occurs less often than non-small cell lung cancer (NSCLC) but is more aggressive and challenging to treat.

, Dr. Ravi Salgia, the Arthur & Rosalie Kaplan Chair in Medical Oncology and associate director of clinical sciences at City of Hope’s comprehensive cancer center, talks about the state of SCLC.

®: What is changing in small cell lung cancer research? 

Lung cancer incidence is decreasing, from the most recent statistics in the United States. Most lung cancer cases are non-small cell, and a small fraction — less than 15 percent &mdash; are small cell. When I started my career almost 30 years ago, SCLC was at a higher incidence, approximately 25 percent or so, and so the incidence is going down. That’s due to smoking rates declining and smoking cessation.

What’s tough about lung cancer is that most of the time, it presents as metastatic disease, and that type of disease is tough to treat. Early-stage disease has a little bit better of an outcome, but we still have a long way to go. Even though we have been doing research for a long time, we know that we haven’t made as many strides against SCLC as we have with NSCLC, especially for the targeted therapies and immunothera&shy;pies that have come to fruition. For SCLC, we know that chemo&shy;therapy and radiation therapy work relatively well upfront, but we know it has a high rate of recurrence. Immunotherapy seems to be one of the breakthroughs and, hopefully, that will continue to be as we go forward.

How has immunotherapy changed the course for patients? 

Initially, we used to think that SCLC was not immunogenic and we couldn’t do too much with immunotherapy. Several trials had been tried for a long time in terms of vaccine therapies, and they didn’t work. But immunotherapy with checkpoint inhibitors are seeming to work. In a subset of patients, we know that immunotherapy is quite effective for our patients.

What type of research is being conducted on SCLC at City of Hope? 

We have a large program for SCLC. We need to be able to think about (doing) early detection. As we know, this low-dose CT (scan) has been effective for smokers and previous smokers who developed NSCLC, but it hasn’t been effective for SCLC. So can we develop early-stage disease surveillance or screening for SCLC as biomarkers? Some of the studies that are ongoing at City of Hope are developing biomarkers, whether they be blood based or radiological based, and we are even using mathematical oncology to try to detect these biomarkers themselves. That’s quite exciting.

For limited-disease SCLC, can one think about possibilities of the standard therapy — chemotherapy and radiation therapy &mdash; and maybe immunotherapy as a type of maintenance therapy?

For extensive-stage disease, which involves about two-thirds of our patients who get diagnosed with lung cancer, immunotherapy is going on. But then, we also have a lot of poten&shy;tial for targeted therapeutics. Are there other targets for SCLC that are yet undiscovered? We also have consideration for CAR (chimeric antigen receptor)-T cell therapy for SCLC.

Preclinically, in the old days, it would take us a long time to develop concepts and bring them to clinical fruition. However, we are now developing precision medicine concepts by using different model systems, including various multicellular organisms for high-throughput analysis and, ultimately, novel therapies.

Where do you see research and treatment going in the future? 

Any therapy that works we will take. Immunotherapy has helped us break the code a little bit but not enough. So, clearly, combi&shy;nations of immunotherapies with radiation or with chemo&shy;therapies are going to be important. Therapeutic targeting will also be important. I see, in the next five years, a revolution for SCLC that will help us break open the code even more.

What message do you want to share with patients who are fighting this disease? 

Therapy is very important for SCLC, no matter what stage. Clinical trials are incredibly important, so if clinical trials can be considered, that may help patients do better compared with the standard of care — and also help other people in the future. But then, from the preclinical studies, we should be able to learn much faster and bring that to clinical fruition. I’m optimistic for patients with SCLC, but we need to do more, and we clearly need to have much more funding to be able to do this kind of research.

RAVI SALGIA, M.D., PH.D., is the Arthur & Rosalie Kaplan Chair in Medical Oncology and the associate director for clinical sciences at City of Hope’s comprehensive cancer center.

Articles

Research News and Updates

With nearly 30 years of experience in thoracic oncology, one expert discusses what lies ahead for patients with small cell lung cancer.

The Future Looks Brighter: State of Treatment for Small Cell Lung Cancer

had one goal: to live long enough to make it to the LUNGevity HOPE Summit in Washington, D.C., that April. She accom&shy;plished her mission but was also in hospice care and on oxygen when she attended. Inspired by other patients with lung cancer and with renewed hope in research and information about therapy advance&shy;ments, Marshall sought another medical opinion and together with her doctor, decided to come off hospice and seek treatment. A year later, she again attended the annual summit, this time without her oxygen tank and with her disease stable, to reunite with her lung cancer community.

HOPE Summit, a weekend-long educational conference offered by LUNGevity Foundation, is for all people affected by lung cancer. Attendees learn how to live well with the disease through informational sessions, inspirational speakers, clinician and research experts, caregiver-specific sessions and opportunities for survivors to connect with each other.

