Breath Testing in Laryngeal Cancer- Comparing in Situ Cancer and Advanced Cancer

Worldwide there are 130 000 new larnx cancers diagnosed annually resulting in 82 000 deaths.Survival after diagnosis of larynx cancer depends on initial stage. For T3N0Mo laryngeal cancers 5-year survival ranges from 59 to 66%. Patients survivals are as follows: receiving either chemoradiation (59.2%), irradiation alone (42.7%) ,patients after surgery with irradiation (65.2%) and surgery alone (63.3%) By contrast in early stage larynx cancer survivals range from 90-100%. Tamura et al reported therapeutic outcomes of 130 cases with laryngeal cancer treated at Kyoto University Hospital between 1995 and 2004[3] In all, 121 males and 9 females were involved. Their ages ranged from 40 years to 92 years (average 66 years). All tumors were squamous cell carcinoma - arising at the glottis in 111 cases, the supraglottis in 18, and the subglottis in 1 case. Most glottic cancers (77.5%) were classified as stage I or II, while most supraglottic cancers (77.8%) were at stage III or IV. Stage I/II cancers were basically treated by conventional radiotherapy (60-66 Gy) and twice-daily hyperfractionated radiotherapy (70-74 Gy), respectively, attempting to preserve the larynx. Total laryngectomy with neck dissection was performed in the treatment of stage III/IV cases. Five-year disease-specific survival rates were 100%, 96%, 100%, and 68% for stage I, II, III, and IV, respectively. Five-year laryngeal preservation rates were 98%, 100%, 86%, 0%, and 0% for T1a, T1b, T2, T3, and T4 of glottic cancer, respectively. Local recurrence occurred in five cases of stage I/II glottic cancer, which was successfully salvaged.

Chera et al reported excellent treatment outcomes of definitive radiotherapy (RT) for early-stage squamous cell carcinoma (SCCA) of the glottic larynx. Endoscopic laser resection can also have an excellent outcome in early stage larynx cancer. Schrivers et al [5]reported survival analysis on 100 patients with T1a glottic carcinoma treated with CO(2) laser surgery (n = 49) or radiotherapy (n = 51). No significant differences in local control and overall survival were found. Ultimate 5-year laryngeal preservation was significantly better in the CO(2) laser surgery group (95% vs 77%, p = .043).

Volatile organic compound (VOC) breath testing in cancer detection The concept for VOC testing is that VOCs, mostly alkanes and aromatic compounds, are preferentially produced and exhaled by cancer patients and can be used as accurate markers of malignancy. As early as 1971, testing on normal breath identified more than 100 volatile organic compounds In the 1980s Gordon and Preti used mass spectroscopy and gas chromatography to identify specific alterations in the profile of volatile organic compounds in the breath of lung cancer patients[16]. In two papers in 1999 and 2003, Phillips further refined this original data to identify a group of 9 volatile organic compounds which were highly sensitive and specific for the presence of lung cancer . The concentration of these alkane and methylalkane oxidative stress products was reduced in the breath of lung cancer patients.

Cross-sectional studies have investigated exhaled biomarkers as a function of disease, both as biomarkers of disease state and as predictive markers. In cross-sectional studies, a control group is compared with a patient or diseased group, and breath markers are analyzed to identify qualitative or quantitative differences between the two groups. Phillips and coworkers [14] investigated alveolar gradients (i.e., the abundance in breath minus the abundance in room air) of C4 to C20 alkanes and monomethylated alkanes in the breath as tumor markers in primary lung cancer. They concluded that a breath test for C4 to C20 alkanes and monomethylated alkanes provided a rational new set of markers that identified lung cancer in a group of patients with histologically confirmed disease. The analytical methodology was described in 2003 , where it was reported that amongst smokers and ex-smokers there was a sensitivity for malignancy of 86% (55/64) and a specificity of 83% (19/23). This compared with sensitivity and specificity in non smokers of 66% (2/3) and 78% (14/18). Overall therefore the VOC breath test was not affected by smoking status.

Changes in breath VOC patterns are independent of the size of the lung cancer in that T1 tumours (<3cm) have a similar breath pattern of abnormality to T4 tumours, raising the possibility that VOC abnormalities may even be detectable at the preneoplastic (severe dysplasia or carcinoma in situ) stage. It describes a comparison between 212 controls without lung cancer and 195 patients with primary lung cancer. The breath test was as likely to be abnormal in stage 1 disease as in stage 4 disease. This implies firstly that as a screening tool VOC breath testing has potential to detect operative curable cases. Secondly, it implies that oxidative changes leading to altered breath VOCs are an early feature of lung cancer development, and that the method may therefore detect the presence of preneoplastic lesions in the bronchial tree.