REVIEW ARTICLE
The Clinical Respiratory Journal
Epidemiology of active tuberculosis in lung cancer patients: a systematic review Antonis Christopoulos1, Muhammad W. Saif2, Evangelos G. Sarris3 and Kostas N. Syrigos3 1 School of Health & Welfare Professions, Department of Nursing, Technological Educational Institute of Patras, Patra, Greece 2 Division of Hematology/Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA 3 Oncology Unit GPP, Sotiria General Hospital, Athens School of Medicine, Athens, Greece
Abstract Objectives: The aim of this review article is to evaluate the available literature concerning the prevalence of active tuberculosis in lung cancer patients. Data Source: MEDLINE, PubMed, EMBASE and Medscape databases were searched for studies with quantitative data on the interaction between tuberculosis (TB) and lung cancer, published since 1952. We used the Medical Subject Headings’ term ‘tuberculosis’ and the text-word terms ‘TB’ and ‘Mycobacterium infection’, and also, the Medical Subject Headings’ terms ‘neoplasm’ and ‘lung neoplasm’, or the text-word term ‘lung cancer’. Data Selection: We selected studies with cases verified by bacteriological examinations and biopsies that contained enough data to estimate tuberculosis prevalence. We did not exclude any study on the basis of language. Results: The prevalence of active tuberculosis among lung cancer patients varies depending on spatial and regional factors. Lung cancer patients who are more prone to developing tuberculosis are Asian and Caucasian males, with an average age of 60 years old. The prevalence of tuberculosis is higher in patients with chest X-ray evidence of old tuberculosis and/or history of tuberculosis, chronic obstructive pulmonary disease, heavy cigarette smoking, increased alcohol consumption, and/or diabetes mellitus. A high mortality rate because of tuberculosis in lung cancer patients was also estimated. Conclusion: Active tuberculosis complicating lung cancer is a significant clinical issue in countries with high prevalence of tuberculosis. However, as the there is a lack of reports from developed countries over the last 20 years, the significance of this interaction in countries with low tuberculosis burden remains controversial. Please cite this paper as: Christopoulos A, Saif MW, Sarris EG and Syrigos KN. Epidemiology of active tuberculosis in lung cancer patients: a systematic review. Clin Respir J 2014; 8: 375–381.
Objectives The interaction between lung cancer and active pulmonary tuberculosis (TB) has been the center of significant clinical and pathological interest and research for many years. The first case of coexistent TB and lung cancer was reported by Bayle in 1810 (1).
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Key words lung cancer – malignancy – mycobacterium infection – neoplasm – tuberculosis Correspondence Kostas Syrigos, MD, PhD, Sotiria General Hospital, Athens School of Medicine, GR 152 Mesogeion, GR 115 27 Athens, Greece. Tel: +30 21 0770 0220 Fax: +30 21 0778 1035 email: [email protected] Received: 03 April 2013 Revision requested: 17 November 2013 Accepted: 13 December 2013 DOI:10.1111/crj.12094 Authorship and contributorship Study Concepts: Kostas Syrigos, Antonis Christopoulos. Study Design: Kostas Syrigos, Muhammad W. Saif. Data Acquisition: Antonis Christopoulos. Data Analysis and Interpretation: Antonis Christopoulos. Manuscript Preparation: Antonis Christopoulos. Manuscript Editing: Evangelos G. Sarris, Antonis Christopoulos. Manuscript Review: Muhammad W. Saif, Kostas Syrigos. Conflicts of Interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
The results of later attempts to etiologically correlate these two diseases varied from no significant interaction, or even antagonism, to a direct cause and effect relationship. Several studies in the past have shown a purely circumstantial or random coexistence between these two diseases, attributing the increasing appearance to changes in epidemiology
375
Tuberculosis in lung cancer patients
and increased life expectancy as a result of efficacious treatment and improved diagnosis. Nowadays, TB is an established independent factor of increased risk for lung cancer (2). However, a conflict remains regarding the frequency of active pulmonary TB in patients with lung cancer. Thus, a systematic review was performed to investigate and elucidate the prevalence of active pulmonary TB in lung cancer patients.
Data source A search in MEDLINE, PubMed, EMBASE and Medscape databases was conducted for studies presenting quantitative data on the interaction between TB and lung cancer. Because the introduction of anti-TB therapy in 1952 changed the overall prognosis of TB, we searched for reports since 1952 (last research September 2013). Studies were searched by using the Medical Subject Headings’ term ‘tuberculosis’ and the text-word terms ‘TB’ and ‘Mycobacterium infection’, and also, the Medical Subject Headings’ terms ‘neoplasm’ and ‘lung neoplasm’, or the text-word term ‘lung cancer’. The reference lists of the obtained articles were studied to identify more eligible references that were then retrieved. The following information was extracted and coded by using standard form: year of publication, country/ region and quantitative data on the interaction between TB and lung cancer. All data were abstracted independently by one reviewer and checked by a second.
Data selection In order to select and maintain a large group of homogenous, multinational studies, we did not exclude any study on the basis of language and used wide eligibility criteria. The studies selected should contain at least minimum information in order to estimate the prevalence of active TB in lung cancer patients. We only included studies in which lung cancer and TB were verified with biopsy and bacteriological examination, respectively. All studies used in the review should include unique cases in order to avoid giving double weight to repeated data. In case of studies using data from the same population, during the same period of time, only the first publication was included. An exception was made when conflicting data were presented.
Results The prevalence of TB was calculated by dividing the number of lung cancer patients with active TB by the
376
Christopoulos et al.
total number of lung cancer patients. We classified regions as TB high-burden regions (Western Pacific, Eastern Europe, Southern America and Africa) and TB low-burden regions (Western Europe and North America). Mortality was ascribed to TB only when respiratory failure occurred due to TB or when TB expansion was observed involving multiple organs, while cancer disease was not extended and there was no other obvious cause of death. A total of 79 articles were retrieved to determine eligibility for inclusion in this systematic review. Fifty three of them did not provide sufficient information in order to estimate TB prevalence, and the rest 20 did not include unique cases. Sixteen of the retrieved studies contained the necessary data to estimate TB prevalence and were eventually included. Sixteen case-control studies were eventually used for the estimation of TB prevalence in lung cancer patients (3–18). All studies reported findings concerning cases of active pulmonary TB complicating lung cancer, verified with biopsy and bacteriological examination. All studies were unique as to the reported region and time period. In Table 1, details such as the year and country reported are presented. In the retrieved studies, sample size ranged from 193 to 4805, with a total of 692 cases of TB among 33 126 lung cancer cases eventually being studied. The type of control population used, as well as the population at risk, varied between studies and included randomly selected community population, general hospital patients and/or even sanatorium data. There was a male predominance reported in all the included studies (mean value 13:1), and the median age of the reported TB cases was 60 ± 14.1 years (range from 44 to 70 years of age). An increased prevalence of active TB was reported in lung cancer patients (8–10 times higher compared with general background population). However, evidence of heterogeneity across the contributing studies (range 0.7%–18.7%) was reported, with the exception of studies published in Japan. In these studies, a stable TB prevalence, estimated at 1%–2%, has been reported over the last 20 years. In two studies (12, 15), active pulmonary TB was significantly higher among lung cancer patients with old TB lesions or a past history of TB than in lung cancer patients without such lesions or history. Also, an active TB diagnosis was associated with more advanced lung cancer stages (III–IV). With regard to the histological subtypes of lung cancer most commonly associated with TB, the results are conflicting; nine studies (6, 12–14, 16–20)
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Christopoulos et al.