JILL FELDMAN is a 10-year lung cancer survivor. 

Since its inception in 2011, HOPE Summit has grown from 17 lung cancer survivors to nearly 400 participants that also include caregivers, advocates and health care professionals. Jill Feldman, a 10-year lung cancer survivor, has attended every year since 2013. “Cancer fosters an instant intimacy. There is nothing like connecting with someone else in the trenches,” she says. “From the outside looking in, no one can understand, and from the inside looking out, it can’t be explained. We get it in a way that no one else can who has not lived it. HOPE Summit provides that community.”

However, that sense of community might not come easy for people with lung cancer who may feel isolated or stigmatized. “My family felt alone when several family members died of lung cancer,” Feldman says. “Now, no one has to suffer in silence. Social media has helped, but if it weren’t for this event, many connections would remain online, which just isn’t the same.”

She adds: “To me, the most important part of HOPE Summit is the connection and friendships that last all year long, and knowing there is a large, caring community fighting with you and for you and (is) there anytime you have questions or need strength. That is hope — knowing you’re not alone and believing that nothing, even cancer, can defeat the human spirit.”

This year, HOPE Summit has grown into the International Lung Cancer Survivorship Conference and anticipates close to 500 participants. The Conference is now made up of three individual summits: HOPE Summit for patients, COPE Summit for caregivers and the Survivorship Summit for advocates and survivors who want to hear about more advanced topics.

DENISE MARSHALL and her daughter, CORRINE RICHARDSON, at the 2018 HOPE Summit. 

Patients with lung cancer can have more hope now than ever before. Research has not only accelerated therapy but is also pointing to promising new ways to find the disease early, when it is most treatable. These advancements allow many patients to live their lives with the disease — working, parenting and traveling.

“HOPE Summit started out as a small group of people and has grown into this large caring community,” says Feldman. “Cancer knows no boundaries, but neither does the strength of community. HOPE Summit embodies strength, resilience and hope, and over the years has grown and adapted to the changes and needs of lung cancer patients and their families. HOPE Summit has proved to be lifesaving for some who gained knowledge from some of the sessions, but HOPE Summit has proved to be life changing for everyone who feels the undeniable strength, love and spirit that is firm and fierce.”

The Advocate

LUNGevity’s annual summit helps people with lung cancer live better and stay informed.

Creating a Community of Hope for Lung Cancer Survivors

Thousands of new patients are now able to enroll in Lung Cancer Master Cancer Protocol (Lung-MAP), a National Cancer Institute (NCI) trial. Criteria have been expanded to allow patients with all types of non-small cell lung cancer (NSCLC).

The trial previously tested treatments for people with advanced-stage squa&shy;mous cell lung cancer. NSCLC is the most common type of lung cancer; com&shy;bined with small cell lung cancer, it affects more than 200,000 people in the United States each year.

“The Lung-MAP trial has already proven its value by successfully complet&shy;ing trials with new targeted agents in selected, molecularly defined subsets of squamous cell lung cancer,” Meg Mooney, M.D., acting associate director of the NCI’s Cancer Therapy Evaluation Program, said in a press release. “This amend&shy;ment to the trial will allow patients with all types of non-small cell lung cancer to potentially benefit. Checkpoint inhibitors have produced a major advance in this refractory cancer, and Lung-MAP now intends to build on the success of these immunotherapy agents by adding new agents to further increase the effective&shy;ness of this approach.”

Other key changes of the trial: a new screening protocol to include the addi&shy;tion of liquid biopsies and a streamlined informed consent form; two new drug substudies, one testing a PARP inhibitor and another testing a PD-L1 and VEGF inhibitor combination; and a new mandate that requires hospitals, clinics and other sites that open the trial to use the NCI’s Central Institutional Review Board to oversee trial changes.

Thousands of new patients are now able to enroll in Lung Cancer Master Cancer Protocol, a National Cancer Institute trial. Criteria have been expanded to allow patients with all types of non-small cell lung cancer.

Lung-MAP Trial Opens Enrollment to Patients With All Types of NSCLC

In 2015, Greg and Gina Hollenbeck were like many busy young couples raising families. Their lives in Collierville, Tennessee, revolved around their two boys (Hudson and Hayden, then 11 and 7), their jobs, their families and each other. Gina Hollenbeck, 38 at the time and a registered nurse, was a self-described “career-oriented business woman” working full time in a surgery center and as clinical director of a nonprofit organization. Greg Hollenbeck was a pilot for FedEx. Life was good — a controlled whirlwind of school, sports and the day-to-day business of family life.

Then a diagnosis took them both by surprise: Gina Hollenbeck, who has no family history of cancer and never smoked, was told she had stage 4 lung cancer. Suddenly, what she called their “traditional” marriage was flipped on its head as the couple went into survival mode. As she focused on her treatment, Greg Hollenbeck became the caregiver and family manager — roles for which they were not fully prepared.

