A small proof-of-concept study suggests that volatile organic compounds (VOC) in exhaled breath could become a useful biomarker to assess treatment response in patients with malignant pleural mesothelioma. A study in 15 mesothelioma patients demonstrated 89% accuracy in distinguishing between stable disease and progressive disease during a series of follow-ups with patients undergoing treatment. There were no significant differences in treatment approaches between patients with stable disease and progressive disease, suggesting that specific VOCs may correlate with general mechanisms or tumor microenvironments in mesothelioma rather than being treatment specific.
“Mesothelioma is a very fatal cancer with a very low survival rate,” said Kevin Lamote, MD, PhD, Assistant Professor of Translational Research in Immunology and Inflammation, University of Antwerp, Antwerp, The Netherlands. “Current treatment options are limited—chemotherapy with platinum salts combined with pemetrexed and, more recently, immune inhibition with ipilimumab and nivolumab. But response rates are low, which subjects many patients to ineffective treatments. There is a need to improve survival and identify biomarkers to predict who is responding and who is likely to respond to treatment.”
Dr. Lamote presented “Treatment Response in Malignant Pleural Mesothelioma Patients Can Be Predicted by Exhaled Breath Analysis” as a poster on Thursday, September 7, during the 2023 World Conference on Lung Cancer.
About 90% of mesothelioma is caused by asbestos exposure, Dr. Lamote said. Multiple VOCs have been identified as metabolic byproducts of oxidative stress induced by asbestos in mesothelioma patients. These VOCs can be used to distinguish between individuals with mesothelioma and similar individuals with asbestos exposure who have not developed the disease.
The eNose device, which detects VOCs, has been used to predict checkpoint inhibition therapy outcomes in malignant melanoma and non-small cell lung cancer. It was not clear whether VOC detection technology could identify differences in VOC content in exhaled breath, or breath prints, between responders and nonresponders after treatment. Nor was it clear if exhaled breath profiles could predict treatment outcome.
Researchers performed CT scans and exhaled breath analysis before mesothelioma treatment and every three months during treatment. Breath samples were analyzed using multi-capillary column-ion mobility spectrometry (MCC-IMS) to identify VOCs in each sample. Researchers also analyzed samples of ambient air to isolate any potential compounding effects from atmospheric VOCs.
MCC-IMS results were compared to assess whether there were significant differences between responders and nonresponders following treatment. At the same time, a predictive model was trained on the results to predict treatment outcome with the same level of accuracy demonstrated at baseline.
Median age of patients was 67 years; about 75% were male. There were no differences in smoking status or treatments between responders and nonresponders.
MCC-IMS identified six VOCs that were predictive of therapy outcome, identified as P15, P31, P47, P63, P79, and P95. The discriminative model was able to identify treatment response with 81.2% accuracy and the predictive model showed the same accuracy as at baseline
“Exhaled breath can be promising in predicting therapeutic outcomes based on certain VOCs, which need to be further validated in a larger population,” Dr. Lamote said. “We will also elaborate more on the VOC differences between chemotherapy and immunotherapy and identify the underlying metabolites that we are detecting.”
ILCN Editor Corey J. Langer, MD, FACP, concurred.
“These results are intriguing,” said Dr. Langer, who is Director of Thoracic Oncology at the Abramson Cancer Center and Professor of Medicine at the University of Pennsylvania. “However, they will require validation in a much larger series.”