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Dethroning lung cancer: How Massey is working to improve survival of the deadliest form of cancer

Donna Sarver and Sherman Baker, M.D.

This year, more than 150,000 Americans will die from lung cancer. It is the leading cause of cancer-related deaths for both men and women, and it often develops without much warning. Richmond’s only National Cancer Institute-designated cancer center, VCU Massey Cancer Center is discovering new and better ways to prevent, detect and treat lung cancer. It will take new, innovative treatments, early detection and an eye toward prevention to save lives, and our doctors and researchers are stepping up to the challenge in a variety of ways.

Leading Virginia in precision oncology

Every year, scientists develop new drugs designed to target specific cancer-causing mutations. However, in order to know which drug is needed, doctors need to know which genetic mutation is driving the patient’s cancer. This process of using DNA sequencing to match patients with targeted therapies is known as precision medicine. Last year, Massey led cancer providers in Virginia by becoming the first to perform in-house DNA sequencing for cancer treatment with the introduction of Oncogenomic DX One. Oncogenomic DX One looks for defects in more than 50 cancer-promoting genes. Soon, as more targeted therapies become available, the diagnostic test will be expanded to analyze more than 400 genes implicated in a variety of cancers and other chronic diseases. And because it can do this with just one tissue sample, it reduces the potential of additional biopsies required by other diagnostic tests.

Prince George resident Donna Sarver is an early example of the exciting potential of precision medicine. Donna was diagnosed with stage IV lung cancer; the disease had spread throughout her body. Most patients diagnosed at this stage of the disease do not survive more than six months. But four years later, thanks to a targeted therapy, Donna is celebrating her daughter’s high school graduation and another holiday season with her family.

Sarver’s doctor, Sherman Baker, M.D., medical oncologist and member of the Developmental Therapeutics research program at VCU Massey Cancer Center, suspected her cancer was driven by a genetic mutation. He ordered a limited-use gene-sequencing test and found a rare fusion of two genes that only affects about four percent of non-small cell lung cancer patients. With this information, Baker prescribed for Sarver the drug crizotinib, which targets the protein responsible for her rare genetic fusion. It worked. While the drug did not cure Sarver, it shrank her tumors to the point where standard chemotherapy could control the remaining cancer.

While the Food and Drug Administration (FDA) has approved some targeted therapies for certain cancers, many promising experimental drugs are only available through clinical trials.

Offering innovative clinical trials

Every new cancer therapy must first be tested in clinical trials. Massey has one of the largest offerings of cancer clinical trials in Virginia, providing residents first access to cutting-edge therapies before the FDA approves them for widespread use and before they become part of the standard practice of care. Clinical trials known as ALCHEMIST and Lung-MAP are examples of two promising studies currently available to lung cancer patients at Massey.

ALCHEMIST -- Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial -- uses next-generation DNA sequencing to identify early-stage lung cancer patients who have rare defects in two particular genes: epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK). The goal of this phase 3 trial is to determine whether treatments targeted against those particular genetic alterations are more effective in preventing recurrence and improving survival than the current standard of care involving chemotherapy with or without radiation after surgery. The drugs being tested are erlotinib and crizotinib, which is the same drug that helped save Donna Sarver’s life. The FDA has approved both of these drugs for patients with advanced lung cancer, but ALCHEMIST hopes to discover whether they will help patients earlier—right after their tumor has been surgically removed. More information about ALCHEMIST can be found on Massey’s news blog.

Lung-MAP, short for “lung cancer master protocol,” is a phase 2/3 clinical trial consisting of five sub-studies testing various investigational treatments designed to target different genetic mutations. Like ALCHEMIST, it uses advanced DNA sequencing to screen for mutations in more than 200 cancer-related genes in order to match patients to the sub-studies. This first-of-its-kind approach improves patients’ likelihood of receiving a drug that targets the genetic profile of their tumor while allowing for new, developing therapies to be added to their treatment as the trial progresses. Lung-MAP’s goal is to prove personalized treatments are more effective than the current standard of care involving surgery, radiation and/or chemotherapy. More details about the Lung-MAP clinical trial are available on Massey’s news blog.

Elisabeth Weiss, M.D., and Geoff Hugo, Ph.D.

Raising the bar in radiation oncology

Clinical trials are not limited to testing new drugs; they are used to evaluate any medical intervention that affects health outcomes. The Department of Radiation Oncology at VCU Massey has long been at the forefront worldwide in the development of various radiation therapy technologies that are now considered standard practice, and the department is continuing to find new ways to improve the treatment process.

Massey helped lead the nation in developing 4D computed tomography (CT) imaging for lung cancer, which helps account for motion resulting from a patient’s breath by taking multiple pictures throughout the treatment cycle and combining them to create a clearer image. In addition, Massey was one of the first clinics to apply stereotactic radiotherapy techniques to treat small-cell lung cancers or metastatic tumors in the lung. Stereotactic radiotherapy uses high-powered external-beam radiation focused on a small tumor area in the body. It was developed to treat sensitive brain tumors, but Massey physicians have helped demonstrate that it can be a less-invasive alternative to surgery for some lung cancers while delivering comparable outcomes.

Elisabeth Weiss, M.D., a radiation oncologist and member of the Radiation Biology and Oncology research program at Massey, is leading three clinical trials designed to improve radiation therapy outcomes through enhanced imaging techniques. The studies are based on concepts developed by Weiss and her research program colleague and medical physicist Geoff Hugo, Ph.D.

“Studies have shown that higher doses of radiation often result in better tumor control, but high doses can also cause complications to healthy tissue surrounding the tumor,” says Weiss. “Our clinical trials are addressing this problem by comparing the accuracy of different forms of imaging techniques and by using a device designed to assist patients in breath control so that radiation can be delivered more accurately.”