Tuberculosis in lung cancer patients
Table 1. Reported prevalence of active pulmonary tuberculosis (TB) in autopsied/ biopsied cases of lung cancer (LC) Year
Author
TB cases
LC points
Prevalence
Country
TB mortality%
1953 1959 1965 1968 1970 1971 1975 1990 1991 1991 1991 1994 1998 1999 2007 2007
Nuessle Hamel Holden Berroya Alastair Kaplan Solomon Hara Antkowiak Dacosta Aoki Chen YM Tamura Watanabe Tamura Cicenas
85 54 15 54 92 92 6 142 38 29 6 31 25 16 56 46
1335 4010 80 1218 3064 4805 193 6396 1351 221 442 3928 1315 758 4666 2218
6.3 1.3 18.7 4.4 3.0 0.9 3.1 2.22 2.8 13.1 1.3 0.7 1.9 2.1 1.2 2.0
USA USA Canada USA Australia USA S. Africa Japan Poland India Japan Taiwan Japan Japan Japan Lithuania
50.0
have shown a predominance of squamous cell carcinoma, while three studies (11, 15, 21) have demonstrated a closer association of pulmonary TB with adenocarcinoma. Eight studies evaluated the effect of a concomitant or sequential TB diagnosis in lung cancer prognosis. In seven of them, TB was found to have an adverse effect on lung cancer prognosis and mortality, while one study (20) showed that lung cancer patients with concomitant active TB had a longer median survival than patients without TB (11.6 vs 8.8 months, P < 0.01). Data used for estimating the average mortality rate because of TB (22.6 ± 14.4) were reported in seven of the studies (Table 1).
Discussion Nowadays, there is strong evidence to support that pre-existing TB is an independent factor highly associated with increased risk of lung cancer [relative risk (RR) = 11.14, 1–5 years after TB diagnosis] (21–25). Furthermore, whether lung cancer has the ability to arise from TB lesions or not, as an immunosuppressive disease, lung cancer may promote TB infection or result in reactivation of latent TB infection, or cause new exogenous infection (26). Cancer cells invasion in healed TB lesions might also lead to TB reactivation. In addition, regional tumor peptides, antigens or even radiotherapy might lead to granulomas microenvironment deregulation, allowing TB mycobacteria to proliferate (27).
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
7.0
33.3 12.0 18.7 12.5 30.4
Even though there is a causative association between the two diseases, a significant heterogeneity in TB prevalence was recorded among the retrieved studies, indicating the risk of bias. As all cases were histologically verified, misclassification of TB was not possible in the reported data. Furthermore, factors associated with increased risk of TB, such as smoking, chronic obstructive pulmonary disease, chronic renal failure and/or diabetes mellitus, were equally distributed among studied and control groups in the reviewed studies. The prevalence of TB, however, might have been affected by spatial and temporal variations of TB and/or lung cancer in the general background populations. To support this, we took under consideration the variations of TB prevalence, along with TB and lung cancer epidemiology. Although there had been occasional reports of lung cancer and active pulmonary TB coexistence, it was not until 1935 that Fried published his large series (28). He reported 13 histologically verified cases in which both diseases were combined, and he also reported a logical explanation as to the correlation between these two diseases. Fried reported that pulmonary TB and lung cancer could incidentally coexist or that one could be the causative factor of the other. In one literature review until 1953, Nuessle presented 85 cases of active pulmonary TB among 1335 autopsied patients with lung cancer (prevalence 6.4%) (3). These publications showed that a high percentage of lung cancer cases was complicated by active TB. In the 19th century, the prevalence of active TB was undoubtedly higher compared with nowadays. Furthermore, 377
Tuberculosis in lung cancer patients
in late 19th and early 20th century, an increase in both lung cancer incidence and diagnostic accuracy occurred. Once regarded as a rare disease, primary carcinoma of the lung was the most lethal among all types of cancer (29). Since 1952, when isoniazid was discovered, anti-TB chemotherapy significantly decreased TB mortality rate all over the world and changed the prognosis of the disease, as well as the social impact of TB. Patients previously having a life expectancy of only a few years because of the complications of TB could now be treated and survive significantly longer. An annual decline of approximately 5% in the number of TB cases was observed in the USA since 1950, reaching up to 6%–7% during the years 1981– 1984 (26). Over a 14-year period (1954–1968), Berroya et al. in Missouri State Sanatorium reported an alarming increase in the incidence of lung cancer and a gradual decrease in the incidence of TB. As TB patients, after being effectively treated, were capable of reaching the ‘lung cancer age group’, pulmonary TB and lung cancer often coexisted (prevalence 4.43%) (6). However, Kaplan et al. during the same period (1950–1971) reported only 44 cases of active TB among 4805 lung cancer patients treated in Memorial Hospital (prevalence 0.92%) (7). Obviously, the prevalence of lung cancer among the TB population treated in a sanatorium was higher than the prevalence of TB among lung cancer patients attending a general hospital. Similar data were reported worldwide. In 1970, Campbell and Guilfoyle reported 92 cases of active TB complicating lung cancer in Melbourne, Victoria, Australia during a 6-year period (prevalence 2.98%) (8). Furthermore, in 1979, Solomon et al. reported a high incidence of active pulmonary TB complicating lung cancer in Baragwanath Hospital in Johannesburg (9). Investigators concluded that lung cancer activates dormant TB in a population group also presenting high incidence of TB. Then, between 1984 and 1992, the incidence of TB increased in the USA by 18% mainly because of immigrating populations from high TB-burden countries and because of the continuously increasing incidence of AIDS, which causes immunodeficiency, and therefore, HIV patients are more prone to develop TB (26). Philips et al. from Ohio reported in 1984 five cases of carcinoma of the lung and coexistent active TB arising from the same pulmonary lesion (30). New efforts in disease control, as well as new advances in treatment, resulted in a total decrease in TB incidence by 31% from 1992 to 1998 in the USA (26). However, TB remains one of the world’s major causes of illness and death, and in 1993, the World
378
Christopoulos et al.
Health Organization declared TB to be a global health emergency. Approximately one third of the world’s population is infected. More than 9 million people present every year with active TB, which can be spread to others. Latent TB is not able to spread (31). Regions with the highest incidence and prevalence rates are sub-Saharan countries and Southeastern Asia (32). In 1990, Hara et al. (18) reported 142 cases of coexistent active pulmonary TB and bronchogenic carcinoma with an incidence rate of 2.22% among lung cancer patients; the predominant histological type of lung cancer was squamous cell carcinoma, followed by adenocarcinoma (the proportions of the histological types of lung cancer were not significantly different from those in the general population). Well-known pathologists Dacosta and Kinare in 1991 reported that in King Edward Memorial Hospital in Bombay, coexistence of TB and lung cancer was detected in 29 out of 221 necropsied cases (prevalence 13.1%) (11). In their department, TB was reported in 7%–8% of autopsied cases. The most common histological subtype found was undifferentiated carcinoma (76%), followed by adenocarcinoma (56%) and epidermoid carcinoma (5.44%). However, most cases of undifferentiated lung carcinoma were more likely to represent adenocarcinomas, while all scar cancers were adenocarcinomas. Chen et al. in a low TB-burden region like Taiwan (TB prevalence in the general population, 0.11%) reported a significantly lower prevalence of TB among lung cancer patients (0.79%) (13); epidermoid carcinoma was the most common histological subtype accounting for 64.5% of cases. In the same period, Aoki et al. and Tamura et al. reported that in Tokyo National Hospital, the incidence of active TB among lung cancer patients was 1%–2% (12, 14). Both research groups observed a higher incidence of squamous cell carcinoma in coexisting lung cancer and TB cases. Furthermore, Aoki et al. observed that active pulmonary TB was significantly higher in lung cancer patients with old TB lesions than in those without ones (5.6% vs 0.52%). Since then, many investigators, mainly from Western Pacific region or Eastern Europe, recorded an increased prevalence of active pulmonary TB among lung cancer patients (15–17). In the study by Watanabe et al. (15), specifically, active pulmonary TB development was also associated with a past history of TB (P < 0.005). According to Tamura et al. in 1999 (14) and 2007 (16), Watanabe et al. (15), Chen et al. (13), and Cicenas and Vencevicius (17), most lung cancer patients diagnosed with active TB are advanced-stage (III–IV) cancer patients. Furthermore, Xie et al. (33) suggested that the occurrence of lung cancer was highly correlated to
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Christopoulos et al.
