Lung cancer is one of the leading causes of cancer-related deaths globally, with an estimated 2 million new cases every year. 

The association between cigarette smoking and lung cancer has been known for decades, but epidemiological studies still pin this habit as a leading cause of this disease. It should be noted, though, that lung cancer continues to be diagnosed among never-smokers. 

“Smoking rates are high and the introduction of electronic cigarettes is problematic; the relationship of electronic cigarettes with lung cancer is unclear but there is concern over their popularity and the renormalization of smoking behavior,” Thai and colleagues write in The Lancet. 


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Idiopathic pulmonary fibrosis (IPF), on the other hand, is a progressive interstitial disease of unknown etiology. In North America and Europe, it has an estimated incidence of 3 to 9 cases per 100,000 population annually, and this figure is rising. Some studies suggest that ever-smokers have a higher risk of developing this disease. 

Read more about IPF epidemiology 

Both lung cancer and IPF carry a poor prognosis. Although progress has been made in terms of increasing public awareness of the dangers of cigarette smoking and lung cancer in general, the 5-year survival rate is still estimated to be less than 20%. In IPF, the 5-year survival rate is only slightly better, at 20% to 40%. 

A Tale of Two Diseases 

“IPF has many comorbidities and complications such as pulmonary hypertension, obstructive sleep apnea syndrome, emphysema, gastroesophageal reflux disease, coronary heart disease, and lung cancer is the most severe one of them,” according to Wang and colleagues in PLoS One. 

This suggests that a potential causal relationship exists between IPF and lung cancer. Studies have shown that patients with IPF have a high incidence of lung cancer. The type of lung cancer most common among older male smokers tends to be squamous cell carcinoma. Nevertheless, a comprehensive assessment on the impact of concomitant IPF in patients with lung cancer has not been performed. 

Wang and colleagues conducted a literature review examining the relationship between these two lung diseases. They performed an extensive online search of publications containing keywords such as “idiopathic pulmonary fibrosis,” “lung cancer,” “survival,” and “prognosis,” among others. Twelve studies were included in their final analysis. 

They discovered that there was significant heterogeneity among studies regarding the impact of concomitant IPF on lung cancer prognosis, with the overall picture suggesting that it worsens outcomes. Interestingly, studies demonstrate that IPF and cancer share similar pathophysiological processes such as genetic and epigenetic alterations. In addition, cell proliferation and apoptosis have been characterized in both diseases. 

Read more about IPF diagnosis

Another link between these two diseases is research indicating that nintedanib, an antifibrotic drug, may benefit patients with lung cancer. Patients with lung cancer on nintedanib have better overall survival compared with patients who were not on this medication. This suggests that both diseases may share common therapeutic targets. 

“For the clinical aspect, patients with IPF tend to have worse lung function than those without IPF, characterized by restrictive ventilatory disorder and diffusion dysfunction,” Wang et al write. “Therefore, lung cancer patients with concomitant IPF may have a higher risk for dyspnea and acute exacerbation, which can lead to a worse outcome of survival.” 

In addition, common medications used to treat IPF, such as steroids and immunosuppressants, can suppress the immune system of users; it stands to reason that patients with both IPF and lung cancer would be at a higher risk of infection or dysbiosis, which can only worsen clinical outcomes. 

Treatment Options: More Research Needed 

In view of the Wang et al meta-analysis, it is reasonable to conclude that concomitant IPF in patients with lung cancer leads to poorer survival. The urgent question becomes how physicians should proceed with treating patients who have both diseases. 

“Currently, there is no consensus regarding the treatment of patients with both diseases,” Ballester and colleagues write in the International Journal of Molecular Sciences. 

Nintedanib has been shown to be effective in patients with IPF and lung cancer. In addition, pirfenidone is an IPF medication that has been shown to be effective in extending survival in patients with lung cancer. 

Read more about IPF treatment 

Unfortunately, there are still not any drugs that can effectively halt the progression of either disease, let alone both concurrently. The good news is that research has improved our understanding of IPF and lung cancer, and even if the etiology of IPF remains still unclear, we now know that they are more similar than previously imagined. 

“Therefore, it seems reasonable to investigate whether specific cancer drugs may exert beneficial anti-fibrotic effects that are effective to treat lung cancer-IPF patients,” Ballester and colleagues write. 

Future research should focused on uncovering means to slow and/or stop the progression of either disease. This may translate to the development of better and more potent antifibrotic and anticancer medication. In addition, risk factors need to be identified for both diseases so that treatment modalities can begin more quickly. 

References

Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancerLancet. 2021;398(10299):535-554. doi:10.1016/S0140-6736(21)00312-3

Wang H, Yang R, Jin J, Wang Z, Li W. Impact of concomitant idiopathic pulmonary fibrosis on prognosis in lung cancer patients: a meta-analysisPLoS One. 2021;16(11):e0259784. doi:10.1371/journal.pone.0259784

Ballester B, Milara J, Cortijo J. Idiopathic pulmonary fibrosis and lung cancer: mechanisms and molecular targetsInt J Mol Sci. 2019;20(3):593. doi:10.3390/ijms20030593