I RECENTLY WAS LOOKING at Kindle books and saw a title that resonated with me: “Strong at the Broken Places: Voices of Illness, a Chorus of Hope” by Richard M. Cohen. That is one powerful title.

It inspires me because it describes me: I’m stronger at my broken places. Since my stage 4 lung cancer diagnosis in October 2012, I have learned new skills, participated in activities I never dreamed possible and lived a richer life than I ever did pre-cancer. Before my diagnosis, I owned a small grantwriting business. I wrote newsletters, had a book on CD that taught grant writing and was often given the opportunity to speak to groups. People assumed that because I could write, I could speak to a crowd.

Unfortunately, try as I might, I could not speak publicly, not even to a group of friends. I could talk to a tree informally, but once the presentation was formal, I turned into a quivering bundle of nerves and simply could not share what I knew. I kept trying, and I kept failing. I finally quit trying.

LIVE, LIVE, LIVE YOUR LIFE, NOT YOUR CANCER

Now my cancer journey has brought new opportunities to speak. Because I want to share my story and my hope so much, I accept. And guess what? Finally, I can stand up in a crowd and talk without becoming a bowl of Jell-O. My story is too important not to share it.

My story, like the stories of so many of my friends who share a late-stage diagnosis, is hope. I want everyone who hears those awful words “You have lung cancer” to know that they do not automatically translate into “You are going to die.”

When I first received my diagnosis, my then-oncologist thought I would live about four months. I assumed six months — that’s how long my dad lived after he received the same diagnosis back in the ’70s.

There’s a key word in the paragraph above: “live.” After delivering my prognosis, my oncologist asked, “Do you have any questions?”

“Yes,” I said. “Can I keep running my dogs in agility?” The doctor was dumbfounded and had no idea how to answer. I did want to keep running my dogs in our favorite sport of all time, but what I was really asking him was: “Can I keep living my life even though I have this dire cancer diagnosis?”

The answer is a resounding yes. Yes. Yes!

Every time I do something that I am proud of, I feel like I am thumbing my nose at lung cancer. My dog and I earned a number of major titles after my diagnosis — take that, lung cancer! I’m planning a trip to Israel. Want to guess who my traveling companion will be? It is a friend I met through one of the lung cancer events &mdash; someone who also has stage 4 disease. Hope, anyone?

Every lung cancer survivor has their own story to tell. I have shared mine through the Lung Cancer Registry, a place for patients to share their voice and help build a knowledge base for researchers and clinicians so that they can more fully understand how patients walk with the disease.

No one understands it like us. We wake up with it every single day.

Researchers are making incredible advances in the field of lung cancer. Immunotherapy is keeping me alive. I have friends who never even had to go through the horrors of chemotherapy because they were immediately put on targeted therapy drugs. (Genetic testing of your tumors is crucial!) These treatments were unknown just a few years ago.

Grow stronger where the disease may have broken you. Walk in hope.

DONNA FERNANDEZ received a diagnosis of stage 4 lung cancer in October 2012. Since then, she has made it her mission to spread hope and awareness about this misunderstood disease.

Articles

Voices

A stage 4 lung cancer survivor walks in hope.

Stronger Where Broken

PALLIATIVE CARE MAY REDUCE the risk of suicide in veterans who receive a diagnosis of stage 3b or 4 lung cancer, according to the findings of a new study.

The large-scale study, which was published in the Annals of the American Thoracic Society, involved 20,900 patients with advanced disease who were enrolled in the Veterans Affairs (VA) Central Cancer Registry. Researchers determined that 30 patients had committed suicide — a rate more than five times greater than the average among all veterans of similar age and gender who use VA health, according to the study authors.

However, even one palliative care visit after diagnosis reduced the risk of suicide by 81 percent, the authors said. Palliative care is meant to improve quality of life by providing relief from side effects and stress associated with serious illness and can help with emotional, psychological and spiritual needs.

“Suicide is a significant national public health problem, especially among lung cancer patients and among veterans,” lead author Donald Sullivan, M.D., M.A., M.C.R., an assistant professor of medicine at the Oregon Health & Science University School of Medicine, said in a press release. “As a result, manifestations of this impact, like social isolation, depression, anxiety, can go undiagnosed and untreated.”

Patients and caregivers should talk with doctors, Sullivan said, and doctors should consider an integrated approach to treatment, such as palliative care and chemotherapy. An earlier introduction of palliative care would also be beneficial, he added.

Research News and Updates

Palliative care may reduce the risk of suicide in veterans who receive a diagnosis of stage 3b or 4 lung cancer, according to the findings of a new study.
 

Study Finds Palliative Care May Benefit Veterans With Advanced Disease

“HOW AM I GOING to make my appointments?” “How will I pay for my treatment?” “How can I remember to take my medications?”

Those are among the common questions that arise after a patient with cancer, working with their health care team, decides on a treatment a plan. A nurse or social worker can provide many of the answers and assist with overcoming obstacles. Other resources also help, depending on individual needs and treatment plans.

Money-related concerns are often the biggest hurdle to treatment. The Bonnie J. Addario Lung Cancer Foundation’s 2017 focus group research findings showed that more than half of patients surveyed agreed that the cost of care delayed or prevented treatment. If this a concern, a person should talk openly with their health care team and ask what programs might be available. National organizations, such as Patient Advocate Foundation, CancerCare and Nancy’s List, may also be helpful.

