1. Perron, Michelle

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At the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, the approach to lung cancer treatment is up close and personal. From next generation targeted immunotherapy to epigenetic research to grassroots community outreach, the team at Hopkins is laser-focused on improving outcomes for a disease that kills more people than any other type of cancer.

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"Our hope for the future is to better personalize care for our patients, all the way from treatment for cancer to treatment that improves quality of life," said Julie R. Brahmer, MD, Director of the Thoracic Oncology Program and Associate Professor of Oncology.


The Hopkins Sidney Kimmel Comprehensive Cancer Center opened in 1973 and was one of the first programs to earn comprehensive cancer center status and recognition as an NCI Center of Excellence. The center focuses on clinical research, laboratory research, education, community outreach, and prevention and control of cancer. The lung cancer program at the center provides patients with access to multidisciplinary medical and nursing teams and cutting-edge research.


"We are proud of the fact that we are leading clinical trials in early-stage disease and hope to increase chance of cure and truly evaluate how immunotherapy is working," said Brahmer, whom colleagues at Hopkins describe as a "pioneering researcher who is taking immunotherapy to the next level."


Current Research

Brahmer has spearheaded several trials of immunotherapies for lung cancer, including studies that led to the approval of nivolumab and pembrolizumab for second-line treatment of advanced-stage lung cancer. Within the Hopkins lung cancer program, new research into applications of immunotherapy is ongoing.


"We have initiatives to personalize immunotherapy through genomic as well as other potential biomarkers of response," she said. "... I believe that immunotherapy is the future, but the other treatments aren't going to go away. Patients will continue to receive chemotherapy with immunotherapy, but we will be able to tailor it."


Epigenetic therapies, a group of medications that turn genes on and off, is another area of focus at Hopkins. Research focused on DNA methylation, in particular, has improved scientists' understanding of lung cancer pathogenesis.


"In the lab, we have found that combining demethylating agents and histone deacetylase inhibitors has the most effect on genes involved in lung cancer," Brahmer said. "We have trials looking at combining epigenetic therapy with immunotherapy to determine if that will be effective. Our program is particularly interested in new combinations of therapies with checkpoint inhibitors to increase response."


Brahmer, who has worked at Hopkins since 2000, said the professionals working throughout the lung cancer program have the gamut of particular expertise necessary to make important strides against lung cancer.


"I hope to get to the point that we have easier ways of telling whether patients are benefitting from therapy," she told Oncology Times. "We have much work to do."


The Team Approach

Two of the specialists who are also working toward these goals are Jarushka Naidoo, MBBCh, and Joy Feliciano, MD. Naidoo is Assistant Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center and the Bloomberg-Kimmel Institute for Cancer Immunotherapy. Feliciano is Assistant Professor of Oncology at the Johns Hopkins University School of Medicine, Clinical Director of the Thoracic Oncology Program at Johns Hopkins Bayview Medical Center, and Co-Director of the outpatient oncology clinic at Bayview.


Naidoo said Brahmer's stellar research track record, coupled with the well-rounded multidisciplinary team and collegial atmosphere at Hopkins, drew her to Hopkins 2 years ago. Naidoo's primary research interest is immunotherapy for lung cancer, and she is working on several novel studies that aim to identify why immunotherapy may work better in some patients more than others and how immunotherapy can be combined with radiation therapy in patients with stage III lung cancer.


The first study focuses on collecting a variety of specimens from patients who are receiving immunotherapy to describe the microbes that exist in various places in their bodies and how this may influence response to immunotherapy.


"Recent headlines reported that microbes in the body may be implicated in how well a patient responds to immunotherapy," Naidoo said. "This data is from melanoma patients. Leveraging that experience, we are looking at the microbiome-the specific features in different parts of the body-and analyzing them carefully along with models in the laboratory to understand how the microbes in the body respond to immunotherapy. With this information, we hope to potentially bring 'good' microbes to patients who are less likely to respond to immunotherapy and, in turn, make them responders."


The second study is a neoadjuvant therapy trial that will offer patients with stage III lung cancer the opportunity to receive immunotherapy and radiation therapy together prior to surgery. "We will get samples before surgery and then from surgical specimens," Naidoo explained. "This allows us to understand how immunotherapy may work in the body while also giving patients the opportunity to get these therapies early in their cancer journey."


This trial is particularly impactful because "there have been no significant advances in stage III lung cancer in more than 20 years," Naidoo said.


On the health care outcomes and care delivery front, Feliciano is working on projects that reflect the lung cancer program's commitment to the entire range of patient needs.


"My focus has been on improving clinical outcomes for underserved populations or at-risk populations, as well as determining how we can improve the care delivery system in our clinic," Feliciano said. "We are doing things to become more family-centered and patient-centered, and to improve outcomes for all these groups of patients."


One of the projects Feliciano has pursued since joining Hopkins earlier this year focuses on smoking cessation among patients in the center's multidisciplinary clinic and among residents of nearby low-income housing. "We are recruiting households and providing education, counseling, and nicotine replacement to families," she explained, noting that the effort has a pharmacy component. "Lots of behaviors and risk factors for lung cancer exist as a group and put a group of people at risk."


Another project involves using a focus group to determine ways to improve the family-centered nature of the lung cancer clinic. "We realized that lung cancer is experienced as a family disease, from behavioral tendencies to access to insurance to treatment needs," Feliciano said. "The focus group discussed their preferences as well as how their diagnoses might be a teachable moment for their family members who may have risk factors.


"What came out of it is that patients do want us to talk to their family members about their increased risk for lung cancer," she continued. "We know that a family history increases risk, and we found that patients are receptive to us talking about this."


The next step for the focus group project is to talk with family members to determine how receptive they are to hearing about the fact that genetic predisposition and behaviors place them at risk, Feliciano said. "There is a small amount of literature that people can be more receptive to changing behaviors ... it may be a time when people will be open to talking about it," she said. "Whether they stop smoking is a different question. We want to find out whether, by creating a family clinic, we can make this a place where we can address concerns as a family."


Another area of study, this one a little further away on the horizon, is a pilot project Feliciano said would be a first among lung cancer centers. The goal of the project is to provide cancer care plans in a manner similar to that used by project planners in other industries. It would provide written visual care plans designed to increase patient understanding and better coordinate care among specialties; this concept has been used at a few medical centers for breast cancer.


"We want to see how receptive patients are to this visual presentation, and whether this improves care coordination," Feliciano said. "In breast cancer, for example, talking to a geneticist before going into surgery might change what happens in that surgery. The same may be true for lung cancer."


Not Out of the Park Yet

The studies and projects taking place within the lung cancer program at Hopkins reflect a sort of renaissance occurring in lung cancer research around the world.


"In the last couple of years, we have experienced an absolute revolution in how we treat lung cancer," Naidoo said. "Any patient who receives chemotherapy will be qualified to get immunotherapy afterward. This is a major breakthrough. There hasn't been this sort of breakthrough since the discovery of genetic alterations and targeted therapy in lung cancer.


"There is still more work to be done," she concluded. "We're seeing responders, but we're not at the stage of breast cancer where it is standard for patients to survive for many years. The take home to the oncology community is that, while there has been an initial breakthrough, it's not a home run yet. However, there is hope."


Michelle Perron is a contributing writer.


2017 Projections for Lung Cancer


* About 222,500 new cases of lung cancer: 116,990 in men and 105,510 in women


* Approximately 155,870 deaths from lung cancer: 84,590 in men and 71,280 in women


Source: American Cancer Society