That situation is becoming increasingly common as more younger women are receiving lung cancer diagnoses. A study published in the 

in May 2018 showed that rates of lung cancer incidence among women born since the mid-1960s are now higher than the rates among men — and this trend is not fully explained by differences in smoking behaviors between men and women. To shed light on this shift, researchers say, more studies of sex-specific risks for lung cancer must be done.

Now, four years after his wife’s diagnosis, Greg Hollenbeck describes the shock: He went numb. Then he got mad — and he got busy. “I went into fight mode,” he says, focusing on his wife’s immediate care, finding the right medical team and trying to keep the boys’ routines going. “We were both very independent people, especially her,” he says. “She’s a go-getter, and she wanted to do everything from dishes and laundry to feeding the kids. After her diagnosis, she couldn’t. It made me realize how much I wasn’t doing around the house.”

A quote on GINA HOLLENBECK’S wrist is a reminder to see the positive in their journey.

Relationships, including the roles and respon&shy;sibilities of each person, often come under a microscope following a cancer diagnosis. “The dynamics that already existed in the partnership set the tone for what happens next,” says Sarah Paul, M.S.W., a licensed clinical social worker and child, adolescent and young adult program manager at Cancer

in New York City, a national orga&shy;nization providing free professional support services to those affected by cancer. For some men, taking on new roles in the relationship poses an additional challenge, on top of their partner having cancer, she says.

These new duties might include acting as a patient advocate, which requires organiza&shy;tion, talking with medical professionals and managing the details of treatment. Some men become information managers, responsible for updating friends and family on their partner’s status. Other men may step into the role of primary parent for the first time — a particular challenge when Mom has been the main caretaker and children might not be used to listening to Dad, Paul says. “Some dads say things like ‘I’m not a good parent’ when they feel like the kids aren’t listening to them,” she says.

The changes can be tough on women too, especially if their relation&shy;ship tended toward a more traditional gender split of roles. “Little things she did may fall to the wayside,” Paul says. “It can be overwhelming if you’re not prepared for it.” Still, such role reversals aren’t always negative. “There’s often an opportunity to learn more about your partner and strengthen your relation&shy;ship,” she says.

The caregiver role can deepen bonds not only between partners, but between family members, too. That’s been the case for Jim Filipiak of Ottawa Hills, Ohio, whose 48-year-old wife, Bobbi, learned of her lung cancer shortly after giving birth to their daughter, Kate, now 6. He is a musician in a local band, and his nontraditional job has always given him the flexibility to be his family’s on-call person, he says, allowing him to help take care of family members who’ve needed him through the years. That flexibility and those close relationships were incredibly impor&shy;tant to him after his wife’s diagnosis, he says. “Our family members were and continue to be a source of great support to us,” Filipiak says.

Finding support is key to managing the physical, emotional and practical stresses for men in the caregiver role, especially because men tend to experience the role in more isolation, says Allison Applebaum, Ph.D., a licensed clinical psychologist and director of the Caregivers Clinic at Memorial Sloan Kettering Cancer Center in New York City. Some men are self-isolating, saying things like “I feel alone in this role,” she says, adding that others struggle to find a support network because there are fewer men in the caregiver role.

Caregivers also need support for the practical challenges they face. Men who manage transporting their partner to treatment and medical appointments and providing care at home may require help with taking care of young children or chauffeuring older kids to sports and other activities. They may also need to ask for time off work to care for their partner, which can create financial stress or job uncertainty. To find support, they may need to ask for help — something that isn’t always easy to do, Paul says.

FILIPIAK, a musician, relied on music as an outlet.

Although little research has been done on gender differences in caregiving, Applebaum says that generally, an “ethic of care” is instilled in women early on: “It’s normalized among women to be a caregiver.”

Paul agrees, adding, “Women tend to be nurturers and are more likely to ask for help. Men tend to be more private. They don’t want to be seen as vulnerable.”

Greg Hollenbeck says he feels fortunate that his fellow pilots pitched in to help, picking up his flights so he could be home with his wife but still get paid. “Some were good friends of mine, and some guys I didn’t even know,” he says. “And Gina’s mom and my parents, as well as parents of other kids, helped get the kids to practices and keep the routine going.”

Still, he relates to wanting to keep things private. “Once we got to a place where she was getting better, I wanted to go fly,” he says. “I got to sit in a cockpit with some dude I didn’t know, who didn’t know what was going on with me, and not talk about it.”

Between a wife with a new diagnosis and a newborn daughter, Filipiak also had to get comfortable with asking for help. “I had to be able to say, ‘I need you to come over now. I need to be with her at this appointment, and I don’t want someone who’s not a family member watching this baby,’” he says.

Filipiak describes that period as overwhelming. “(Before,) we lived independent lives, and we were an energetic couple with an active social life,” he says. “Even if you took cancer out of it, having a child is overwhelming and a complete lifestyle change.”