Many patients with lung cancer have trouble getting to doctor’s and treatment appointments. This is especially true for patients in rural areas. Patients can begin by asking family and friends or their place of worship for help. Options in cities include Uber, Lyft, paratransit services and other local ride-share programs. Some Medicaid programs offer transportation support, and hospitals might provide gas cards to help cover that expense. The American Cancer Society offers Road to Recovery, a no-cost service that takes patients to and from treatment, and may offer lodging options if a patient must receive treatment far from home. A social worker can discuss available transportation options.

Oral medications are now available for some patients with lung cancer. This at-home therapy offers greater convenience and control than receiving treatment at a hospital or doctor’s office but presents its own set of challenges. The biggest and most pressing concerns involve remembering to take the medication at the right time and getting refills before the medication runs out.

Several memory tricks and tools can help an individual remember to take their medication as directed:

• Make it part of an established routine. For example, if a medication must be taken in the morning with food, a person should keep the bottle where they prepare or eat breakfast, such as near the coffeepot or toaster. Another convenient spot is on top of a cellphone. If medication is needed before bed, the bottle might be kept next to a toothbrush or on a bed pillow. Before long, taking the medication will be incorporated into another routine. Be mindful of small children and pets if using this method.

• Set a reminder on a device, such as an alarm clock or smartphone. Amazon’s Alexa cloud-based voice service can announce a daily reminder to take medication at a specific time. There are also many smartphone apps designed for this purpose.

• Seek help from others. Ask a friend or family member to call or text every day at a certain time. Some pharmacies, insurance plans and pharmaceutical companies offer reminder services; a nurse, social worker or pharmacist can advise patients regarding available programs.

• Write it down. People who prefer a pen-and-paper approach can add “take medication” to a daily to-do list or mark an X on a calendar after taking medication.

• Place medications in Bubble Wrap packets or a pillbox. These can both offer a reminder and verify that the medication was taken.

A combination of methods is ideal. It’s easy to overlook or forget a reminder when it can’t be acted on immediately, so having at least one backup can close any gaps.

Anticipating and managing side effects can also prove challenging. Before beginning treatment, an individual must fully understand common side effects, how to manage them and when to call the clinician’s office. Because this information is so important, a friend or family member should act as an extra set of ears and eyes, accompanying the patient to office visits or, if that’s not possible, listening in via videoconference or by phone. Even better: recording the visit so that the audio can be played when questions arise later.

The Bonnie J. Addario Lung Cancer Foundation focuses on patient empowerment and education. The foundation offers many resources to help patients and their families during active treatment and beyond, including the handbook “Navigating Lung Cancer: 360° of HOPE” (lungcancerfoundation. org/handbook/), monthly education and support sessions that can be joined in person or via YouTube or Facebook, and a patient services team that can discuss treatment options, second opinion referrals and financial resources. For more information, email info@lungcancerfoundation.org or visit lungcancerfoundation.org.

KIM PARHAM, BSN, RN, is the senior manager of Patient Navigation and Clinical Program Development for the Bonnie J. Addario Lung Cancer Foundation. Parham has been a nurse for over 30 years practicing as a navigator and systemwide cancer support director.

Speaking Out

These expert tips can help ensure that treatment plans are followed.

Overcoming Obstacles to Adherence

MORE THAN HALF OF women under 50 who were treated with chemotherapy for lung cancer experienced early menopause, according to study findings published in 

, making these patients vulnerable to the unwanted effects: infertility, hot flashes, vaginal dryness and bone thinning.

“When recommending chemotherapy initiation to a premenopausal patient with lung cancer, physicians should discuss the risk of premature menopause and, for those who have not yet completed their desired childbearing, the options for fertility preservation,” said study author Kathryn J. Ruddy, M.D., an associate professor of oncology at Mayo Clinic in Rochester, Minnesota.

A team of Mayo Clinic researchers examined 182 premenopausal women with lung cancer — 85 received chemotherapy and three received targeted therapy. The remaining 94 did not receive chemotherapy.

The women were surveyed between 1999 and 2016, at diagnosis and then annually, regarding menstrual status. In the chemotherapy group, 64 percent reported that they were menopausal within a year of diagnosis compared with 15 percent of women in the non-chemotherapy group.

Among women who received targeted therapy, two were premenopausal when the final survey was completed, a median of three years after diagnosis.

The way chemotherapy works — by killing cancer cells &mdash; can also affect organs beyond the tumor site. “Chemotherapy damages the ovaries by causing cell death,” Ruddy said. Women who might want to become pregnant later should consider harvesting their eggs and freezing them before chemotherapy to optimize future fertility, she said.

Women who experience menopausal symptoms during or after chemotherapy should tell their oncology team, Ruddy added: “There are both hormonal and nonhormonal ways to combat the symptoms of menopause.

For example, for women with hot flashes, antidepressants such as Effexor XR (venlafaxine) can be helpful.

For those who develop menopause-related osteoporosis, a bisphosphonate or RANK ligand-inhibiting medication should be considered. For vaginal dryness, use of a vaginal moisturizer and vaginal lubricant is usually the first-line treatment.”

Since 1975, the rate of lung cancer diagnosis has fallen by 32 percent in men but has risen 94 percent in women, according to Mayo Clinic. The disease has now surpassed breast cancer as the leading cause of cancer death in American women. Although lung cancer is more common in older adults, women — including about 5,000 premenopausal women a year &mdash; receive diagnoses at a younger age compared with men, wrote the study authors.

Ruddy hopes to further examine these issues in a larger group of lung cancer survivors and in young women who have been treated for other cancers, such as head and neck.

Features

Younger women who were treated with the cancer therapy saw their menstrual cycles end within a year of diagnosis.

