80 G. Taino et al.: Radioprotection 2025, 60( 1), 76 – 83
and genetic mutations associated with the development and progression of neoplastic pathology.
Phillips et al., about 20 years ago( Phillips et al., 1999), identified a possible correlation between exhaled compounds and the presence of neoplasia, analyzing 108 subjects. In a subsequent study in 2008( Phillips et al., 2008) they collected samples of exhaled air from 193 subjects with neoplasia and 211 healthy controls, highlighting the presence of neoplasia with a specificity of 81 % and a sensitivity of 84.5 %, with a model of 30 VOCs. The limitation of this method is the need of a mass spectrometer capable of gas chromatography, a complex, time consuming, and expensive assessment. For this reason, the researchers focused on new, more sensitive and economical methods, such as the use of electronic sensors similar to those used in the food industry, called“ artificial noses”. Gasparri et al.( 2016) conducted a study, with an electronic nose with a quartz microbalance, on 146 patients( 70 with neoplasia and 76 healthy controls). The pattern of patients with cancer was differentiated from that of healthy controls, with a specificity of 91 % and a sensitivity of 81 %. Peled et al.( 2012) instead evaluated the combination of spectrography and electronic nose in 53 patients with neoplasia and 12 with benign pulmonary nodules. The spectrography showed higher concentrations of 1-octene in patients with cancer and the electronic nose could distinguish benign from malignant nodules with a specificity of 96 % and a sensitivity of 86 %.
AUTOANTIBODIES. Seven autoantibodies were identified from Chapman’ s group( Chapman et al., 2012) that were 90 % specific for lung cancer, but with a sensitivity of 40 %. Bigbee and colleagues instead identified a pattern of 10 serum biomarkers( Bigbee et al., 2012), used to identify subjects with neoplasia, with a specificity of 76.2 % and a sensitivity of 77.1 %.
URINE ANALYSIS. In 2010 Carrola et al.( 2011) examined urinary metabolites( hippuric acid, trigonellin and hydroxyisovalerate, hydroxy-isobutyrate, aceyl-glutamine and creatinine), to identify individuals affected by neoplasia. Haznadar et al.( 2016) analyzed, by mass spectrometry, 178 urine samples from affected individuals and 351 from healthy controls, identifying an association between the development of the disease and the elevated levels of creatine-riboside. More recently, Park et al.( 2017) evaluated the association with urinary nicotinic equivalents and CYP2A6 activity( ratio between 3’ hydroxycotinine and urinary cotinine).
6 Discussion
Lung cancer is still a disease with a high mortality rate responsible, worldwide, for about one in five deaths due to cancer. Among the main causes of lung cancer have been identified air pollution and smog, exposure to toxic agents of industrial origin and, above all, smoking. Many substances of occupational origin are recognized as pulmonary carginogens. An important role is played by Radon, present in homes and workplaces. This noble gas is the second leading cause of lung cancer after cigarette smoking, accounting for 10-20 % of lung cancer cases in Western countries and causing about 3,000 deaths per year in Italy. The carcinogenic potential of
Radon increases about 25 times in smokers( WHO Handbook on Indoor Radon, 2009).
Since the therapeutic failure of lung cancer is mostly caused by the presence of metastatic disease at the time of diagnosis, it is therefore of fundamental importance to identify the disease at the early stages.
At present, however, screening strategies are proposed only in populations at high risk of developing the disease, as it is difficult to find a single very sensitive and highly specific biomarker. This situation implies that healthy subjects are subjected to CT only after the onset of symptoms, leading to often late diagnosis, without a survival benefit.
Currently, the use of biomarkers( miRNA, MSC) associated with CT and LDCT for early diagnosis and even more so for primary prevention seems promising.
An optimization in the future of these tools and the costbenefit ratio will open their use in early diagnosis, as well as also in the health surveillance of those exposed to Radon. The challenge for the future will be to use biomarkers in clinical practice in an efficient and practical way, as well as to develop markers capable of detecting tumors at a preclinical stage of the disease, regardless of their aggressiveness. Anticipating the clinical diagnosis by one or two years could in fact significantly change the tumor burden and improve the effectiveness of systemic therapies and the chances of recovery.
The objective in the future will then be to replace the use of imaging( CT, HRCT) with these biomarkers( also in the context of health surveillance), according to the screening concept which involves: safety of the method; acceptability by the population( compliance); possibility of modifying the course of the pathology; sustainable costs for the community; high reliability( sensitivity and specificity) also minimizing the effects of ionizing radiation administered with HRCT( even more with CT)( Bertho and Habib, 2023) according to the principles of justification and optimization which establish, respectively, that“ the exposure of the individual and the population to additional doses of radiation is justifiable only if the benefits deriving from the practices that generate the additional doses are greater than the set of statistically foreseeable negative effects” and“ that, if justified, the exposure of the population must be kept at the lowest level reasonably achievable( ALARA principle = As Low As Reasonably Achievable) also taking into account economic and social factors”( ICRP, 2007).
An important theme to consider is whether it is always justified, in terms of radiation protection, to expose“ healthy” people to radiations, even if for primary prevention and health surveillance in a population at risk of cancer. It is therefore necessary to carry out a risk-benefit assessment to protect the worker as much as possible. If we consider a population of selected workers at risk of developing a neoplasm( for example in this case lung cancer), it may be justified to subject them to radiological examinations to monitor their conditions. Even more so, it would be optimal to use biomarkers for monitoring that potentially have the same degree of sensitivity and specificity as CT and HRCT without the use of ionizing radiation.
Taking into account the analysis of the Literature and the options currently available regarding the prevention / early diagnosis of lung cancer, in the context of the health