the site of TB, and Chen et al. (13) reported that in most patients, lung cancer and TB lesions were ipsilateral, while Tamura et al. (14) concluded that the location of lung cancer and TB seemed to be independent. Finally, Kim et al. (34) reported that out of 219 patients with coexisting bronchogenic carcinoma and TB, 51 had both lesions in the same lobe, with a predominance of upper lobes. With regards to the histological cancer subtypes associated with active TB, Watanabe et al. (15) and Silva et al. (35) reported more cases of adenocarcinoma in lung cancer patients with coexisting TB, while Tamura et al. (16), Cicenas and Vencevicius (17), and Xie et al. (33) showed a predominance of squamous cell carcinoma. Kuo et al. (20) also demonstrated that squamous cell carcinoma was an independent factor for active TB [odds ratio 2.09, 95% confidence interval (CI) 1.06–4.14, P < 0.05]. However, in the association of specific histological subtypes of lung cancer with TB, results remain conflicting overall. The large metaanalysis of Liang et al. (2), involving 37 case-control and 4 cohort studies from 1966 to 2009, demonstrated a significant association of coexistent TB with adenocarcinomas (RR 1.6, 95% CI 1.2–2.1), but not with the squamous and small cell type. However, the issue has not yet been resolved. With the exception of the earlier mentioned study by Kuo et al. (20), most studies have demonstrated an adverse effect of concomitant or sequential active TB on lung cancer prognosis. Chen et al. (13) reported that patients who had an active pulmonary TB diagnosis concurrently with or before the diagnosis of lung cancer survived for a shorter period than those without TB (P = 0.007), while survival from diagnosis of TB was longer in patients who developed TB earlier than or concurrently with lung cancer than in those who developed active TB later (P = 0.046). Engels et al. (36), in a large retrospective cohort study performed in Xuanwei, China, observed that lung cancer mortality was substantially higher in lung cancer patients with TB than among those without TB [hazard ratio (HR) 6.1, 95% CI 4.3–8.7]. Heuvers et al. (37) and Leung et al. (38) also reported that a history of pulmonary TB was associated with a significantly shorter survival in lung cancer patients, while Shieh et al. (39), in a large retrospective study in Taiwan, observed that lung cancer patients with comorbid TB had a shorter survival duration than patients without TB (7-year survival rate, 10% vs 21%; P = 0.03 in multivariate analysis). In a more recent analysis, Zhou et al. (40) reported that the median survival of patients with squamous cell carcinoma specifically was significantly shorter in patients with old TB lesions compared with patients
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Tuberculosis in lung cancer patients
without TB (1.7 vs 3.4 years, P < 0.01); the presence of an old pulmonary lesion was found to be an independent predictor of poor survival (HR 1.72; 95% CI 1.12– 2.64). Finally, it is worth mentioning a study by Luo et al. (41) coming from China and associating old TB lesions with a higher probability (P = 0.018) of lung adenocarcinoma patients having epidermal growth factor receptor (EGFR) mutations (especially exon 19 deletions). Among patients with EGFR mutations, those who had old TB lesions survived for a shorter period than those who did not (P = 0.035). The increased prevalence of active TB and latent TB reactivation in lung cancer patients and the negative effect of pulmonary TB in lung cancer prognosis underline the need for a more thorough screening of lung cancer patients for latent and active TB. Kamboj and Sepkowitz (42), from the Memorial-SloanKettering Cancer Center, New York, do not consider cancer patients (with the exception of head and neck cancer patients) as a risk group for the development of TB and, therefore, do not suggest routine PPD (purified protein derivative) testing, but other authors suggest otherwise. Lonnröth et al. (43) do not refer specifically to lung cancer patients; however they consider people with chronic respiratory disease/smokers and people with immunocompromising disorders/ treatments – conditions often associated with lung cancer – as high-risk groups who should be screened for TB. The 2011 National Institute for Health and Clinical Excellence guidelines (44) suggest that people who are immunocompromised should have an interferon-gamma test alone or with a concurrent Mantoux test; if either test is positive, active TB should be excluded through clinical assessment, and if excluded, latent TB should be treated.
Conclusion Variations in epidemiology offer a solid explanation of the observed heterogeneity in TB prevalence among lung cancer patients and explain the numerous reports in TB high-burden countries over the last two decades. However, during the last 20 years, there is a lack of reports of coexistent TB and lung cancer in TB lowburden countries. Whether the coexistence of both diseases can be considered as a rare, well-known clinical problem, not deserving further investigation, or not is something that we are not able to answer. However, even in the latest reported data concerning the prevalence of coexistent TB and lung cancer in the USA (0.92%), among estimated 222 520 new lung cancer cases in 2010, there might be as many as 2048 cases of active pulmonary TB waiting to be discovered (31). 379
Tuberculosis in lung cancer patients
References 1. Bayle GL. Recherches sur la phthisie pulmonaire: ouvrage lu à la Société de la faculté de médecine de Paris, dans diverses séances, en 1809 et 1810. Paris, Gabon, 1810. 2. Liang HY, Li XL, Yu XS, Guan P, Yin ZH, He QC, Zhou BS. Facts and fiction of the relationship between preexisting tuberculosis and lung cancer risk: a systematic review. Int Journal of Cancer. 2009;125(12): 2936–44. 3. Nuessle WF. Association of bronchogenic carcinoma and active pulmonary tuberculosis: with report of four cases. Dis Chest. 1953;23: 207–16. 4. Hamel NC, Briggs JN, Ludigton LG. Cancer of the lung in tuberculous patients. Calif Med. 1959;91(3): 131–3. 5. Holden HM, Quinlan JJ, Hiltz JE. Co-existing pulmonary tuberculosis and bronchogenic carcinoma: report of 15 cases. Can Med Assoc J. 1965;18(93): 1306–10. 6. Berroya RB, Polk JW, Raju P, Bailey AH. Concurrent pulmonary tuberculosis and primary carcinoma. Thorax. 1971;26(4): 384–7. 7. Kaplan MH, Armstrong D, Rosen P. Tuberculosis complicating neoplastic disease. Cancer. 1974;33: 850–8. 8. Campbell AH, Guilfoyle P. Pulmonary tuberculosis, isoniazid and cancer. Br J Dis Chest. 1970;64(3): 141–9. 9. Solomon A, Hurwitz S, Conlan AA. Broncogenic carcinoma with coexisting active pulmonary tuberculosis in urban blacks. S Afr Med J. 1979;55: 979–81. 10. Mose-Antkwiak R. Tuberculosis and lung cancer. Pneumonol Alergol Pol. 1991;59(1–2): 48–54. 11. Dacosta NA, Kinare SG. Association of lung cancer in tuberculosis. J Postgrad Med. 1991;37: 185–9. 12. Aoki Y, Kuroki S, Hura K, Katoh O, Yamada H. A clinical study of pulmonary tuberculosis in lung cancer patient. Kekkaku. 1991;66(11): 727–32. 13. Chen YM, Chao J-Y, Tsai C-M, Lee P-Y, Perng R-P. Shortened survival of lung cancer patients initially presenting with pulmonary tuberculosis. Jpn J Clin Oncol. 1996;26(5): 322–7. 14. Tamura A, Hebisawa A, Tanaka G, et al. Active pulmonary tuberculosis in patients with lung cancer. Kekkaku. 1999;74(11): 797–802. 15. Watanabe A, Tokue Y, Takahashi H, Sato K, Nukiwa T, Honda Y, Fujimura S. Management of mycobacteriosis in general hospital without isolation word for tuberculosis patients. Clinical study on pulmonary tuberculosis associated with lung cancer patients. Kekkaku. 1999;74: 157–62. 16. Tamura A, Hebisawa A, Masuda K, et al. Coexisting lung cancer and active pulmonary tuberculosis. Nihon Kokyuki Gakkai Zasshi. 2007;45(5): 382–93. 17. Cicenas S, Vencevicius V. Lung Cancer in patients with tuberculosis. World J Surg Oncol. 2007;5: 22. 18. Hara H, Soejima R, Matsushima T. A study of the coexistence of pulmonary tuberculosis and bronchogenic carcinoma: results of a questionnaire in Chugoku and Shikoku areas. Kekkaku. 1990;65(11): 711–17.