Chemotherapy May Cause Early Menopause

DON STRANATHAN has benefitted from targeted therapy and immunotherapy living with stage 4 disease. - PHOTO BY DANIELLE FAGAN

In 2017, Don Stranathan, a nine-year survivor of stage 4 non-small cell adenocarcinoma, thought his luck had finally run out. He had survived radiation, chemotherapy and targeted therapy, but the side effects from 37 infusions of the checkpoint inhibitor Opdivo (nivolumab) to treat a new tumor in his left lung had rapidly become life-threatening.

“I developed immune-mediated toxicity,” says Stranathan, 66, of Santa Rosa, California. “My pericardial sac filled up with fluid. I was in intensive care, where they drained 3 liters of fluids.” That episode was followed by a blood clot in his lung and an abnormal heartbeat. “They had to bring me back with paddles,” recalls Stranathan.

Miraculously, he survived those setbacks. Furthermore, his doctor had more options to offer. Stranathan’s lifesaving plan B was the newly approved triplet therapy of Keytruda (pembrolizumab), Alimta (pemetrexed) and Paraplatin (carboplatin). He continues to do well on this regimen.

Stranathan is the new face of lung cancer survivors. He’s part of a growing group of patients who have been able to segue from one therapy to another as old ones stop working and new ones are approved. Much of this transformation can be attributed to targeted therapy and immunotherapy.

“It’s been a sea change,” says Kristen Kreamer, a nurse practitioner in the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia. “Only 15 years ago, a stage 4 lung cancer diagnosis was a death sentence. There was nothing you could do. Now these patients are living far longer, though cancer is still very much a part of their lives.”

Edward S. Kim, M.D., chair of solid tumor oncology and investigational therapeutics and the Donald S. Kim Distinguished Chair for Cancer Research at Atrium Health’s Levine Cancer Institute in Charlotte, North Carolina, agrees. “New lung cancer treatments have transformed the landscape quite stunningly,” he says. “It really has been amazing.”

Recent statistics about mortality rates for patients with stage 4 disease show a positive trend. Based on results from the National Institutes of Health’s Surveillance, Epidemiology and End Results program for 2008-2014, the five year-survival rate was 18.6 percent. By comparison, in 1975, this rate was about 11 percent. Furthermore, thanks to new technology, 16.1 percent of patients receive diagnoses at an earlier stage, and their five-year survival rate is about 56.3 percent.

Yet even that has its costs. Most lung cancer survivors live with an array of side effects that can be brought on by older treatments, such as radiation and chemotherapy, or newer ones like targeted drugs and immunotherapies.

Few of these individuals are languishing at home, however. “People are incredibly resilient,” says Rachel Odo, LCSW, an online group moderator with CancerCare, the leading national organization dedicated to providing free, professional support services, including counseling, support groups, educational workshops, publications and financial assistance to anyone affected by cancer. “They are figuring out how to live fully and well.”

Each cancer treatment brings its own set of potential side effects, adding an extra layer of complication. Most patients receive more than one treatment type, compounding the number of side effects they experience. “If a patient has a lung removed, there is less pulmonary reserve, resulting in long-term breathing problems,” Kreamer says. “Radiation on top of surgery can cause scarring, adding to the breathing problem. These issues tend to be worse for smokers, who may also have emphysema and chronic obstructive pulmonary disorder (COPD).”

The stage at the time of diagnosis also affects long-term survival. “Patients diagnosed earlier are really a separate population from those diagnosed at a later stage,” Kim says. “(Although) they may undergo surgery, chemo and radiation, their treatment has a conclusion, whereas those with stage 4 lung cancer are being treated continuously. Increasingly, though, these patients are being treated successfully for longer periods of time.”

Chemotherapy, especially regimens that are taxane- and platinum-based, may cause peripheral neuropathy — numbness and tingling in the hands and feet &mdash; hearing loss and changes in kidney function.

BONNIE J. ADDARIO, a 14-year survivor, created one of the leading lung cancer nonprofit organizations focused on eliminating the disease. - PHOTO BY ROBERT HOUSER

Bonnie J. Addario, a 14-year lung cancer survivor and founder of the Bonnie J. Addario Lung Cancer Foundation, had both a difficult surgery for her stage 3b/4 non-small cell adenocarcinoma and an unexpected traumatic recovery. Her tumor was close to the aorta and the subclavian artery, making the procedure particularly complex.

It lasted 14 hours and involved removing her left lung and part of her aorta and subclavian artery. She also had targeted radiation during the operation.

About three months later, she felt a sharp pain in her hip while crossing the street. It turned out to be the first sign of necrosis, a condition that occurs when bone, deprived of a steady blood supply, disintegrates. She had to undergo multiple surgeries, including hip replacement, to correct the problems in her hip and leg.

“I had several pulmonary embolisms after the necrosis surgery,” Addario recalls. “It is very important that patients watch for swelling in their legs, which can be an indicator of a pulmonary embolism — a very dangerous development.”

Addario also lives with chronic hoarseness. She lost functioning of one of her vocal cords during surgery, which also affected her esophagus. Now whenever she drinks anything cold, she coughs.

But Addario, who is in her late 60s, doesn’t let those issues stand in her way. She has become a powerful advocate for lung cancer survivors. Her foundation includes a strong education component and provides funds for cutting-edge clinical research. “Through our programs, we share what we’ve learned about surviving lung cancer, including how to cope with side effects, such as the ones I’ve experienced,” she says. “Simple things like resting my voice after I’ve done a lot of talking or drinking tea with honey can make a big difference.”

