|Year : 2017 | Volume
| Issue : 1 | Page : 193-196
Clinical profile of nonsmall cell lung carcinoma patients treated in a single unit at a tertiary cancer care center
DC Doval1, R Sinha2, U Batra3, KD Choudhury3, S Azam2, A Mehta4
1 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi; Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
2 Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
3 Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
4 Department of Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
|Date of Web Publication||1-Dec-2017|
Dr. D C Doval
Department of Medical Oncology; Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi
Source of Support: None, Conflict of Interest: None
BACKGROUND: Recent advances and understanding in the field of lung cancer and advent of newer treatments have shown a significant improvement in survival in the patients. The present study was conducted to analyze the clinical profile of nonsmall cell lung cancer (NSCLC) patients treated in a single unit at a tertiary cancer care center. MATERIALS AND METHODS: In this retrospective analysis, 322 consecutive NSCLC patients from the year 2011 to 2012 treated in a single unit were included in the study. Patients with proven NSCLC were included in the study. The details of the patients included the demographic profile, pathological diagnosis as well as imaging data, tumor profile, details of treatment, and follow-up information. RESULTS: The majority of the patients (95.6%) were in the age group >40 years. A large group of the patients (57.1%) were present/reformed smokers. The major histological type was adenocarcinoma (60.9%), of which 22.8% patients were found to be epidermal growth factor receptor positive. Anaplastic lymphoma kinase rearrangement positivity rate was 4.8%. Furthermore, 68% patients had Stage 4 disease. Upfront palliative chemotherapy (CT) was offered in 61.8% patients and pemetrexed with platinum compounds was the main CT regimen (46.6%). Partial response was achieved in 45.7% patients, whereas stable disease was observed in 10.9% cases. Median progression-free survival was 5 months and overall survival was 55% at 36 months. CONCLUSION: NSCLC forms the largest subgroup of lung cancer with the patients presenting with advanced stages of disease. This area needs to be explored for the early detection and subsequently the radical treatment of the patients. Personalized approach may be considered for the management of lung cancer by identifying new predictive and prognostic biomarkers of this disease.
Keywords: Adenocarcinoma, chemotherapy, lung cancer, nonsmall cell lung cancer, survival
|How to cite this article:|
Doval D C, Sinha R, Batra U, Choudhury K D, Azam S, Mehta A. Clinical profile of nonsmall cell lung carcinoma patients treated in a single unit at a tertiary cancer care center. Indian J Cancer 2017;54:193-6
|How to cite this URL:|
Doval D C, Sinha R, Batra U, Choudhury K D, Azam S, Mehta A. Clinical profile of nonsmall cell lung carcinoma patients treated in a single unit at a tertiary cancer care center. Indian J Cancer [serial online] 2017 [cited 2019 Oct 18];54:193-6. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/193/219591
| » Introduction|| |
Lung cancer is one of the most commonly diagnosed malignancies and one of the leading causes of death accounting for 1.6 million of the total cancer cases and 1.4 million of the total cancer deaths worldwide in the year 2008. It is the most frequently diagnosed malignancy in Indian males and the 4th most common together in both the sexes. Lung cancer is usually associated with positive smoking history. However, of all the lung cancers diagnosed in the world, approximately 25% were never smokers.
Recent advances and the understanding in the field of lung cancer and advent of newer treatments including targeted therapy have shown a significant improvement in survival in the patients who were diagnosed and received the treatment in time. The treatment decision is largely based on the histopathological characterization of tumor. The two major subtypes are small cell lung cancer (SCLC) and non-SCLC (NSCLC). NSCLC is further characterized into adenocarcinoma and squamous cell carcinoma (SCC). Overall, NSCLC accounts for 75%–80% of all diagnosed cases of lung cancer. Surgery remains the mainstay of the treatment for the early stage disease; however, advanced stage treatment options could be chemotherapy (CT) or chemoradiotherapy or radiotherapy alone. The identification of activating gene mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) rearrangements, and the targeted therapy against such mutations has changed the scenario of the overall management of NSCLC with better response rate and survival., The present study was conducted to analyze the clinical profile of NSCLC patients treated in a single unit at a tertiary cancer care center.
| » Materials and Methods|| |
In this retrospective analysis, 401 consecutive patients of lung cancer from the year 2011 to 2012 treated in a single unit in the Department of Medical Oncology were identified. Of these, 322 patients had proven NSCLC and were included in the study. The details of the patients included the demographic profile, pathological diagnosis as well as imaging data, tumor profile, details of treatment, and follow-up information.
EGFR mutation detection has been routinely carried out in the clinical practice at our institute in the patients who have histological proven adenocarcinoma. For the EGFR mutation, paraffin-embedded tissue blocks were used. Exons 18–21 of EGFR gene were amplified on the genomic DNA by polymerase chain reaction as described in our earlier study. ALK gene rearrangement was carried out in patients with histologically proven adenocarcinoma and EGFR negative. ALK rearrangement was detected by fluorescence in situ hybridization using the Vysis ALK Break Apart Rearrangement Probe Kit (Abbott Molecular) following the manufacturers instruction.
