The main finding of the current study is that patients with coexisting lung cancer and active tuberculosis could safely receive both anti-cancer and anti-tuberculosis treatments. This information will help physicians make clinical management decisions for patients with coexisting lung cancer and active tuberculosis.
Lung cancer and tuberculosis are two major public health problems in China. It was demonstrated that there were 28.49 lung cancer-related deaths per 100,000 population in 2014  and 2.6 tuberculosis-related deaths per 100,000 population in 2017 in China . Meanwhile, lung cancer and tuberculosis have a complicated relationship, which means that they are risk factors for each other. As a tuberculosis high-burden country, the incidence of tuberculosis in cancer patients was as high as 12.72% in our past research . In the current study, the features of patients were elderly with advanced NSCLC. In addition, most patients in the TB treatment group were newly diagnosed. Hence, caution should be paid to the risk of tuberculosis in lung cancer patients.
Tuberculosis treatment in cancer patients is still not conclusive, especially for advanced non-small cell lung cancer patients with synchronous anti-tuberculosis and anti-cancer treatments. Kim et al. showed that in cancer patients (lung cancer patients accounted for 8% of subjects), anticancer chemotherapy is not an obstacle to treating tuberculosis . Hirashima et al demonstrated that in patients with metastatic colorectal cancer, both cancer chemotherapy and tuberculosis treatment could be concurrently administered safely and efficiently . The scholar furtherly demonstrated that anti-cancer and anti-tuberculosis treatments can be safely and effectively administered in patients with different types of malignancies (including lung cancer) and active TB. In our study, most patients received the 6HRE treatment regimen (74%), 2 patients received the 2HRZE/4HR treatment regimen and 6 patients received the 9HR treatment regimen because of liver/renal injury at baseline. The TB treatment success rate was as high as 80.7%, just a little lower than that of new and relapse cases in China in 2017 . On the other hand, no serious adverse effects related to anti-tuberculosis treatments were encountered. The most common side effect in TB treatment group was liver injury, most of which were non-serious and recovered by appropriate intervention. The results suggested that anti-tuberculosis treatments would be able to perform in lung cancer patients with active TB.
In our study the sum of rate of TB treatment failure and lost to follow-up reached nearly 20%. The anti-tuberculosis treatment regimen adjustment and withdrawal were probably accounted for the failure (regimen adjustment in 5 patients, treatment interruption in 2 patients, and active withdrawal in 4 patients). The other reason may be because of MRT-TB/RR-TB. Due to limited resources, drug susceptibility testing to TB was performed in 3% of new cases in China in 2013. MRT-TB/RR-TB was not routinely tested during the study period. Hence, more caution should be paid to the MRT-TB/RR-TB infection in lung cancer patient.
Our study focused on lung cancer patients with active TB, not latent TB. Screening and treatment of latent TB nowadays becomes a new priority action for eliminating TB strategy in high-risk population. The prevalence of latent TB diagnosed by interferon-gamma release assay in China ranged between 13% and 20% in a population-based study . Due to large size of latent TB population, latent TB treatment is not systemically adopted in national guideline, but restricted to patients with diverse immune deficiencies, such as HIV, silicosis, receiving anti-tumour necrosis factor treatment, receiving dialysis, organ or hematologic transplantation [20, 21]. Because of simpler treatment regimen for latent TB compared with active TB, preventive chemotherapy of latent TB may be preferable in lung cancer patients. However, the cost-efficacy of preventive treatment of latent TB in lung cancer patients deserves further research.
As for anti-cancer treatment, no differences were found between two groups, such as treatment regimen, response rate, median survival time, change in KPS and serious side effect. The result implied that anti-tuberculosis treatment did not interfere with anti-cancer treatment in lung cancer patients with active TB. The median survival time in TB treatment patients was 52 weeks, which was shorter than that in Shanghai (16 months in stage III/IV non-small cell lung cancer). This may be because the difference in economic and medical level between two regions. Therefore, our findings suggest that both anti-cancer and anti-tuberculosis treatments could be safely and effectively administered in advanced lung cancer patients with tuberculosis.
Nowadays cancer immunotherapy, such as immune checkpoint inhibitors (ICBs) targeting cytotoxic T-lymphocyte associated antigen 4, programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1), has revolutionized the treatments of a variety of different cancers, including lung cancer. However, TB infection associated with these agents has been increasingly reported [23, 24]. The mechanisms of TB activation after ICBs treatments are not yet defined. Boosting Th1-mediated inflammatory responses with PD-1 blockade, administrating steroids or anti-tumor necrosis factor-alpha agents to overcome immune-related adverse events and lymphopenia are among the potential mechanisms [25, 26]. Hence, more attention should be paid to the TB infection during ICBs treatment. Latent TB screening and chemoprophylaxis before checkpoint therapy may be indicated to prevent active TB.
First, this was a retrospective study with inevitable selection bias. Second, the sample size was a small cohort of patients, limiting the power of the statistical analysis. Third, patients receiving molecular targeted therapy were excluded because there were no cases for analysis. Fourth, due to limited resources, MRT-TB/RR-TB was not tested in our study. Fifth, non-tuberculous mycobacteria could not be completely ruled out from our patients because of the limitations of sputum smear and/or culture. However, the influence is small because anti-Tb treatments failed in only two patients.