Immunotherapy is still quite new, and its associated side effects are just starting to emerge. Over the short term, they appear to be minimal, with fatigue and shortness of breath topping the list.

“I get tired easily, and after a while, I don’t have the air to talk,” says Joe Ruchala, of New York, who has been on Keytruda since 2017 to manage stage 4 lung cancer. He also has idiopathic pulmonary fibrosis and COPD. “And food doesn’t taste the same anymore. I force myself to eat, but it’s not as much fun as it used to be.”

But Ruchala, 73, strives to not be defined by his cancer. “I know what I can and cannot do,” he says. “I can’t walk and talk at the same time. I can play golf, but I can’t walk the course. I’ve learned my limits.”

Recently, oncologists became aware that over the long term, immunotherapy can have a more serious impact.

The benefit of this therapy is that it turns off the brakes off the immune system, unleashing the body’s power to attack pernicious cancer cells. Over time, that power can turn on the patient’s own organs.

“We’re seeing inflammation in the body’s organs, particularly the colon,” Kim says. “The inflammation can lead to colitis, which causes diarrhea and discomfort. The thyroid, adrenal and pituitary glands can also be affected.” Skin reactions are common, too, including rashes, redness, blistering and dryness.

Immunotherapies may also make the skin on the fingertips crack and increase skin’s sensitivity to sunlight.

Kim advises patients to alert their oncologist as soon as symptoms emerge — the issues are easier to manage if caught early. “We try to nip these problems in the bud,” he says. “Often, simple remedies can help. It’s especially important for patients to maintain their weight by keeping their caloric intake up and staying as active as possible.”

Targeted therapy, too, has its share of side effects. Tarceva (erlotinib) and Iressa (gefitinib), two medications approved for patients with the EGFR mutation, can cause a rash, diarrhea and shortness of breath. “The rash can be a big problem,” Kreamer says. “A newer medication, Tagrisso (osimertinib), appears to cause this side effect less frequently.”

Despite the prevalence of side effects, the mood among survivors is increasingly upbeat. Many turn to online support groups to discuss emotional concerns that have emerged since their diagnosis. “They share hard feelings and anxiety about upcoming scans and other issues, but then they have the opportunity to put those feelings into perspective and move forward,” Odo says.

Resourcefulness is another hallmark of survivors. People who develop serious voice issues turn to technology to continue communicating with family and friends. “They send text messages and type notes into their phones,” Odo says.

But survivors do more than just cope. They ponder the future and ways to make their lives meaningful. They make plans, whether that means scheduling a lunch date for next week or attending a graduation six months away.

“The paradigm of survivorship is shifting,” Odo says. “The emphasis is on long-term living.”

Lasting side effects of lung cancer can challenge quality of life, but patients are finding ways to cope to have an improved quality of life.

Alive & Kicking: Managing Cancer's Side Effects

After consulting multiple doctors about her ongoing cough and congestion, LeeAnn Devore asked one of her physicians if she might have lung cancer.

“He said the symptoms weren’t right,” says Devore, 66, of Magnolia, Texas. Three X-rays in five months confirmed that she had pneumonia in her right lung, yet she wasn’t responding to traditional treatments. Finally, in November 2016, one doctor decided to do a biopsy of her lung tissue, and the results were positive for small cell lung cancer (SCLC). The 4-centimeter mass had been hidden in X-rays by the pneumonia.

“I was devastated,” says Devore, who had retired two years earlier. “The diagnosis scared me because lung cancer grows so quickly, and my mother died of lung cancer.”

The standard first-line treatment for patients with SCLC is chemotherapy, which is usually effective for a few months, and then the cancer recurs. But Devore’s oncologist at The University of Texas MD Anderson Cancer Center in Houston asked if she was interested in joining a clinical trial that could boost her odds of survival by adding veliparib, a PARP inhibitor, to her chemotherapy regimen. Veliparib is a targeted therapy: It blocks the PARP proteins in cancer cells that are responsible for repairing damaged DNA.

“Breaks in DNA are common in cancers that are trying to divide rapidly, and chemotherapy causes additional breaks in the cancer DNA,” says Lauren Averett Byers, M.D., an associate professor of thoracic head and neck medical oncology at MD Anderson. “If you add a PARP inhibitor that prevents the cancer cells from repairing damaged DNA, this can increase the likelihood that those cells will die.”

It turns out that many cases of SCLC already have abnormalities in DNA repair ability, rendering them especially sensitive to PARP inhibitors.

Devore’s response was phenomenal. After six rounds of chemotherapy plus veliparib, she stopped the chemotherapy because the cancer shrank so significantly. The disease was in remission for nearly a year. Although Devore discontinued the PARP inhibitor when the cancer spread to bones in her back and a membrane surrounding her brain, radiation and chemotherapy treatments have further extended her life.

Patients such as Devore are benefiting from a proliferation of new research in the field of SCLC, a disease that accounts for 10 to 15 percent of lung cancer diagnoses and has a median survival rate of less than one year. In August — after two decades with no new drug approvals for this type of lung cancer &mdash; the Food and Drug Administration (FDA) approved Opdivo (nivolumab), an immunotherapy, to treat patients with SCLC that has progressed after at least two types of therapy. Several other immunotherapies have also shown promising results in clinical trials, as has lurbinectedin, a synthetic version of a marine-based compound.