SPSS version 22 for Windows (SPSS™ Inc., Chicago, IL, USA) was used for all the statistical analysis. For the survival analysis, Kaplan–Meier method was applied.
| » Results|| |
In a period of 2 years, a total of 322 patients with NSCLC were included in the analysis. Median age of the patients was 60 years (range 24–90 years). Demographic profile of the patients is presented in [Table 1]. The majority of the patients (95.6%) were in the age group >40 years. Males constituted around 80.1% of all these patients. A large group of the patients (57.1%) were present/reformed smokers. A total of 60.6% of the patients presented with disease in the right lung. The major histological type was adenocarcinoma (60.9%) followed by SCC (31.7%). Out of 196 adenocarcinomas, EGFR mutation status was known only in 145 patients, of which 22.8% patients were found to be EGFR positive. ALK rearrangement status was known in 62 cases of EGFR negative tumors and positivity rate was 4.8% [Table 2].
|Table 2: Details of patients tested for epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase rearrangement (in adenocarcinoma histology, n=196*)|
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Majority of patients presented with advanced stages of disease, of which 68% patients had Stage 4 disease. Furthermore, 50.3% patients had good Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1 at presentation. Most common presenting complaints were cough with or without expectoration, fever, shortness of breath. Major comorbidities were hypertension and diabetes mellitus.
The treatment and follow-up information are presented in [Table 3]. Upfront palliative intent of treatment in the form of CT was offered in 61.8% patients followed by neoadjuvant CT (NACT) in 22.4% patients. Pemetrexed combined with platinum compounds (carboplatin or cisplatin) in a palliative setting was the main CT regimen (46.6%) followed by gemcitabine with platinum (26.7%). Partial response (PR) was achieved in 45.7% patients. Clinical benefit in terms of stable disease (SD) was observed in 10.9% cases. The median progression-free survival (PFS) of the patients was 5 months and overall survival (OS) was 55% at 36 months [Figure 1].
| » Discussion|| |
We analyzed the data of 322 patients with NSCLC registered and treated in a single unit of a tertiary cancer care hospital in Northern India. In the present study, the gender representation of males was more than that of females (80% vs. 20%). From the data, it seems that lung cancer is more prevalent in males. The male to female ratio in our study was 4:1 which is similar in the study reported by Sundaram and Sanyal(4.2:1). The median age at presentation of the patients was 60 years with the youngest patient of age 24 years. Majority of the patients were in the age group of 41–60 years which is also reported in the previous studies from India, suggesting the disease onset in later stage of life.,
Tobacco smoking is a well-established factor and one of the major causes in lung cancer development. Lung cancer in never smokers is also frequently experienced worldwide. In our analysis, 43.2% of the patients were smokers of either cigarette or beedi. Lung cancer is a disease of male smokers across the globe with the risk increasing with early age at initiation, duration, and frequency of smoking. Other studies have reported a smoking population of 60%–81.2%., Never smoker population was 55.8% when we took into account the adenocarcinoma patients. Similar results have also been reported in other studies,, indicating that lung adenocarcinoma is never smokers' disease. In this subgroup, the development of lung cancer does not happen through carcinogens present in tobacco. It may involve genetic mutation in EGFR, ALK rearrangement, and other activating mutations. These are predominantly found in the nonsmokers and/or female lung cancer population with adenocarcinoma. EGFR mutation in the present study was observed in 22.8% and ALK gene rearrangement in 4.8% patients with adenocarcinoma which is in accordance with the frequency of 10%–66% reported in the published papers, irrespective of region, and ethnicity., The variation in the results may have been due to the selection bias in terms of patients, types of mutation, and different methodology of mutation detection. To date, there is only one published report from India, on ALK gene rearrangement demonstrating a positivity of 2.7%. These mutations are therapeutic targets for the tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and crizotinib. Treatment with these inhibitors has shown good treatment response in mutation positive tumors in NSCLC.,,
Major histological type observed was adenocarcinoma (60.9%) followed by SCC (31.7%). Characterization of subtypes was proved by the immunohistochemical expression of various biomarkers. It helps in the decision of line of treatment. Other reports have also shown a similar trend for the histological subtypes.,,
Furthermore, 68% patients were diagnosed in the later stages of the disease and treated with palliative intent (61.8%) of CT. The ECOG PS 1 was observed in most of the patients. Different types of CT were offered based on major histological subtypes of the tumor as well as PS. In the case of adenocarcinomas, pemetrexed plus platinum and in SCC, gemcitabine plus platinum, was the mainstay of the CT regime. These are well-established regimens with better response rate, tolerance as well as survival benefits.,,
Oral TKIs were offered as the first line of treatment to the EGFR positive patients. The data of some of the EGFR positive patients, who received the oral TKIs as first line of treatment on outpatients' basis, might have been skipped due to the selection of only inpatients who got admitted due to poor PS or CT and/or supportive treatment. Furthermore, considerable number of patients also received anti-EGFR therapy in the maintenance phase. If all the patients were included in the study, the percentage might have been increased.
