|Year : 2020 | Volume
| Issue : 1 | Page : 16-24
Demographic characteristics, clinical presentation, risk factors and pathological types of lung cancer: A prospective study
M Soumya1, Alladi Mohan1, J Harikrishna1, KM Bhargav1, A Ravisankar2, N Rukmangadha3, Ranadheer Mantri4
1 Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of Medical Oncology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
3 Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
4 Department of Nucelar Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
|Date of Submission||21-Sep-2019|
|Date of Decision||17-Oct-2019|
|Date of Acceptance||28-Dec-2019|
|Date of Web Publication||2-Jun-2020|
Professor and Head, Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Alipiri Road, Tirupati 517 507, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: Sparse published data are available regarding the epidemiology of lung cancer from Rayalaseema area of Andhra Pradesh State.
Methods: Consecutive patients (n = 133) diagnosed to have and treated for lung cancer in medicine and medical oncology departments at our tertiary care teaching hospital in Tirupati, South India from March 2017 to June 2018, were prospectively studied. In all patients, risk factors, clinical manifestations, method of confirmation of diagnosis and histopathological and cytopathological types were documented.
Results: Their mean age was 56.4 ± 11.2 years; there were 93 (70%) males. No risk factors were evident in 110 (83%) patients. Tobacco smoking (n = 69, 52%) (all males) was the most frequently evident risk factor; other risk factors included exposure to arsenic, silicone, passive smoking, environmental exposure, old pulmonary tuberculosis. Their mean Fagerstrom score for nicotine dependence was 8.2 ± 1.7. In 17% of patients, lung cancer was incidentally detected; the remaining 83% were symptomatic. Chief presenting complaints were cough (59%), dyspnoea (50%), haemoptysis (11%), amongst others. Cytopathological and histopathological diagnosis was done in 3% and 97%, respectively. Majority (n = 123, 92%) had non-small cell lung cancer (NSCLC) (60% adenocarcinoma and 17% squamous cell carcinoma), while small cell lung cancer was evident in 10 (8%). Most of them (52%) had presented in stage 4.
Conclusions: Our observations suggest that tobacco smoking still remains the most common risk factor for lung cancer; majority of the patients had NSCLC, and most patients presented late with stage 4 disease.
Keywords: Diagnosis, India, lung cancer
|How to cite this article:|
Soumya M, Mohan A, Harikrishna J, Bhargav K M, Ravisankar A, Rukmangadha N, Mantri R. Demographic characteristics, clinical presentation, risk factors and pathological types of lung cancer: A prospective study. J Clin Sci Res 2020;9:16-24
|How to cite this URL:|
Soumya M, Mohan A, Harikrishna J, Bhargav K M, Ravisankar A, Rukmangadha N, Mantri R. Demographic characteristics, clinical presentation, risk factors and pathological types of lung cancer: A prospective study. J Clin Sci Res [serial online] 2020 [cited 2020 Sep 21];9:16-24. Available from: http://www.jcsr.co.in/text.asp?2020/9/1/16/285707
| Introduction|| |
Lung cancer has become the most common cause of cancer-related death accounting for about 26% of all the cancer deaths in the United States. Lung cancer is the second most commonly diagnosed cancer. Comprehensively, lung cancer is estimated for 14% of new cancer cases and 26% of all cancer deaths in the year 2018. In 2016, 15.5% (37.8 million) of adults in the USA were cigarette smokers. Cigarette smoking prevalence was higher amongst males (17.5%) than amongst females (13.5%). In India, 1.8 million new lung cancer cases were estimated to have occurred in 2012.