“It’s really exciting to see some new options coming onto the scene,” says Anna Farago, M.D., Ph.D., a lung cancer specialist at Massachusetts General Hospital and an instructor at Harvard Medical School, both in Boston. “The bottom line is that the overall survival of patients with small cell lung cancer has not significantly improved for the past 30 years. Now the hope is that with these newer approaches, we will see substantial improvements in how long and how well patients are living.”

Patients often experience their first symptoms, such as cough, shortness of breath, chest discomfort, weight loss and infections like bronchitis, after the disease has spread outside the lungs, known as extensive stage SCLC. Smoking is by far the leading risk factor of the disease, followed by radon and asbestos exposure.

Unlike non-small cell lung cancer, which accounts for 80 to 85 percent of lung cancers, SCLC can rarely be treated by surgery because the disease has often spread to areas such as the other lung or other parts of the body at the time of diagnosis, says Neal Ready, M.D., Ph.D., a professor at Duke University School of Medicine in Durham, North Carolina. Although patients respond well to initial chemotherapy treatment, the benefit is typically short-lived in extensive stage SCLC because the cancer quickly becomes resistant to the drugs.

If SCLC is caught before it has metastasized — known as limited stage disease &mdash; up to 25 percent of patients can be cured with a combination of chemotherapy and radiation, says Charles Rudin, M.D., Ph.D., chief of the thoracic oncology service at Memorial Sloan Kettering Cancer Center in New York City.

With the emergence of targeted therapies, researchers are discovering new strategies to tackle the disease by stimulating the immune system to recognize and attack cancer cells. Opdivo, for example, blocks the PD-1 protein, which prevents the immune system’s T cells from attacking cancer cells. The FDA’s approval of the drug was based on a study that compared patients who received Opdivo alone with others who received a combination of Opdivo and another immunotherapy, Yervoy (ipilimumab), which blocks the activity of a protein known as CTLA-4.

The results showed that 11 percent of the participants who took Opdivo alone experienced marked tumor shrinkage that lasted for more than one year; so did approximately 19 percent of those who took the combination. The participants were also tested for a biomarker called PD-L1 to determine if this protein was associated with a higher response to the drug, but no link was found. “To be able to give patients a drug that is well tolerated and less toxic than chemotherapy is a significant breakthrough,” Ready says. “Oncologists are almost always unhappy about using the currently indicated second-line chemotherapy because it causes a lot of nausea and fatigue, and it may not have much benefit, so these new treatments are meeting a major area of need.”

Although his patients usually experience fewer side effects from immunotherapies than chemotherapies, Ready says, stimulating the immune system can lead to rashes, diarrhea, joint pain, fatigue and inflammation in the adrenal glands or thyroid and, in rare cases, the lungs or bowels.

SALERNO began to build a wood plank wall in his office before his small cell lung cancer diagnosis. He stopped when he got sick and thought he wouldn't finish. But the new treatment he received has enabled him to finish the project. - PHOTO BY JOLIE RODRIGUEZ

Robert Salerno, who received a diagnosis of SCLC in September 2017, was grateful when his oncologist recommended that he try Opdivo after his cancer recurred following six rounds of chemotherapy. During treatment, Salerno had been hospitalized three times due to the possibility of infections. “My white blood cells, platelets and red blood cells sank to an all-time low when I was on chemotherapy,” says Salerno, 74. “I needed to be in the hospital to bring my numbers back to safe levels.”

He started receiving a combination of Opdivo and Yervoy in July 2018 and has experienced just mild side effects, such as fatigue and shortness of breath. A CT scan in September revealed that his tumors had shrunk by over 25 percent. “When I was first diagnosed, I was hoping to live at least six months,” says Salerno, who lives in Castle Rock, Colorado. “But it’s been more than a year now, and I’ve had the chance to go on vacation in Florida and continue with house projects. I hope this new therapy gives me more time.”

Clinical trials are showing great promise for treatment of the disease. In September, researchers on the Impower133 trial reported a survival benefit from Tecentriq (atezolizumab) in patients with extensive stage SCLC in the first-line setting — a benefit seen for the first time in 20-plus years.

The drug added two months to patients’ lives when given along with standard of care chemotherapy, which is a combination of carboplatin and etoposide, compared with those who received chemotherapy plus placebo. Similarly, patients in the Tecentriq group also lived longer without disease progression than the placebo group (5.2 months versus 4.3 months, respectively).

Keytruda (pembrolizumab) is another promising immunotherapy, and results of a recent phase 2 clinical trial showed the drug to be especially effective in patients with the PD-L1 biomarker. Their overall response rate was 35.7 percent, compared with 6 percent among those without the biomarker.

Finding biomarkers to identify which patients will benefit from different treatments has been difficult in SCLC, but a recent study conducted by Byers suggests that there may be a marker to determine who is more likely to respond to PARP inhibitors such as veliparib. In the retrospective study, Byers’ team found that patients who had high levels of the SLFN11 gene benefited most. “When a cell has DNA damage, the SLFN11 gene forces it to die rather than continue living,” Byers says. “Half of all small cell tumors have high levels of this biomarker, and the overall survival of patients in this category who took a PARP inhibitor was five months longer than (for) those who had lower levels of the gene.”

Researchers are also exploring whether measuring tumor mutational burden (TMB) might be another way to predict who will respond to immune checkpoint inhibitors. “Now we have methods of sequencing tumor DNA to identify the number of mutated genes, and people with higher TMB may have a higher response to combinations like Opdivo and Yervoy,” Ready says.

If lurbinectedin continues to produce positive results, patients may have a second-line treatment option in addition to PARP inhibitors and immunotherapies. The drug inhibits the activated transcription process, making it difficult for the cancer to produce proteins and other factors involved in tumor growth.