380
Christopoulos et al.
19. Cha SI, Shin KM, Lee JW, Lee SY, Kim CH, Park JY, Jung TH. The clinical course of respiratory tuberculosis in lung cancer patients. Int J Tuberc Lung Dis. 2009;13(8): 1002–7. 20. Kuo CH, Lo CY, Chung FT, Lee KY, Lin SM, Wang CH, Heh CC, Chen HC, Kuo HP. Concomitant active tuberculosis prolongs survival in non-small cell lung cancer: a study in a tuberculosis-endemic country. PLoS One. 2012;7(3): e33226. 21. Zheng W, Blot WJ, Liao ML, Wang ZX, Levin LI, Zhao JJ, Fraumeni JF Jr, Gao YT. Lung cancer and prior tuberculosis infection in Shanghai. Br J Cancer. 1987;56(4): 501–4. 22. Tocque K, Convery RP, Bellis MA, Beeching NJ, Davies PD. Elevated mortality following diagnosis with a treatable disease. Int J Tuberc Lung Dis. 2005;9(7): 797–802. 23. Yu YH, Liao CC, Hsu WH, Chen HJ, Liao WC, Muo CH, Sung FC, Chen CY. Increased lung cancer risk among patients with pulmonary. J Thorac Oncol. 2011;6(1): 32–7. 24. Wu CY, Hu HY, Pu CY, Huang N, Shen HC, Li CP, Chou JY. Pulmonary tuberculosis increases the risk of lung cancer: a population-based cohort study. Cancer. 2011;117(3): 618–24. 25. Brenner AV, Wang Z, Kleinerman RA, Wang L, Zhang S, Metayer C, Chen K, Lei S, Cui H, Lubin JH. Previous pulmonary diseases and risk of lung cancer in Gansu Province, China. Int J Epidemiol. 2001;30(1): 118–24. 26. American Thoracic Society/Centers for Disease Control. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161: 221–47. 27. Li R, Ruttinger D, Li R, Si LS, Wang YL. Analysis of the microenvironment at the tumor site in patients with non-small cell lung cancer. Lagensbecks Arch Surg. 2003;388(6): 406–12. 28. Fried BM. Bronchogenic carcer combined with tuberculosis of the lung. Am J Cancer. 1935;23: 247–66. 29. Wayl P. Difficulties in the diagnosis of coexistent brochogenic carcinoma and active pulmonary tuberculosis. Dis Chest. 1955;28: 568–73. 30. Philips LG Jr, Cunningham J, Hillman NM, Lewis J. Carcinoma of the lung and coexisting active pulmonary tuberculosis: diverse morphologic and radiographic presentations. J Natl Med Assoc. 1984;76(2): 125–30. 31. WHO. Tuberculosis fact sheet. No. 104, March 2010. 32. WHO. Global Tuberculosis Report. 2012. 33. Xie BX, Ding JA, Jiang GN. Cooccurrence of pulmonary tuberculosis and carcinoma: diagnosis and the prognostic factors for surgical effects. Zhonghua Jie He He Hu Xi Za Zhi. 2005;28(4): 230–2. 34. Kim YI, Goo JM, Kim HY, Song JW, Im JG. Coexisting bronchogenic carcinoma and pulmonary tuberculosis in the same lobe: radiologic findings and clinical significance. Korean J Radiol. 2001;2(3): 138–44. 35. Silva DR, Valentini DF Jr, Müller AM, Almeida CPB, Dalcin PTR. Pulmonary tuberculosis and lung cancer:
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Christopoulos et al.
36.
37.
38.
39.
40.
simultaneous and sequential occurrence. J Bras Pneumol. 2013;39(4): 484–9. Engels EA, Shen M, Chapman RS, Pfeiffer RM, Yu YY, He X, Lan Q. Tuberculosis and subsequent risk of lung cancer in Xuanwei, China. Int J Cancer. 2009;124(5): 1183–7. Heuvers ME, Aerts JG, Hegmans JP, et al. History of tuberculosis as an independent prognostic factor for lung cancer survival. Lung Cancer. 2012;76(3): 452–6. Leung CC, Hui L, Lee RS, et al. Tuberculosis is associated with increased lung cancer mortality. Int J Tuberc Lung Dis. 2013;17(5): 687–92. Shieh SH, Probst JC, Sung FC, Tsai WC, Li YS, Chen CY. Decreased survival among lung cancer patients with co-morbid tuberculosis and diabetes. BMC Cancer. 2012;12: 174. Zhou Y, Cui Z, Zhou X, Chen C, Jiang S, Hu Z, Jiang G. The presence of old pulmonary tuberculosis is an
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Tuberculosis in lung cancer patients
41.
42.
43.
44.
independent prognostic factor for squamous cell lung cancer survival. J Cardiothorac Surg. 2013;8: 123. Luo YH, Wu CH, Wu WS, Huang CY, Su WJ, Tsai CM, Lee YC, Perng RP, Chen YM. Association between tumor epidermal growth factor receptor mutation and pulmonary tuberculosis in patients with adenocarcinoma of the lungs. J Thorac Oncol. 2012;7(2): 299–305. Kamboj M, Sepkowitz KA. The risk of tuberculosis in patients with cancer. Clin Infect Dis. 2006;42(11): 1592–5. Lönnroth K, Corbett E, Golub J, Godfrey-Faussett P, Uplekar M, Weil D, Raviglione M. Systematic screening for active tuberculosis: rationale, definitions and key considerations. Int J Tuberc Lung Dis. 2013;17(3): 289–98. NICE. NICE clinical guideline 117 guidance.nice.org.uk/ cg117. Issued: March 2011.
