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Q&A: What's Going On With Lung Cancer Research?

In August, UVA Cancer Center became the first in Virginia to offer lung cancer patients the new drug tarlatamab, approved in May as immunotherapy to supercharge the body's immune system to fight small-cell lung cancer in combination with chemotherapy.

The drug went through Phase 3 testing for the FDA at the Cancer Center and was one of several potential treatments investigated by the center's researchers.

"We have a number of clinical trials at any given time for various subtypes and stages of the disease," said Dr. Ryan Gentzler, a long-time thoracic medical oncologist at UVA Health treating patients with cancer in the chest, predominantly lung cancer.

"Some of those are early phase clinical trials developing brand-new drugs without a lot of track record, and some are later-phase trials, like in Phase 3 trials that have the potential to change the standard of care and get an FDA approval."

UVA Today asked Gentzler about research involving lung cancer and its possible treatments.

Q. Can you contextualize lung cancer among other types of cancer? 

A. Lung cancer is the most common cause of cancer in the United States and globally in terms of incidence. It's second to breast cancer in women and prostate cancer in men, but the mortality rate is much higher. It remains the No. 1 cause of cancer-related deaths, and 80% of cases are typically attributed to tobacco exposure.

Typically, heavier tobacco users are more likely to get lung cancer, but interestingly, about 20% of lung cancers happen in patients who have never smoked. We typically see this in younger individuals and women.

Fortunately, lung cancer rates have been dropping since smoking rates have started declining over the last couple of decades. We've also seen new lung cancer diagnoses dropping and survival rates improving due to advanced therapies. 

Q. What other trends have we seen in the past decades?

A. One worrying trend is that lung cancer is on the rise within the group of patients who never smoked and tends to be on the rise faster in women. We don't fully understand why that may be.

Other causes of lung cancer are well known, like radon gas exposure, which happens to be fairly prevalent in Appalachia. It's harder to quantify and pin down, especially as society has become more mobile, and people are not living in one house their entire lives.

There's also some research and interest in particulate-matter pollution and smaller fine particles in the air and their links to developing cancer. In large cities in China, for example, higher rates of lung cancer are potentially attributed to environmental exposure and air pollution.

Portrait of Dr. Ryan Gentzler.

Dr. Ryan Gentzler is a thoracic medical oncologist at UVA Health specialized in treating patients with lung cancer. (Photo by Matt Riley, University Communications)

Probably the biggest change in lung cancer in the last decade has been our ability to identify molecular subsets based on genetic profiles and create individual treatments based on the genetic makeup of a tumor. The other big thing is immunotherapy, which was initially used in patients with late-stage or Stage 4 cancer and is now being used in Stage 2 and 3 patients in addition to things like chemotherapy.

Lung cancer screening has been around for more than a decade now, so patients who are at higher risk of developing lung cancer are eligible. This is typically older individuals who have smoked for 15 years or longer. The original guidelines have been tweaked, and the ages for recommended screening have come down from 55 to 80 years to 50 to 80 years.

Q. As increased legalization of marijuana leads to more legal consumption, vapes maintain popularity and hookahs gain popularity, how will those activities affect lung cancer risks?

A. We really don't know. Things like vaping are brand-new phenomena, and we don't have decades of follow-up research to know if they increase the risk of lung cancer.

Vapes have been linked to other pulmonary diseases, including fibrosis. When inhaling substances, whether marijuana or vapes, there's potential for lung injury and damage or at least irritation and inflammation.

Chronic use over many years could potentially lead to cancer development. It is probably a different mechanism than tobacco smoke, which is known to have multiple carcinogens in it. Marijuana itself is not a carcinogen.


Stage III Lung Cancer

Doctors use stages to describe how much cancer you have and where it is in your body. People with stage III lung cancer can be a very mixed group. Their tumors can differ in size, location, and how distant they are from where the cancer started.

But almost always, stage III cancer is in just one lung. It's also limited to the lymph nodes, organs, and other tissue near that organ. The cancer has not spread, or metastasized, beyond that. That's why this stage is also called locally advanced or locoregional disease.

The next stage, stage IV, is the last and most serious stage of lung cancer.

Nearly 9 out of 10 people with lung cancer have non-small-cell lung cancer (NSCLC). A rarer and more aggressive type is called small-cell lung cancer. But the numbered stages are used mainly for the more common NSCLC.

Staging uses three key criteria called TNM:

  • Tumor (T): How big and where is the tumor?
  • Nodes (N): Is the cancer in nearby lymph nodes?
  • Metastasis (M): How far has the cancer spread from its original spot?
  • Doctors split stage III non-small-cell lung cancer into three main subtypes. It helps them get a more detailed picture of your cancer and decide on the best treatments.

    Stage IIIA. You have one or more tumors in one lung. The cancer is in nearby lymph nodes. The cancer may be in certain nearby tissues, but it hasn't reached distant organs.

    Stage IIIB. You have one or more tumors in the same lung. Your cancer may have spread to lymph nodes above your collarbone and may be in lymph nodes on the opposite side of your chest. The cancer may be in certain nearby tissues but not in distant organs.