When researchers studying lurbinectedin recently presented results at the American Society of Clinical Oncology Annual Meeting, the phase 2 clinical trial findings impressed Suresh Ramalingam, M.D., deputy director of the Winship Cancer Institute of Emory University in Atlanta, Georgia. “What caught my attention is that the researchers treated patients who had progressed on other therapies, and after they received lurbinectedin, their median survival was a year,” he says. “This is remarkable, given that the benefit of standard chemotherapy lasts only for a few months.” The phase 3 clinical trial for the drug has been completed, and the results will be released within the next year. “Overall, the side effect profile seems comparable to other treatments in this setting,” he says.

A monoclonal antibody drug, Rova-T (rovalpituzumab tesirine), which focuses on the protein DLL3 in cancer cells, is also being studied. “Scientists have created a protein that recognizes the DLL3 and delivers a potent chemotherapy to the cancer cell,” Ready says.

Findings showed that the drug produced a response rate of 14.3 percent among patients with SCLC that expressed DLL3 and who had received at least two prior lines of chemotherapy. Several clinical trials are comparing Rova-T with standard chemotherapy options in SCLC.

Pharmacological options are vital in the field of SCLC, but radiation also plays an important role. For people with limited stage SCLC who have had a good response to initial chemotherapy and lung radiation treatment, prophylactic (preventive) radiation to the brain may be offered because there is a high risk that the cancer will spread to the brain. “The brain can be a sanctuary site for small cell lung cancer because the chemotherapy doesn’t penetrate as well to the brain as other tissues,” Rudin says. “A lowdose of radiation can reduce the risk of recurrence and increase survival.”

For people with extensive stage disease, the benefits of prophylactic radiation are less clear, he says. In one Japanese study, a group of these patients experienced no survival benefits from prophylactic radiation. “Radiation can have adverse side effects like fatigue and short-term memory loss,” Rudin adds.

DOUG CLARKE, who is a firefighter with the Rocky Hill Fire Department in Connecticut, hopes his clinical trial participation will help save others. - PHOTO BY SARAH CRUZ

Doug Clarke underwent prophylactic cranial irradiation after finishing chemotherapy and radiation treatment for SCLC in his right lung and nearby lymph nodes. The 54-year-old was surprised by the diagnosis, which he received in July 2016, because he had never smoked and was in the best shape of his life. Clarke, who lives in Rocky Hill, Connecticut, had recently joined a team of volunteer firefighters to climb 700 flights of stairs in the American Lung Association’s annual Fight for Air Climb.

Nine months after he started treatment, the cancer had spread to his adrenal gland, multiple lymph nodes and skin. Clarke started a combination of Opdivo and Yervoy, and the immunotherapies were effective for nearly one year. When the cancer started growing again, Clarke joined a clinical trial for another investigational immunotherapy drug that blocks the protein Tim-3.

For Clarke, the opportunity to participate in clinical trials brings hope that he can participate in next year’s Fight for Air Climb, just as he has the last two years as a survivor. “I’m going to continue using my cancer to speak out, raise money and move closer to a cure,” he says. “I may not be able to find a cure for myself, but the results from these clinical trials might help someone else down the line.”

Treatments with PARP inhibitors and immunotherapies are helping patients with small cell lung cancer live better and longer.

Targeting Innovation in Small Cell Lung Cancer

In June 2014, 46-year-old Juanita Segura couldn’t stop wheezing. Within a few months, she developed a persistent cough and started on medications for asthma, though she doubted the diagnosis. In October, she landed in the emergency room with severe shortness of breath and was admitted for possible pneumonia. Again, she questioned the diagnosis, and an X-ray showed what looked like a flattened lung. It turned out that an enlarged lymph node, revealed during a bronchoscopy, was squeezing her lung and airway closed. This diagnosis shocked her: stage 3b ALK-positive adenocarcinoma non-small cell lung cancer (NSCLC). “I was a mother of five in the best shape of my life,” she says. “I could do 95 overhead squats, 300 deadlifts and 250 back squats. I had just lost a lot of weight. And I don’t even smoke.”

Between 85 and 90 percent of lung cancers are NSCLC, estimates the American Cancer Society. The remaining 10 to 15 percent are small cell lung cancer. Each year in the United States, more than 234,000 new lung cancer cases are diagnosed. Although Segura isn’t a smoker, she’s been around secondhand smoke her whole life. Nonsmokers have a 20 to 30 percent greater chance of developing lung cancer if exposed to secondhand smoke, according to the American Lung Association.

Treatment for stage 3 NSCLC hasn’t changed much in the last 25 years — typically, chemotherapy and radiation therapy &mdash; but immunotherapy approved by the Food and Drug Administration (FDA) in early 2018 has slowed the disease’s progression in some patients. Clinicians sometimes also add a more intense and short-term radiation therapy, and researchers continue to look for the best mix of treatments and scheduling.

A stage 3 diagnosis usually means the lung tumor has spread to the lymph nodes, often the mediastinal lymph nodes in the middle of the chest or the supraclavicular nodes at the base of the neck. To stage the cancer and evaluate the patient for treatment, doctors typically order imaging including a chest X-ray, a PET/CT full-body scan to detect cancer in the lungs and elsewhere, and an MRI to look for cancer that may have spread to the brain or spinal cord. Doctors may perform a bronchoscopy or other procedures to determine lymph node involvement. A pulmonary function test gauges lung capacity to see if the patient is a candidate for surgery and aids in radiation planning. Basic blood tests check red and white blood cell counts, and also see if someone’s organs can handle the treatment.

