Targeting lung cancer
By Colleen Steelquist




Last October, Terry Stoltenberg began to cough. And cough and cough. For four months.

As a longtime firefighter in one of the nation’s largest airports, he often delivered first aid to sniffly travelers who exposed him to viruses.

He also dismissed his cough as a byproduct of Seattle’s long and dank winter. It was his foot doctor, of all people, who off-handedly remarked, “Still got that pesky cough? Maybe you should go see someone about that.”

Terry Stoltenberg
Terry Stoltenberg

It’s pneumonia, another doctor told him after looking at a chest X-ray. Antibiotics followed but the cough did not go away. Finally, a CT scan unveiled a more ominous diagnosis last spring: A tumor in the lower lobe of his left lung. Stoltenberg was shocked by the diagnosis. He had never smoked and here he was, facing a tumor that could kill him very quickly.

Thousands of Americans face a similar crisis each year, even though many have never smoked. As many as 25 percent of all lung cancers are not due to smoking, making lung cancer in nonsmokers the seventh most common cause of cancer deaths worldwide.

Overall, lung cancer remains the leading cause of cancer death in the United States. Last year, it killed 157,300 men and women, more than breast, prostate, colon, liver and bladder cancers combined. Within this group, about 15,000 died from lung cancer even though they had never smoked.


While these are certainly grim statistics, the outlook is improving for lung cancer patients as researchers make unprecedented strides in the diagnosis and treatment of lung tumors.

Fred Hutchinson Cancer Research Center and its treatment partner, Seattle Cancer Care Alliance, are leading the way in a number of key research areas, from landmark biomarker discoveries for early detection to precise screening techniques and targeted therapies.

Just a few short years ago, Stoltenberg’s treatment choices would have been severely limited. But thanks to a team of Hutchinson Center and SCCA lung cancer experts armed with the most advanced technology, his malignancy was diagnosed and the fist-sized tumor removed, using the least invasive and most precise methods—methods perfected over the last decade with the help of Hutchinson Center and SCCA clinicians.

“Ten or 20 years ago, it’s safe to say that Terry’s lung cancer would have been found much later in its development, and his treatment options would have been limited. His prognosis for survival would have been poor,” said Dr. David Madtes, a pulmonary researcher at the Hutchinson Center and director of SCCA’s Lung Cancer Early Detection and Prevention Clinic. “The new treatments he received here have given him the best possible chance for long-term survival and possibly for a cure.”

Madtes’ specialized, three-year-old multidisciplinary clinic is one of only a few in the country that assesses people’s risk of lung cancer and expedites evaluations of suspicious findings, using state-of-the-art diagnostic techniques. The clinic’s emphasis on early detection—including a new CT screening program—and prevention through smoking cessation help make the clinic a unique resource in the region.

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For lung cancer patients in the near future, Hutchinson Center researchers are pioneering better ways to detect lung cancer long before symptoms—even easily ignored coughs—appear.

Dr. Sumir Hanash
Dr. Samir Hanash
A research team led by the Center’s Dr. Samir Hanash has discovered proteins in the blood associated with early lung cancer development. This advance—a landmark in the field—brings us closer to developing a simple blood test for the early detection and diagnosis of lung cancer.

The study revealed that these telltale proteins—known as biomarkers—were present in blood samples from people with lung cancer at the time of their diagnosis as well as in samples from people before they experienced symptoms who were later diagnosed with lung cancer.

A blood test looking for these proteins could soon be developed to screen for lung cancer among high-risk individuals, such as current and former smokers, and to aid in diagnosis, distinguishing between various subtypes of the disease, including small-cell lung cancer and lung adenocarcinoma (see “Lung cancer at a glance,” below).

Hanash and his colleagues envision such a test being used together with imaging technologies like CT screening to monitor people at high risk of developing the disease, as well as to help detect, classify and scrutinize cancer progression and regression.

The biomarker research could lead to a two-stage screening process, where a first, inexpensive test like the one Hanash is developing could identify individuals who might benefit from a second, more costly and intensive screening test.

In another effort to identify biomarkers in the blood that could aid in lung cancer treatment, Madtes and his Center colleague, Dr. Mandy Paulovich, are evaluating the blood of late-stage lung cancer patients receiving the chemotherapy drug cisplatin. The treatment shrinks tumors in some patients but not others. They are looking for biomarkers that could identify which patients will benefit from cisplatin. The goal, Madtes said, is personalized medicine.

“We want to be able to profile a patient’s tumor so the chemotherapy received is better tailored for a high probability of success,” he said. “It will help expedite the best treatment for the patient and minimize side effects and toxicities.”

