Impact of Interstitial Lung Disease on Survival for Patients with Non-small Cell Lung Cancer

Discussion

ILD such as IPF and CDPF remains a devastating and progressive pulmonary disease that is characterized by alveolar destruction, excess matrix production and varying levels of inflammation leading to impaired gas exchange (10). As patients with ILD have pulmonary functional impairment and poor reserve of cardiopulmonary function, many patients may not match indications for standard therapies and need palliative care. Moreover, it is well known that ILD is associated with an increased risk of lung cancer, with a relative risk of 7.0 to 14.0 compared with the general population (11, 12). On the other hand, however, only a few studies have shown the incidence of ILD in NSCLC patients (6, 7, 13). Park et al. showed that 63 (2.3%) out of 2,723 lung cancer patients were diagnosed as having IPF (13). Kumar et al. reported that 22 (2.2%) out of 995 NSCLC patients had pulmonary fibrosis (7). In a study by Chiyo et al., 36 (3.9%) out of 931 patients with resectable lung cancer had ILD (6). In the present study, we showed that 53 (2.4%) out of 2,165 NSCLC patients were diagnosed as having IPF. This result was almost the same incidence of ILD in NSCLC patients as the previous studies, although the definition with regard to ILD was different.

Because of the design of clinical trials, including criteria of entry that preclude involvement of patients with impairment of organ function, many published studies have not shown the outcome of treatment of NSCLC patients with comorbid disease such as ILD. As a result, there is little published information regarding the results of treatment and prognostic factors in unselected groups of NSCLC patients including those with both diseases. Therefore, we evaluated the results of treatment and prognostic factors in unselected NSCLC patients who were admitted to our two hospitals. In the present series of patients, we confirmed that female gender, early clinical stage and good PS were favorable prognostic factors for NSCLC, as has been reported in previous studies (14, 15). Additionally, we revealed that patients with ILD had worse overall survival than those without, and existence of ILD was one of the unfavorable prognostic factors for survival in NSCLC patients. Some previous thoracic surgeons reported that existence of ILD had an impact on survival in patients with resectable NSCLC (6, 7, 13). In these studies, however, patients who had severe impairment of pulmonary function were excluded from operative indication, and only selected ILD patients who were thought to tolerate operation were included (6, 7, 13). In addition to this, there was a possibility that incomplete or limited resection, which might have some relation to prognosis, was performed in some ILD patients. Postoperative deterioration of ILD necessitating mechanical ventilation and tracheostomy was a major cause of death and occurred more frequently in ILD patients than in non-ILD patients (6, 7, 13). For NSCLC patients with locally advanced disease having ILD, chest irradiation is usually contraindicated by the reason of development respiratory failure due to deterioration of ILD (16-18). The epidermal growth factor receptor tyrosine kinase inhibitors such as gefitinib and erlotinib are not prescribed for patients with metastatic NSCLC for the same reason (19-21). These contraindications narrow the choice of treatment and may have some relationship with poor prognosis of NSCLC patients with ILD.

The limitations of this study are inherent to its retrospective design, therefore necessarily complicated by lead time and length time biases. In this study, almost all of our patients were pathologically diagnosed using specimens obtained by transbronchial biopsy. Therefore, patients who had severe pulmonary functional impairment for carrying out diagnostic procedures might had been excluded, and only selected NSCLC patients with ILD who were thought to tolerate these procedures were included. Another limitation is the lack of information about the assessment of respiratory function and precise pathological diagnosis of ILD. Randomized, prospective studies comparing prognosis in NSCLC patients with or without ILD are the only way to obtain an unconfounded estimate of the prognostic effect of ILD. However, we recognize that it has some clinical importance for the management of future patients of unselected groups. When NSCLC patients have ILD, our results apparently showed that the therapeutic approach is complicated. Our results imply that existing ILD does adversely affect the outcome of NSCLC. When deciding whether or not to offer an intensive therapy which may increase treatment-related mortality, the individual patient's medical condition, including coexistence of ILD, should be taken into consideration, although favorable results have been reported in a small number of patients with ILD (6, 7, 13). Therefore, detailed history taking and physical examination are required to elucidate the presence of signs and/or symptoms of ILD.

In summary, chest CT scan is indicated not only to evaluate metastatic lesion from lung cancer but also to detect findings of ILD. Appropriate pre-evaluation for the indication of standard therapy or adequate palliative care is essential to provide prolonged quality survival, which is the primary goal of therapy for NSCLC patients with ILD.