Then the patient often sees a multidisciplinary care team, including a medical oncologist, a radiation oncologist and a thoracic surgeon, for a treatment plan. In addition to considering the NSCLC stage, doctors factor in the patient’s age, overall health, severity of symptoms, lung capacity and treatment preferences. “I often describe stage 3 as one of the most challenging clinical scenarios because traditionally, there are a variety of opinions without clear data on the direction,” says Edward Garon, M.D., an associate professor of hematology and oncology at the David Geffen School of Medicine at UCLA. “Often in our own tumor board, there’s significant debate on the likely success from a surgical approach with a stage 3 NSCLC.” Opinions and practices vary by the facility. Patients who get surgical resections usually receive chemotherapy or a combination of chemotherapy and radiation before surgery, he says.

However, most stage 3 NSCLCs are unresectable — they can’t be surgically removed &mdash; due to extensive lymph node involvement or because the tumor location is not amenable to surgery at this spot, says John Heinzerling, M.D., a radiation oncologist at Southeast Radiation Oncology Group in Charlotte, North Carolina. For the past 15 to 20 years, treatment for these unresectable cancers has remained consistent: chemotherapy and radiation, usually at the same time. “Most of the research in the last 20 years has been what chemotherapy to use; whether to use chemotherapy at the same time as radiation; and whether to use it before or after and what radiation dose to use,” he says. The current standard of care is to give a two-drug chemotherapy regimen concurrent with radiation. That includes six weeks of radiation, five days a week, and up to six cycles of chemotherapy.

Although chemotherapy is used, radiation is the most effective treatment for lung cancer, says Ronald McGarry, M.D., Ph.D., a clinical professor in the department of radiation medicine at the University of Kentucky in Lexington. “Chemotherapy has two roles in stage 3,” he says. “It makes the cancer cells more sensitive to the killing effect of radiation, and, in theory, it decreases the risk of metastatic disease.”

Immunotherapy — the use of substances to stimulate the immune system to help the body fight cancer &mdash; is the latest option to be added to stage 3 NSCLC treatment.

The FDA approved Imfinzi (durvalumab) for stage 3 unresectable NSCLC in February. The agency based its decision on findings from the phase 3 PACIFIC trial, which showed that patients who received Imfinzi went almost a year longer without worsening disease compared with those who didn’t get it (17.2 months versus 5.6 months, respectively). In September, newly published results showed a 24-month overall survival rate of 66.3 percent for those who received Imfinzi compared with 55.6 percent for those who did not.

“That’s the ultimate measure of benefit in oncology — do patients actually live longer?” says Julie Brahmer, M.D., co-director of the upper aerodigestive program at Johns Hopkins Medicine’s Bloomberg-Kimmel Institute for Cancer Immunotherapy in Baltimore. The study showed a significant prolonged overall survival.

Imfinzi blocks the PD-L1 pathway, which in turn stimulates the immune system to kill cancer cells. The drug is associated with a slight rise in toxicity and side effects, but it’s thought to be manageable. Imfinzi’s most common side effects involve the immune system attacking the body’s organs or healthy cells, and making a person more susceptible to infections. Because of the higher risk of complications, some patients with autoimmune disorders might not be offered Imfinzi. “Even that premise is being challenged now, in that there are some published reports indicating that patients with autoimmune diseases who have received it can be safely treated,” Garon says. “One place we’ve seen absolute contraindication is solid organ transplant.” That is due to a risk of organ rejection, he says, noting that clinicians are trying to define the risk factors.

Researchers are looking at different combinations of chemotherapy and radiation, along with adding immunotherapy at the same time as radiation, Brahmer says. Also, some studies are investigating whether Imfinzi treatment time can be shortened with the same benefit; others are looking at combinations of immunotherapies.

Stereotactic radiation has been given by radiation oncologists for stage 1 and 2 NSCLC for almost two decades, but now clinicians are testing the best sequence for treating stage 3 disease. Stereotactic radiation delivers a high dose of precisely targeted radiation to a smaller amount of tissue in fewer sessions than traditional radiation therapy. Heinzerling is conducting a trial, radiating the primary tumor in patients with stage 3 NSCLC in three to five treatments before beginning traditional radiation therapy. “We think that it prompts the immune system more, creating massive death of tumor cells, and that attracts the immune cells to go after the cancer,” he says. He then gives Imfinzi after traditional chemotherapy and radiation therapy, per current standards. He’s investigating whether the four elements provide better control of the chest tumor. Although the study is small, he says that they are seeing some very good responses in addition to low incidences of lung-related and other side effects.

One of his patients, 68-year-old Virginia Huerter, participated in the trial. Her lung cancer was discovered as an incidental finding when she had a septic bowel in February — she had two spots on her left lung, close to her throat. She received five treatments of stereotactic radiation before her radiation and chemotherapy began. “They say if they didn’t do anything, I had six months to a year,” she says. “I was told if they did something, there was a 30 percent chance it would work.” Her most recent CT scan, in August, showed no evidence of cancer, and she was able to skip her last two rounds of chemotherapy. Although Huerter knows about Imfinzi, she was unable to get it because of an autoimmune disorder.