Non-small cell lung cancer (NSCLC) constitutes 80% of lung cancers, remaining 15% as small cell lung carcinoma (SCLC). Different types of NSCLC include squamous cell carcinoma (SQCC), large cell carcinoma (LCC), adenocarcinoma (ADCC) and all can occur in unusual histological variants. SCLC is a systemic disease, and systemic chemotherapy is the mainstay of the treatment. The prognosis of SCLC varies with stage, while limited stage has survival of about 24 months, late-stage patients seldom survive beyond 12 months. In Asian countries and most of the western countries, the incidence of ADCC is on the rise owing to a change in smoking habits like increased use of filtered cigarettes. The smoking habits of Indians are unique Bidi smoking, carries a higher risk of lung cancer compared to cigarette smoking. Cigarette smokers have a ten-fold or greater risk compared to those who have never smoked. Large cell neuroendocrine carcinoma of the lung is rare but aggressive and is often seen in heavy smokers. Higher concentration of nitrate in tobacco is thought to be responsible for the development of ADCC.,
Non-smokers account for 15% of lung cancer cases, ADCC being the predominant histological type in these. The magnitude of lung cancer may rise in future in non-smokers., In the United States of America (USA) indoor radon exposure (a naturally occurring radioactive gas) is the second most essential environmental risk agent for lung cancer besides tobacco smoke. In Europe, it is estimated for 9% lung cancer deaths. Independent of smoking, family history of lung cancer has been shown to result in a two-fold increase in risk.,
Other risk factors which are on rise for developing lung cancer are air pollution, pre-existing diseases of the lungs, such as tuberculosis or pneumonia, high doses of radiation and exposure to industrial or chemical carcinogens such as asbestos, silica and arsenic.,, For non-smokers especially women household air pollution from cooking and heating oil fumes appear to play a greater role in the aetiology of lung cancer.
Keeping the conflicting reports in the background, it is essential to study the contributing risk factors and varying histopathological patterns of lung cancer. Limited studies are available in the recent past in this geographical area; hence, the present study is therefore aimed to study the demographic characteristics, clinical presentation, risk factors, method of confirmation of diagnosis and pathological types of lung cancer at the time of initial presentation at our tertiary care teaching hospital in Tirupati.
| Material and Methods|| |
Consecutive patients diagnosed and treated for lung cancer at medicine and medical oncology out-patient departments admitted to the medical, medical oncology wards and the Medical Intensive Care Unit (MICU) at the Sri Venkateswara Institute of Medical Sciences, a tertiary care teaching hospital in Tirupati, South India, between March 2017 and June 2018 were studied.
Patients with histopathological and/or cytopathologically proven primary lung cancer, age >18 years, and those patients who were willing to participate in the study were included, while Patients with metastatic lung disease of non-pulmonary origin and those who were not willing to participate in the study were excluded.
The study was approved by the Institute's Ethics Committee. Written informed consent has been obtained from all patients participating in the study. In all patients included, a detailed history was obtained especially focussing on aetiological cause of lung carcinoma, and a thorough physical examination was carried out. Detailed history regarding tobacco smoking, presence of other risk factors, such as, exposure to agriculture, mining, arsenic, beryllium, polycyclic hydrocarbons, radon, ionising radiation, formaldehyde, chromium, nickel, asbestos, vinyl chloride, synthetic rubber, air pollution, wood dust and family history was recorded.
A detailed smoking history was obtained from all the patients. 'Pack years' of smoking were calculated as described below. One pack contains 20 cigarettes. For the calculation of pack-years of smoking, one bidi was considered equal to one cigarette.
Number of pack-year = (no. of cigarettes/bidis smoked per day × no. of years smoked)/20
Ex-smokers (smoked ≥100 cigarettes per lifetime, quit ≥1 year) or never smokers (smoked <100 cigarettes per lifetime) were considered. The Fagerstrom test for nicotine dependence was administered to all patients.
The Government of Andhra Pradesh (AP) issues 'white ration card' (WRC) to people 'below poverty line' (BPL). As per the Government of AP criteria, persons with annual household income <Rs 75,000/- per annum in urban areas and <Rs 60,000/- per annum in rural areas are categorised as BPL (G. O. Ms No. 27, Dated: 23-07-2008, Department of Consumer Affairs, Food and Civil Supplies (CSI), Government of AP). Patients with lung cancer who were WRC holders were categorized as belonging to BPL category
Diagnostic workup included relevant laboratory, imaging, interventional and invasive investigations required to establish the aetiological cause of lung carcinoma. Chest radiograph (postero-anterior view) was obtained in all patients. Other imaging modalities, such as, computed tomography (CT), positron-emission tomography-CT, ultrasonography, amongst others were carried out where required. Methods for establishing the diagnosis of lung cancer include sputum cytopathology, pleural biopsy, transthoracic image-guided fine-needle aspiration cytopathology (FNAC)/biopsy for histopathological examination. Further, in patients with a radiological suspicion of lung cancer, FNAC/biopsy from a metastatic site of involvement (e.g., peripheral lymph node) was done.
