|Year : 2017 | Volume
| Issue : 1 | Page : 267-270
Metastatic nonsmall cell lung cancer in South India: A regional demographic study
KC Lakshmaiah1, MP Kamath1, KG Babu1, U Amirtham2, D Loknatha1, AS Komaranchath1
1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
2 Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
|Date of Web Publication||1-Dec-2017|
Dr. M P Kamath
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
BACKGROUND: Nonsmall cell lung cancer (NSCLC) has varying epidemiological patterns in different countries and also in different regions of each country. In a country with a high prevalence of lung cancer such as India, regional variations in demography exist. AIM: A study of unique demographic trends of metastatic NSCLC patients presenting to our regional cancer center. MATERIALS AND METHODS: We did a retrospective analysis of histologically confirmed metastatic NSCLC patients who presented to our Department of Medical Oncology between August 2012 and July 2014. RESULTS: A total of 304 patients were analyzed. About 55.6% of the patients were in the age group of 41–60 years. About 79.6% of the patients were symptomatic for <6 months before presentation. About 63.5% of the patients were smokers presenting with a median age of 59 years whereas nonsmokers formed 36.51% of the patients presenting with a median age of 47 (P < 0.001). About 82.6% of the male patients and 4.1% of female patients were smokers. Equal number of all patients had adenocarcinoma (AC) and squamous cell carcinoma (SCC) histology. AC histology was more common in the nonsmoking group (62% of patients). SCC histology was seen in 54.3% of smokers. Metastasis to the contralateral lung and pleura was seen in 58.2% of patients. CONCLUSION: NSCLC presents at a young age. Smoking is a significant risk factor and it is common in the urban populations as in the rural areas. Both AC and SCC histologies presented in equal proportions.
Keywords: Adenocarcinoma, metastatic nonsmall cell lung cancer, smoking, squamous cell carcinoma
|How to cite this article:|
Lakshmaiah K C, Kamath M P, Babu K G, Amirtham U, Loknatha D, Komaranchath A S. Metastatic nonsmall cell lung cancer in South India: A regional demographic study. Indian J Cancer 2017;54:267-70
|How to cite this URL:|
Lakshmaiah K C, Kamath M P, Babu K G, Amirtham U, Loknatha D, Komaranchath A S. Metastatic nonsmall cell lung cancer in South India: A regional demographic study. Indian J Cancer [serial online] 2017 [cited 2020 Mar 31];54:267-70. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/267/219566
| » Introduction|| |
Lung cancer is consistently the most common and most lethal malignancies worldwide over the last few decades. The majority of lung cancers occur in the developed countries from Europe and North America. In developing countries, the proportion of cancer deaths attributed to lung cancer is about 15%., The incidence of lung cancer is increasing in countries such as China and other countries of Asia where the prevalence of smoking and environmental pollution continues to increase.
The incidence rates of lung cancer in the Population-Based Cancer Registry in India, is as of now, much lower than registries elsewhere in the world. However, this may be due to under-reporting of cases. The incidence rates are the highest in the Eastern states, followed by the Western states of India. As in the majority of countries, incidence rates are higher in urban than in the rural areas and 2–6 times higher in men than in women. Overall, among males, cancers of sites associated with tobacco smoking are the most frequent, with lung cancer being the most common. It is the second leading site among males presenting to our cancer institute and 1 of the 10 leading sites of cancer in females.
Lung cancer is most commonly caused by smoking. The risk of developing lung cancer is associated with age of initiation, duration, quantity, and pattern of cigarette smoking. The cumulative probability of lung cancer in the general population for individuals up to 74 years of age is 10–15% in those who smoke one or more packs of cigarettes per day. The relative risk is >20 times higher for regular smokers than for nonsmokers. Bidi smoking which is more common in India and other South Asian countries, is known to more carcinogenic than cigarette smoking.
Even though lung cancer is often viewed solely as a smoker's disease, a significant number of patients with lung cancer have no history of smoking. The incidence of lung cancer in nonsmokers is rising and is expected to increase in the future also. Globally, lung cancer in never smokers demonstrates a marked gender bias, occurring more frequently among women.,,,,
Through the 1960's, the predominant type of nonsmall cell lung cancer (NSCLC) was squamous cell carcinoma (SCC). Over the last two decades, the relative incidence of SCC has decreased and adenocarcinoma (AC) has become the predominant histology subtype of NSCLC. Although smoking-related carcinogens act on both proximal and distal airways inducing all the major forms of lung cancer, cancers arising in never smokers target the distal airways and favor AC histology.