His stress level rose, he says, because the two of them were unaware of the growing number of women in their 40s, who had never smoked, getting lung cancer. “It was surreal. For the first year, I was pretty much in shock,” he says.

Caregivers can face different sets of challenges depending on the type of cancer their partner has, says Shirley Otis-Green, M.S.W., OSW-C, a licensed clinical social worker in Toluca Lake, California and founder of Collaborative Caring, a consulting firm that works with cancer and palliative care programs.

“A cancer center may have a wealth of resources, but the pictures, stories and examples in those resources may be for an ‘other’ (such as a much older caregiver) and may not resonate with him, leading to increased feelings of isolation,” she says.

Applebaum tries to address that isolation when she tells caregivers that cancer is a disease of the family. “Sometimes people say, ‘I’m not the patient, so why do my feelings matter?’” she says. “But in a family, you’re all affected.”

She often asks the men who come to her center: What brought you to this role? “Some say, ‘I’m the only person available.’ Others say, ‘I’m bound by the vows I made,’ while others say, ‘I watched my father take care of my mother,’” she says. “I tell them we have a counseling center here because coping with cancer is very challenging. We normalize that need for support.”

Greg Hollenbeck received a folder about support services from the hospital but put it aside. “That may be more a man thing,” he says. He noted that counseling was available. “I never used it,” he says, “but it was good to know it was there.”

GREG HOLLENBECK says he went numb after learning of his wife, GINA’s, stage 4 lung cancer diagnosis.

Support groups specifically for lung cancer caregivers, such as those offered by CancerCare, can also be a good resource — especially an online group for someone who is not comfortable with a face-to-face situation. “It’s less commitment than in person,” Paul says. “You don’t have to identify with a picture, and you can use a username.”

Applebaum, who has written a new book, “Cancer Caregivers,” says men may also benefit from a caregiver mentoring program, an informal support system that pairs experienced and new caregivers. Comprehensive cancer centers and organizations, such as the American Cancer Society, can help caregivers connect with resources and support groups. “Sometimes, just one conversation is all it takes,” she says. “Some people just want information. It’s about finding the right type of support for you.”

Filipiak says he sees no shame in therapy or in reaching out for support, although he didn’t take part in support groups recommended to him. Instead, he relies on his close relationships with friends and family and taking walks with his beagle to clear his head. “Being able to play music in the evenings really helped, too, and continues to help,” he says.

Paul encourages caregivers to look after their own well-being. Something as simple as a 10-minute walk or meeting a friend for coffee can help relieve stress, as can maintaining healthy habits, such as exercising, eating well, getting enough sleep and seeing a doctor for personal health care, she says.

Ultimately, balancing your own needs as a caregiver, those of your partner, and the needs of the relationship itself, comes down to communication, clear expectations and patience, according to Paul. “There is no guidebook for how to be a completely different person than you were two months ago,” she says. “It’s challenging.”

Features

Two husbands embrace changing and challenging roles at home when they learn of their spouses’ cancer diagnoses.

Overnight Caregiver: Two Husbands Embrace Caregiving for Wives with Lung Cancer

When J. Timothy Sherwood, M.D., a thoracic surgeon at Mary Washington Healthcare in Fredericksburg, Virginia, sees new patients slated for lung cancer surgery, he has his own preliminary assessment system: Can they climb up and down a flight of stairs? “It’s an easy, effective way to find out if patients are ready for surgery,” Sherwood says.

Beth Ann Palmento, 79, failed the test — she could barely make it up one flight of stairs. She had received a diagnosis of stage 1A lung cancer in 2015 and had a good prognosis from the stand point of her cancer. But she also had a range of other health problems, including chronic obstructive pulmonary disease (COPD) and arthritis. Therefore, Sherwood thought she might do even better if she participated in a program being piloted at Mary Washington: prehabilitation, or prehab, which focuses on getting patients in shape before surgery to make it easier for them to recover afterward. In addition to exercise, prehab might include nutrition counseling, smoking cessation and stress reduction.

Sherwood’s initial suspicions were confirmed following a more comprehensive assessment. He found that Palmento had several issues, including arthritis, limited mobility due to knee and back problems, and shortness of breath. “I told her that she would likely experience poor outcomes following surgery and would need to go to a rehabilitation facility to recover,” Sherwood recalls. “After hearing that news, she decided to try prehab.”

Twice a week for about six weeks, Palmento went to Mary Washington for an exercise session. Her regimen included walking on a treadmill and riding a stationary bike to increase aerobic endurance and using resistance bands to build strength. Although Palmento diligently attended her exercise sessions, when she went back for her second assessment, she received disappointing news. “I still wasn’t ready,” she says.

After another week, Sherwood gave the green light for surgery and performed the procedure. Palmento did even better than expected. “She was out of the hospital in two days and was able to go home, not to a rehab facility,” Sherwood says. “And she only needed oxygen at home for about three weeks. After four weeks of outpatient rehab at Mary Washington, she returned to the YMCA to continue regular exercise in her community.”

