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Despite Challenges, Pioneer in CT Screening for Early Lung Cancer Works to Move the Field Forward

A Conversation With Claudia I. Henschke, PhD, MD


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In 1999, a team of researchers from Weill Cornell Medical College advocated the use of a then-novel practice: low-dose radiation CT screening for lung cancer. It captures a full thoracic image in a single breath hold, and can recognize a tumor in its earliest stages when the chance for cure is greatest.

The American Lung Association estimates that early screening for lung cancer could potentially save upward of 25,000 lives per year in the United States alone. According to data from the Lung Cancer Alliance, the 5-year survival rate for lung cancer drops dramatically from stage I diagnosis (85%–92% survival) to a stage IV diagnosis (0–10% survival) with early screening. Notwithstanding the proven benefits of early detection, the National Cancer Institute estimates that as few as 5.9% of at-risk adults receive cancer screening.

Claudia I. Henschke, PhD, MD

Claudia I. Henschke, PhD, MD

The ASCO Post recently spoke with one of the leading champions of low-dose CT screening for lung cancer, Claudia I. Henschke, PhD, MD, Director of the Lung Screening Program at the Icahn School of Medicine at Mount Sinai.

Update on Screening Program at Mount Sinai

It’s been a long, challenging journey in low-dose CT screening since early work during the 1990s. Please bring our readers up to speed on your current work.

Implementing a high-quality screening program is a challenging task because of the multiple billing and hospital administrative issues; in some ways, these issues are more difficult than the research that got us here. This problem is not isolated to New York; we see people across the country struggling to get programs up and running. We are at an advantage here at Mount Sinai because we have already developed the infrastructure and the computer software necessary to the process.

We offer at-risk people a life-saving opportunity where we not only look at the lungs but also at the heart and provide smoking cessation treatment.
— Claudia I. Henschke, PhD, MD

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Part of what I do, which is extremely rewarding, is community outreach; we offer at-risk people a life-saving opportunity where we not only look at the lungs but also at the heart and provide smoking cessation treatment. It takes seconds to get the scan, but you also receive a host of other health benefits. We have continuously published on this vital issue and are working on the integration of artificial intelligence techniques into all of our screening programs. So, there is a lot going on right now.

Seminal Article on Early Screening

In 1999, you and your associates at the Early Lung Cancer Action Program (ELCAP) published a seminal paper in The Lancet (354:99-105). What effect did that article have on your research to bring low-dose CT into the mainstream of lung cancer care?

Well, it certainly stirred the world, and we began receiving about 200 calls per day from smokers who understood the importance of the low-dose CT paper, which pointed out that chest x-ray did not detect lung cancer early enough. People wanted to be screened, and we wanted to make that happen, because we knew it would save countless thousands of lives.

We put in an institutional review board–approved study to screen individuals 40 years and older, never smokers, current smokers, and former smokers, because we believed that you needed to have thorough evidence in the way of images that we could use for future research. That’s what we’ve been doing all along. Through that effort, ELCAP has developed the largest international database. So, we’ve accumulated a lot of vital information, and all of the participants in the studies have helped us produce a considerable body of published literature on CT screening.

Interestingly, at the 2019 World Conference on Lung Cancer in September in Barcelona, there was a sea change in the number of presentations about screening and, more important, the positive attitudes toward CT screening. In fact, pharmaceutical companies were interested in supporting screening studies and programs. In a sense, this is what I expected 20 years ago when we published The Lancet article.

Solidifying the Data

Please talk a bit about how you accumulated the body of solid research that helped demonstrate the clinical value of CT screening in high-risk populations.

For one, it was the continuous publications of important papers and the long-term follow-up that led to the National Lung Cancer Screening Trial (NLST), which, of course, made a huge difference. Then, the U.S. Preventive Service Task Force became involved and reviewed the data, which eventually led to the Centers for Medicare & Medicare Services (CMS) approving coverage for low-dose CT.

To this day, I am still amazed at how long it took to reach this point of recognition for a life-saving early detection methodology. I believe it wasn’t until 2015 that we were given the green light to begin rolling out the implementation process.

Natural Evolution of Advocacy Groups

What effect did lung cancer advocacy have in your struggle to gain support for low-dose CT?

The early problem with garnering support from advocacy groups was that there just weren’t that many survivors in lung cancer. However, as we began finding early, treatable tumors, we saw more survivors, and the advocacy groups were a natural evolution.