At the time of initial presentation, staging of the disease was done as per the American Joint Committee/Union for International Cancer Control 8th edition Tumor-Node-Metastasis (TNM) staging (2010) Cancer Staging Manual criteria.
Data were recorded on a predesigned proforma and managed using Microsoft Excel worksheet (Microsoft Corp, Redmond, WA). All the entries were double-checked for any possible error. Descriptive statistics was reported as mean ± standard deviation, median (interquartile range). Categorical variables were reported as percentages. The statistical software IBM SPSS Statistics Version 20 (IBM Corp Somers NY, USA); Stata/IC 12 for Windows (Stata Corp LP, Texas, USA); and MedCalc Version 11.3.0 for Windows 2000/XP/Vista/7 (MedCalc Software bvba, Belgium) was used for statistical analysis.
| Results|| |
During the study (March 2017 and June 2018), all patients admitted to medical, medical oncology wards and the MICU (n = 133) were screened for inclusion in the study. The study plan is shown in [Figure 1]. Majority of the patients with lung cancer were in their fifth and sixth decades of life. Their mean age was 56.4 ± 11.2 years. Males (n = 93; 70%) outnumbered female (n = 40; 30%). At the time of initial presentation, 110/133 (82.7%) were symptomatic. Common presenting symptoms included cough (n = 78, 58.6%); dyspnoea (n = 66, 49.6%); fever (n = 15, 11.3%); haemoptysis (n = 15, 11.3%); loss of weight (n = 11, 8.3%); loss of appetite (n = 12, 9%); and swelling in neck (n = 4, 3%). In 23/133 (17.3%) patients, who were asymptomatic, lung cancer was incidentally diagnosed. Risk factors were evident in 78/133 (58.6%) patients as shown in [Table 1]; in 55/133 (41.3%) no risk factors could be documented. In 133 patients with lung cancer 69 (52%) were tobacco smokers (bidis (n = 69), bidis plus cigarettes [n = 10]) their mean pack-year was 34.6 years, amongst tobacco smokers other risk factors such as arsenic exposure (n = 4), silicone exposure (n = 1) and old pulmonary tuberculosis (PTB) (n = 6) were also evident. In 59/69 (85%) tobacco smokers, high nicotine dependence with FG score more than 8 was noted and in 10/69 (15%) tobacco smokers moderate nicotine dependence with FG score <8 was documented. Amongst non-smokers (n = 64, 48%), there were other risk factors arsenic exposure (n = 4), silicone exposure (n = 2), old PTB (n = 2) and passive smoking (n = 1). In the present study, 76.6% of patients were BPL and 51.8% of patients were not BPL.
|Figure 1: Study plan.|
MICU = Medical intensive care unit; SCLC = Small-cell lung carcinoma; NSCLC = Non-small cell lung carcinoma
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|Table 1: Risk factors and type of malignancy in 133 patients with lung cancer|
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In the present study, the most common method of diagnosis is biopsy from lung 93 (69.9%), other methods were FNAC of lung 13 (10%), FNAC of lymph node 9 (7%), fluid for cytology 4 (3%), biopsy from lymph node 5 (3.8%), biopsy from other organs 8 (6%) and in only 1 (0.8%) patient, it was diagnosed by sputum cytology. Histological types of lung cancer are shown in [Table 2]. In the present study, the most common type of lung cancer was ADCC (n = 94, 70.6%)[Figure 2], SQCC [Figure 3] was second-most common type with (n = 22, 16.5%) patients, SCLC [Figure 4] was in (n = 10, 7.5%) patients. Spindle cell carcinoma was in (n = 3, 2.3%) patients, adenosquamous cell carcinoma [Figure 5] was in (n = 2, 5%) patients, and the least common was bronchoalveolar variety and pleomorphic variety seen in only one patient each. In 63 (47.4%) patients, the right lung is affected; in 42 (32%) patients, the left lung is affected; and in 28 (21%) patients, both lungs were affected.