With the increasing burden of lung cancer cases in our country, there is a need to not only know the demographic trends but also to study and understand the regional variations of lung cancer in India. This information may help in establishing measures to reduce the incidence of lung cancer and fuel the design of effective screening programs.
In our study, we attempted to study the demographic trends of metastatic NSCLC presenting to our regional cancer center in South India.
| » Materials and Methods|| |
We did a retrospective analysis of metastatic NSCLC patients who presented to our Department of Medical Oncology between August 2012 and July 2014. Demographic data including age, gender, socioeconomic status, duration of complaints before presentation, and smoking history were collected. The patients were interviewed regarding their history of smoking (never smokers, light smokers, and heavy smokers). Never smokers were defined as those who have smoked <100 bidi/cigarettes in their life until disease onset. Light smokers were defined as those who smoke <10–100 bidi/cigarette pack years. Heavy smokers were defined as those who smoke more than 100 bidi/cigarette pack years until disease. All lung cancer biopsy specimens were histologically characterized by morphology and immunohistochemistry (IHC). A diagnosis of AC was made if IHC staining was positive for CK7, TTF1, and napsin A; similarly, SCC was diagnosed if CK5/6 and p63 staining was positive. After confirmation of the histology subtype, patients were confirmed to have metastatic disease after assessment with contrast-enhanced computerized tomography thorax, abdomen scan, and radiolabeled bone scan. Our study did not include the small cell lung cancer patients. The data were analyzed on SPSS version 22 (IBM) software.
| » Results|| |
A total of 304 patients were analyzed. The details are summarized in [Table 1], [Table 2], [Table 3].
Age and gender
About 55.6% of the patients were in the age group of 41–60 years, 31.9% of the patients were in the age group of 61–80 years, and 12.5% of the patients were of <40 years age. About 75.7% of the patients were males.
About 56.6% of the patients were of the low socioeconomic status. Eighty-five percent of the low socioeconomic status group of patients was from the rural area. Ten percent of the higher socioeconomic group was from the rural background.
Duration of complaint
About 79.6% of the patients were symptomatic for <6 months before presentation while 20.3% were symptomatic for longer than 6 months.
About 63.5% of the patients were smokers (light and heavy smokers, n = 193), presenting with a median age of 59 years (range 26–85) whereas nonsmokers formed 36.51% of the patients presenting with a median age of 47 (range 31–80) (P< 0.001). About 82.6% of the male patients were smokers (either light or heavy smokers) and 4.1% of female patients were smokers (P< 0.001). Both the low and higher socioeconomic status group of patients had an equal proportion of smokers (63.4% and 63.6%).
Nonsmall cell lung cancer histology
Equal number of all the patients had AC and SCC histology. AC histology was more common in the nonsmoking group (62% of patients). SCC histology was seen in 54.3% of smokers [Figure 1].
Metastasis to the contralateral lung and pleura was seen in 58.2% of patients, with almost equal proportions being of SCC and AC histology. The other common sites of metastasis were bone (48%) and adrenal glands (23.4%). Bone metastasis was associated with AC histology in 52.7% patients [Figure 2].
| » Discussion|| |
The age distribution of our patients was similar to recent studies from other regional referral institutes, in which the maximum number of cases was between the age group of 40 and 60 years age.,,,
About 75.7% of our patients were males; this proportion was similar to that seen in other recent Indian studies.,,, The higher proportion of males presenting with lung cancer can be attributed to both an increased exposure to smoking and environmental pollution. About 56.6% of the patients were of the low socioeconomic status, of which 85% were from the rural area.
About 63.5% of the patients were smokers (light and heavy smokers, n = 193), presenting with a median age of 59 years (range 26–85) whereas nonsmokers formed 36.51% of the patients presenting with a median age of 47 (range 31–80) (P< 0.001). Several recent studies in India and South Asia have similarly observed that the presenting age of nonsmokers is significantly lower than that of smokers.,,,,,
Interestingly, the distribution of smokers in both the low and high socioeconomic status was similar at 63.6%. This finding was in contrast to the study by Dey et al., in which it was observed that smoking habit was more common in the rural population. Our study suggests that smoking may be as prevalent in the lower and higher socioeconomic group. Therefore, measures to reduce smoking should be directed toward populations from all economic backgrounds.