381
The Clinical Respiratory Journal
Epidemiology of active tuberculosis in lung cancer patients: a systematic review Antonis Christopoulos1, Muhammad W. Saif2, Evangelos G. Sarris3 and Kostas N. Syrigos3 1 School of Health & Welfare Professions, Department of Nursing, Technological Educational Institute of Patras, Patra, Greece 2 Division of Hematology/Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA 3 Oncology Unit GPP, Sotiria General Hospital, Athens School of Medicine, Athens, Greece
Abstract Objectives: The aim of this review article is to evaluate the available literature concerning the prevalence of active tuberculosis in lung cancer patients. Data Source: MEDLINE, PubMed, EMBASE and Medscape databases were searched for studies with quantitative data on the interaction between tuberculosis (TB) and lung cancer, published since 1952. We used the Medical Subject Headings’ term ‘tuberculosis’ and the text-word terms ‘TB’ and ‘Mycobacterium infection’, and also, the Medical Subject Headings’ terms ‘neoplasm’ and ‘lung neoplasm’, or the text-word term ‘lung cancer’. Data Selection: We selected studies with cases verified by bacteriological examinations and biopsies that contained enough data to estimate tuberculosis prevalence. We did not exclude any study on the basis of language. Results: The prevalence of active tuberculosis among lung cancer patients varies depending on spatial and regional factors. Lung cancer patients who are more prone to developing tuberculosis are Asian and Caucasian males, with an average age of 60 years old. The prevalence of tuberculosis is higher in patients with chest X-ray evidence of old tuberculosis and/or history of tuberculosis, chronic obstructive pulmonary disease, heavy cigarette smoking, increased alcohol consumption, and/or diabetes mellitus. A high mortality rate because of tuberculosis in lung cancer patients was also estimated. Conclusion: Active tuberculosis complicating lung cancer is a significant clinical issue in countries with high prevalence of tuberculosis. However, as the there is a lack of reports from developed countries over the last 20 years, the significance of this interaction in countries with low tuberculosis burden remains controversial. Please cite this paper as: Christopoulos A, Saif MW, Sarris EG and Syrigos KN. Epidemiology of active tuberculosis in lung cancer patients: a systematic review. Clin Respir J 2014; 8: 375–381.
Objectives The interaction between lung cancer and active pulmonary tuberculosis (TB) has been the center of significant clinical and pathological interest and research for many years. The first case of coexistent TB and lung cancer was reported by Bayle in 1810 (1).
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Key words lung cancer – malignancy – mycobacterium infection – neoplasm – tuberculosis Correspondence Kostas Syrigos, MD, PhD, Sotiria General Hospital, Athens School of Medicine, GR 152 Mesogeion, GR 115 27 Athens, Greece. Tel: +30 21 0770 0220 Fax: +30 21 0778 1035 email: [email protected] Received: 03 April 2013 Revision requested: 17 November 2013 Accepted: 13 December 2013 DOI:10.1111/crj.12094 Authorship and contributorship Study Concepts: Kostas Syrigos, Antonis Christopoulos. Study Design: Kostas Syrigos, Muhammad W. Saif. Data Acquisition: Antonis Christopoulos. Data Analysis and Interpretation: Antonis Christopoulos. Manuscript Preparation: Antonis Christopoulos. Manuscript Editing: Evangelos G. Sarris, Antonis Christopoulos. Manuscript Review: Muhammad W. Saif, Kostas Syrigos. Conflicts of Interest The authors have stated explicitly that there are no conflicts of interest in connection with this article.
The results of later attempts to etiologically correlate these two diseases varied from no significant interaction, or even antagonism, to a direct cause and effect relationship. Several studies in the past have shown a purely circumstantial or random coexistence between these two diseases, attributing the increasing appearance to changes in epidemiology
375
Tuberculosis in lung cancer patients
and increased life expectancy as a result of efficacious treatment and improved diagnosis. Nowadays, TB is an established independent factor of increased risk for lung cancer (2). However, a conflict remains regarding the frequency of active pulmonary TB in patients with lung cancer. Thus, a systematic review was performed to investigate and elucidate the prevalence of active pulmonary TB in lung cancer patients.
Data source A search in MEDLINE, PubMed, EMBASE and Medscape databases was conducted for studies presenting quantitative data on the interaction between TB and lung cancer. Because the introduction of anti-TB therapy in 1952 changed the overall prognosis of TB, we searched for reports since 1952 (last research September 2013). Studies were searched by using the Medical Subject Headings’ term ‘tuberculosis’ and the text-word terms ‘TB’ and ‘Mycobacterium infection’, and also, the Medical Subject Headings’ terms ‘neoplasm’ and ‘lung neoplasm’, or the text-word term ‘lung cancer’. The reference lists of the obtained articles were studied to identify more eligible references that were then retrieved. The following information was extracted and coded by using standard form: year of publication, country/ region and quantitative data on the interaction between TB and lung cancer. All data were abstracted independently by one reviewer and checked by a second.
Data selection In order to select and maintain a large group of homogenous, multinational studies, we did not exclude any study on the basis of language and used wide eligibility criteria. The studies selected should contain at least minimum information in order to estimate the prevalence of active TB in lung cancer patients. We only included studies in which lung cancer and TB were verified with biopsy and bacteriological examination, respectively. All studies used in the review should include unique cases in order to avoid giving double weight to repeated data. In case of studies using data from the same population, during the same period of time, only the first publication was included. An exception was made when conflicting data were presented.
Results The prevalence of TB was calculated by dividing the number of lung cancer patients with active TB by the
376
Christopoulos et al.
total number of lung cancer patients. We classified regions as TB high-burden regions (Western Pacific, Eastern Europe, Southern America and Africa) and TB low-burden regions (Western Europe and North America). Mortality was ascribed to TB only when respiratory failure occurred due to TB or when TB expansion was observed involving multiple organs, while cancer disease was not extended and there was no other obvious cause of death. A total of 79 articles were retrieved to determine eligibility for inclusion in this systematic review. Fifty three of them did not provide sufficient information in order to estimate TB prevalence, and the rest 20 did not include unique cases. Sixteen of the retrieved studies contained the necessary data to estimate TB prevalence and were eventually included. Sixteen case-control studies were eventually used for the estimation of TB prevalence in lung cancer patients (3–18). All studies reported findings concerning cases of active pulmonary TB complicating lung cancer, verified with biopsy and bacteriological examination. All studies were unique as to the reported region and time period. In Table 1, details such as the year and country reported are presented. In the retrieved studies, sample size ranged from 193 to 4805, with a total of 692 cases of TB among 33 126 lung cancer cases eventually being studied. The type of control population used, as well as the population at risk, varied between studies and included randomly selected community population, general hospital patients and/or even sanatorium data. There was a male predominance reported in all the included studies (mean value 13:1), and the median age of the reported TB cases was 60 ± 14.1 years (range from 44 to 70 years of age). An increased prevalence of active TB was reported in lung cancer patients (8–10 times higher compared with general background population). However, evidence of heterogeneity across the contributing studies (range 0.7%–18.7%) was reported, with the exception of studies published in Japan. In these studies, a stable TB prevalence, estimated at 1%–2%, has been reported over the last 20 years. In two studies (12, 15), active pulmonary TB was significantly higher among lung cancer patients with old TB lesions or a past history of TB than in lung cancer patients without such lesions or history. Also, an active TB diagnosis was associated with more advanced lung cancer stages (III–IV). With regard to the histological subtypes of lung cancer most commonly associated with TB, the results are conflicting; nine studies (6, 12–14, 16–20)
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Christopoulos et al.
