The multidisciplinary lung cancer program at USC Norris Comprehensive Cancer Center is helping to transform a once-dire prognosis with attitude and evidence.

Not long ago, lung cancer was thought of as a disease that only affected the elderly — specifically, lifelong, heavy smokers. And it nearly always had a terrible prognosis. Those stereotypes are now out the window. Today — thanks to some stunning advances in immunotherapy, radiation oncology, minimally invasive surgery, molecular-based therapies, new diagnostic tools and more — surviving lung cancer in the long term is becoming more and more possible.

“Previously when I saw a Stage IV patient, I told them that the lung cancer almost certainly was going to be the cause of their death. Because of all the progress we have made, I don’t have to say that anymore,” says Jorge Nieva, MD, associate professor of clinical medicine at the Keck School of Medicine of USC and medical oncologist at the USC Norris Comprehensive Cancer Center.

USC Norris is front and center in this revolution, thanks to a lung cancer program that is pushing boundaries with ambitious research and cutting-edge, personalized care. It is one of the few programs in the country where patients can be evaluated in a one-stop visit by physicians of different specialties, including a thoracic surgeon, pulmonologist, medical oncologist and radiation oncologist. In addition, a nurse navigator guides patients from their first visit on.

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Care is delivered by subspecialists “who devote their careers to treating lung cancer and, therefore, understand the disease better,” says Anthony W. Kim, MD, MS, professor of clinical surgery and chief of the division of thoracic surgery.

Today’s lung cancer

The USC Norris lung cancer team meets weekly in a multidisciplinary Tumor Board to discuss individual cases and rapidly emerging treatment options.

This high-level expertise is needed because, despite advances, each year more people die of lung cancer than of colon, breast and prostate cancers combined, according to the American Lung Association.

The most significant cause is still attributable to tobacco use, but a decline in smoking in the U.S. has led to a new phenomenon — an increase in lung cancer among young non-smokers. Doctors do not yet fully understand the reason, but what they do know is leading to new experimental therapies.

“The majority of non-smoking patients with lung cancer have DNA alterations treatable with targeted medications in pill form,” Nieva explains.

Another surprising discovery in the last five years is that the lung cancer that typically strikes older, current or past smokers is highly sensitive to immunotherapy.

In 2016, the U.S. Food and Drug Administration (FDA) approved an immunotherapy drug called pembrolizumab (marketed in the U.S. as Keytruda®) to treat metastatic, non-small cell lung cancer, based on a clinical trial in which the drug did better than chemotherapy in extending patient survival. Known as a “checkpoint inhibitor,” pembrolizumab works by unleashing the body’s immune system on the cancer cells and it’s had some impressive results, like helping halt former President Jimmy Carter’s brain cancer in 2016.

Looking for the genetic key

At USC Norris, everything begins with making sure all patients have appropriate genomic characterization of their tumors. Fine-tuning those DNA distinctions with accurate biopsies and biomarker studies “makes a difference in our approach and our patients’ outcomes,” Nieva notes.

USC Norris has earned a reputation for matching aggressive forms of lung cancer with aggressive treatments. “When patients come see us, they know we’re jumping into the trenches with them,” Kim says. “We’re going to fight with them. That brings a lot of peace of mind.” Underlying this attitude are the program’s standardized protocols — guidelines rooted in what’s best for the patient that ensure consistent, systematic treatment. “As long as the evidence is there,” Kim says, “then you move forward.”

New diagnostic tools

Part of what makes lung cancer such a deadly disease is that symptoms often don’t appear until the cancer is advanced, complicating its prognosis. Until recently, lung cancer was the only major cancer without a screening method. But in 2011, the National Lung Screening Trial — involving 55,000 current or former smokers ages 55 to 74 — showed that low-dose CT scans can help lower the risk of dying from lung cancer by 20 percent compared to chest X-ray.

USC’s robust Lung Cancer Screening program has already logged success stories. “We’ve caught a few cases of early-stage lung cancer and were able to treat them for cure,” says its director Christopher Lee, MD, associate professor of clinical radiology.

Armed with a grant from the California Community Foundation, Lee recently headed up a project to provide free screening for more than 300 socioeconomically disadvantaged south Los Angeles County residents considered at high risk for lung cancer. USC is also one of a select few sites for a multicenter study that is coupling screening with blood tests to look for biomarkers for lung cancer. The goal: catch the disease even earlier.