Palmento is grateful that she had prehab before her surgery. “I still have my health problems,” she says. “I have COPD and allergies, but I’m cancer-free and able to live a full life. Prehab made me strong enough for the surgery. I feel very lucky.”

The pilot program at Mary Washington, although small, showed that prehab could improve outcomes. Of the 12 patients referred to the program over a 17-month period, six completed the full program. These patients showed a 21 percent improvement in their ability to walk or the distance they could cover. Importantly, their length of stay in the hospital was shortened, from the average duration of five days to three days.

“A shorter period of time in the hospital is good news for insurance companies,” Sherwood says. “That means they’re more likely to cover prehab because it will save money in the long run. Insurance coverage removes a key barrier for patients.”

Other researchers have reported similar outcomes. Roberto Benzo, M.D., a pulmonary and critical care physi&shy;cian at Mayo Clinic in Rochester, Minnesota, and colleagues conducted a small study of 19 patients, published in 

in 2011, comparing the standard of care exercise protocol for patients with COPD and lung cancer with a customized protocol. The customized version took place over 10 sessions and included exercise, muscle training and slow breathing, which not only expanded lung function but also served as a stress-reduction activity. Like the pilot program at Mary Washington, the findings showed that the customized plan led to a shorter length of stay following surgery and fewer days when patients needed a chest tube. The researchers concluded that short-term prehab may improve outcomes following surgery.

Julie Silver, M.D., an associate professor of physical medicine and rehabilitation at Harvard Medical School and associate chair at the Spaulding Rehabilitation Network, both in Boston, was instrumental in spreading the word about prehab. She and a colleague conducted the first literature review on prehab in 2013, which brought this topic front and center for the cancer community. “Prehab has been around for a while,” Silver says. “During World War II, programs were in place to help soldiers become stronger before going into a war zone. By placing prehab as the first phase in the cancer care continuum, we’re hoping to show that it can make patients stronger before having surgery or another form of treatment.”

Silver believes that in a perfect world, prehab would be more than just exercise. Patients with cancer should follow a regimen similar to that of runners training for the Boston Marathon. “Runners supplement their diet with protein to help build up their muscle mass, which cancer patients should do as well,” Silver says. “If anyone in either group is still smoking, those individuals should stop. Lifestyle changes like these can help both groups cross the finish line, either by completing the race or having a better recovery following treatment.”

Although not yet widespread, prehab can be found in some community programs in addition to academic institutions. About 10 years ago, Carol Michaels, a cancer exercise specialist trainer based in West Orange, New Jersey, saw a need for both prehab and rehab after many friends and neighbors received a cancer diagnosis. “(They) were told not to do a whole lot,” Michaels says. “But I knew that inactivity and staying in bed was the wrong approach and could cause other problems.”

After doing her own research and working with family members who were physicians, Michaels created a program called Recovery Fitness, which emphasizes breathing, stretching and aerobic exercise. The aerobic component might be an easy walk outdoors with a friend or family member.

“For lung cancer patients not in optimal physical condition, I see prehab as mandatory,” Michaels says. “If nothing else, prehab can provide a baseline fitness level that can be used as a point of comparison down the road. But I’ve also seen many benefits, including increased lung capacity, improved endurance and strength, less fatigue and a higher overall quality of life.”

Not all oncologists and surgeons are convinced that prehab is the best approach for patients with lung cancer. One area of concern is the timing — prehab can delay when the patient undergoes surgery. For Sherwood, however, the benefits outweigh that concern. “Patients are often getting other tests during the period immediately following diagnosis,” he says. “Given that these patients have a more meaningful treatment plan, I don’t see the time lag as problematic.”

Other surgeons disagree. An Ngo-Huang, D.O., a physi&shy;cian specializing in physical medicine and rehabilitation at The University of Texas MD Anderson Cancer Center in Houston, notes that the center’s thoracic surgeons often offer surgery soon after diagnosis of early-stage lung cancer but would consider delaying for prehab if patients were frail or weak.

However, some findings suggest that intensive exercise during that two-week pre-surgical period can be effective. For example, a study conducted in China in 2016 with 101 patients with lung cancer showed that intensive daily exercise over a seven-day period increased the distance they were able to walk over a six-minute period and improved their lung capacity. It also reduced their length of hospital stay and the occurrence of post-operative complications.

There are barriers to prehab. “Insurance companies typically cover only two to three days of prehab per week,” Ngo-Huang says. “Another issue at our institution is that many patients are from out of town. They don’t have the time to stay for two additional weeks to have prehab, and even if we write them a prescription for prehab at home, we have no way of knowing if they follow through.”

