Illustration of man with bird for lungs

(Illustration/Curtis Parker)

When physician Jorge Nieva first started treating patients diagnosed with advanced lung cancer, he rarely got to know many of them for long. Most died in a year or less.

Much has changed over two decades. Now, Nieva, associate professor of clinical medicine at Keck Medicine of USC in Los Angeles, still sees patients he met the first week he joined USC’s faculty as a medical oncologist in 2014.

More patients than ever are beating advanced lung cancer thanks to improved diagnostics and treatments. Physicians are even using the word “cure” for many patients with stage 4 lung cancer — advanced disease in which tumor cells have spread beyond the lungs. As many as 40% of lung cancer patients have stage 4 disease at the time they’re diagnosed.

For a determined team of lung cancer experts at USC Norris Comprehensive Cancer Center, this progress can’t come fast enough. “Treating this disease isn’t a job — it’s a calling,” says Anthony W. Kim, chief of thoracic surgery at Keck Medicine of USC and an expert in thoracic oncology.

Today, physicians like Kim and Nieva are rewriting the story on hopes for survival.

Optimal Lung Cancer Treatment Starts with Early Detection

Physicians have long needed better tools to fight lung cancer. Despite improvements, lung cancer remains the leading cause of cancer death among men and women in the United States. Every year, more people die of the disease than of colon, breast and prostate cancers combined.

But medical science offers reasons for optimism. The first-ever screening tool for lung cancer — a low-dose computed tomography, or CT, scan — now enables physicians to find cancer early. That’s a major achievement, since symptoms rarely show until the disease has spread and it’s harder to treat.

Experts recommend the screenings for certain people at high risk for lung cancer: patients ages 55 to 80 with a history of heavy smoking. A national lung screening trial showed that patients screened with CT had a 20% lower risk of dying from lung cancer compared to patients screened using x-rays. Last year, a similar clinical trial in Europe found even higher survival rates.

Yet fewer than 5% of the Americans eligible for the screenings get them. One reason: Many smokers (and sometimes their doctors) shy away from the screenings because they perceive a stigma around smoking, says Keck Medicine radiologist Christopher Lee, director of USC’s Lung Cancer Screening Program. Lee and colleagues regularly reach out to smokers to come to Keck Medicine’s facility. The Lung Cancer Alliance has named it a Screening Center of Excellence. Besides smokers screened as part of routine care, Lee has provided free screenings to more than 800 people in underserved Southern California communities with the help of grants.

Lung cancer hits more than smokers, though. Nearly one-fourth of all lung cancer patients in California — and one-fifth nationwide — have never smoked. Scientists lack evidence that using CT to screen these “never-smokers” is effective. So, screening tools for the broader population remain a needed but elusive target.

Doctors also have no definitive answer to why never-smokers develop lung cancer. They do know that some factors beyond cigarette smoking can put people at risk. The second-leading cause is environmental exposure to radon, a colorless, odorless gas present in soil.

Drugs for a New Era

USC lung cancer treatment experts don’t treat all lung cancers the same, because lung tumors can be different from patient to patient. Although lung cancer is typically divided into two broad classifications — non-small cell lung cancer (about 85%) and small cell lung cancer (15%) — it comprises many types of disease. Each person’s lung tumor has its own fingerprint and behavior. As scientists make discoveries about different types of lung cancer, treatment milestones have quickly followed.

The U.S. Food and Drug Administration approved more therapies for lung cancer in the last two-and-a-half years than in the previous decade. The reason is twofold. Scientists accelerated the development of new drugs, and the FDA okayed the use of those drugs quickly. They moved them ahead as soon as therapies showed they could shrink tumors, for example, instead of requiring proof of long-term survival, as they did in the past.

Many recently approved drugs work against cancers with certain genetic mutations by interfering with mechanisms that cancers use to grow and spread. “Our understanding of the biology of the disease is changing, so how we take care of it is changing as well,” says Elizabeth A. David, Keck Medicine thoracic surgeon and associate professor of clinical surgery in the Keck School of Medicine of USC.