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As Madtes points out, lung cancer can be cured, but it has to be detected early, while the tumor is still small and confined to the lung in which it developed. Unfortunately, by the time the cancer causes symptoms, it is usually too far advanced to cure.

The five-year survival rate for lung cancer is low, just 15 percent, a number that hasn’t budged for three decades. By comparison, survival rates for breast and prostate cancers over the same span have improved to 87 percent and 99 percent, respectively.

So, like some other cancers, it would make sense to undergo screening at regular intervals. One problem: There hasn’t been clear scientific evidence to support routine lung cancer screening. But that is changing.

In August, the National Cancer Institute published the very promising results of the National Lung Screening Trial, a large-scale study using low-dose CT scans as a method of screening patients at high risk for lung cancer. The study of more than 53,000 current and former heavy smokers ages 55 to 74 found those screened with a low-dose CT scan cut their risk of dying of lung cancer by 20 percent.

More will be known when NCI publishes additional detailed analyses of the screening trial. But it appears likely that low-dose CT screening will have profound implications for lung cancer detection.

Madtes said repeat CT scans in short intervals might be the best course for high-risk patients because it could identify a growing tumor (lung cancer can double in volume in fewer than 400 days).

Dr. David Madtes
Dr. David Madtes

“We’ll want to see if a lesion grows from the size of a pea to a marble in a short period of time,” he said.

The promising direction of low-dose CT screening doesn’t mean everyone should line up for a scan. The exam’s radiation can have serious downsides, including false alarms that could lead to unnecessary surgery.

Acknowledging the potential to do harm with overaggressive screening, Madtes said a balance must be struck. “Nobody has really worked out the ideal algorithm yet,” he said. “It’s part of our mission to sort that out.”

Madtes and his colleagues at SCCA’s Lung Cancer Early Detection and Prevention Clinic will be at the forefront of sorting it out as they launch their new low-dose CT scan screening program—one of only a handful in the country linked to a multidisciplinary team for lung cancer diagnosis and treatment

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Detecting lung cancer earlier is an important first step that keeps more treatment options open to patients. Once cancer is found, having better treatment options will ultimately improve survival rates. One area that is showing great promise is targeted therapy.

Dr. Renato Martins, a lung cancer specialist at SCCA and University of Washington and Hutchinson Center researcher, has been on the leading edge of research aimed at finding and treating faulty genes or proteins that contribute to cancer development and growth.

One particular faulty gene is found in more than 50 percent of the most common type of non-small cell lung cancers. For reasons that remain unclear, these mutations are most often seen in patients who are female, Asian and nonsmokers.

To treat this mutation, Martins helped drive a major study that led to the approval of the first targeted therapy drug, known as erlotinib. It blocks cancer cells from multiplying—helping to slow or stop the spread of cancer in some patients.

In addition, SCCA is conducting several clinical studies to test the efficacy of a number of drugs to treat lung cancer.

“We have a robust program, and we’re the leading center in the country for a new drug called MDX-1105 that stimulates the patient’s immune system to fight the cancer,” Martins said. “If I had been told 10 years ago that we would be able to keep someone’s disease under control for two years plus just by taking a pill, I would have difficulty believing that we could have come this far along,” said Martins in a recent interview. “Hopefully, this is just the beginning.”

Thanks to the advances being made at the Hutchinson Center in early detection and targeted therapies, rising survival rates may be on the horizon for cancer’s biggest killer. This gives researchers like Hanash, Madtes and Martins good reason to be optimistic.

“We need to improve outcomes,” Madtes said. “It’s been a real push to improve outcomes in advanced stage disease. With better early detection, we’ll be able to surgically remove tumors before they advance. That’s where the cure is.”

Lung cancer at a glance

Lung cancer, like many other cancers, is not just one disease. There are two main types:

Small-cell lung cancer (about 15 percent of cases) grows rapidly and aggressively but is very sensitive to chemotherapy and radiation treatments, so surgery is rarely performed. However, two-thirds of all patients with SCLC are diagnosed after the disease has already spread throughout the body, diminishing survival.

Non-small cell lung cancer accounts for about 85 percent of cases in the U.S.:

  1. Adenocarcinoma is the single most common type of lung cancer (40 percent); it often occurs at the outer edges of the lungs and has the best prognosis.
  2. Squamous cell carcinoma (30 percent) is often found in the center of the lungs. The risk of developing this type of lung cancer increases in direct proportion to the number of cigarettes smoked over time.
  3. Large cell carcinoma (15 percent) tends to begin in the outer regions of the lungs and grows rapidly.
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