About 36.5% of our NSCLC patients were nonsmokers. This high proportion was similar to that seen in recent Indian and South Asian studies.,,,, This observation contrasts with that of studies from the United States and other developed countries where only 10% of lung cancer cases occur in nonsmokers. This indicates that a high proportion of Indian patients develop lung cancer due to etiologies other than cigarette and bidi smoking.
More than 80% of the male patients were smokers (either light or heavy smokers) while only 4.1% of female patients were smokers (P< 0.001) [Table 4]. The proportion of male smokers with NSCLC was higher than that of previous Indian and South Asian studies.,,,,, The proportion of female smokers was lower than that of all the recent studies.,,,,, This observation reflects the cultural difference where bidi/cigarette smoking in South India is very uncommon among females.
The substantial proportion of nonsmoking females suggests that other factors are causative. Although multiple risk factors, including environmental, hormonal, and genetic have been implicated in the pathogenesis of lung cancer in never smokers, no distinct etiopathogenetic explanation has emerged for the relatively high incidence of lung cancer in never smokers and the marked geographic differences in gender proportions. Primary factors closely tied to lung cancer in never smokers include exposure to known and suspected carcinogens including second-hand smoke exposure , and other indoor air pollutants. Several other occupational exposures, preexisting lung diseases, diet, estrogen exposure, etc., have been implicated., Several studies by environmental scientists have equated the effect of an open fire in one's kitchen with burning 400 cigarettes an hour. Hence, details of indoor cooking using solid fuels such as wood, coal, and cow-dung which are commonly used in low socioeconomic strata patients in India should not be ignored.
In the first three quarters of the 20th century, the most common histology in NSCLC was SCC. SCC was thought to be mainly smoking-related, rather than AC. The recent increase in the proportion of AC was thought to be mainly due to changes in smoking pattern and an increased preference for filter cigarettes which have low tar, but high nitrate content. Initial studies reported that the increased incidence of AC was also confined to smokers., In our study, we found equal proportions of AC and SCC histology. In the subset analysis, we found a nonsignificant predominance of AC in nonsmokers and increase of SCC in both light and heavy smokers. The predominance of AC in nonsmokers is similar to other recent studies in the literature.,,, SCC has been reported to be more common in recent studies from North-Eastern India whereas some studies from the West and South report otherwise.,,,,,, In our study, almost 95% of the patients originating from the rural areas and almost 90% of the patients from the urban low socioeconomic status were predominantly bidi smokers. Bidis are known to be more carcinogenic than cigarettes. However, it is not known if bidi-smoking preferentially causes a particular lung cancer subtype or if there are any clinical or pathologic features that are different from that caused by filter cigarette smoking., It is hypothesized that smoke from bidis may be shallowly inhaled, resulting in central airway chemical carcinogen deposition giving rise to SCC. Smoke from filtered cigarettes may be more deeply inhaled, resulting in peripheral carcinogen deposition giving rise to ACs. Another hypothetical explanation points to the nature of carcinogens – bidi smoking generates higher levels of carcinogenic polycyclic aromatic hydrocarbons which are inducers of SCC, while an increase in the yields of carcinogenic tobacco-specific N-nitrosamines from cigarette smoking causes ACs.
The most common site of metastasis in our study patients was the opposite lung and pleura. This observation was similar to that seen in the study by Noronha et al.
| » Conclusion|| |
Our study presents the trends of NSCLC in the Southern Regional Cancer Center of India and highlights the key differences in demography between the different regions of India. It has been a common observation in all the regional cancer centers of India that a high majority of lung cancer patients present at an advanced stage. Effective measures are needed to detect lung cancer at an earlier stage. It is also important to study and understand the etiological and biological differences which may perhaps help in better prevention and management of NSCLC patients, especially those who are nonsmokers.
The authors gratefully acknowledge Dr. Geetashree Mukherjee, Retired Professor and Head of the Department, Department of Pathology, Kidwai Memorial Institute of Oncology, for her guidance and continuous encouragement toward completion of the work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11. Lyon, France: International Agency for Research on Cancer; 2013.
Ganesh B, Sushama S, Monika S, Suvarna P. A case-control study of risk factors for lung cancer in Mumbai, India. Asian Pac J Cancer Prev 2011;12:357-62.
Youlden DR, Cramb SM, Baade PD. The international epidemiology of lung cancer: Geographical distribution and secular trends. J Thorac Oncol 2008;3:819-31.