McGarry offers his patients a so-called stereotactic boost after the chemotherapy and radiation are complete. “There’s up to (a) 30 to 40 percent chance the cancer will return in the chest,” he says. “The bigger the mass, the more likely it is to recur.” He gives the patients a little time off after chemotherapy and traditional radiation, then repeats a CT scan. If there’s residual disease, he gives stereotactic radiation treatments over three days and says that outcomes are much better for patients with stage 3a NSCLC. Although a stereotactic boost is not commonly offered, he says, he’s been doing it for 18 years, and insurance pays for it.

Experts agree that most patients can tolerate receiving chemotherapy and radiation during the same time, but this type of regimen does increase toxicity. The main pulmonary side effects are coughing, shortness of breath and lung scarring. Patients can also develop sore throats, fatigue and an irritated esophagus from the radiation. Chemotherapy raises the risk of infection and anemia, plus nausea. Both medical and radiation oncologists follow up with patients every week or two during treatment to check on side effects and blood counts. “Sometimes we end treatment early or modify it, but that’s pretty uncommon. Most can make it through the regimen,” Heinzerling says. That’s because the treatment is designed for each patient.

Some facilities offer integrative oncology, which combines complementary therapies such as acupuncture, guided imagery, massage and yoga — mainly for side effect management and stress relief &mdash; with medical treatment. Heinzerling says that at his facility, a staff member sees patients on an ongoing basis or recommends supplements or other therapies to try before or during treatment. Tips may include simple strategies, such as taking honey to ease pain when swallowing and esophageal irritation from radiation. To combat patients’ fatigue, the integrative staff may advise on dietary changes and ways to keep up with activities.

When 30-year-old Diane Spry got chemotherapy for her stage 3 lung cancer, she also received acupuncture to combat side effects, such as anxiety. “I was apprehensive about them sticking needles in me,” she says, but the thin needles inserted into her forehead, arms and legs ultimately helped. Spry also got magnets placed in her ears to help with nausea and vomiting. “Whenever I felt nauseous, I was to pinch my ears,” she says.

When stage 3 treatment is completed, patients are typically monitored for cancer and side effects for at least five years. “There’s no standard way to follow up and timing of scans is a clinical decision,” Brahmer says, although experts mentioned interim visits with the medical and radiation oncologists, including repeat chest CT scans every three to six months for three years followed by chest CT scans every six months for an additional two years. The scans then change to every year with low dose non-contract enhanced chest CT scans.

“They’re typically done with every six-month scans at five years,” Brahmer says. Patients are at risk not only of recurrence or spread of the original cancer but also the development of a new lung cancer.

Some clinics offer survivorship visits to discuss quality of life and potential long-term side effects of therapy that could occur in the next five to 10 years. “That way, if they have symptoms, (patients) will bring them to a doctor’s attention, as opposed to ignoring (them) or not telling the oncologist because they are aware that it may be related to their treatment,” Heinzerling says.

For example, three to 12 months after completing radiation, patients can get a pneumonia-like reaction called pneumonitis, which can affect the ability to be active and exercise but is reversible if treated properly with steroids. However, some clinicians confuse the diagnosis with bacterial pneumonia, for which antibiotics are prescribed. Other therapy-related side effects that may arise later include hormonal deficiencies from immunotherapy’s effects on endocrine glands like the thyroid or adrenals, or neuropathy from taxane- or platinum-based chemotherapy.

Metastases pose the biggest challenge in treating stage 3 patients, according to McGarry. “Ultimately, we can get good local control in the chest, and still the median survival is 24 months,” he says. “Most die of local failure or metastatic disease,” which is why he gives stereotactic radiation.

Both Segura and Spry’s lung cancers spread not long after their initial regimen. Segura was treated for stage 4 cancer, but in December 2015 doctors found no evidence of disease, and she takes maintenance chemotherapy daily. “They call me the walking miracle,” Segura says. She opened her own CrossFit studio in September 2016 and challenges her clients to exercise to their fullest, just as she does.

Spry’s cancer also changed to stage 4 after maintenance chemotherapy. Doctors found cancer cells in the fluid around her heart, plus a related blood clot on her heart valve. She takes medications to treat it. “I’m pretty healthy right now,” she says. “I don’t get winded very easily. I can still walk around.” In the five years since her diagnosis, Spry has gotten married and travels to places like California and the Bahamas. She is now looking for a full-time job. “I’m living my life,” she says.

She’s learned to be her own advocate by bringing up questions and concerns to her care team. “Sometimes I feel stupid asking questions, but I have to remember I’m paying them to help me,” Spry says.

Patients with stage 4 disease have new hope in three FDA approvals. In October, Keytruda (pembrolizumab), an immunotherapy, was approved in combination with with carboplatin and either paclitaxel or nab-paclitaxel for first-line treatment of patients with stage 4 squamous NSCLC. The regimen prolonged median overall survival by 4.6 months, compared with placebo, and reduced the risk of disease progression or death by 44 percent.

Two more medications were approved for people who have specific mutations: Lorbrena (lorlatinib) for the treatment of patients with ALK-positive, stage 4 NSCLC who progressed on one or more ALK tyrosine kinase inhibitor, and Vizimpro (dacomitinib) as a frontline treatment of patients with stage 4 NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations.

Although there haven’t been many changes in treatment during the last 25 years, clinicians are excited to see some positive momentum with immunotherapy. “For the first time, we’re seeing changes in treatment that are significant, and so the hope is that treatments continue to evolve at a more rapid pace and make it easier for patients to get their cancer under control — to tolerate the treatment and make a significant impact on this, even though it’s advanced stage disease,” Brahmer says.

Immunotherapy and stereotactic radiation are making a difference for some patients with advanced lung cancer.

Lung Special Issue (2) | CURE