MD Anderson has a randomized prehab clinical trial for patients with early-stage pancreatic cancer, which is a home-based, remote exercise program supervised by Ngo-Huang and the multidisciplinary team, which includes a surgical oncologist, medical oncologist, kinesiologist, dietician and cancer biologist. Participants often undergo four to six weeks of chemotherapy or radiation to shrink the tumor before surgery, followed by a rest period. Because there is a built-in time lag between treatment and surgery, the medical and radiation oncologists and surgeons on the team feel comfortable using this period for prehab. In fact, this window has proved to be the optimal time to initiate a prehab program. Regardless of cancer type, the American Cancer Society and American College of Sports Medicine recommend that cancer survivors engage in 150 minutes of moderate-intensity exercise and two sessions of strengthening exercises each week. The patients with pancreatic cancer in the prehab trial at MD Anderson are following these recommendations. Ngo-Huang also advises patients with lung cancer, who can exercise safely, to follow these recommendations. The exercise may be as simple as going for a 30-minute walk each day.

Just as the care for patients with pancreatic cancer is shifting, so too is it for patients with lung cancer. What is making a difference is the use of low-dose computed tomography (LDCT) screening. As a result of 2013 guidelines that recommended annual LDCT screening for adults age 55 to 80 who have a history of smoking, currently smoke or quit within the past 15 years, Medicare now covers LDCT. But even three years before these guidelines took effect, the National Lung Screening Trial showed a 16 percent reduction in lung cancer mortality because of LDCT screening.

LDCT screening also has another benefit — more patients receive a cancer diagnosis when the disease is at an earlier stage, increasing their chances for long-term survival. What’s more, because their cancer burden isn’t as great as that of those diagnosed at a later stage, these patients may be healthier and in better physical shape.

These factors will likely play a role in how prehab evolves. Although the findings are still emerging, some researchers think that prehab may be a key player in this changing environment. In a 2017 paper, researchers concluded that more patients would be eligible for prehab, but their better health status at the time of diagnosis could result in modifications to the program. For example, the length of time of prehab may need to be shortened. More research is needed to determine the optimal degree of prehab and the best candidates.

In the meantime, thoracic surgeons like Sherwood remain fans of prehab. “I’m passionate about this program,” Sherwood says. “When I see cancer-free patients like Beth Ann who, four years out, are vibrant and physically active, it’s pretty inspiring. Patients like her are the reason why we’re doing all this.”

A pre-surgical shape-up could improve recovery for patients with lung cancer. Although the findings are still emerging, some researchers think that prehab may be a key player that will improve patient outcomes in this changing environment.

Stronger Before Surgery: Better Pre-Surgical Fitness Could Improve Recovery

Amanda Nerstad was 39 years old and a busy working mother of two young children when she learned she had metastatic lung cancer in 2016. She was given between two weeks and nine months to live. Her oncologist at the University of Tennessee Medical Center wanted to send out her tumor biopsy for genomic testing but informed her that the process would take up to two weeks. Nerstad was concerned, especially because her cancer was so aggressive, but agreed to the testing. “It was the longest two weeks of my life,” she says. “But once it came back, my doctor said it was great news. My tumor was ALK positive.”

That meant that Nerstad’s tumor, which was non-small cell lung cancer (NSCLC), tested positive for ALK rearrangement, a gene abnormality that is found in about 5 percent of NSCLC cases and causes the abnormal growth and spread of cancer cells. Only a small percentage of NSCLC tumors have this characteristic, but this is only one of several different gene abnormalities which, like in Nerstad’s case, can respond well to drugs that are designed to block the protein/enzyme made by the mutated gene.

Nerstad was initially put on Xalkori (crizotinib), a twice-daily pill that inhibits ALK. It kept her cancer stable, but it also made her nauseated and suppressed her white blood cells. After six months on Xalkori, she consulted with her oncologist at The University of Texas MD Anderson Cancer Center in Houston, who recommended switching her to another ALK-inhibiting pill, Alecensa (alectinib), because of her abnormal lab results. Her scans have shown complete metabolic response since being placed on Alecensa, which was approved by the Food and Drug Administration (FDA) in late 2017 for the first-line treatment of patients with metastatic ALK-positive NSCLC.

GARY and AMANDA NERSTAD, with their daughters, ISABELLA, left, and GRETA.

“Right now, I’m winning,” says Nerstad, who lives in Knoxville, Tennessee, and works as a flight attendant. “Without genetic testing, I don’t think I would be here.” Aside from a bit of achiness in her feet in the morning and some sun sensitivity, she adds, she doesn’t have any side effects from the Alecensa.

Gene testing is becoming more common in the diagnosis and treatment of NSCLC. Many oncologists believe such testing should be universal due to the discovery of gene mutations and other alterations that drive the disease and, subsequently, the development of more than a dozen drugs that target those abnormalities. By looking for gene abnormalities in tumor samples and sometimes in blood, oncologists can create tailored treatment regimens based on the characteristics of patients’ cancer that are most likely to respond to these new treatments.

