans with lung cancer – as having the same potential to change how doctors treat patients with lung cancer as a 1991 VA larynx trial that compared radiation plus chemotherapy to surgery. “Before that trial,” said Moghanaki, “if you had laryngeal cancer, it was going to get cut out, and you weren’t going to swallow or talk the same ever again.” The larynx trial found no difference in survival between the two treatment methods. “So now when patients have a laryngeal cancer, we start with upfront radiation and chemotherapy, and two-thirds of the time a patient will sustain the ability to swallow and speak, and have the same cure rate as if they’d had up-front surgery.”

It isn’t the VHA’s size alone that enables it to increase the number of veterans who receive innovative cancer treatments, Moghanaki said – it’s also the way its professionals both work together and collaborate with others in the wider world.

The VALOR trial is aimed at a similar question, said Moghanaki: “Can we just start with radiation first, to avoid anesthesia and the risk of complications for surgery? Surgery could still be a backup option for the minority for whom radiation might not work. That’s kind of why this study stands out so much. There are a lot of eyes on it.”

 

Increasing Veteran Access to New Treatments

It isn’t the VHA’s size alone that enables it to increase the number of veterans who receive innovative cancer treatments, Moghanaki said – it’s also the way its professionals both work together and collaborate with others in the wider world. Lung cancer treatment requires a multidisciplinary approach, and in ordinary health care settings, patients are often shuttled from one specialist to another. “Here everything is under one roof,” said Moghanaki, “and it makes it more likely for people to work together. “We also don’t have to deal with complicated issues involving insurance companies. In this trial, you need surgeons and radiation oncologists, and a pulmonologist, most importantly, to work together to talk to vets and help them realize: You actually have an option. You don’t have to have surgery. You can go into this trial instead.”

MVP sample

A sample containing genetic material from the Million Veteran Program (MVP) is identified by barcode. The MVP data set, which includes the genetic, military service, lifestyle, and health information of more than 500,000 veterans, can be analyzed to identify potential targets for cancer detection and intervention. VA photo

Moghanaki also serves as the research chair for a professional society of VA physicians – the Association of VA Hematology/Oncology, or AVAHO, a nonprofit organization, not affiliated with the VA, that provides a forum for interaction for the department’s hematology/oncology professionals. “The research group is working really hard to expand the cancer trials in the VA, in addition to what VA already does.” Vast as the VHA is, he said, “it doesn’t have the bandwidth to solve every health problem. People often look to the National Cancer Institute [NCI] as a better route to help recruit participants in cancer trials. There’s a lot of missed opportunities right here in the VA to get important clinical trials completed.”

Because cancer is, fundamentally, a failure to regulate cell growth, caused by genetic mutation or altered genetic expression, it’s a particularly promising target for study in the emerging field of precision medicine, an approach to diagnosis and treatment that takes into account individual differences in genes, environments, and lifestyles.

NCI, which launched its $1.8 billion Cancer Moonshot initiative last year, is an important partner in the VA’s efforts to expand the knowledge base around cancer and make clinical research trials more accessible to veterans. The VA has partnered with the Department of Energy and IBM to apply some of the world’s most powerful computing assets to the growing data set compiled by the VA’s Million Veteran Program, which has now collected information about the genetics, military service, lifestyle, and health of more than 500,000 veteran volunteers. In collaboration with NCI, the Uniformed Services University of the Health Sciences (USU), and Walter Reed National Military Medical Center, the VA will apply state-of-the-art methods in proteogenomics to analyze data from thousands of patients. Based on these molecular analyses of genetics and protein expression, researchers will identify potential targets for cancer detection and intervention.

Because cancer is, fundamentally, a failure to regulate cell growth, caused by genetic mutation or altered genetic expression, it’s a particularly promising target for study in the emerging field of precision medicine, an approach to diagnosis and treatment that takes into account individual differences in genes, environments, and lifestyles. The ability to sequence the genes of individual patients offers the opportunity to develop drugs that target specific mutations, and NCI has launched a nationwide clinical trial, the MATCH (Molecular Analysis for Therapy Choice) trial, conducted at nearly 1,100 hospitals and clinics, to evaluate the responses of certain tumors to existing drugs and to experimental drugs that show promise for treatment.

Over the last couple of decades, for a variety of reasons, it has become more difficult for veterans enrolled in VHA care to participate in trials conducted outside the VHA and affiliated university settings, but the VA is working with NCI to enable more veterans to enroll in such trials, including the MATCH trial and the Lung-MAP trial, a precision medicine trial testing five new drugs for squamous cell lung cancer at 730 treatment centers throughout the United States. One of the largest research consortiums in the institute’s National Clinical Trials Network, SWOG (formerly the Southwest Oncology Group) administers the VA Integration Support Program, providing grant funding to VA medical centers through its charity arm, the Hope Foundation, to help connect veterans to clinical trials. SWOG is a major component of cancer research infrastructure, with 12,000 members in 47 states and six foreign countries.

precision medicine infographic

The VA is working with the National Cancer Institute to enable more veterans to enroll in clinical trials outside of the Veterans Health Administration, including some precision medicine trials. National Cancer Institute image

The advent of precision medicine, coupled with the capacity of the VHA to conduct large-scale clinical trials using an integrated health system, genomic database, and electronic medical record, has spawned other partnerships as well. Last year, for example, the VA and the Prostate Cancer Foundation (PCF) announced a $50 million precision oncology initiative to expand veteran access to prostate cancer clinical research and speed the development of new treatment options and cures. An estimated 12,000 veterans are diagnosed with prostate cancer each year, making it the most frequently diagnosed cancer among veterans.