    Stage IIIC. This is the most advanced stage within stage III. You have one or more tumors in the same lung. Your cancer has spread to lymph nodes above your collarbone or to lymph nodes on the opposite side of your chest. The cancer may be in the chest wall, heart, breastbone, and other nearby tissues but hasn't spread to distant organs.

    Most non-small-cell lung cancer is found after it's become advanced. That's partly because the disease worsens quickly and often doesn't have signs in the early stages. But symptoms may include:

    If your stage III lung cancer has spread beyond your lungs, it can cause other symptoms. For example, you may have bone pain if it has spread to your bones.

    Your doctor probably found your lung cancer after checking your symptoms. Most people aren't routinely checked for the disease unless they smoke or otherwise face a higher risk.

    If you have symptoms of lung cancer, your doctor will likely order a chest X-ray to learn more. (Photo Credit: Stockbyte/Getty Images)

    A chest X-ray is often the first image test. If it suggests you have cancer, you'll have follow-up tests, such as:

    CT scan. Your doctor may order a "contrast-enhanced" version of this scan, which can take more detailed images.

    Your doctor may run other tests to check the extent of your cancer. They might include:

    Biopsy. A doctor will examine a sample of your tissue under a microscope to confirm that it's cancer.

    Your doctors have several ways to treat you based on the size, location, and other characteristics of your cancer, including:

  • Chemotherapy. This drug therapy uses chemicals to kill and limit the growth of new cancer cells. You may get this after surgery to help suppress any future cancers.
  • Radiation. Your doctor will use powerful radiation to destroy cancer cells. If surgery fails to take out all of the cancer, you may get radiation therapy, or you may have chemotherapy followed by radiation therapy.
  • Chemoradiation. If surgery isn't an option, you may get chemotherapy, radiation therapy, or both at the same time.
  • Immunotherapy. This therapy uses drugs to rally your body's immune system to fight the cancer. Your doctor may use immunotherapy as a first treatment if surgery isn't a good choice, or use it after chemoradiation.
  • Stage III lung cancer surgery

    If possible, your doctor may opt for an operation to remove all the tumors from your lungs. If your lung cancer has spread into your lymph nodes, they may not be able to remove all of it. Some surgical options include:

  • Lobectomy. Your lungs are made of lobes, or sections. Your right lung is slightly larger, with three lobes, while the left has only two. During this surgery, the entire lobe containing the tumor will be removed. 
  • Wedge resection. This is when only part of a lobe is removed. Your doctor may refer to this surgery as a "segmentectomy."
  • Adjuvant therapy

    After you have a primary treatment for your lung cancer, such as surgery, chemotherapy, or radiation, your health care team may recommend adjuvant therapy, or treatments that try to keep your cancer from coming back. Adjuvant therapy may include additional chemotherapy, targeted drug therapy, or immunotherapy. You may receive adjuvant therapy for a few weeks or up to 10 years, depending on your overall health and how likely it is for your cancer to come back.

    Talk with your doctor to understand your treatment plan.

    More people in the U.S. Die of lung cancer than of breast, colon, and prostate cancers combined. About 1 in 3 people diagnosed with stage IIIA lung cancer live for at least 5 years after their diagnosis. For stage IIIB, the average 5-year survival rate is 26%. For stage IIIC, it's 13%.

    Your long-term outlook may be better if you:

  • Have lost less than 5% of your weight before starting treatment
  • Are a woman or were assigned female at birth
  • Do not have a lung infection, collapsed lung, or fluid buildup around the lung
  • Have a type of cancer cell that responds well to certain treatments
  • Any serious illness can bring worry, uncertainty, and other challenges to you and your loved ones. Try to:

    Manage your pain. You may feel pain not only from your cancer but also from treatments as well. Work with your doctors to control your pain as well as you can. That also may help lower your chances of depression.

    Ease other symptoms. Weight loss is common when you have cancer. Eat well to help keep up your strength and to prevent infections. For constant coughs, you might find relief with:

    Pulmonary rehab may also improve your symptoms and quality of life. It may help you breathe easier and stay more active.

    Quit smoking. It's never too late to stop. People who give up smoking before their cancer treatments tend to respond better. If it's hard for you to quit, a smoking cessation program may help.

    Connect with others. There is no such thing as too much support. It may help to talk to a medical social worker, mental health counselor, or other professionals. Join a cancer support group, either in person or online. Find out if any local groups offer free rides to appointments and other help. The American Cancer Society has a searchable directory of programs.

    If you've smoked heavily in the past, your doctor may recommend you get screened for lung cancer each year. Using a low-dose CT scan (LDCT), a type of noninvasive X-ray, your doctor can check for early signs of lung cancer before you even have symptoms. 