Tuberculosis in lung cancer patients
Table 1. Reported prevalence of active pulmonary tuberculosis (TB) in autopsied/ biopsied cases of lung cancer (LC) Year
Author
TB cases
LC points
Prevalence
Country
TB mortality%
1953 1959 1965 1968 1970 1971 1975 1990 1991 1991 1991 1994 1998 1999 2007 2007
Nuessle Hamel Holden Berroya Alastair Kaplan Solomon Hara Antkowiak Dacosta Aoki Chen YM Tamura Watanabe Tamura Cicenas
85 54 15 54 92 92 6 142 38 29 6 31 25 16 56 46
1335 4010 80 1218 3064 4805 193 6396 1351 221 442 3928 1315 758 4666 2218
6.3 1.3 18.7 4.4 3.0 0.9 3.1 2.22 2.8 13.1 1.3 0.7 1.9 2.1 1.2 2.0
USA USA Canada USA Australia USA S. Africa Japan Poland India Japan Taiwan Japan Japan Japan Lithuania
50.0
have shown a predominance of squamous cell carcinoma, while three studies (11, 15, 21) have demonstrated a closer association of pulmonary TB with adenocarcinoma. Eight studies evaluated the effect of a concomitant or sequential TB diagnosis in lung cancer prognosis. In seven of them, TB was found to have an adverse effect on lung cancer prognosis and mortality, while one study (20) showed that lung cancer patients with concomitant active TB had a longer median survival than patients without TB (11.6 vs 8.8 months, P < 0.01). Data used for estimating the average mortality rate because of TB (22.6 ± 14.4) were reported in seven of the studies (Table 1).
Discussion Nowadays, there is strong evidence to support that pre-existing TB is an independent factor highly associated with increased risk of lung cancer [relative risk (RR) = 11.14, 1–5 years after TB diagnosis] (21–25). Furthermore, whether lung cancer has the ability to arise from TB lesions or not, as an immunosuppressive disease, lung cancer may promote TB infection or result in reactivation of latent TB infection, or cause new exogenous infection (26). Cancer cells invasion in healed TB lesions might also lead to TB reactivation. In addition, regional tumor peptides, antigens or even radiotherapy might lead to granulomas microenvironment deregulation, allowing TB mycobacteria to proliferate (27).
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
7.0
33.3 12.0 18.7 12.5 30.4
Even though there is a causative association between the two diseases, a significant heterogeneity in TB prevalence was recorded among the retrieved studies, indicating the risk of bias. As all cases were histologically verified, misclassification of TB was not possible in the reported data. Furthermore, factors associated with increased risk of TB, such as smoking, chronic obstructive pulmonary disease, chronic renal failure and/or diabetes mellitus, were equally distributed among studied and control groups in the reviewed studies. The prevalence of TB, however, might have been affected by spatial and temporal variations of TB and/or lung cancer in the general background populations. To support this, we took under consideration the variations of TB prevalence, along with TB and lung cancer epidemiology. Although there had been occasional reports of lung cancer and active pulmonary TB coexistence, it was not until 1935 that Fried published his large series (28). He reported 13 histologically verified cases in which both diseases were combined, and he also reported a logical explanation as to the correlation between these two diseases. Fried reported that pulmonary TB and lung cancer could incidentally coexist or that one could be the causative factor of the other. In one literature review until 1953, Nuessle presented 85 cases of active pulmonary TB among 1335 autopsied patients with lung cancer (prevalence 6.4%) (3). These publications showed that a high percentage of lung cancer cases was complicated by active TB. In the 19th century, the prevalence of active TB was undoubtedly higher compared with nowadays. Furthermore, 377
Tuberculosis in lung cancer patients
in late 19th and early 20th century, an increase in both lung cancer incidence and diagnostic accuracy occurred. Once regarded as a rare disease, primary carcinoma of the lung was the most lethal among all types of cancer (29). Since 1952, when isoniazid was discovered, anti-TB chemotherapy significantly decreased TB mortality rate all over the world and changed the prognosis of the disease, as well as the social impact of TB. Patients previously having a life expectancy of only a few years because of the complications of TB could now be treated and survive significantly longer. An annual decline of approximately 5% in the number of TB cases was observed in the USA since 1950, reaching up to 6%–7% during the years 1981– 1984 (26). Over a 14-year period (1954–1968), Berroya et al. in Missouri State Sanatorium reported an alarming increase in the incidence of lung cancer and a gradual decrease in the incidence of TB. As TB patients, after being effectively treated, were capable of reaching the ‘lung cancer age group’, pulmonary TB and lung cancer often coexisted (prevalence 4.43%) (6). However, Kaplan et al. during the same period (1950–1971) reported only 44 cases of active TB among 4805 lung cancer patients treated in Memorial Hospital (prevalence 0.92%) (7). Obviously, the prevalence of lung cancer among the TB population treated in a sanatorium was higher than the prevalence of TB among lung cancer patients attending a general hospital. Similar data were reported worldwide. In 1970, Campbell and Guilfoyle reported 92 cases of active TB complicating lung cancer in Melbourne, Victoria, Australia during a 6-year period (prevalence 2.98%) (8). Furthermore, in 1979, Solomon et al. reported a high incidence of active pulmonary TB complicating lung cancer in Baragwanath Hospital in Johannesburg (9). Investigators concluded that lung cancer activates dormant TB in a population group also presenting high incidence of TB. Then, between 1984 and 1992, the incidence of TB increased in the USA by 18% mainly because of immigrating populations from high TB-burden countries and because of the continuously increasing incidence of AIDS, which causes immunodeficiency, and therefore, HIV patients are more prone to develop TB (26). Philips et al. from Ohio reported in 1984 five cases of carcinoma of the lung and coexistent active TB arising from the same pulmonary lesion (30). New efforts in disease control, as well as new advances in treatment, resulted in a total decrease in TB incidence by 31% from 1992 to 1998 in the USA (26). However, TB remains one of the world’s major causes of illness and death, and in 1993, the World
378
Christopoulos et al.
Health Organization declared TB to be a global health emergency. Approximately one third of the world’s population is infected. More than 9 million people present every year with active TB, which can be spread to others. Latent TB is not able to spread (31). Regions with the highest incidence and prevalence rates are sub-Saharan countries and Southeastern Asia (32). In 1990, Hara et al. (18) reported 142 cases of coexistent active pulmonary TB and bronchogenic carcinoma with an incidence rate of 2.22% among lung cancer patients; the predominant histological type of lung cancer was squamous cell carcinoma, followed by adenocarcinoma (the proportions of the histological types of lung cancer were not significantly different from those in the general population). Well-known pathologists Dacosta and Kinare in 1991 reported that in King Edward Memorial Hospital in Bombay, coexistence of TB and lung cancer was detected in 29 out of 221 necropsied cases (prevalence 13.1%) (11). In their department, TB was reported in 7%–8% of autopsied cases. The most common histological subtype found was undifferentiated carcinoma (76%), followed by adenocarcinoma (56%) and epidermoid carcinoma (5.44%). However, most cases of undifferentiated lung carcinoma were more likely to represent adenocarcinomas, while all scar cancers were adenocarcinomas. Chen et al. in a low TB-burden region like Taiwan (TB prevalence in the general population, 0.11%) reported a significantly lower prevalence of TB among lung cancer patients (0.79%) (13); epidermoid carcinoma was the most common histological subtype accounting for 64.5% of cases. In the same period, Aoki et al. and Tamura et al. reported that in Tokyo National Hospital, the incidence of active TB among lung cancer patients was 1%–2% (12, 14). Both research groups observed a higher incidence of squamous cell carcinoma in coexisting lung cancer and TB cases. Furthermore, Aoki et al. observed that active pulmonary TB was significantly higher in lung cancer patients with old TB lesions than in those without ones (5.6% vs 0.52%). Since then, many investigators, mainly from Western Pacific region or Eastern Europe, recorded an increased prevalence of active pulmonary TB among lung cancer patients (15–17). In the study by Watanabe et al. (15), specifically, active pulmonary TB development was also associated with a past history of TB (P < 0.005). According to Tamura et al. in 1999 (14) and 2007 (16), Watanabe et al. (15), Chen et al. (13), and Cicenas and Vencevicius (17), most lung cancer patients diagnosed with active TB are advanced-stage (III–IV) cancer patients. Furthermore, Xie et al. (33) suggested that the occurrence of lung cancer was highly correlated to
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Christopoulos et al.