Also changing lung cancer diagnosis is interventional pulmonology. In the past, the only way to determine how far the cancer had advanced was through a surgical biopsy. Now, however, Ramyar Mahdavi, MD, clinical assistant professor of medicine (clinician educator), with expertise in pulmonology, commands a specialized set of minimally invasive tools that include endobronchial ultrasound (EBUS).

This special bronchoscope with a rotating ultrasound probe lets Mahdavi see tumors or other masses beyond the airway walls, or hunt down enlarged lymph nodes. He then deploys a needle into the target to sample the node for cancer staging. Another tool in the team’s diagnostic toolbox is electromagnetic navigational bronchoscopy, which acts as a GPS-like guide through the airways to enable biopsies of very small nodules in the lung periphery. These can be difficult or even impossible to reach with regular bronchoscopy or surgery. And faced with central airway masses due to cancer, the interventional pulmonologist can call on laser therapy or argon plasma coagulation, a form of electrosurgery, to debulk and remove a tumor. “This is a great method to improve a patient’s quality of life,” Mahdavi says.

The fluid biopsy, in use at USC Norris, also can eliminate the need for invasive surgical biopsies. It works by finding the DNA of a tumor in the bloodstream, giving doctors an idea why the cancer occurred and what the best treatment for it might be. That information helps determine whether patients should be treated with chemotherapy, immune therapy or targeted therapies aimed at the drivers of cancer.

Robotic surgery experts

Surgery remains the go-to treatment for early-stage diagnoses, but even surgical options have seen technological advances. Keck Medicine of USC was one of the pioneers of robotic surgery and remains one of a few academic centers to offer a high-caliber level of robotic expertise — with USC Norris thoracic surgeons collectively offering the most experience in the region.

Surgical robotic systems translate the surgeon’s hand movements into highly precise “micro” movements, enabling smaller incisions, which in turn shortens recovery time. Also in the surgeons’ repertoire is video-assisted thorascoscopic surgical (VATS) lung resections, in which a tiny camera and surgical instruments are inserted into the chest through small incisions.

Non-surgical therapies

Increasingly, non-surgical treatments, such as stereotactic body radiation therapy (SBRT) and percutaneous thermal ablation, are being deployed to help lung cancer patients. Early results of SBRT have shown promise in having equivalent or near equivalent outcomes to surgery for some lung cancers. It also is attracting interest for more advanced cancers. Within USC Norris, a 4-D CT scan, which tracks tumor motion throughout a patient’s breathing, is used to develop radiotherapy plans that accurately target the tumor.

Intensity-modulated radiation therapy (IMRT) and volumetric arc therapy use hundreds of tiny beam-shaping devices from multiple angles to deliver precise doses of radiation to the tumor while sparing surrounding healthy tissue. Using the most advanced technology available, doctors are able to track the patient’s breathing motion and tumor position throughout treatment.

“USC Norris is one of the few sites in Los Angeles equipped with this level of technology and expertise,” says assistant professor of clinical radiation oncology Jason Ye, MD. “We are able to see when the tumor is moving and confirm our target is absolutely accurate.”

CT-guided percutaneous thermal ablation is another promising option for patients who are not able to undergo surgery because of age or illness. Thermal ablation kills tumors with extreme cold — literally freezing the tumor — or high heat via microwave. Unlike radiation treatments, which may span weeks, ablation takes place in a single visit.

Bold experiments

USC Norris supports an active clinical trials program that includes investigations of immunotherapy agents in combination with other drugs, including one developed at USC that interferes with a tumor’s communication ability.

It’s also a U.S. site for a study of immunotherapy for early-stage lung cancer sponsored by the National Cancer Institute of Canada. Other ongoing trials focus on drugs that can penetrate the brain to target epidermal growth factor receptor (EGFR) mutation-associated tumors, which affect about 25 percent of USC Norris lung cancer patients.

The bottom line for this expanding list of treatment options: individualized care. According to Kim, “We work hard to make sure our patients get the best possible care, from the most experienced doctors, using the highest level of technology available. Thanks to the expertise of this team, we can identify the therapy or combination of therapies best suited for each patient — that’s our goal.”

By Candace Pearson