In 1999, Peggy McCarthy had become aware of the lack of treatment and resources available to the lung cancer community through her work developing educational programs for health-care professionals throughout the country; this later became the Lung Cancer Alliance, led by Laurie Fenton. This sprouted into multiple advocacy groups that did fundraising events throughout the country. It was the start of lung cancer advocacy that had a huge effect.

Smoking cessation broadens the impact of any lung cancer screening program well beyond the endpoints of cancer diagnosis and cancer mortality to reduce risk from many other diseases.
— Claudia I. Henschke, PhD, MD

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In fact, Laurie Fenton and Sheila Ross did a lot of work with Congress to obtain CMS approval for low-dose CT. Without their input and a growing group of lung cancer survivors, I’m not sure we would have received approval. It’s important to note that when you go to other parts of the world, there are few advocacy movements as well organized as ours in the United States. Right from the outset, the support of the Prevent Cancer initiative by Carolyn “Bo” Aldigé and Dr. James Mulshine has been key to addressing the criticism we were receiving from those opposed to low-dose CT.

NELSON Trial vs NLST

Please tell the readers a bit about the NELSON trial and how it differs from the NLST.

The NLST accrued people who were between the ages of 55 and 74, had a 30-year smoking history, and had quit within the past 15 years. Those criteria were set to accrue a large number of participants who were screened for lung cancer in three rounds. A lower-risk group would have needed a longer study. There was a push to come up with results as quickly as possible. The researchers did a good job, and the results demonstrated a 20% mortality reduction in those screened with low-dose CT.

However, confusion arises between a mortality reduction, which is an endpoint of a clinical trial, and the long-term cure rates that you can detect with screening. When you examine the 20% mortality reduction after three rounds of low-dose CT screening, the results are absolutely compatible with the 80% long-term survival rates that we show with our data. To be clear, to infer that a 20% mortality reduction means that only 1 screened person out of 5 who is diagnosed with lung cancer has a benefit is absolutely wrong. Again, the endpoint of the NLST does not give the true survival rate, which is 80% or better given the stage at diagnosis. This has been a key misunderstanding responsible for hijacking the true benefits of screening.

To that end, my colleague at ELCAP, David Yankelevitz, MD, wrote a Letter to the Editor of The New England Journal of Medicine to explain this somewhat hard-to-explain clinical issue. Once people understand the true benefits of low-dose CT, they get on board with our efforts to roll out this life-saving tool.

We are still anxiously awaiting the write-up of the NELSON trial in Europe, so we can tear into the data. The design of the NELSON trial and its use of volumetric data were strongly influenced by extensive discussions with investigators at international ELCAP conferences and through personal communications. Both the NLST and NELSON trials, when published in 2011 and 2019, respectively, not only confirmed the ELCAP results reported in 1999, but the NLST also provided a large database of CT images with associated clinical outcomes for research.

NELSON researchers decided to look a different age group, 50 years and older, with lower pack-years of smoking. Their control group contained those screened by chest x-ray, as opposed to the NLST. Since they had far fewer people in NELSON—15,000 compared with 50,000 in NLST—they used a longer follow-up. The interesting thing in the NELSON trial was that, although there were considerably fewer women enrolled than men, women had a much higher risk but also a much higher cure rate than men. It was something we pointed out in the data we published in 2004. To date, no one has been able secure funding to study this phenomenon.

Closing Thoughts

Do you have any concluding remarks about low-dose CT screening programs in the detection of lung cancer?

Every screening program has a smoking cessation component, and the overarching goal is not just to find more nodules, or diagnose more cases of cancer, but to help people live longer and healthier lives. Smoking cessation broadens the impact of any lung cancer screening program well beyond the endpoints of cancer diagnosis and cancer mortality to reduce risk from many other diseases; it also can positively impact many more patients than the small percentage who have cancer. These programs will ultimately save hundreds of thousands of lives. 

DISCLOSURE: Dr. Henschke is the President and serves on the board of the Early Diagnosis and Treatment Research Foundation. She receives no compensation from the Foundation. The Foundation is established to provide grants for projects, conferences, and public databases for research on early diagnosis and treatment of diseases. Dr. Henschke is also a named inventor on a number of patents and patent applications relating to the evaluation of pulmonary nodules on CT scans of the chest, which are owned by Cornell Research Foundation (CRF). Since 2009, Dr. Henschke does not accept any financial benefit from these patents including royalties and any other proceeds related to the patents or patent applications owned by CRF.


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