“It changes everything for the patient. It essentially makes the disease like a chronic illness,” says Anne Tsao, M.D., a professor in the department of thoracic/head and neck medical oncology at MD Anderson, “and a lot of patients have a good quality of life.”

NSCLC accounts for 80 to 85 percent of all lung cancer diagnoses, and symptoms include a persistent cough, shortness of breath and chest pain. The problem is, these symptoms usually don’t appear until the cancer has reached an advanced stage, making it difficult to diagnose the disease in its earliest stages, when it’s easiest to treat. Although people who smoke face a higher risk of developing lung cancer, the disease often occurs in nonsmokers, too.

An estimated 60 percent of patients with lung adenocarcinoma, a common NSCLC tumor type, have mutations that are believed to be responsible for their cancers, according to Memorial Sloan Kettering Cancer Center in New York City. Some of the NSCLC mutations that are currently targetable with drugs are EGFR, ALK, NTRK, BRAF and ROS1. The medicines all fall into a class known as kinase inhibitors, meaning they block a type of enzyme that controls cancer cell division, growth and survival.

Many of these drugs have greatly improved the survival outlook for patients with NSCLC. For example, the clinical trial that led to the approval of Alecensa showed that in previously untreated patients with metastatic disease, the medication allowed patients to survive 25.7 months without disease worsening or dying — more than double that of patients who took Xalkori, and three times longer than patients treated with chemotherapy.

Several types of tests can be used to detect tumor mutations in patients with NSCLC. One is next-generation sequencing (NGS), which involves using a single test to detect multiple gene alterations in a tumor biopsy sample. Another option is to test for mutations one at a time, starting with EGFR, which is the most prevalent; waiting for the result; and then testing for another mutation if the patient is EGFR negative.

Many oncologists opt for the one-at-a-time option because they perceive it to be less costly than NGS, says Nathan Pennell, M.D., Ph.D., an associate professor of medicine at Cleveland Clinic in Ohio. But a 2018 study led by Pennell found that NGS is associated with significant cost and time savings. It takes about two weeks to get results back from NGS testing — about half the time it takes for sequential test results. Using a decision-analysis model, Pennell and his co-authors estimated that NGS would save insurance providers up to $250,000 over other testing methods.

“I absolutely think it’s reasonable for patients to ask for NGS,” Pennell says. Some hospitals, including Cleveland Clinic, use their own panel tests that include several of the most common mutations in one test. That’s also acceptable, Pennell says, provided results can be returned in two weeks or less. Obtaining insurance approval for NGS or broad-panel testing can be a challenge, he adds, but oncologists are accustomed to having those conversations with providers of health care plans and most will fight to secure the necessary coverage.

Another testing method that’s gaining ground is the liquid biopsy, which involves searching for tumor DNA that’s been cast off into the bloodstream. One advantage of blood testing is that it’s fast, so patients can often get their results and start treatment sooner than they would if they had to wait for a biopsy to be taken. Also, liquid biopsies can be repeated throughout treatment to test for new mutations that drugs might be able to target.

The challenge is that tumor DNA doesn’t always end up in the bloodstream. That’s one reason Tsao prefers to do both types of testing simultaneously. “Since you can miss a diagnosis with sampling of either tumor or blood, I think both are really crucial to check for a brand-new diagnosis. The amount of time it takes to go through a biopsy and get the next-generation sequencing done can be three to four weeks, which is stressful for the patient,” she says.

In a study released in February, a liquid biopsy technology made by Guardant Health correctly identified EGFR, ALK, BRAF and ROS1 alterations in 77 out of 282 patients — and it did so in nine days versus 15 days for tissue-based testing.

Several emerging gene abnormalities found in NSCLC can be targeted with drugs that are either on the market to treat other cancers or are being studied. They include HER2, RET, MET and PIK3CA. Although the drugs are not yet FDA approved to treat NSCLC, clinical trials investigating their potential in the disease are underway and enrolling new patients.

As important as targeted treatments have been in NSCLC, virtually all patients eventually become resistant to the drugs, a problem that has inspired ongoing research into gene mutations that drive the disease as it progresses. That research has already produced important advances.

For example, about half of patients with EGFR mutations who are treated with first generation drugs develop a second mutation called EGFR T790M. In 2017, the FDA approved Tagrisso (osimertinib) to treat those patients, based on a clinical trial in which the overall response rate — tumors shrunk or disappeared &mdash; to the drug was 65 percent compared with 29 percent for patients who received chemotherapy.

In 2018, the FDA added an approval for Tagrisso for the treatment of newly diagnosed patients with specific EGFR mutations called exon 19 deletion or exon 21 L858R. In a clinical trial comparing the drug to a standard regimen of older EGFR-inhibiting medicines, the progression-free survival rate — meaning a patient’s disease did not worsen &mdash; was significantly longer than it was for standard EGFR blockers.