Shopland DR, Eyre HJ, Pechacek TF. Smoking-attributable cancer mortality in 1991: Is lung cancer now the leading cause of death among smokers in the United States? J Natl Cancer Inst 1991;83:1142-8.
Prasad R, Ahuja RC, Singhal S, Srivastava AN, James P, Kesarwani V, et al.
Acase-control study of bidi smoking and bronchogenic carcinoma. Ann Thorac Med 2010;5:238-41.
] [Full text]
Toh CK, Gao F, Lim WT, Leong SS, Fong KW, Yap SP, et al.
Never-smokers with lung cancer: Epidemiologic evidence of a distinct disease entity. J Clin Oncol 2006;24:2245-51.
Zhou W, Christiani DC. East meets West: Ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians. Chin J Cancer 2011;30:287-92.
WHO. Tobacco or Health: A Global Status Report. Geneva: World Health Organization; 1997. p. 20.
Zang EA, Wynder EL. Differences in lung cancer risk between men and women: Examination of the evidence. J Natl Cancer Inst 1996;88:183-92.
Bain C, Feskanich D, Speizer FE, Thun M, Hertzmark E, Rosner BA, et al.
Lung cancer rates in men and women with comparable histories of smoking. J Natl Cancer Inst 2004;96:826-34.
Malik PS, Sharma MC, Mohanti BK, Shukla NK, Deo S, Mohan A, et al.
Clinico-pathological profile of lung cancer at AIIMS: A changing paradigm in India. Asian Pac J Cancer Prev 2013;14:489-94.
Noronha V, Dikshit R, Raut N, Joshi A, Pramesh CS, George K, et al.
Epidemiology of lung cancer in India: Focus on the differences between non-smokers and smokers: A single-centre experience. Indian J Cancer 2012;49:74-81.
] [Full text]
Rawat J, Sindhwani G, Gaur D, Dua R, Saini S. Clinico-pathological profile of lung cancer in Uttarakhand. Lung India 2009;26:74-6.
] [Full text]
Krishnamurthy A, Vijayalakshmi R, Gadigi V, Ranganathan R, Sagar TG. The relevance of “Nonsmoking-associated lung cancer” in India: A single-centre experience. Indian J Cancer 2012;49:82-8.
] [Full text]
Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest 2003;123 1 Suppl: 21S-49S.
Koo LC, Ho JH. Worldwide epidemiological patterns of lung cancer in nonsmokers. Int J Epidemiol 1990;19 Suppl 1:S14-23.
Dey A, Biswas D, Saha SK, Kundu S, Kundu S, Sengupta A. Comparison study of clinicoradiological profile of primary lung cancer cases: An Eastern India experience. Indian J Cancer 2012;49:89-95.
] [Full text]
Brennan P, Buffler PA, Reynolds P, Wu AH, Wichmann HE, Agudo A, et al.
Secondhand smoke exposure in adulthood and risk of lung cancer among never smokers: A pooled analysis of two large studies. Int J Cancer 2004;109:125-31.
Driscoll T, Nelson DI, Steenland K, Leigh J, Concha-Barrientos M, Fingerhut M, et al.
The global burden of disease due to occupational carcinogens. Am J Ind Med 2005;48:419-31.
Yu IT, Chiu YL, Au JS, Wong TW, Tang JL. Dose-response relationship between cooking fumes exposures and lung cancer among Chinese nonsmoking women. Cancer Res 2006;66:4961-7.
Janssen-Heijnen ML, Coebergh JW, Klinkhamer PJ, Schipper RM, Splinter TA, Mooi WJ. Is there a common etiology for the rising incidence of and decreasing survival with adenocarcinoma of the lung? Epidemiology 2001;12:256-8.
Devesa SS, Bray F, Vizcaino AP, Parkin DM. International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer 2005;117:294-9.
Behera D, Balamugesh T. Lung cancer in India. Indian J Chest Dis Allied Sci 2004;46:269-81.
Prasad R, James P, Kesarwani V, Gupta R, Pant MC, Chaturvedi A, et al.
Clinicopathological study of bronchogenic carcinoma. Respirology 2004;9:557-60.
Singh N, Aggarwal AN, Gupta D, Behera D, Jindal SK. Unchanging clinico-epidemiological profile of lung cancer in North India over three decades. Cancer Epidemiol 2010;34:101-4.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]