the site of TB, and Chen et al. (13) reported that in most patients, lung cancer and TB lesions were ipsilateral, while Tamura et al. (14) concluded that the location of lung cancer and TB seemed to be independent. Finally, Kim et al. (34) reported that out of 219 patients with coexisting bronchogenic carcinoma and TB, 51 had both lesions in the same lobe, with a predominance of upper lobes. With regards to the histological cancer subtypes associated with active TB, Watanabe et al. (15) and Silva et al. (35) reported more cases of adenocarcinoma in lung cancer patients with coexisting TB, while Tamura et al. (16), Cicenas and Vencevicius (17), and Xie et al. (33) showed a predominance of squamous cell carcinoma. Kuo et al. (20) also demonstrated that squamous cell carcinoma was an independent factor for active TB [odds ratio 2.09, 95% confidence interval (CI) 1.06–4.14, P < 0.05]. However, in the association of specific histological subtypes of lung cancer with TB, results remain conflicting overall. The large metaanalysis of Liang et al. (2), involving 37 case-control and 4 cohort studies from 1966 to 2009, demonstrated a significant association of coexistent TB with adenocarcinomas (RR 1.6, 95% CI 1.2–2.1), but not with the squamous and small cell type. However, the issue has not yet been resolved. With the exception of the earlier mentioned study by Kuo et al. (20), most studies have demonstrated an adverse effect of concomitant or sequential active TB on lung cancer prognosis. Chen et al. (13) reported that patients who had an active pulmonary TB diagnosis concurrently with or before the diagnosis of lung cancer survived for a shorter period than those without TB (P = 0.007), while survival from diagnosis of TB was longer in patients who developed TB earlier than or concurrently with lung cancer than in those who developed active TB later (P = 0.046). Engels et al. (36), in a large retrospective cohort study performed in Xuanwei, China, observed that lung cancer mortality was substantially higher in lung cancer patients with TB than among those without TB [hazard ratio (HR) 6.1, 95% CI 4.3–8.7]. Heuvers et al. (37) and Leung et al. (38) also reported that a history of pulmonary TB was associated with a significantly shorter survival in lung cancer patients, while Shieh et al. (39), in a large retrospective study in Taiwan, observed that lung cancer patients with comorbid TB had a shorter survival duration than patients without TB (7-year survival rate, 10% vs 21%; P = 0.03 in multivariate analysis). In a more recent analysis, Zhou et al. (40) reported that the median survival of patients with squamous cell carcinoma specifically was significantly shorter in patients with old TB lesions compared with patients
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Tuberculosis in lung cancer patients
without TB (1.7 vs 3.4 years, P < 0.01); the presence of an old pulmonary lesion was found to be an independent predictor of poor survival (HR 1.72; 95% CI 1.12– 2.64). Finally, it is worth mentioning a study by Luo et al. (41) coming from China and associating old TB lesions with a higher probability (P = 0.018) of lung adenocarcinoma patients having epidermal growth factor receptor (EGFR) mutations (especially exon 19 deletions). Among patients with EGFR mutations, those who had old TB lesions survived for a shorter period than those who did not (P = 0.035). The increased prevalence of active TB and latent TB reactivation in lung cancer patients and the negative effect of pulmonary TB in lung cancer prognosis underline the need for a more thorough screening of lung cancer patients for latent and active TB. Kamboj and Sepkowitz (42), from the Memorial-SloanKettering Cancer Center, New York, do not consider cancer patients (with the exception of head and neck cancer patients) as a risk group for the development of TB and, therefore, do not suggest routine PPD (purified protein derivative) testing, but other authors suggest otherwise. Lonnröth et al. (43) do not refer specifically to lung cancer patients; however they consider people with chronic respiratory disease/smokers and people with immunocompromising disorders/ treatments – conditions often associated with lung cancer – as high-risk groups who should be screened for TB. The 2011 National Institute for Health and Clinical Excellence guidelines (44) suggest that people who are immunocompromised should have an interferon-gamma test alone or with a concurrent Mantoux test; if either test is positive, active TB should be excluded through clinical assessment, and if excluded, latent TB should be treated.
Conclusion Variations in epidemiology offer a solid explanation of the observed heterogeneity in TB prevalence among lung cancer patients and explain the numerous reports in TB high-burden countries over the last two decades. However, during the last 20 years, there is a lack of reports of coexistent TB and lung cancer in TB lowburden countries. Whether the coexistence of both diseases can be considered as a rare, well-known clinical problem, not deserving further investigation, or not is something that we are not able to answer. However, even in the latest reported data concerning the prevalence of coexistent TB and lung cancer in the USA (0.92%), among estimated 222 520 new lung cancer cases in 2010, there might be as many as 2048 cases of active pulmonary TB waiting to be discovered (31). 379
Tuberculosis in lung cancer patients
References 1. Bayle GL. Recherches sur la phthisie pulmonaire: ouvrage lu à la Société de la faculté de médecine de Paris, dans diverses séances, en 1809 et 1810. Paris, Gabon, 1810. 2. Liang HY, Li XL, Yu XS, Guan P, Yin ZH, He QC, Zhou BS. Facts and fiction of the relationship between preexisting tuberculosis and lung cancer risk: a systematic review. Int Journal of Cancer. 2009;125(12): 2936–44. 3. Nuessle WF. Association of bronchogenic carcinoma and active pulmonary tuberculosis: with report of four cases. Dis Chest. 1953;23: 207–16. 4. Hamel NC, Briggs JN, Ludigton LG. Cancer of the lung in tuberculous patients. Calif Med. 1959;91(3): 131–3. 5. Holden HM, Quinlan JJ, Hiltz JE. Co-existing pulmonary tuberculosis and bronchogenic carcinoma: report of 15 cases. Can Med Assoc J. 1965;18(93): 1306–10. 6. Berroya RB, Polk JW, Raju P, Bailey AH. Concurrent pulmonary tuberculosis and primary carcinoma. Thorax. 1971;26(4): 384–7. 7. Kaplan MH, Armstrong D, Rosen P. Tuberculosis complicating neoplastic disease. Cancer. 1974;33: 850–8. 8. Campbell AH, Guilfoyle P. Pulmonary tuberculosis, isoniazid and cancer. Br J Dis Chest. 1970;64(3): 141–9. 9. Solomon A, Hurwitz S, Conlan AA. Broncogenic carcinoma with coexisting active pulmonary tuberculosis in urban blacks. S Afr Med J. 1979;55: 979–81. 10. Mose-Antkwiak R. Tuberculosis and lung cancer. Pneumonol Alergol Pol. 1991;59(1–2): 48–54. 11. Dacosta NA, Kinare SG. Association of lung cancer in tuberculosis. J Postgrad Med. 1991;37: 185–9. 12. Aoki Y, Kuroki S, Hura K, Katoh O, Yamada H. A clinical study of pulmonary tuberculosis in lung cancer patient. Kekkaku. 1991;66(11): 727–32. 13. Chen YM, Chao J-Y, Tsai C-M, Lee P-Y, Perng R-P. Shortened survival of lung cancer patients initially presenting with pulmonary tuberculosis. Jpn J Clin Oncol. 1996;26(5): 322–7. 14. Tamura A, Hebisawa A, Tanaka G, et al. Active pulmonary tuberculosis in patients with lung cancer. Kekkaku. 1999;74(11): 797–802. 15. Watanabe A, Tokue Y, Takahashi H, Sato K, Nukiwa T, Honda Y, Fujimura S. Management of mycobacteriosis in general hospital without isolation word for tuberculosis patients. Clinical study on pulmonary tuberculosis associated with lung cancer patients. Kekkaku. 1999;74: 157–62. 16. Tamura A, Hebisawa A, Masuda K, et al. Coexisting lung cancer and active pulmonary tuberculosis. Nihon Kokyuki Gakkai Zasshi. 2007;45(5): 382–93. 17. Cicenas S, Vencevicius V. Lung Cancer in patients with tuberculosis. World J Surg Oncol. 2007;5: 22. 18. Hara H, Soejima R, Matsushima T. A study of the coexistence of pulmonary tuberculosis and bronchogenic carcinoma: results of a questionnaire in Chugoku and Shikoku areas. Kekkaku. 1990;65(11): 711–17.