    You may be a candidate for yearly lung cancer screening if you:

  • Are between 50 and 80 years old
  • Smoke currently or quit in the last 15 years
  • Have at least a "20-pack year" smoking history. You can determine your pack years by multiplying how many years you've smoked by how many packs of cigarettes you smoke(d) each day.
  • LDCT scans expose you to a small amount of radiation, which can increase your risk of cancer, but this test uses less radiation than a standard CT scan. The benefits of the scan typically outweigh its risks, as earlier stages of lung cancer are easier to treat if your doctor sees any early signs of cancer.

    Stage III lung cancer is when you have cancer in one or more lobes, or sections, of one lung. Depending on how progressed it is, cancer at this stage may have also spread to nearby lymph nodes and tissue. The diagnosis is serious, but treatments for stage III lung cancer, including chemotherapy, radiation, and surgery, may be able to improve your outlook. If you smoke now or have smoked heavily in the last 15 years, talk with your doctor to see if you're a good candidate for yearly lung cancer screening.

    Is stage III lung cancer terminal?

    No. Everyone's cancer and response to treatment are different. However, therapies for stage III lung cancer are improving, and survival rates have gotten better in recent years.

    How long can you live with stage III lung cancer?

    Everyone's outlook is different, but on average, 15 in 100 people with stage III cancer will live 5 years after they've been diagnosed.

    What is the most aggressive form of lung cancer?

    Small cell lung cancer is the most aggressive form of the illness. It usually begins in the airways and can quickly spread to other parts of the body.


    Dave Coulier Has Stage 3 Cancer: 'Doesn't Sound Great,' But It's 'very Treatable'

    "Full House" star Dave Coulier, who played the Tanner family's zany Uncle Joey, has cancer.

    The 65-year-old publicly disclosed his diagnosis Wednesday, telling People and appearing on NBC's "Today" to confirm that he was diagnosed with Stage 3 non-Hodgkin's lymphoma five weeks prior.

    Representatives for Coulier did not immediately respond Wednesday to The Times' requests for comment.

    The "Fuller House" actor said he was diagnosed with the blood cancer in October after contracting an upper respiratory infection that caused major swelling in his lymph nodes. The swelling increased quickly and a node in his groin swelled to the size of a golf ball, he said. He asked his doctors to remove it and conduct a biopsy, which came back cancerous.

    "[M]y doctors called me back and they said, 'We wish we had better news for you, but you have non-Hodgkin's lymphoma and it's called B cell and it's very aggressive,'" he told People. "I went from, I got a little bit of a head cold to I have cancer, and it was pretty overwhelming."

    Non-Hodgkin's lymphoma develops in B-lymphocytes, which are part of the body's immune system and account for the majority of non-Hodgkin lymphomas, according to the American Cancer Society. More than 80,000 Americans are diagnosed with the disease each year, and the five-year relative survival rate is 74%. That percentage can vary widely depending on the type of lymphoma and the stage it was diagnosed and treated in.

    Coulier made light of his prognosis during his "Today" sit-down with host Hoda Kotb.

    "My joke is that in four short weeks I've gone from a Virgo to a Cancer," he quipped. "I've tried to retain a sense of reality but also a sense of humor about it."

    As he, his wife Melissa and his doctors figured out his treatment plan, he was relieved to learn that the cancer had not spread to his bone marrow.

    "[Stage 3] doesn't sound great," Coulier said, noting that curability rate is higher than 90%. "It's very treatable."

    The "Robot Chicken" and "American Dad!" voice actor has already undergone surgery to place a chemotherapy port to facilitate treatments. He started chemo two weeks after his diagnosis and is expected to have six rounds every 21 days through February 2025. After that, his doctors told him he could expect "total remission."

    "You hear 'chemo,' and it scares the daylights out of you," Coulier told Kotb. "The first round was pretty intense because you don't know what to expect. You don't know how you're going to feel. Is this going to hit me immediately? Is it going to be devastating? Am I going to walk out of here?"

    "It's been a bit of a roller coaster. There [are] days where I feel unbelievable," he added. "Then there's other days where … I'm just going to lay down and let this be what it's going to be."

    "The Real Ghostbusters" alum said he has lost at least three family members to cancer, including his mother and sister. He hoped that sharing his story would encourage people to be screened or get other exams to help detect the presence of cancer, saying, "It's a really simple thing to do and it can add years to your life."

    While Coulier hasn't been able to continue to play his beloved hockey, he is looking forward to becoming a grandfather when his son welcomes his first child and has continued to record episodes of the "Full House Rewind" podcast. He's also expecting a visit from his longtime co-star John Stamos later this week.

    Coulier, Stamos and late comedian Bob Saget played a trio of "Three Men and a Baby"-style dads and uncles in the ABC sitcom "Full House" and its Netflix revival, "Fuller House." But instead of a baby they were raising a widower's three young daughters and expanded their San Francisco home to accommodate the growing family. Coulier played the basement-dwelling Uncle Joey, a struggling stand-up comedian who used the catchphrase "Cut it out" and a puppet to help teach the Tanner girls life lessons.

    The situation comedy, which ran for eight seasons from 1987 to 1995, also starred Candace Cameron Bure, Jodie Sweetin, Lori Loughlin, Andrea Barber and Mary-Kate and Ashley Olsen.






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