Combination treatments in EGFR-mutated NSCLC might also result in longer-lasting treatment success for patients, says David Carbone, M.D., Ph.D., Barbara J. Bonner Chair in Lung Cancer Research and medical oncologist at The Ohio State University James Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. When cancers are treated with these drugs, responses are rapid (occurring within a few weeks), but the drugs fail to eliminate all of the cancer and eventually these persisting cells become resistant to the drug and begin to regrow. Carbone has been studying EGFR-mutated cancer cells that persist in spite of targeted treatments. He discovered that a protein called beta-catenin protects these persisting cancer cells from dying and that blocking this second protein in animal models improves the duration of response and survival to EGFR inhibitors. He’s now hoping to put together a clinical trial of a beta-catenin inhibitor with an EGFR blocker.

Immunotherapy drugs that enable the immune system to recognize and attack cancer are also being tested in combination with other approaches, Carbone says, including in patients who don’t have easily targetable mutations. One particularly encouraging result came from a clinical trial that combined two chemotherapy treatments with two targeted therapies, Tecentriq (atezolizumab) and Avastin (bevacizumab), in patients with stage 4 NSCLC. Tecentriq blocks the checkpoint PD-L1, which normally prevents the immune system from recognizing and attacking cancer. Avastin inhibits VEGF, a protein that’s essential for forming the blood vessels that feed tumors and allow them to grow but is also known to modulate the immune system.

In results presented in 2018, the four-drug combination reduced the risk of death by 22 percent over a combination of Avastin and chemotherapy. The FDA has approved the four-drug treatment for first-line treatment of patients with NSCLC without EGFR or ALK alterations, but the trial also demonstrated an overall survival benefit, even greater than the general population, in patients with EGFR or ALK alterations who had previously been treated with targeted drugs. “That shows that combining immunotherapy with anti-VEGF could be another way of improving the immune responses to these tumors with these gene mutations,” Carbone says.

Carbone is also encouraged by the newer targeted treatments’ ability to attack NSCLC that has metastasized to the brain. In a clinical trial of the ALK-targeting drug Alecensa, patients with brain metastases had an overall response rate in the brain of 81 percent; for 59 percent of those patients, the response lasted more than a year. Alecensa has also been shown to reduce the risk of ALK-positive NSCLC spreading to the brain.

In a clinical trial of LOXO-292, an oral investigative treatment being developed for patients with NSCLC who have a genetic abnormality called RET fusion, all patients with measurable brain metastases responded to the drug. LOXO-292 was granted breakthrough therapy designation by the FDA in September 2018, which could help speed its path to market.

“Some of these new targeted drugs have a much better ability to penetrate the brain, so we’re seeing these very significant responses in patients with brain metastases that we’ve never seen before,” Carbone says. “That’s extremely exciting. Many of these people never need whole-brain radiation.” That treatment can be effective but also can cause side effects like forgetfulness, he adds.

The proliferation of targeted treatments is benefiting patients like Patty Watkins, who in January 2014 received a diagnosis of NSCLC, which had metastasized to the area around her heart. Her tumor tested positive for a mutation in the gene ROS1. She was treated with two months of chemotherapy, after which she entered a clinical trial of Xalkori — FDA approval of the medication to treat ROS1- positive NSCLC occurred in 2016. But after 21 months, the cancer spread to her brain.

PATTY WATKINS, center, won tickets to Super Bowl 53 through the Chris Draft Family Foundation. Ahead of the game, she was interviewed by CNN news anchor CHRISTI PAUL, left, along with former NFL linebacker CHRIS DRAFT, right.

In 2016, Watkins was accepted on a compassionate-use basis into a clinical trial of Lorbrena (lorlatinib), a drug that is approved to treat ALK-positive NSCLC and is now being tested in patients with the ROS1 mutation.

Her cancer disappeared, and she remains on the drug today. Her only side effects are a bit of weight gain plus neuropathy in her hands and feet, and she takes a statin to hold down the elevated cholesterol caused by the drug.

Watkins considers herself lucky to have her cancer diagnosed at a time when so many targeted drugs are being developed and tested. “My doctors told me I had a couple of days to live and that I should bring my kids home from college,” recalls Watkins, 62, who lives in Atlanta.

“Thanks to research I’m a five-year survivor ready to rock my first grandchild.”

Testing for genomic mutations in lung cancer helps pinpoint targeted therapies.

Lung Special Issue (1) | CURE

The Future Looks Brighter: State of Treatment for Small Cell Lung Cancer

Creating a Community of Hope for Lung Cancer Survivors

Lung-MAP Trial Opens Enrollment to Patients With All Types of NSCLC

Overnight Caregiver: Two Husbands Embrace Caregiving for Wives with Lung Cancer

Stronger Before Surgery: Better Pre-Surgical Fitness Could Improve Recovery

Know Your Genes: Testing for Genomic Mutations in Lung Cancer

Latest News