Indian Journal of Medical Research

: 2015  |  Volume : 141  |  Issue : 1  |  Page : 5--7

Lung cancer: Prevalent trends & emerging concepts

Prabhat Singh Malik1, Vinod Raina2,  
1 Department of Medical Oncology, Dr B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi 110 029, India
2 Department of Medical Oncology & Haematology, Fortis Memorial Research Institute Sector 44, Gurgaon 122 002, Haryana, India

Correspondence Address:
Vinod Raina
Department of Medical Oncology & Haematology, Fortis Memorial Research Institute Sector 44, Gurgaon 122 002, Haryana

How to cite this article:
Malik PS, Raina V. Lung cancer: Prevalent trends & emerging concepts.Indian J Med Res 2015;141:5-7

How to cite this URL:
Malik PS, Raina V. Lung cancer: Prevalent trends & emerging concepts. Indian J Med Res [serial online] 2015 [cited 2019 Jul 16 ];141:5-7
Available from:

Full Text

Lung cancer is one of the commonest cancers and cause of cancer related deaths all over the world. It accounts for 13 per cent of all new cancer cases and 19 per cent of cancer related deaths worldwide. There were 1.8 million new lung cancer cases estimated to occur in 2012 [1] . In India, lung cancer constitutes 6.9 per cent of all new cancer cases and 9.3 per cent of all cancer related deaths in both sexes, it is the commonest cancer and cause of cancer related mortality in men, with the highest reported incidences from Mizoram in both males and females (Age adjusted rate 28.3 and 28.7 per 100,000 population in males and females, respectively) [2] . The time trends of lung cancer show a significant rise in Delhi, Chennai and Bengaluru in both sexes. The incidence and pattern of lung cancer differ as per geographic region and ethnicity and largely reflect the prevalence and pattern of smoking. The overall 5-year survival rate of lung cancer is dismal with approximately 15 per cent in developed countries and 5 per cent in developing countries [3] . s0 creening by low dose computed tomography (CT) in high risk population demonstrated a relative risk reduction of 20 per cent in lung cancer mortality but with a false positive rate of 96 per cent [4] . In India where tuberculosis is prevalent, the applicability of such screening tool is questionable. Development of newer non invasive methods/ biomarkers for early diagnosis and screening of high risk population is warranted.

Over the years, our understanding of disease biology has evolved. The histological classification is now stretching to molecular classification. Newer molecular targets and driver mutations have been identified which play a major role in pathogenesis that can be addressed with therapeutic interventions [5] . These advancements have led to the development of more individualized treatment modalities, the so called era of "personalized medicine". There has been a new interest in the histological characterization of lung cancer in view of newer histology guided therapeutic modalities and genomic classification [6],[7] . The use of generic terms non small cell and small cell lung cancer (NSCLC and SCLC), is being challenged [8] . In the Western countries and most of the Asian countries [9],[10] adenocarcinoma has surpassed squamous cell carcinoma [9],[10] . This shift might be attributable partly to the smoking habits, particularly filtered cigarettes; moreover, there is also increasing incidence of lung cancer in females and non smokers [9],[11],[12] . Most of the previous Indian studies have described squamous cell carcinoma as the commonest histology [13],[14] however, some recent studies from two major centres are showing a changing pattern in India [15],[16] . We have reported that adenocarcinoma has become the commonest subtype provided a careful pathology review is done [16] . The use of appropriate immunohistochemistry improves the histological sub-typing and should be used more often.

At present more than 50 per cent of lung adenocarcinomas and about a third of squamous cell carcinomas can be characterized based on the mutation profile [17] . This molecular classification has led to development of targeted therapeutic strategies. Mutations in epidermal growth factor receptors (EGFR) best illustrate the therapeutic importance of molecular classification. EGFR mutations strongly predict the efficacy of inhibitors of EGFR with response rates higher than 70 per cent seen in many studies [18] . Two prospective, randomized, phase 3 studies of patients with untreated metastatic NSCLC (Iressa Pan-Asia Study and WJTOG3405) have found that first-line gefitinib leads to longer progression-free survival (PFS) in patients with tumours positive for EGFR mutations than does platinum based doublet chemotherapy [18],[19] . Similarly erlotinib has also shown better response rates and PFS as compared to chemotherapy for first line treatment in EGFR mutation positive advanced NSCLC [20],[21] .

genomic expression, mutational and proteomic profiling studies, as well as various mouse lung tumour models have led to the identification of additional molecular driver mutations [22],[23] . Another such example of mutation driven therapy is targeting EML4-ALK (echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase) rearrangement. Biologically, EML4-ALK fusions result in protein oligomerisation and constitutive activation of the kinase [24] . The frequency of EML4-ALK translocation ranges from 3 to 7 per cent in unselected NSCLC [24] . Detection methods include reverse-transcriptase PCR, fluorescence in-situ hybridization, and immunohistochemistry. EML4-ALK translocations are generally found in tumours with wild type EGFR and KRAS [25] . Tyrosine kinase inhibitor targeting ALK, crizotinib has shown a response rate of 65 per cent in previously treated patients of NSCLC that harbour ALK rearrangement and has been approved for this indication [26],[27] . Another ALK inhibitor certinib has also been recently approved based on its encouraging response rates of 56 per cent in patients who have progressed on crizotinib [28] .

The prevalence of specific mutation varies among various ethnic and geographic populations. For example, the prevalence of EGFR mutation is around 10 per cent in Caucasians while it has been reported to be as high as 60 per cent in Asians [29],[30] . In India the frequency of EGFR mutations has been found to be between 25-50 per cent in various studies [31],[32],[33],[34] .

