A Potential New Test for Lung Cancer: The Noninvasive E-Nose

Dr. Gaetano Rocco is seen holding a component of the E-nose lung cancer test.

Thoracic surgeon Gaetano Rocco, MD, holding a component of the "E-Nose," a noninvasive lung cancer test that produced promising results in a clinical trial at Memorial Sloan Kettering.

Detecting lung cancer as early as possible has long been a goal of the specialists at MSK, because it gives doctors the most treatment options, which can improve outcomes for patients.   

A team led by MSK thoracic surgeon Gaetano Rocco, MD, reported results in a clinical trial that tested a screening method known as “E-nose.”

The trial suggests that E-nose could one day become an important tool in detecting lung cancer because the approach is noninvasive, highly accurate, inexpensive — and may one day even be small enough to slip inside a clinician’s pocket.

“E-nose looks really worthwhile,” Dr. Rocco says. “We anticipate this method could revolutionize the diagnosis of early-stage lung cancer, making screening accessible to more people.” 

How the E-Nose Detects Lung Cancer                         

The E-nose uses technology that can “smell” lung cancer in a person’s breath. “Chemicals called volatile organic compounds (VOCs) are emitted by cancer cells,” Dr. Rocco explains. “And they can be detected even at early stages of the disease.”

The E-nose was given that name because “it mimics what our own noses do,” he says, “by sensing the various combinations of VOCs and recognizing those that signal cancer.”

The E-nose involves two procedures. First, a person breathes into a collection device for three minutes. A sensor the size of a USB drive converts VOCs in the person’s breath into electronic signals called a “breathprint.” The breathprint is then analyzed by a separate machine that can detect the presence of cancer in just a few hours.

Right now, the analysis machine is at an academic medical center in Italy, which means that the collected breathprint samples get shipped overseas. But Dr. Rocco is hopeful that the machine will be replicated and miniaturized so that the technology could be easily used in a doctor’s office to quickly test for lung cancer at very low cost. 

E-Nose Clinical Trial Results

Dr. Rocco’s experience with the E-nose began nearly 10 years ago in his native Italy, where the E-nose was shown to perform very well in two key aspects of a screening test, known as sensitivity (86%) and specificity (95%). He explains that “sensitivity means you can believe the test if it says you have a disease, and specificity means you can believe the test if it says you do not have a disease.”

Those findings prompted Dr. Rocco to lead a phase 2 clinical trial at MSK to investigate the E-nose, which is formally known as BIONOTE (BIOsensor-based multisensorial system for mimicking NOse, Tongue, and Eyes). The results were published in the Journal of Thoracic Oncology in May 2024.

The trial involved 100 participants from 21 to 85 years of age who were referred to MSK with a lung nodule and presumed to be at high risk for having lung cancer. A lung nodule is a small, dense mass of tissue in the lungs that can be cancerous or noncancerous. 

In the trial, breathprints were created for each participant, and the E-nose found:

  • Cancer in 86 of the 88 patients who were confirmed to have lung cancer
  • 86 true positives
  • 2 false negatives
  • 12 false positives

Dr. Rocco says, “The E-nose reliably detected early-stage lung cancer and was very accurate when compared with the long-established available imaging methods” such as X-rays and CT and PET scans.

The final diagnosis of lung cancer relies on a biopsy of the lung nodule, which often uses needles to remove a small amount of tissue to study. In the MSK clinical trial, the E-nose agreed with the results of biopsy in 86% of the patients. He adds “our results suggest the E-nose would be an excellent addition to the current techniques for diagnosing lung cancer—and would pose no risk to the patient because it’s noninvasive.”

Learn more about lung cancer screening guidelines

Learn more about how we screen for lung cancer at MSK

The People Who Would Most Benefit from E-Nose

Dr. Rocco believes that adding a noninvasive, inexpensive screening option like E-nose may encourage more people who should get screened to do so. Research finds that only 1 in 5 people who are eligible for lung cancer screening actually get it.

Declines in smoking and advances in treating lung cancer have helped lower the incidence and death rate from lung cancer. But the grim truth about lung cancer, according to the American Cancer Society, is that it is the second most common cancer in both men and women in the U.S.

Even worse, lung cancer is by far the leading cause of cancer death in the U.S. — more than colon, breast, and prostate cancers combined.

Dr. Rocco believes one of the first use cases for the E-nose would be for people “who really don’t want to undergo a biopsy or can’t because of severe respiratory disease. That is one of the main aims of the E-nose.” 

He says the E-nose could also be useful for large-scale lung cancer screening, particularly in remote areas where imaging and biopsy options are limited.

Dr. Rocco is hopeful that philanthropic support will help further refine the E-nose technology, and that continuing clinical trials will lead to widespread adoption.

“E-nose could be a valuable addition to diagnosing and treating lung cancer,” he says, “and MSK’s expertise and leadership in the field means it’s the right place to make this a reality.”


The Journal of Thoracic Oncology paper was supported in part by a National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748 and MSK’s Fiona and Stanley Druckenmiller Research Center for Lung Cancer ResearchDr. Rocco reported a financial interest with Scanlan International, Merck, and Medtronic. Refer to the paper for disclosures from other authors.