Cancer Breath Test Enters Clinical Trials

 

Breath tester: Inside Metabolomx’s device, breath is pumped over arrays of 120 chemical reactants that change color in response to volatile breath biomarkers.
Technology Review

 

 

A startup says its test can distinguish between subtypes of lung cancer.

 

 

MIT Technology Review, by Katherine Bourzac, February 23, 2012  —  Someday soon a breath test could do more than just tell if you’ve been drinking. Metabolomx, a startup in Mountain View, California, recently completed a clinical trial that shows that its breath test can spot lung cancer with 83 percent accuracy and can also distinguish between several different types of the disease, something that usually requires a biopsy. The accuracy of the test matches what’s possible with low-dose computerized tomography imaging of the lungs.

Existing tests for lung cancer—the leading cause of cancer death worldwide—cause too many false positives, which means patients face unnecessary biopsies or exposure to radiation from imaging, and none are currently approved by Medicare. A breath test promises much simpler, safer screening.

Chemical results of a tumor’s metabolism are dissolved in the blood, and can end up in the breath. Trained dogs can identify breath samples from patients with lung cancer with 98 percent accuracy. Researchers have been working on a noninvasive cancer breath test for years, but have struggled to make one that is simple, reliable, and portable enough. A method called gas chromotography-mass spectrometry can detect metabolites in the breath, but it can’t be done at the bedside, and requires some expertise to operate.

Paul Rhodes, the founder and CEO of Metabolomx, says the company is now running additional lung and colon cancer clinical trials of equipment that is 1,000 times more sensitive to biomarkers carried on the breath than the one used in its recently completed clinical trial. That could help them get to 90 percent accuracy, which Rhodes believes will be necessary to get the test to market.

 

Breath tester: An engineer at Metabolomx breathes into a breath-analysis machine. Credit:Technology Review

 

 

Peter Mazzone, a pulmonologist at the Cleveland Clinic, who is running clinical trials of the new system, says a noninvasive metabolic breath test could help doctors make a better decision when a CT scan looks suspicious. Today, when doctors find a nodule in a patient’s scan, they have to follow up periodically to see if the nodule gets bigger, and then do a biopsy. And eventually Mazzone hopes a metabolic breath test could help predict the behavior of a particular cancer and what drugs it will respond to: “How aggressive is it? Do we need to simply remove it, or remove it and give chemotherapy?”

In the current version of the system, a patient must breathe through a tube for about five minutes. Pumps draw the breath through a series of filters to dry it out and remove bacteria, then over an array of sensors. Metabolomx has shown that the system can distinguish breath samples from patients with different subtypes of lung cancer.

The sensor array consists of colored reactants that are each sensitive to a different group of volatile compounds. Depending on what’s in the sample, different spots in the array—24 in the version used for the initial clinical trial, 130 in the current one—will change color to varying degrees. The system takes a photo of the array of colored reactants before and after they’re exposed to the breath sample, subtracts one image from the other, and generates a colored pattern for that sample.

Rhodes expects a test to cost $75. Also, because it’s not specific to a particular group of chemicals, the Metabolomx sensor could, in theory at least, be used to screen for any disease that has a metabolic breath signature—the company is currently exploring tests for other diseases, including tuberculosis. “A breath signature could give a snapshot of overall health,” Rhodes says.

 

A Call for Help

“I can’t wake my wife up!” The voice on the phone was panicked. The couple were lying in bed when the 43-year-old woman began to snore, something she’d never done before. Her husband tried to wake her, but she didn’t respond. He shouted her name; he shook her shoulder. Nothing. Terrified, he called 911.

An Otherwise-Ordinary Night

He couldn’t imagine what was wrong with his healthy, active wife, he told the medics when they arrived. That day had been pretty normal. His wife got home from work in the late afternoon. She made dinner and then went to her kickboxing class. She got home, put the kids to bed and had a drink — vodka and cranberry juice. Then the couple went to bed, too. Normally the husband stayed up later than she did, but this evening they turned in at the same time. As they lay in bed, talking, his wife began to snore. It was so sudden and unexpected that, at first, he thought it was a joke.

The medics tried to wake her. They called her name; they shook her. They gave her Narcan, a drug that counteracts narcotics, even though her husband told them she didn’t use drugs. All they got from her was a moan. They loaded her in the ambulance and hurried her to the University of Michigan Medical Center emergency room.

 

 

At the Emergency Room

Dr. Robert Silbergleit, the doctor on duty at the E.R. that night, met the ambulance on arrival. “Comatose 43-year-old woman found by husband,” the E.M.T.’s reported as they moved the patient into the area reserved for the critically ill. “Snoring. Unresponsive except to pain.”

The patient, a thin woman, seemed to Silbergleit to be perfectly fit and healthy, except that she was asleep. He rubbed her chest hard with his knuckle — a sternal rub, it’s called — a very painful maneuver, designed to elicit a response. “Stop,” she moaned, but she didn’t open her eyes. And she didn’t wake up.

What is the most common cause of a sudden loss of consciousness in a young person?