380
Christopoulos et al.
19. Cha SI, Shin KM, Lee JW, Lee SY, Kim CH, Park JY, Jung TH. The clinical course of respiratory tuberculosis in lung cancer patients. Int J Tuberc Lung Dis. 2009;13(8): 1002–7. 20. Kuo CH, Lo CY, Chung FT, Lee KY, Lin SM, Wang CH, Heh CC, Chen HC, Kuo HP. Concomitant active tuberculosis prolongs survival in non-small cell lung cancer: a study in a tuberculosis-endemic country. PLoS One. 2012;7(3): e33226. 21. Zheng W, Blot WJ, Liao ML, Wang ZX, Levin LI, Zhao JJ, Fraumeni JF Jr, Gao YT. Lung cancer and prior tuberculosis infection in Shanghai. Br J Cancer. 1987;56(4): 501–4. 22. Tocque K, Convery RP, Bellis MA, Beeching NJ, Davies PD. Elevated mortality following diagnosis with a treatable disease. Int J Tuberc Lung Dis. 2005;9(7): 797–802. 23. Yu YH, Liao CC, Hsu WH, Chen HJ, Liao WC, Muo CH, Sung FC, Chen CY. Increased lung cancer risk among patients with pulmonary. J Thorac Oncol. 2011;6(1): 32–7. 24. Wu CY, Hu HY, Pu CY, Huang N, Shen HC, Li CP, Chou JY. Pulmonary tuberculosis increases the risk of lung cancer: a population-based cohort study. Cancer. 2011;117(3): 618–24. 25. Brenner AV, Wang Z, Kleinerman RA, Wang L, Zhang S, Metayer C, Chen K, Lei S, Cui H, Lubin JH. Previous pulmonary diseases and risk of lung cancer in Gansu Province, China. Int J Epidemiol. 2001;30(1): 118–24. 26. American Thoracic Society/Centers for Disease Control. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161: 221–47. 27. Li R, Ruttinger D, Li R, Si LS, Wang YL. Analysis of the microenvironment at the tumor site in patients with non-small cell lung cancer. Lagensbecks Arch Surg. 2003;388(6): 406–12. 28. Fried BM. Bronchogenic carcer combined with tuberculosis of the lung. Am J Cancer. 1935;23: 247–66. 29. Wayl P. Difficulties in the diagnosis of coexistent brochogenic carcinoma and active pulmonary tuberculosis. Dis Chest. 1955;28: 568–73. 30. Philips LG Jr, Cunningham J, Hillman NM, Lewis J. Carcinoma of the lung and coexisting active pulmonary tuberculosis: diverse morphologic and radiographic presentations. J Natl Med Assoc. 1984;76(2): 125–30. 31. WHO. Tuberculosis fact sheet. No. 104, March 2010. 32. WHO. Global Tuberculosis Report. 2012. 33. Xie BX, Ding JA, Jiang GN. Cooccurrence of pulmonary tuberculosis and carcinoma: diagnosis and the prognostic factors for surgical effects. Zhonghua Jie He He Hu Xi Za Zhi. 2005;28(4): 230–2. 34. Kim YI, Goo JM, Kim HY, Song JW, Im JG. Coexisting bronchogenic carcinoma and pulmonary tuberculosis in the same lobe: radiologic findings and clinical significance. Korean J Radiol. 2001;2(3): 138–44. 35. Silva DR, Valentini DF Jr, Müller AM, Almeida CPB, Dalcin PTR. Pulmonary tuberculosis and lung cancer:
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Christopoulos et al.
36.
37.
38.
39.
40.
simultaneous and sequential occurrence. J Bras Pneumol. 2013;39(4): 484–9. Engels EA, Shen M, Chapman RS, Pfeiffer RM, Yu YY, He X, Lan Q. Tuberculosis and subsequent risk of lung cancer in Xuanwei, China. Int J Cancer. 2009;124(5): 1183–7. Heuvers ME, Aerts JG, Hegmans JP, et al. History of tuberculosis as an independent prognostic factor for lung cancer survival. Lung Cancer. 2012;76(3): 452–6. Leung CC, Hui L, Lee RS, et al. Tuberculosis is associated with increased lung cancer mortality. Int J Tuberc Lung Dis. 2013;17(5): 687–92. Shieh SH, Probst JC, Sung FC, Tsai WC, Li YS, Chen CY. Decreased survival among lung cancer patients with co-morbid tuberculosis and diabetes. BMC Cancer. 2012;12: 174. Zhou Y, Cui Z, Zhou X, Chen C, Jiang S, Hu Z, Jiang G. The presence of old pulmonary tuberculosis is an
The Clinical Respiratory Journal (2014) • ISSN 1752-6981 © 2013 John Wiley & Sons Ltd
Tuberculosis in lung cancer patients
41.
42.
43.
44.
independent prognostic factor for squamous cell lung cancer survival. J Cardiothorac Surg. 2013;8: 123. Luo YH, Wu CH, Wu WS, Huang CY, Su WJ, Tsai CM, Lee YC, Perng RP, Chen YM. Association between tumor epidermal growth factor receptor mutation and pulmonary tuberculosis in patients with adenocarcinoma of the lungs. J Thorac Oncol. 2012;7(2): 299–305. Kamboj M, Sepkowitz KA. The risk of tuberculosis in patients with cancer. Clin Infect Dis. 2006;42(11): 1592–5. Lönnroth K, Corbett E, Golub J, Godfrey-Faussett P, Uplekar M, Weil D, Raviglione M. Systematic screening for active tuberculosis: rationale, definitions and key considerations. Int J Tuberc Lung Dis. 2013;17(3): 289–98. NICE. NICE clinical guideline 117 guidance.nice.org.uk/ cg117. Issued: March 2011.
381