 

From Labs to Clinics

The PCF partnership is multifaceted: It’s aimed at increasing the number of VHA investigators applying to the foundation for funding, the number of VHA facilities involved in precision medicine/prostate cancer clinical trials, the number of minority participants enrolled in PCF studies, and the number of early career scientists working on prostate cancer research. But according to Michael Kelley, M.D., VA’s national program director for oncology and a professor at the Duke University School of Medicine, the initiative shares one overarching objective with VA’s other cancer partnerships: to expand veteran access to cutting-edge treatments. “The core of the PCF partnership is to bring therapies that are not yet approved for use by the FDA [Food and Drug Administration] to patients in the VA system,” he said, “so that when we identify that they have a particular gene alteration that might be targeted by a drug that isn’t yet approved, they might be able to access that treatment. The pharmaceutical partners are also a big part of this, because they are able to help us bring new drugs to clinical trials, and work with us in terms of delivering care to veterans that need new types of therapies.” Several other VA partnerships, to study the effectiveness of precision oncology treatments for other types of cancer, such as breast cancer, leukemia, and lymphoma, are in the developmental stages.

According to the VA, however, about 35 percent of the veterans who receive precision oncology services live in rural areas – which means these rural residents are receiving precision oncology care in roughly the same proportion as their urban counterparts.

In 2016, Kelley and Dr. Neil Spector, VA’s national director of precision oncology, established the VA’s Precision Oncology Program (POP), which makes genetic testing available to VA cancer patients for whom testing may help determine either a course of treatment or a prognosis. Originally launched within the New England Healthcare System, the program has now been expanded nationwide. Through its various activities, the POP system encourages access to modern oncology genomic practice in the VA, improves quality outcomes across the VA network of clinical centers, and works to remove disparities of access to cutting-edge therapies.

The question of access is particularly acute for the VA, Kelley said. “We know VA serves a population which is more highly rural than the national population. About 14 percent of Americans live in rural areas, whereas about 33 percent of those enrolled in the VA are rural residents. … When you look at the cutting-edge therapies that are coming out in academic medical centers, these are often focused on individuals who live in more urban areas. Rural Americans and rural veterans have not had equal access.” Given the vast amounts of data involved in precision oncology diagnosis and treatment, it can be challenging for clinicians – urban or rural – to deliver on its promise.

Watson

VA oncologists Michael Kelley (left) and Neil Spector, who established the VA’s Precision Oncology Program, review a Watson for Genomics DNA analysis report. The VA and IBM have launched a public-private partnership to help doctors expand and scale access to precision medicine over the next two years for 10,000 American veterans with cancer. Martha Hoelzer

According to the VA, however, about 35 percent of the veterans who receive precision oncology services live in rural areas – which means these rural residents are receiving precision oncology care in roughly the same proportion as their urban counterparts. “VA is able to deliver the latest paradigm in oncology care throughout our system,” Kelley said. “We’ve done that with our various partnerships, and we’re increasing the therapeutic options in several ways.” VA’s partnership with IBM, for example, will allow for VA pathologists and clinicians to sequence DNA for cancer patients, and then feed data to Watson, IBM’s supercomputer. Watson’s technology platform will enable comparison of a patient’s information to existing medical literature to identify likely cancer-causing mutations and possible treatment options – tasks that would otherwise be incredibly time consuming and beyond the resources of many community clinicians. Of course, the purpose of the Precision Oncology Program itself is to extend guidance to clinicians and pathologists throughout the system who are not fully up to speed on a new and rapidly evolving field of medicine.

While VA’s current precision oncology efforts emphasize matching veterans to clinical trials of existing and experimental therapies, Kelley said the POP also provides an opportunity for big-picture studies of how to improve precision oncology implementation throughout the VHA. In many ways, the system already has an impressive record, he said. “We’re above 80 percent screening for colorectal cancer, and have been since 2009. That’s 10 years ahead of the national goal to get to that level. How did we do that? It’s been through stuff that can be kind of boring if you’re an oncologist: implementation science. Operational engineering. It’s making sure the car that rolls off the production line doesn’t have any flaws in it. So how do you do that in a patient care setting, where there are so many more variables?”

VA researchers are already discussing ways of evaluating how the existing POP system might be expanded to allow even greater numbers of veterans with cancer to receive treatments matched to their specific proteogenomic information. “Precision oncology was designed to be a platform to handle research built on it,” Kelley said. “And it’s happening already. We’re very interested in partnering with all types of entities – commercial, nonprofit, and government partners – to leverage all the opportunities available and improve cancer care for veterans.”

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Craig Collins is a veteran freelance writer and a regular Faircount Media Group contributor who...