Case Study A nanomaterial-based breath test for short-term follow-up after lung tumor resection Yoav Y. Broza, PhD a , Ran Kremer, MD b , Ulrike Tisch, PhD a , Arsen Gevorkyan, BSc a , Ala Shiban, MSc a , Lael Anson Best, MD b , Hossam Haick, PhD a, ⁎ a The Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa, Israel b Thoracic Surgery Division, Rambam Health Care Campus, Haifa, Israel Received 4 June 2012; accepted 31 July 2012 Abstract In this case study, we demonstrate the feasibility of nanomaterial-based sensors for identifying the breath-print of early-stage lung cancer (LC) and for short-term follow-up after LC-resection. Breath samples were collected from a small patient cohort prior to and after lung resection. Gas-chromatography/mass-spectrometry showed that five volatile organic compounds were significantly reduced after LC surgery. A nanomaterial-based sensor-array distinguished between pre-surgery and post-surgery LC states, as well as between pre-surgery LC and benign states. In contrast, the same sensor-array could neither distinguish between pre-surgery and post-surgery benign states, nor between LC and benign states after surgery. This indicates that the observed pattern is associated with the presence of malignant lung tumors. The proof-of-concept presented here has initiated a large-scale clinical study for post-surgery follow-up of LC patients. From the Clinical Editor: Monitoring for tumor recurrence remains very challenging due to post-surgical and radiation therapy induced changes in target organs, which often renders standard radiological identification of recurrent malignancies inaccurate. In this paper a novel nanotechnology-based sensor array is used for identification of volatile organic compounds in exhaled air that enable identification of benign vs. malignant states. © 2013 Elsevier Inc. All rights reserved. Key words: Lung cancer; Post-surgery; Follow-up; Volatile organic compound; Sensor Lung cancer (LC) causes 1.4 million deaths per year worldwide. 1 The management of LC depends critically on the ability to follow up the development of the disease during the course of the treatment. Breath analysis is of high interest as a potential future non-invasive and cost-effective complementary method for LC treatment follow-up. Several studies have used spectrometric methods and/or chemical sensor arrays to show that the profiles of volatile organic compounds (VOCs) in the breath of LC patients differ from those of healthy persons without lung nodules (see for example Refs. 2–11 as well as Ref. 12 and references therein). Some studies have addressed the possibility of post-surgery follow-up, but no short term changes of the VOC profiles in the breath of LC patients have been reported to date. 3,9,10 Phillips et al. 3 used gas-chromatography/mass-spectrometry (GC-MS) to follow-up VOC patterns in exhaled breath of LC patients after a surgical removal of the tumor. They predicted that resection of the LC tumor would have no effect at all on the breath signal. Poli et al. 9,10 used GC-MS after pre-concentrating the breath VOCs on a carboxen/polydimethyl-siloxanesolid phase micro-extraction (SPME) fiber. They observed that VOC levels were unaffected by tumor resection in the short term (i.e. one month after surgery), except for isoprene. Their long-term follow-up showed that the concentrations of some of these VOCs (e.g. pentane, toluene and ethylbenzene) were significantly different three years after surgery. Here, we present a case study with an array of nanomaterial- based sensors for the follow-up of the breath print of pre-surgery and post-surgery LC states. We show that the observed breath pattern is associated with the presence of malignant lung tumors, and that it ceased shortly after tumor resection. 13 Complemen- tary GC-MS show that several VOCs are significantly reduced in LC patients after surgery. This proof-of-concept indicates that breath analysis can indeed be used for short-term follow-up after LC-resection. POTENTIAL CLINICAL RELEVANCE Nanomedicine: Nanotechnology, Biology, and Medicine 9 (2013) 15 – 21 nanomedjournal.com Conflict of interest statement: none of the authors declare a conflict of interest. Sources of Support: The research leading to these results has received funding from the FP7's ERC grant under DIAG-CANCER (grant agreement no. 256639; H.H.). ⁎ Corresponding author: Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of technology, Haifa 32000, Israel. E-mail address: hhossam@technion.ac.il (H. Haick). 1549-9634/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.nano.2012.07.009 Please cite this article as: Broza Y.Y., et al. A nanomaterial-based breath test for short-term follow-up after lung tumor resection. Nanomedicine: NBM 2013;9:15-21, http://dx.doi.org/10.1016/j.nano.2012.07.009