The first study is comparing Magnetic Resonance Imaging (MRI) to conventional CT imaging for treatment planning purposes and to observe changes in tumor volumes and tumor activity during treatment. Because radiation therapy destroys cancer cells and causes tumors to shrink, the observations in this study will inform doctors about whether radiation therapy should be adapted throughout the treatment process to account for these changes. The second clinical trial addresses this issue as well, but this time the researchers are comparing MRI to positron emission tomography (PET) imaging. MRI and PET provide different types of image information, and the study will help determine which is better at displaying changes in tumor biology. The third study aims to improve the accuracy of radiation therapy by combining CT scanning with active breathing control (ABC). ABC is achieved by using a device that helps the patient hold their breath in a reproducible way for 10-30 seconds while CT images are taken. ABC has the potential to allow doctors to more clearly see tumors, which helps reduce radiation exposure to healthy tissue during therapy.

First in the state

Lung cancer survival rates are much higher for those who are diagnosed at early stages of the disease. Studies have shown that computed tomography (CT) imaging is an effective lung cancer screening tool, and it is now recommended for individuals at high risk. The Department of Radiology at VCU Health is the first facility in the state of Virginia to be designated by the American College of Radiology as a Lung Cancer Screening Center, which acknowledges a high level of dedication to screening care and patient safety.

The US Preventive Services Task Force recommends annual lung cancer screening CT for anyone between the ages of 55-77 with a history of smoking a pack of cigarettes a day for at least 30 years--even if they have quit in the past 15 years. A lung cancer screening CT may also be recommended by a primary care provider for someone experiencing lung cancer symptoms. The test is covered under traditional Medicare for eligible populations, and many insurance providers will also cover the test for qualified individuals. Those interested in learning more should call (804) 828-3768.

A team of thoracic radiologists, qualified experts trained in interpreting medical images, reviews each CT scan. If cancer is suspected, the radiologists will work with the patient’s primary care provider or refer them to a pulmonologist (lung doctor) who can help determine the best course of action. For those diagnosed with lung cancer, there is hope. Thanks to relentless research at cancer centers like Massey, there have been huge advancements in lung cancer care, such as new medicines.

Discovering new treatments

VCU Massey Cancer Center played a part in the development of what is now a leading medication for lung cancer. Massey researcher Rick Moran, Ph.D., who is the Paul M. Corman, M.D., Chair in Cancer Research, associate director for basic research and co-leader and member of the Developmental Therapeutics research program at Massey as well as professor of pharmacology and toxicology at the VCU School of Medicine, co-developed the drug pemetrexed (brand name Alimta) by discovering the mechanism by which pemetrexed is involved with lung cancer. In September 2008, the FDA granted approval of pemetrexed as a first-line treatment, in combination with another drug known as cisplatin, against locally advanced and metastatic non-small cell lung cancer (NSCLC) in patients with non-squamous histology. Massey continues to research new uses for pemetrexed in combination with other drugs and for the treatment of other forms of cancer.

Defining the danger of new tobacco products

Research at Massey is also evaluating prevention of lung cancer. Researchers in Massey’s Cancer Prevention and Control program are studying the risk of new tobacco products such as electronic cigarettes and hookahs.

While smoking may be on the decline, the use of novel tobacco products like electronic cigarettes and hookahs are on the rise, especially among youth. Members of Massey’s Cancer Prevention and Control research program and the VCU Center for the Study of Tobacco Products (CSTP) are among the first to assess the potential danger of these novel tobacco products. Named a World Health Organization Collaborating Center, the VCU CSTP is partnering with researchers all over the world in this endeavor. Their research will help inform policy makers in many countries as they consider whether these novel products should be regulated in the same way as traditional tobacco products such as combustible cigarettes.

One recent study helped develop a model to predict nicotine emitted from electronic cigarettes. Led by Thomas Eissenberg, Ph.D., director of the CSTP, member of the Cancer Prevention and Control research program at Massey and professor in the Psychology Department at the VCU College of Humanities and Sciences, researchers working with investigators at the American University of Beirut developed this first ever, evidence-based prediction model that is up to 90 percent accurate. This model also sets the framework for a clinical trial that recently opened at the VCU CSTP as well as Penn State University’s Tobacco Center of Regulatory Science in Hershey, PA, that is evaluating novel tobacco products, including e-cigarettes, on health indicators and cigarette smoking behavior in people who are currently smoking tobacco cigarettes and who are interested in reducing their cigarette use.

Another international collaboration aims to determine whether hookah smoking causes DNA changes associated with cancer risk. Eissenberg is working with Caroline Cobb, Ph.D., who is also a member of the Cancer Prevention and Control program at Massey and a professor in the Psychology Department at the VCU College of Humanities and Sciences, as well as researchers at the Jordan University of Science and Technology (JUST). Together, they will analyze blood and oral tissue samples from hookah smokers for traces of DNA methylation as well as changes in genes known to be affected by other types of tobacco smoking. DNA methylation is a process that can "inactivate" a gene without altering the underlying DNA sequence. Methylation is implicated in silencing tumor suppressor genes and promoting cancer growth. It is considered a biomarker for future cancer development.

From prevention to detection to treatment and long-term survival, VCU Massey Cancer Center is dedicated to lessening the burden of lung cancer. To learn more, visit the Chest Tumor Center section of our website, subscribe to one of our several publications or follow us on Facebook, Twitter or Instagram for regular updates on research, events and educational opportunities.

Written by: John Wallace

Posted on: November 24, 2015

Category: Center news & funding