Prognostic models can facilitate discussion between physicians and patients, help to identify high-risk patients individualized treatments and clinical trials can be developed, and may provide insight into the biology of disease. Nomograms have been developed to predict various clinical end points for patients with all kinds of malignancies.
In recent years, multi-national cohort studies had found that OSA increases the mortality of cancer, among which lung cancer is the most common [12, 13],Dreher et al proposed that the incidence of OSA in newly diagnosed lung cancer was 49%, in which the incidence of moderate/severe OSA was 17%༌Perez et al proposed that the incidence of OSA in lung cancer patients was 77.5%, in which moderate/severe OSA accounted for 41.1%,which is consistent with the results of this study. It was found that 31% of lung cancer had different degrees of OSA. Li et al found that the overall survival rate of lung cancer patients with severe OSA was lower than that of patients with mild OSA, suggesting that the occurrence and severity of OSA are risk factors to promote cancer development。The univariate and multivariate logistic analysis indicated that age, AHI༌TNM stage, cancer types, BMI and ODI4 were risk factors for overall survival, Now studies have confirmed that age is an important factor in the occurrence of lung cancer and is an independent risk factor for survival and prognosis of lung cancer patients. The incidence rate of OSA in elderly people is 24%~62%, and the severity of OSA increases with age. Another study found that the incidence rate of OSA did not increase linearly with age, but reached the peak at 55 years old, and the incidence rate increased slowly༌which is consistent with the results of this study. We found that age is an independent risk factor for lung cancer patients with OSA, and the nomogram score increases fastest in the age range of 50–60 years༌The elderly patients with lung cancer complicated with OSA should be closely monitored to prevent the occurrence of disease-related complications.
Li et al reported that tumor staging is related to the severity of OSA, and jointly affect the prognosis of lung cancer patients with OSAS.The American Joint Committee Cancer (AJCC) and The Union for International Cancer Control ༈UICC༉released the eighth edition of the TNM lung cancer staging system,the TNM stage is based on the latest database of The International Association for the Study of Lung Cancer (IASLC), which contains information on 94708 patients diagnosed with lung cancer from 1999 to 2010, most of them from Asia. This study explored the effect of TNM stage on the prognosis, results show TNM stage was an independent risk factor for the prognosis of lung cancer patients with OSA. In addition, the nomogram score of patients with TNM stage IV increased significantly, TNM stage was not a simple linear relationship with survival and prognosis, we should pay attention to the progress of the disease of patients with advanced lung cancer, actively treatment intervention to slow down the progress of the disease and improve the quality of life while prolonging the survival time. According to histological classification, lung cancer can be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), non-small cell lung cancer accounts for 80% of lung cancer. After multi-disciplinary comprehensive treatment in recent years, the 5-year survival rate has been greatly improved, however, only 20% − 30% of patients are in the early stage of lung cancer when diagnosed, and most of them fail to carry out standardized treatment in time delaying the best treatment period. This study analyzed the prognosis of lung cancer patients with OSA, results show the prognosis of patients with small cell lung cancer was poor and the survival time was significantly reduced, although small cell lung cancer had a good response to treatment, it was often too late to make radical resection.
Wisconsin Cohort results show severe sleep disordered breathing increases nearly five times death risk of cancer,Lung cancer patients are more prone to intermittent hypoxia, apnea and daytime sleepiness༌This study show ODI4 was an independent risk factor for lung cancer patients with OSA. Hypoxia environment plays an important role in the development of lung cancer, On the one hand, adequate oxygenation plays an important role in maintaining the normal function of cells, tissues and organs. Hypoxia is prevalent in tumor tissues, even in the absence of severe respiratory diseases. Hypoxia is the result of high proliferation rate of cancer cells, when the speed of neovascularization is slower than that of tumor growth, it can’t provide the amount of oxygen for metabolism. On the other hand, lung cancer patients are prone to sleep disorders. In addition to the persistent hypoxia of tumor tissue, vascular compression also promotes intermittent hypoxia and any factors causing intermittent hypoxia and apnea can aggravate OSAS.
Apnea hypopnea index (AHI) is the basis for the diagnosis of OSA. AHI refers to the average number of apnea and hypoventilation per hour during sleep. AHI is also a standard for grading the severity of OSA. The results suggest that the higher AHI, the lower the survival rate of lung cancer patients with OSA, and the hypoxia microenvironment promotes the growth of lung tumors. This conclusion has been confirmed by relevant studies, simulating the intermittent hypoxia in patients with OSAS induced pulmonary metastasis of melanoma , other evidence also suggests that hypoxic microenvironment contributes to the development of non-small cell lung cancer . In vitro studies further proved that intermittent hypoxia lung cancer cells are more resistant and more prone to metastasis ,indicates that lung cancer and OSAS promote each other, leading to disease progression and reduced survival. Obesity is one of the most important risk factors for OSAHS. Obesity is related to the increase of throat fat, tongue fat and volume [24, 25]. Obesity patients have severe upper airway stenosis, abdominal and thoracic fat make longitudinal tracheal traction and pharyngeal wall tension weaken, chest wall compliance decreases, lung capacity decreases, aggravating the severity of OSAHS. The increase of BMI is accompanied by an increase in the incidence of respiratory events and more severe nocturnal hypoxemia , indicated that the higher the degree of obesity, the higher the severity of OSAHS . However, there is no consensus on the prognosis of lung cancer patients with BMI. Some studies suggest that BMI affects the prognosis of lung cancer patients by influencing all aspects of physical fitness of the body , Others studies suggest that high BMI is closely related to the overall survival benefit of lung cancer patients . But smoking is also an important confounding factor of lung cancer, so the influence of BMI on lung cancer needs to be further explored. The results of this study show BMI is an independent prognostic factor for lung cancer patients with OSA. In short, obesity not only aggravates the severity of OSA, but also reduces the survival time of lung cancer patients with OSA. Therefore, obese patients with lung cancer and OSA are at high risk of death.
This research has some limitations. This is a single center retrospective study, the number of samples included is limited, and the follow-up time is long, so there are incomplete clinical information. Therefore, it is still necessary to carry out external verification with large sample and multi center.
In summary,age, AHI༌TNM stage, cancer types, BMI and ODI4 are clinical factors affecting the prognosis of lung cancer patients with OSA༌The nomogram established in this study can be used to predict the prognosis of lung cancer patients with OSA and can provide help for patients to formulate individualized treatment strategies.