Patients with Stage 3 disease are usually considered for the NACT followed by the radiological and surgical assessment of the response and tumor resectability. If the tumors are not resectable surgically, these patients may then be considered for chemoradiaiton or CT alone. Palliative radiotherapy was also offered to the patients with bone or brain metastasis. The SWOG 9900 randomized trial of surgery alone versus NACT followed by surgery has demonstrated that NACT is a considerable option with a good response and no effect on the postoperative complication. There is, however, no significant difference between the OS of the two groups.
A total of 45.7% of the patients showed a PR to the treatment and only a few patients (1.9%) achieved complete response. Clinical benefit in terms of SD was seen in 10.9% patients. Progressive disease was observed in 11.5% of patients after the initial therapy. The median PFS of the patients was 5 months and OS was 55% at 36 months. The response rate and survival data may not give a true picture of the actual survival because of heterogeneity in the data in the form of different CT regimens, stage, histology, and treatment intent. However, in NSCLC, which saw major advancements including targeted therapies, the survival has improved significantly.,,
The present study has limitation of selection bias which may be due to its retrospective nature and the selection of only inpatients in a single unit who got admitted due to poor PS or CT and/or supportive treatment.
| » Conclusion|| |
Overall, NSCLC forms the largest subgroup of lung cancer. Most of the patients present with advanced stages of disease. This area needs to be considered for the early detection and subsequently the radical treatment of the patients. Personalized approach may be considered for the management of lung cancer by identifying the predictive as well as prognostic biomarkers that provide better safety and efficacy of the treatment.
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Conflicts of interest
There are no conflicts of interest.
| » References|| |
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
Behera D. Lung cancer in India. Med Update 2012;22:401-7.
Majumdar A, Puri T. Evolution of systemic therapy in advanced non-small-cell lung cancer. J Indian Acad Clin Med 2012;13:138-41.
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, et al.
Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N
Engl J Med 2009;361:947-57.
Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, et al.
Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N
Engl J Med 2013;368:2385-94.
Doval DC, Azam S, Batra U, Choudhury KD, Talwar V, Gupta SK, et al.
Epidermal growth factor receptor mutation in lung adenocarcinoma in India: A single center study. J Carcinog 2013;12:12.
] [Full text]
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
Sundaram V, Sanyal N. Clinicopathological profile of bronchogenic carcinoma in a tertiary care hospital in eastern part of India. Clin Cancer Investig J 2014;3:220-4. [Full text]
Bhattacharyya SK, Mandal A, Deoghuria D, Agarwala A, Aloke GG, Dey SK. Clinico-pathological profile of lung cancer in a tertiary medical centre in India: Analysis of 266 cases. J Dent Oral Hyg 2011;3:30-3.
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]
Gao B, Sun Y, Zhang J, Ren Y, Fang R, Han X, et al.
Spectrum of LKB1, EGFR, and KRAS mutations in Chinese lung adenocarcinomas. J Thorac Oncol 2010;5:1130-5.
Smits AJ, Kummer JA, Hinrichs JW, Herder GJ, Scheidel-Jacobse KC, Jiwa NM, et al.
EGFR and KRAS mutations in lung carcinomas in the Dutch population: Increased EGFR mutation frequency in malignant pleural effusion of lung adenocarcinoma. Cell Oncol (Dordr) 2012;35:189-96.
Desai SS, Shah AS, Prabhash K, Jambhekar NA. A year of anaplastic large cell kinase testing for lung carcinoma: Pathological and technical perspectives. Indian J Cancer 2013;50:80-6. [Full text]
Noronha 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. PLoS One 2013;8:e61561.
Shankar S, Thanasekaran V, Dhanasekar T, Duvooru P. Clinicopathological and immunohistochemical profile of non-small cell lung carcinoma in a tertiary care medical centre in South India. Lung India 2014;31:23-8.
] [Full text]
Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al.
Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26:3543-51.
Azzoli CG, Temin S, Aliff T, Baker S Jr., Brahmer J, Johnson DH, et al.
2011 focused update of 2009 American society of clinical oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 2011;29:3825-31.
Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E; ESMO Guidelines Working Group. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23 Suppl 7:vii56-64.
Ball D, Mitchell A, Giroux D, Rami-Porta R; IASLC Staging Committee and Participating Institutions. Effect of tumor size on prognosis in patients treated with radical radiotherapy or chemoradiotherapy for non-small cell lung cancer. An analysis of the staging project database of the International Association for the Study of Lung Cancer. J Thorac Oncol 2013;8:315-21.
Manegold C. Treatment algorithm in 2014 for advanced non-small cell lung cancer: Therapy selection by tumour histology and molecular biology. Adv Med Sci 2014;59:308-13.
Melosky B. Treatment algorithms for patients with metastatic non-small cell, non-squamous lung cancer. Front Oncol 2014;4:256.
Byers LA, Rudin CM. Small cell lung cancer: Where do we go from here? Cancer 2015;121:664-72.
[Table 1], [Table 2], [Table 3]