Treatment outcomes of tuberculosis in patients with lung cancer: a retrospective analysis

Lung tuberculosis (TB) and cancer have a complex relationship. Data concerning TB treatment in lung cancer patients are still incomplete. The aim of this study was to investigate the clinical characteristics and treatment responses of lung tuberculosis in lung cancer patients. In a retrospective cohort study, lung cancer patients with tuberculosis were identified between January 2013 and December 2016. These patients were divided into a TB treatment group and a TB nontreatment group. Age- and sex-matched lung cancer patients without tuberculosis were selected as control subjects. The clinical courses and responses of patients with and without tuberculosis were examined and compared.


Background
Lung tuberculosis (TB) and cancer have a complex relationship. Data concerning TB treatment in lung cancer patients are still incomplete. The aim of this study was to investigate the clinical characteristics and treatment responses of lung tuberculosis in lung cancer patients.

Methods
In a retrospective cohort study, lung cancer patients with tuberculosis were identified between January 2013 and December 2016. These patients were divided into a TB treatment group and a TB nontreatment group. Age-and sex-matched lung cancer patients without tuberculosis were selected as control subjects. The clinical courses and responses of patients with and without tuberculosis were examined and compared.

Results
A total of 98 consecutive lung cancer patients were diagnosed with lung tuberculosis (47 patients in the TB treatment group and 51 patients in the TB nontreatment group). Fiftyone lung cancer patients without TB were enrolled as control subjects. Most patients in the three groups were elderly, had advanced non-small cell lung cancer and had tumor burdens. Compared with patients in the TB nontreatment group, the patients in the TB treatment group had more active TB (66% vs. 5.9%, p < 0.001) and were newly diagnosed (55.3% vs. 23.5%, p < 0.001). The anti-cancer chemotherapy response rate in the TB nontreatment group was not different from that in the TB treatment group (58.8% vs.
76.6%, p = 0.061), but it was significantly lower than that in the lung cancer group (58.8% vs. 88.2%, p < 0.001). The median survival times of patients in the TB treatment group, TB nontreatment group and cancer patients (control group) were not different (56, 55 and 3 were observed among the three groups.

Conclusion
Both anticancer and antituberculosis treatments can be safely and effectively administered in lung cancer patients with tuberculosis. Attention should be paid to the risk of tuberculosis in lung cancer patients in tuberculosis high-burden countries.

Background
Lung cancer and tuberculosis (TB) represent major public health problems worldwide, especially in developing countries. In China, the annual numbers of new cases of lung cancer and tuberculosis were estimated to be nearly 3,804,000 cases in 2014 [1] and 889,000 cases in 2017 [2], respectively.
The possible relationship between lung cancer and TB has attracted attention for several decades. An increasing number of studies have demonstrated that TB is associated with an increased risk and mortality of lung cancer and vice versa [3][4][5][6]. However, data concerning tuberculosis treatment in lung cancer patients are still incomplete, except for studies involving a small number of patients and showing inconsistent results [7,8].
To investigate the treatment responses of TB in lung cancer patients, we performed a retrospective case-control study in a cohort of patients.

Setting
The study was performed at Anhui Provincial Chest Hospital, a tertiary referral hospital for TB in Anhui Province that has an intermediate incidence of active TB cases (58.4/100,000) [9].

Design
The study was approved by the ethics committee of our hospital. Using the electronic patient data system, patients with lung cancer and lung TB were screened from January 2013 until December 2016. According to TB treatment status, patients were divided into the TB treatment group or the TB nontreatment group. Age-, sex-and cancer stagematched control subjects were randomly selected from lung cancer patients without TB during the same period at Anhui Provincial Chest Hospital. The diagnosis of tuberculosis was made on the basis of bacteriologic, pathologic, or clinical findings [10]. The diagnosis of cancer was confirmed by histopathological examination [11]. We excluded multidrugresistant tuberculosis in the analysis to avoid bias caused by the cases.
The treatment of lung cancer and TB was in accordance with national guidelines [10,11].
In brief, antituberculosis chemotherapy was initially administered with three drugs: rifampicin, isoniazid, and ethambutol for at least 6 months. Anticancer chemotherapy was administered with third-generation platinum-based regimens for non-small cell lung cancer or cisplatin plus etoposide for small cell lung cancer. No molecular targeted therapy or radiotherapy for lung cancer was given to any patient during the study period.
The responses to anticancer treatment were defined according to the response evaluation criteria in solid tumors (RECIST) [12]. The outcome of antituberculosis treatment was defined according to the national guideline [11]. The side effects of chemotherapy were graded using the National Cancer Institute Common Terminology Criteria for adverse events, version 4.0.

Statistical Analysis
Continuous variables were expressed as the median (interquartile range), and differences between groups were analyzed using the Mann-Whitney test. Categorical variables were expressed as absolute values and percentages and were analyzed using the chi-square or Fisher's exact tests. P < 0.05 was considered to be statistically significant. A statistical software package was used for the analyses (SPSS 16.0, SPSS, Chicago, USA).

Results
During the study period, 98 consecutive lung cancer patients were diagnosed with lung tuberculosis. Among them, antituberculosis treatment was administered in 47 patients (TB treatment group). The other 51 patients did not receive tuberculosis treatment (TB nontreatment group). The lung cancer control group included 51 age-, sex-and cancer stage-matched patients without TB.
The clinical characteristics of the patients in the three groups ( Hypoalbuminemia was defined as a serum albumin concentration < 35 g/L. Anemia was defined as a hemoglobin level < 120 g/L in women and < 130 g/L in men. Liver dysfunction was defined as the total bilirubin levels ≥50 μmol/L and/or prothrombin time index <50%. Renal dysfunction was defined as serum creatinine ≥ 1.5 mg/dL. ESR (erythrocyte sedimentation rate) elevation was defined as ESR ≥ 100 mm/h The median ages in the three groups were approximately 65 years. The age of patients in the TB nontreatment group was older than that of the patients in the TB treatment group.
Male patients comprised 84%-95% of each group. Compared to the TB nontreatment group, the lung cancer patients had a higher body mass index (BMI).
The laboratory findings, including hypoalbuminemia, anemia, liver and renal dysfunction, were nearly similar among the three groups. However, the erythrocyte sedimentation rate (ESR) in the TB treatment group was higher than that in the TB nontreatment group.
The cancer type and stage were similar among the three groups. Most patients had advanced non-small cell lung cancer and had tumor burdens. The anticancer chemotherapy regimens and treatment completion rates were similar among the three groups. The response rates were similar between the TB treatment and TB nontreatment groups, although more patients in the TB treatment group were in stable disease. However, the response rate was significantly higher in the lung cancer group compared to the TB nontreatment group. The median survival time and KPS changes were similar among the three groups.

Discussion
The main finding of the current study is that patients with coexisting lung cancer and active tuberculosis could safely receive both anticancer and antituberculosis treatments. antituberculosis and anticancer treatments did not lower the response rate of the anticancer treatment and did not increase the severe side effects. Therefore, our findings suggest that both anticancer and antituberculosis treatments could be safely and effectively administered in advanced lung cancer patients with tuberculosis.

Limitations
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 too few cases for analysis.

Conclusion
Our results indicate that both anticancer and antituberculosis treatments can be safely

Funding
None.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Consent for publication
none

Ethics approval and consent to participate
The study was approved by the Ethics Committee of Anhui Chest Hosptial.

Competing interests
The authors declare that they have no competing interests.

Figure 1
Comparison of Kaplan-Meier curves of survival of three groups