|Figure 2: Chest radiograph (postero-anterior view) showing a well-defined opacity (arrow) in the left upper- and mid-zone. Hilar vessels are clearly seen with in the opacity, and the mass is showing acute angle with aortic silhouette-suggestive of a lung pathology (a). Axial NCCT of the chest (mediastinal window) (b), CECT of the chest (mediastinal window) (c), (lung window) (d) showing a mass lesion in the apico-posterior segment of the left upper lobe (red arrow) with peripheral enhancing solid component and central non-enhancing necrotic area. Maximum intensity projection image showing physiological FDG uptake in the brain, liver, kidney and bladder and abnormal FDG uptake in neck, thorax region (e). Axial CT (f) another patient and fused PET-CT (g) image showing soft-tissue density lesion in the anterior segment of the left lung upper lobe abutting the mediastinum measuring 5.1 cm × 2.4 cm with SUVmax 6.4 and right massive pleural effusion. Sagittal CT (h) and fused PET-CT (i) showing increased FDG uptake in multiple mixed lytic and sclerotic lesions in dorsal, lumbar and sacral vertebrae. Photomicrograph of CT-guided lung biopsy specimen showing cuboidal cells with mild nuclear pleomorphism, eosinophilic cytoplasm arranged in the form of glands in a suggestive of adenocarcinoma (Haematoxylin and eosin, × 200) (j). Photomicrograph (x 200) of immunohistochemistry showing diffuse cytoplasmic positivity of cytokeratin 7(k), thyroid transcription factor-1 (TTF-1) (l), Napsin-A (m) in the lesional cells of Tru-cut lung biopsy suggestive of adenocarcinoma. NCCT = Non-contrast computed tomography; CECT = Contrast-enhanced computed tomography; CT = Computed tomography; PET-CT = Positron emission tomography-computed tomography; SUVmax = Maximum standardised uptake value; FDG = Fluorodeoxyglucose |
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|Figure 3: Chest radiograph (postero-anterior view) showing ill-defined lobulated opacity (arrow) in the right lower zone obscuring the right dome of the diaphragm and right costophrenic angle and extending superiorly along the right lateral chest wall into mid and upper zones (a). Axial NCCT of the chest (mediastinal window) (b); CECT of the chest (mediastinal window) (c), (lung window) (d) showing a lobulated mass lesion in the superior segment of right lower lobe (arrow) which is isodense on NCCT (b) and is enhancing homogeneously on CECT (c). Maximum intensity projection image of another patient showing physiological FDG uptake in brain, tonsils, liver, kidney and bladder and abnormal FDG uptake in the left side of thorax (e). Axial CT (f,h) and fused PET-CT (g,i) showing moderately increased FDG concentration in an ill-defined soft-tissue density in the lingular segment in the upper lobe of the left lung measuring 7.4 cm × 7.1 cm × 10 cm with a SUVmax 4.9. The lesion is displacing the trachea and oesophagus to the contralateral side. Axial CT (j) and fused PET-CT (k) showing conglomerate lymph nodal mass in subcarinal, left paratracheal and left hilar regions measuring 6.2 cm × 6.3 cm × 5 cm with SUVmax 3.7. Photomicrograph of CT-guided lung biopsy obtained from the patient shown in Figures a,b,c and d, showing polygonal cells with pleomorphic hyperchromatic nuclei and abundant eosinophilic cytoplasm arranged diffusely suggestive of squamous cell carcinoma (l) (Haematoxylin and eosin, ×200). Photomicrograph of immunohistochemistry showing diffuse cytoplasmic positivity for cytokeratin 5 (m), cytokeratin 6 (n), P63 (o) in the lesional cells of Tru-cut lung biopsy specimen suggestive of squamous cell carcinoma. NCCT = Non-contrast computed tomography; CECT = Contrast-enhanced computed tomography; CT = Computed tomography; PET-CT = Positron emission tomography-computed tomography; SUVmax = Maximum standardised uptake value; FDG = Fluorodeoxyglucose|
