Nov 062013

Diagnosing lung cancer without a biopsy may seem like science fiction, but breath testing to identify lung cancer has made steady gains in accuracy in recent years. A study abstract presented by Peter Mazzone et al at Chest 2013 in Chicago shows just how far one of the new technologies -- volatile organic compound analysis --  has come.

Authors compared exhaled breath of 51 patients with lung cancer (treatment-naive) with 99 patients with benign pulmonary nodules or risk factors for lung cancer, recruited from Cleveland Clinic and National Jewish hospitals. VOC testing of exhaled breath had a high predictive accuracy, with models producing area-under-the curve C-statistics of:

  • 0.851 for identifying patients with lung cancer vs. those without;
  • 0.903 for identifying adenocarcinoma vs. control patients;
  • 0.947 for identifying squamous cell cancer vs. control patients.

Accuracy was lower after the models were validated "using repeated random partition or bootstrap out-of-bag estimation" -- these techniques help predict how well a model will perform on an independent future data set -- with ROC C-statistics of 0.763 to 0.870.

The test uses a disposable chip that changes color in the presence of certain volatile compounds previously linked to lung cancer.

Gerard Silvestri of the Medical University of South Carolina in Charleston was impressed, telling MedPage Today, "It's incredible. I don't understand why it hasn't taken off ... If you could imagine the least invasive way to get an answer for patients, instead of having bronchoscopy or surgery or multiple biopsies, it would make so much sense."

Barring large further gains in accuracy, it's hard to imagine breath testing ever fully replacing the need for tissue biopsy, since oncologists need 100% certainty before giving chemotherapy or radiation (not to mention the newer needs for ALK, EGFR, KRAS genotyping).

But breath testing could still be a game changer, by improving the screening and diagnostic processes for lung cancer. Breath testing could help identify the highest-risk individuals for CT screening programs, and help refine pretest probabilities for suspicious nodules found on imaging. Resources could be better used, unnecessary biopsies prevented, and harm from false positive scans potentially reduced.

Since there is no commercial product available, cost and pricing for the breath tests are unknown. Metabolomx makes the breath sensors used in the study and provided funding to the investigators. The company has been described as being in the "valley of death" -- surviving on investors' funding but dependent on the development of new demand to survive.

That will require proven benefit in larger multicenter clinical trials. Metabolomx got a $1.1 million grant from the National Cancer Institute to perform Phase 1 and 2 clinical trials in 2011, but their web site hasn't reported any funding news since then.

Peter Mazzone et al. The Analysis of Volatile Organic Compound Profiles in the Breath as a Biomarker of Lung Cancer. Chest 2013 meeting: October 2013, Vol 144, No. 4_MeetingAbstracts

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Breath tests can accurately diagnose lung cancer