With these advances, the validation of targeted therapeutic compounds should ideally parallel with the development of predictive biomarkers [35] . In this context, the availability of high quality molecular testing is pivotal and should be integrated into treatment guidelines. The accessibility of such testing to majority of our population is largely limited due to the high cost. Lack of quality control and uniformity of techniques and standards among various laboratories are also issues of concern. Bulk use of these new techniques are likely to reduce the cost of these tests. Adequacy of tumour tissue for molecular profiling is an important issue and even more relevant in lung cancer where the tissue yield is limited by small core biopsies. Judicious use of immunohistochemistry and conservation of samples for molecular testing would be helpful. Cell free circulating tumour DNA is also emerging as a useful tool in these situations and can be used for mutation testing and therapeutic monitoring [36] . The genetic heterogeneity among various ethnic populations has brought to the stage the issue of molecular characterizations in lung cancer and the need for regional studies.


1Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013. Available from:, accessed on January 21, 2014.
2National Cancer Registry Programme. Three Year Report of Population Based Cancer Registries: 2009-2011. Indian Council of Medical Research; 2013. Available from:, accessed on January 21, 2014.
3Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 : 74-108.
4National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365 : 395-409.
5Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol 2011; 12 : 175-80.
6Standfield L, Weston AR, Barraclough H, Van Kooten M, Pavlakis N. Histology as a treatment effect modifier in advanced non-small cell lung cancer: a systematic review of the evidence. Respirol Carlton Vic 2011; 16 : 1210-20.
7Scagliotti G, Brodowicz T, Shepherd FA, Zielinski C, Vansteenkiste J, Manegold C, et al. Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer. J Thorac Oncol 2011; 6 : 64-70.
8Ettinger DS. NCCN Clinical Practice Guidelines in Oncology for Non Small Cell Lung Cancer, Ver 2.2012. National Comprehensive Cancer Network; 2012. Available from:, accessed on January 21, 2014.
9Valaitis J, Warren S, Gamble D. Increasing incidence of adenocarcinoma of the lung. Cancer 1981; 47 : 1042-6.
10Janssen-Heijnen MLG, Coebergh J-WW. The changing epidemiology of lung cancer in Europe. Lung Cancer 2003; 41 : 245-58.
11Thun MJ, Henley SJ, Burns D, Jemal A, Shanks TG, Calle EE. Lung cancer death rates in lifelong nonsmokers. J Natl Cancer Inst 2006; 98 : 691-9.
12Wakelee HA, Chang ET, Gomez SL, Keegan TH, Feskanich D, Clarke CA, et al. Lung cancer incidence in never smokers. J Clin Oncol 2007; 25 : 472-8.
13Behera D, Balamugesh T. Lung cancer in India. Indian J Chest Dis Allied Sci 2004; 46 : 269-81.
14Singh 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.
15Noronha 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.
16Malik 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.
17Stella GM, Luisetti M, Pozzi E, Comoglio PM. Oncogenes in non-small-cell lung cancer: emerging connections and novel therapeutic dynamics. Lancet Respir Med 2013; 1 : 251-61.
18Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361 : 947-57.
19Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11 : 121-8.
20Zhou C, Wu Y-L, Chen G, Feng J, Liu X-Q, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011; 12 : 735-42.
21Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012; 13 : 239-46.
22Motoi N, Szoke J, Riely GJ, Seshan VE, Kris MG, Rusch VW, et al. Lung adenocarcinoma: modification of the 2004 WHO mixed subtype to include the major histologic subtype suggests correlations between papillary and micropapillary adenocarcinoma subtypes, EGFR mutations and gene expression analysis. Am J Surg Pathol 2008; 32 : 810-27.
23Fisher GH, Wellen SL, Klimstra D, Lenczowski JM, Tichelaar JW, Lizak MJ, et al. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes Dev 2001; 15 : 3249-62.
24Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448 : 561-6.
25Shaw AT, Yeap BY, Mino-Kenudson M, Digumarthy SR, Costa DB, Heist RS, et al. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009; 27 : 4247-53.
26Camidge DR, Bang Y-J, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol 2012; 13 : 1011-9.
27Shaw AT, Kim D-W, Nakagawa K, Seto T, Crinó L, Ahn M-J, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013; 368 : 2385-94.
28Shaw AT, Kim D-W, Mehra R, Tan DSW, Felip E, Chow LQM, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014; 370 : 1189-97.
29Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7 : 169-81.
30Shi Y, Au JS-K, Thongprasert S, Srinivasan S, Tsai C-M, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 2014; 9 : 154-62.
31Noronha V, Prabhash K, Thavamani A, Chougule A, Purandare N, Joshi A, et al. EGFR mutations in Indian lung cancer patients: clinical correlation and outcome to EGFR targeted therapy. P l0 oS One 2013; 8 : e61561.
32Veldore VH, Rao RM, Kakara S, Pattanayak S, Tejaswi R, Sahoo R, et al. Epidermal growth factor receptor mutation in non-small-cell lung carcinomas: a retrospective analysis of 1036 lung cancer specimens from a network of tertiary cancer care centers in India. Indian J Cancer 2013; 50 : 87-93.
33Chougule A, Prabhash K, Noronha V, Joshi A, Thavamani A, Chandrani P, et al. Frequency of EGFR mutations in 907 lung adenocarcioma patients of Indian ethnicity. P l0 oS One 2013; 8 : e76164.
34Sahoo R, Harini VV, Babu VC, Patil Okaly GV, Rao S, Nargund A, et al. Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer 2011; 73 : 316-9.
35Li T, Kung H-J, Mack PC, Gandara DR. Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 2013; 31 : 1039-49.
36Oxnard GR, Paweletz CP, Kuang Y, Mach SL, O'Connell A, Messineo MM, et al. Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA. Clin Cancer Res 2014; 20 : 1698-705.