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|Figure 4: Chest radiograph (postero-anterior view) showing an ill-defined opacity (arrow) in the left hilar region and Ill-defined areas of consolidation in the right upper- and mid-zones (a). Axial NCCT of the Chest (mediastinal window) (b), CECT of the chest (mediastinal window) (c) (lung window) (d) showing a lobulated mass lesion in the superior segment of the left lower lobe (arrow) which is isodense on NCCT (b) and is enhancing homogeneously on CECT (c). Maximum intensity projection image showing physiological FDG uptake in the brain, heart, liver, kidney and bladder and abnormal FDG uptake in thorax and mediastinum (e). Axial CT (f) and fused PET-CT (g) showing intensely increased FDG concentration in an irregular soft-tissue density lesion in the left hilar region measuring 5.2 cm × 4.5 cm with SUVmax 13.7. Axial CT (h) and fused PET-CT (i) showing right lower paratracheal lymph nodes measuring 2.1 cm × 1.2 cm with SUVmax 8.2. Photomicrograph of CT-guided lung biopsy shows tumour cells with hyperchromatic nuclei, inconspicuous nucleoli, nuclear moulding and scanty cytoplasm arranged diffusely in foci with necrosis suggestive of small cell carcinoma (j) (Hematoxylin and eosin, × 200). Photomicrograph showing positivity for CD56 (k), synaptophysin (l), chromogranin (m) in tumour cells of Tru-cut lung biopsy suggestive of small cell carcinoma. NCCT = Non-contrast computed tomography; CECT = Contrast-enhanced computed tomography; CT = Computed tomography; PET-CT = Positron emission tomography-computed tomography; SUVmax = Maximum standardised uptake value; FDG = Fluorodeoxyglucose; CD = cluster of differentiation|
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|Figure 5: Chest radiograph (postero-anterior view) showing an ill-defined opacity (arrow) in the left hilar region (a). Axial NCCT of the chest (mediastinal window) (b), CECT of the chest (mediastinal window) (c), (lung window) (d) showing an ill-defined lesion in the apicoposterior segment of the left upper lobe (arrow) which is minimally enhancing after contrast administration (c). Photomicrograph of CT-guided lung biopsy showing cuboidal cells arranged in the form of glands and polygonal cells arranged as nests suggestive of adenosquamous carcinoma (Hematoxylin and eosin, ×200) (e). NCCT = Non-contrast computed tomography; CECT = Contrast enhanced computed tomography|
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| Discussion|| |
In the present study, majority of the patients were in their fifth decade of life and the median age at presentation was 57 years. This observation confirms the view that lung cancer is an important medical problem in middle-aged individuals. In studies conducted in Mumbai in India, Egypt, median age at presentation in patients with lung cancer was reported to be 56 years. In another study from New Delhi, median age at presentation was 55 years. In the study from Malaysia, median age at presentation was 60 years. Overall men outnumbered women, male:female (M:F) ratio was 2.3:1. A similar demographic trend was evident in other published studies,, from India where the M:F ratio ranged from 3.5:1 in Mumbai; 4.6:1 in New Delhi; 5.2:1 in Chandigarh;. and 4:1 in Egypt. The possible reasons for male preponderance could be that men seek and receive medical attention earlier compared to females. The other probable reasons may be more exposure to tobacco smoke, air pollution and other hazards that men face more compared to women.
Patients with central or endobronchial primary tumour may present with cough, haemoptysis, wheeze, stridor, dyspnoea or post-obstructive pneumonitis. Peripherally located primary tumour may cause pain from pleural or chest wall involvement, dyspnoea and symptoms of a lung abscess resulting from tumour cavitation. In the present study, most of the patients presented with cough (68%), dyspnoea (49%)and this could possibly be because peripherally located ADCC was the most common tumour type. A study from Mumbai most of them presented with loss of weight (84.7%) and cough (76%). In a study from Chandigarh most common presenting symptoms were cough and haemoptysis; this may be because SQCC, which is centrally located was the most common type of cancer. In a study from Egypt chest pain (26%) and dyspnoea (23%) were the most common symptom because ADCC a peripherally located tumour was the most common type of lung cancer.
