Detection of Cancer Through Exhaled Breath

Use of volatile organic compound (VOC) measurements in exhaled breath tests has potential as a noninvasive cancer diagnostic, but increased methodologic standardization is required, according to the results of a meta-analysis published in JAMA Oncology.

George B. Hanna, FRCS, PhD, of Imperial College, London, and colleagues conducted a systematic review and meta-analysis of 63 publications that included 3,554 patients to evaluate the diagnostic accuracy and methodologic challenges of VOC-based exhaled breath tests for detecting cancer. Studies included patients with a wide range of cancers, including lung, breast, esophageal, colorectal, oral cavity, thyroid, and liver, among others.

The review and analysis of these phase I studies showed a mean area under the receiver operating characteristic analysis curve of 0.94, with a sensitivity of 79% and a specificity of 89%.

Based on this method’s potential as a noninvasive diagnostic for cancer, Hanna and colleagues proposed a framework to guide the conduct of future breath tests in cancer studies.

The first milestone needed to further research the role of exhaled VOCs in cancer diagnosis is a standardization of breath sampling, according to the study. The analysis showed that results of breath testing samples depended on the method of sample collection, patients’ physiologic condition, and the testing environment.

Next, researchers must consider the instrumentation used for breath analysis.

“To obtain accurate results in clinical practice and gain the confidence of practitioners and cancer scientists, the reliability of instruments and reproducibility of results should be tested, optimized, and reported for exhaled VOC analysis in clinical studies,” the researchers wrote.

In addition, future research must test breath tests against positive control groups and within multicenter studies among the target population within the environment in which the test will ultimately be used. “Establishing test threshold for separating patients with cancers of different stage and tumor subtypes from controls is needed before embarking on masked validation studies,” Hanna and colleagues wrote.

Although more research is required before use of VOC breath tests could be implemented in clinical practice, ongoing thought should be given to practicalities of implementation as research is conducted.

“Implementation of breath analysis on a wider scale in clinical practice requires careful consideration,” the researchers wrote. “Although there is a need for the accuracy of breath tests to be confirmed in large-scale, multicenter clinical trials among the intended population before the introduction into clinical practice, models for implementation should be considered at an early stage to direct future research and clinical studies.”