 

What NYT Readers Voted

Trauma
19%

Stroke
8%

Meningitis
3%

Syncope
13%

Drugs or alcohol

 

 

Possible Diagnoses

 

Drug overdose: A common cause of a sudden loss of consciousness in an otherwise-healthy adult. Her husband said she didn’t use drugs and the Narcan didn’t do any good, so narcotics were unlikely. Silbergleit sent off blood and urine to look for other sedating drugs or alcohol.

Traumatic brain injury: Had she been hit in the head during her kickboxing class? A well-placed blow could cause bleeding inside the skull, resulting in a loss of consciousness hours later. She hadn’t complained of a headache or mentioned an injury. Still, Silbergleit ordered a CT scan of the head. Untreated, bleeding around the brain can cause permanent injury or death.

Stroke: The sudden onset of symptoms sounded like a stroke, even though the symptom itself, a sudden loss of consciousness, did not. Still, stroke needed to be considered, because the damage caused by a stroke can be reduced or even prevented by medications that open the clogged artery and restore blood flow throughout the brain. But these drugs have to be given within four and a half hours of the onset of symptoms. And because these are powerful drugs that can cause life-threatening bleeding, a definitive diagnosis of a stroke is important.

Test Results

The drug tests were all negative. Her blood-alcohol level was consistent with the reported single drink after dinner. The CT scan of her head didn’t show any evidence of bleeding or a stroke. Silbergleit ordered a CT angiogram — an image that outlines the arteries of the brain — to look for any obstruction that would suggest a stroke. It, too, was normal.

Given the results of the testing, what do you think caused this woman to become comatose?

What Others Voted

  • Trauma that wasn’t seen in the imaging ordered by the E.R. doctor

13%

  • An overdose of a drug that wasn’t tested for

5%

  • A seizure

29%

  • A stroke

13%

  • An infection

40%

 

 

A Neurologist Gets Involved

Silbergleit spoke with Lesli Skolarus, a neurologist with special training in strokes. It was late, and Skolarus was at home. Silbergleit described the case and explained that he was planning to get an EEG to see if the young woman was having continuing seizures.

Skolarus arrived at the hospital around 1 a.m. By the time she finished reviewing the E.R. test results, two hours had passed since the patient first fell asleep.

Like Silbergleit, Skolarus was struck by the sudden onset of symptoms. Was this a stroke? If it was, it was an odd one. Because of the way arteries course through the brain, any obstruction will cut off blood and oxygen to only one side of the brain. So the typical stroke causes weakness or paralysis on one side of the body, and the patient is usually wide awake. The part of the brain that keeps us awake is known as the reticular activating system, or R.A.S. The R.A.S. is usually fed by one artery on each side of the brain, a redundancy that provides important protection if either of these vessels should be blocked. A small segment of the population, however, has only one vessel delivering blood to the R.A.S., and a well-positioned clot to this single vessel, called the artery of Percheron, could completely block blood flow to the R.A.S. and cause unconsciousness. Could that be the case with this patient?

 

Deadline Testing

 

 

MRI image.

 

 

Skolarus had seen this kind of stroke once before, when she was in training. It took days to figure out why an older man had suddenly lost consciousness. By the time they discovered this rare stroke, the damage was permanent.

Skolarus looked at the clock. Three hours had passed since the young woman’s symptoms started. If she had a clot in the artery of Percheron, there was still time to use a clot buster to reopen the vessel before the injury became permanent. But first they would need an M.R.I. for a closer look.

A half-hour later the scanner clattered as the patient’s brain slowly came into view on the monitor. Skolarus watched as the skull, then the top of the brain and finally the midbrain appeared before her. And there it was — a bright spot indicating damage to the R.A.S. from a blockage to the artery of Percheron. Skolarus called the E.R. to get the clot-busting drug ready.

 

 

Concern About Brain Damage

The medication was started just moments before the four-and-a-half-hour deadline. As the medicine dripped in, Skolarus showed the husband the damaged region. Then she had to tell him the bad news: even if the medicine worked, there was still a chance she would not wake up. And if she did, she would probably have residual damage. Chances were, she would never be the same.

Suddenly the husband heard his wife’s voice. He and Skolarus rushed to the bedside. She looked a little scared, but her eyes were open and she was talking. She knew her name. She knew his name. She knew the name of the current president. She was back.

 

Searching for the Cause

 

 

The patient stayed in the hospital for the next several days. She felt fine, but the doctors needed to figure out why she had this stroke. A sonogram of the patient’s heart provided the answer. It showed that there was an opening in the wall that separated the right side of the heart from the left. Normally blood comes into the right side of the heart, then passes through the lungs, where it is oxygenated, before going into the left side of the heart. From there it’s pumped into the rest of the body. Because lungs also serve as a kind of filter, trapping clots and other particles in its tiny capillaries, the hole in this patient’s heart allowed a tiny clot from somewhere in the body to travel through the heart and into the brain.

 

 

I spoke to the patient recently. She says she feels back to her old self and is amazed and grateful.

“There were so many ways I was lucky that night. If my husband had come to bed at his usual time, he might not have noticed anything. If the neurologist hadn’t come in, if the M.R.I. hadn’t been available — ” She stopped, unwilling to even talk about the possibility. “It’s all a little scary.”

Source: The New York Times, February/March 2012