In a study from Mumbai reported 48% smokers and 58% non-smokers. A study from Delhi documented 68% smokers and 32% non-smokers. From Chandigarh, a study reported 48% smokers and 52% non-smokers. In the present study, 52% were smokers and 48% were non-smokers. Other risk factors were arsenic exposure and old tuberculosis. As in our study, tobacco smoking was the most common risk factor in the other studies as well.,, The findings in the present study suggest that smoking in men is an important aetiological factor for lung carcinoma in India as in the West. In the present study, smokers were exclusively men; there were no female smokers, and amongst smokers majority of them had high nicotine dependence which could be the reason for a higher occurrence of carcinoma in the smokers.
The high proportion (64%) of patients in the present study who were non-smokers points to the possible existence of some carcinogenic factors other than smoking. A study has reported a rise in mortality from bronchogenic carcinoma amongst non-smokers in the United States and suggested various factors that might have been responsible. In India, domestic air pollution, to which women are particularly likely to be exposed, may be one such factor. It has recently been postulated that kerosene, which is widely used for cooking in towns and villages in India, may be carcinogenic. A study had shown that a diet of fresh vegetables and fruits and food rich in micronutrients, such as carotene, carotenoid, beta carotene, alpha-carotene, lycopene, phycoxanthin, Vitamin C, Vitamin E and selenium, along with physical activity are preventative factors against lung cancer.
SCC was diagnosed in 8% of patients, while 92% of the patients had NSCLC. Within NSCLC, the most common histology was ADCC (60%) followed by SQCC (12.8%), and others (20%). There was a higher occurrence of ADCC in both smokers and non-smokers, whereas in Noronha study, there was a higher occurrence of ADCC in the non-smokers and SCC and SQCC amongst smokers. Historically, SQCC of the lung was thought to be smoking related, rather than ADCC. The increase in the incidence of ADCC was thought to be mainly due to a change in smoking pattern and an increased choice for filter cigarettes that have low tar, but high nitrate content, Earlier studies reported that the increased incidence of ADCC was confined to smokers. In contrast, we found a higher occurrence of ADCC in both smokers as well as non-smokers. This is supported by other studies in the literature.,, Thus, our study and other recent studies suggest that the increase in ADCC is not solely due to a change in the pattern of cigarette smoking, but must be due to non-smoking-related factors, since the increase is demonstrated in non-smokers as well.
Most of the patients in the present study had advanced disease (stage 4) at the time of presentation. In the studies,, from across the world and India, 50%-70% cases of NSCLC and up to two-thirds of SCLC usually present in advanced stages. In fact, most lung cancers in India are diagnosed late because of many reasons varying from delay from the part of patient in seeking expert medical care and delayed referrals to the insufficiency of health-care delivery systems. In the present study, most of the patients presented in the last stage. This may be attributed to the fact that most of the patients in the present study belong to BPL who, due to various socio economic factors, ignore the initial symptoms and seek medical advice only at last stages.
In our study, in most of the patients right lung was affected [63 (47.4%)], in 42 (32%) patients left lung was affected, and in 28 (21%) patients both lungs were affected. Similar observations were reported in an earlier report from Mumbai where right lung was affected in most of the patients. Whether the predilection for the right lung involvement is incidental or whether it has pathological consequences merits further study.
A high level of clinical suspicion is required for early diagnosis of lung cancer. Future studies should focus on potential non-tobacco-related risk factors, further biologic and molecular differences and further refine treatment strategies.
Financial support and sponsorship
This study was supported by Sri Balaji Arogya Varaprasadini Scheme, Sri Venkateswara Institute of Medical Sciences, Tirumala Tirupati Devasthanams, Tirupati (Grant No. SBAVP-RG/MD/45).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30.
Jamal A, Phillips E, Gentzke AS, Homa DM, Babb SD, King BA, et al
. Current Cigarette Smoking Among Adults – United States, 2016. MMWR Morb Mortal Wkly Rep 2018;67:53-9.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al
. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
Zaizen Y, Azuma K, Kurata S, Sadashima E, Hattori S, Sasada T, et al
. Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy. Eur J Radiol 2012;81:4179-84.