Keck Medicine physician-scientists are now analyzing each patient’s lung cancer for any known genetic mutations (and hunting for new ones), all so they can match each patient with the most effective medicine. One of these drug targets is a mutation in a gene that holds the formula for the protein EGFR, or epithelial growth factor receptor. EGFR gene mutations cause the body to produce too much of this protein, which can fuel aggressive cancer.

These mutations frequently are found among people of Asian or Latino descent with lung cancer, who comprise 25% of Keck Medicine’s lung cancer patient population. The FDA has approved five oral drugs for EGFR mutations so far.

For other patients, doctors are finding ways to fire up the immune system to fight lung cancer cells and make them more vulnerable to treatment. A 2018 study found that adding immune-boosting drugs to conventional chemotherapy resulted in longer survival without disease progression for patients with advanced lung cancer.

The caveat: Immunotherapy hasn’t proven effective for many never-smokers with lung cancer. Even among current or former smokers, immunotherapy only works for about 20 percent of patients, so researchers continue their search for better treatments.

Illustration of woman with bird for lungs

(Illustration/Curtis Parker)

USC Lung Cancer Treatment Experts Have Lots of Options

One option is adding radiation therapy to the mix. A recent study suggests that adding radiation to chemotherapy and immunotherapy improves the odds of survival for patients with stage 3 lung cancer. The researchers used what’s called stereotactic body radiation therapy, or SBRT, which enables physicians to precisely deliver high doses of radiation and spare healthy tissue.

Keck Medicine physicians are part of a national study using their TrueBeam STx radiosurgery machine to test the strategy’s benefits. They’re also studying whether radiation can help the immune system recognize cancer cells through different research protocols. “We’re excited to explore such promising options for our patients,” says Jason Ye, assistant professor of radiation oncology.

For patients with stage one lung cancer, SBRT is also proving to be a viable alternative to surgery. For many patients, the cure rate is the same as with a surgical procedure, so it’s especially promising for those who cannot tolerate surgery. New technology can deliver doses three times faster than previously possible. For some patients with lung cancer, Ye is able to reduce radiation treatment to a single session.

Surgery remains the gold standard of treatment, and it’s often more effective when paired with other therapies. Sometimes patients go through chemotherapy and radiation to shrink tumors before surgeons operate. Keck Medicine is the largest recruiting center for a major international study exploring whether immunotherapy and chemotherapy before surgery can prolong life for lung cancer patients. And other trials are looking at chemotherapy’s capacity to kill remaining cancer cells after surgery.

To devise the best treatment plan, specialists spanning many disciplines meet face to face in twice-weekly sessions to look at all the facts about each patient’s cancer and chart the best possible approach.

Patient Jay Gordonson experienced the advantages of this multidisciplinary powerhouse. “Very professional,” he says. He should know. Gordonson, 82, joined the staff at LAC+USC Medical Center as a diagnostic radiologist in the late 1960s and is an assistant professor of radiology at the Keck School of Medicine.

In early 2018, Gordonson began experiencing pain in his jaw and his groin. He also felt run down. Physicians diagnosed him with stage 2 lung cancer. He had been exposed to secondhand smoke much of his adult life and smoked cigarettes on and off in his 20s and 30s. But he hadn’t smoked for more than four decades. He turned to the Keck Medicine of USC lung cancer treatment team for help.

After thoracic surgeon Anthony Kim removed a lobe of one of Gordonson’s lungs, his medical team found the cancer was more extensive than expected. Nieva and Ye met with Gordonson to outline their plan for his care after surgery, which involved four cycles of chemotherapy, followed by radiation therapy a month later. “The sessions were streamlined, which made it very easy,” Gordonson says.

His daughter, Krista Gordonson, found the plan comforting. “We knew the steps we’d go through. It made us feel proactive and taken care of at the same time,” she says.

A recent follow-up scan showed no signs of cancer.

As many patients are finding answers to their cancer, big questions remain. What can physicians offer patients whose cancer becomes resistant to targeted medications? Why are women who quit smoking more likely to develop lung cancer than men who quit? And why are so many women who never smoked developing the disease?

Researchers see potential for discovery in the questions — and for hope. Ten years ago, curing advanced lung cancer seemed like a crazy concept, Nieva says. “It’s no longer an impossible dream. We can cure some. Now let’s cure more.”

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