Wingo PA, Ries LA, Giovino GA, Miller DS, Rosenberg HM, Shopland DR, et al
. Annual report to the nation on the status of cancer, 1973-1996, with a special section on lung cancer and tobacco smoking. J Natl Cancer Inst 1999;91:675-90.
Rossi A, Martelli O, Di Maio M. Treatment of patients with small-cell lung cancer: From meta-analyses to clinical practice. Cancer Treat Rev 2013;39:498-506.
Wakelee 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.
Fishman AP, Elias JA, Fishman JA, Michael A, Robert MG, AllanLS AA, editors. Fishman's pulmonary diseases and disorders. New York: Mc Graw Hill Professional; 2008. p. 1801-946.
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]
Alberg AJ, Ford JG, Samet JM; American College of Chest Physicians. Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd
edition). Chest 2007;132:29S-55S.
Wakelee 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.
Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers – A different disease. Nat Rev Cancer 2007;7:778-90.
Darby S, Hill D, Auvinen A, Barros-Dios JM, Baysson H, Bochicchio F, et al
. Radon in homes and risk of lung cancer: Collaborative analysis of individual data from 13 European case-control studies. BMJ 2005;330:223.
Nitadori J, Inoue M, Iwasaki M, Otani T, Sasazuki S, Nagai K, et al
. Association between lung cancer incidence and family history of lung cancer: Data from a large-scale population-based cohort study, the JPHC study. Chest 2006;130:968-75.
Matakidou A, Eisen T, Houlston RS. Systematic review of the relationship between family history and lung cancer risk. Br J Cancer 2005;93:825-33.
Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest 2003;123:21S-49S.
Bilello KS, Murin S, Matthay RA. Epidemiology, etiology, and prevention of lung cancer. Clin Chest Med 2002;23:1-25.
Subramanian J, Govindan R. Lung cancer in never smokers: A review. J Clin Oncol 2007;25:561-70.
Kumar R, Prakash S, Kushwah AS, Vijayan VK. Breath carbon monoxide concentration in cigarette and bidi smokers in India. Indian J Chest Dis Allied Sci 2010;52:19-24.
Horn L, Lovly CM, Johnson DH. Neoplasms of the lung. In: Kasper DL, Hauser SL, Jameson JL, Fauci AS, Longo DL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 19th
ed. New York: McGraw Hill Education; 2015. p. 506-23.
Lubin JH, Blot WJ. Assessment of lung cancer risk factors by histologic category. J Natl Cancer Inst 1984;73:383-9.
Edge SB, Compton CC. The American Joint Committee on Cancer: The 7th
edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471-4.
Stellman SD, Garfinkel L. Lung cancer risk is proportional to cigarette tar yield: Evidence from a prospective study. Prev Med 1989;18:518-25.
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.
Yokota J, Kohno T. Molecular footprints of human lung cancer progression. Cancer Sci 2004;95:197-204.
Jindal SK, Malik SK, Dhand R, Gujral JS, Malik AK, Datta BN. Bronchogenic carcinoma in Northern India. Thorax 1982;37:343-7.
Samet JM. Radon and lung cancer. J Natl Cancer Inst 1989;81:745-57.
Nilsson R. Environmental tobacco smoke revisited: The reliability of the data used for risk assessment. Risk Anal 2001;21:737-60.
Alavanja MC, Brownson RC, Boice JD Jr, Hock E. Preexisting lung disease and lung cancer among nonsmoking women. Am J Epidemiol 1992;136:623-32.
Marel M, Melinová L, Stastný B, Skácel Z, Marelová R, Jechová M, et al
. [Trends in epidemiologic indicators of lung cancer in the Czech Republic 1970-1990]. Cas Lek Cesk 1996;135:487-92.
Takezaki T, Hirose K, Inoue M, Hamajima N, Yatabe Y, Mitsudomi T, et al
. Dietary factors and lung cancer risk in Japanese: With special reference to fish consumption and adenocarcinomas. Br J Cancer 2001;84:1199-206.
Thun MJ, Lally CA, Flannery JT, Calle EE, Flanders WD, Heath CW Jr. Cigarette smoking and changes in the histopathology of lung cancer. J Natl Cancer Inst 1997;89:1580-6.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]