Journal of the Scientific Society

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 47  |  Issue : 1  |  Page : 17--22

How does age affect clinicopathology and survival in non-small-cell lung cancer? An institutional retrospective analysis from North-East India


Srigopal Mohanty1, Yumkhaibam Sobita Devi2, Vimal Sekar2, James Chongthu2, Deiwakor Chyrmang2,  
1 Department of Medical Oncology, Kilpauk Medical College, Chennai, Tamil Nadu, India
2 Department of Radiation Oncology, RIMS, Imphal, Manipur, India

Correspondence Address:
Dr. Yumkhaibam Sobita Devi
Department of Radiation Oncology, RIMS, Lamphelpat, Imphal - 795 004, Manipur
India

Abstract

Context: Worldwide, lung cancer is the most common type of cancer and the most frequent cause of cancer-related mortality. There are limited numbers of studies on the prognostic impact of age on non-small cell lung cancer (NSCLC) in developing countries such as India. Aims: The aim was to compare the clinicopathology and survival between younger and older age NSCLC. Subjects and Methods: A retrospective review was carried out on 780 diagnosed cases of NSCLC, treated between 2007 and 2015. The patients were divided into two age groups, younger (<50 years) and older (≥50 years) age groups. Results: Younger NSCLC patients constituted 6.2% of the total study population and were found to have greater proportion of female patients (P = 0.000), lesser prevalence of smokers (P = 0.000), higher rate of positive family history of lung cancer (P = 0.000), metastatic disease at presentation (P = 0.009), adenocarcinoma as the most common histopathology (P = 0.000), greater proportion of patients received combined modality treatment (P = 0.001), and had better overall survival (P = 0.04), whereas older age NSCLC patients were diagnosed more frequently with poor performance status (Eastern Cooperative Oncology Group 3 or 4) (P = 0.000), more likely to be smokers (P = 0.000), higher prevalence of comorbidities, i.e., diabetes mellitus (P = 0.012), hypertension (P = 0.067), bronchial asthma or chronic obstructive pulmonary disease (P = 0.018), squamous cell carcinoma as the most common histopathological subtype, and greater proportion of patients received either single modality treatment or no treatment (P = 0.000). Multivariate analysis revealed age to be an independent prognostic factor (P = 0.019). Conclusions: Younger NSCLC patients, in spite of aggressive disease at diagnosis, are good candidates for combined modality treatment and have better survival.



How to cite this article:
Mohanty S, Devi YS, Sekar V, Chongthu J, Chyrmang D. How does age affect clinicopathology and survival in non-small-cell lung cancer? An institutional retrospective analysis from North-East India.J Sci Soc 2020;47:17-22


How to cite this URL:
Mohanty S, Devi YS, Sekar V, Chongthu J, Chyrmang D. How does age affect clinicopathology and survival in non-small-cell lung cancer? An institutional retrospective analysis from North-East India. J Sci Soc [serial online] 2020 [cited 2020 Jul 12 ];47:17-22
Available from: http://www.jscisociety.com/text.asp?2020/47/1/17/287492


Full Text



 Introduction



Worldwide, lung cancer is the most commonly diagnosed malignancy and the most frequent cause of malignancy-related mortality.[1] Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers and often diagnosed in the older population; however, there is a significant rate (1%–10%) of young patients being diagnosed under the age of 45 or 50 years.[2],[3],[4],[5] Prognostic importance of age in NSCLC is controversial. Some studies have reported the NSCLC among the younger population to be more aggressive and worse prognosis;[6],[7] some have reported this cohort of patients to have better survival;[8],[9] however, other studies have reported no difference in overall survival between these two age groups.[10] However, a limited number of studies available from India in this context, which have reported age to have no significant impact on overall survival in NSCLC patients.[11],[12]

Hence, keeping in view of the results from previous Indian studies, showing nondependence of overall survival on the age factor,[11],[12] with a hypothesis of no difference in survival between younger and older age NSCLC patients, the present study was aimed to evaluate the difference in clinicopathological presentation, stage-wise treatment received, overall survival, and the factors affecting overall survival among patients of younger and older NSCLC, treated in a regional cancer center in North-East India over a period of 9 years.

 Subjects and Methods



The retrospective study was performed by retrieving data from the institutional cancer registry. The study population included patients with histopathologically or cytologically confirmed cases of NSCLC registered and treated in the center between January 2007 and December 2015. After exclusion of cases with unconfirmed histopathology or cytology, and unknown clinical stage, a total of 780 patients were included in the study. The patients were divided into two groups; the younger age group consisted of patients <50 years, and the older age group consisted of patients of ≥50 years of age. The primary outcome variable was (i) overall survival in the two age groups, and the secondary outcome variables were (i) clinicopathological characteristics in the two age groups, (ii) proportions of patients received combined modality treatment in each age group, and (iii) factors affecting 2 years overall survival. Statistical analyses were performed using IBM SPSS statistics for windows, version 21.0 (Armonk, NY: IBM Corp). Qualitative variables such as age group, sex, performance status, family history of lung malignancy, history of type 2 diabetes mellitus (DM-2), hypertension (HTN), pulmonary tuberculosis, bronchial asthma (BA), chronic obstructive pulmonary disease (COPD), side of lung lesion, histopathological subtype, stage, and modality of treatment received were compared using Chi-square testing. Factors affecting survival were evaluated by multivariate analysis (with P < 0.05 and 95% confidence interval). Survival analysis was done by the Kaplan–Meier method and was compared between the two age groups using log-rank testing. P < 0.05 was considered statistically significant.

 Results



In the present study, the median age at diagnosis was 65 years (range from 28 to 92 years). Majority of patients (93.8%) were diagnosed in the age group of ≥50 years. Male constituted 56.4% and female constituted 43.6% of the total 780 patients, whereas significantly higher proportion of female patients were found among younger age groups compared to the older age group [Table 1].{Table 1}

The performance status during initial diagnosis was the Eastern Cooperative Oncology Group (ECOG) 0 in 0.9%, 1 in 39%, ECOG 2 in 37.3%, ECOG 3 in 19.5%, and ECOG 4 in 1.7% of patients. A significantly greater proportion of patients in the older age group (≥50 years) were diagnosed with poor performance status (ECOG 3 or 4) as compared to younger NSCLC patients (<50 years) (i.e., 22.3% vs. 4.2%, respectively, P = 0.000) [Table 1].

Most of the patients were smoker (73.3%) in the whole study population, whereas the proportion of smokers in the younger age group was significantly lesser as compared to the older age group (25% vs. 76.5%, respectively, P = 0.000) [Table 1].

Out of 780 patients, comorbidities were found in 11.4% for HTN, 14.6% for Type 2 (DM-2), and 15% for BA or COPD. Significantly lower prevalence of comorbidities were found among younger NSCLC patients as compared to the older NSCLC patients, i. e., DM-2 (0% vs. 15.6%, respectively, P = 0.012), HTN (4.2% vs. 11.9%, respectively, P = 0.067), and BA/COPD (4.2% vs. 15.7% respectively, P = 0.018) [Table 1].

Family history of lung cancer was found in 1% of total study population, which was found significantly greater among younger NSCLC patients as compared to older age group (4.2% vs. 0.8%, respectively, P = 0.000) [Table 1].

Overall, among 780 patients, the most common histopathologic subtype was squamous cell carcinoma (57.2%), as also found among older NSCLC patients. Adenocarcinoma constituted the most common histological subtype (66.7%) among younger NSCLC patients.

Disease stage at diagnosis was found most commonly to be stage 3 (39%), stage 2 (32.6%), followed by stage 4 (26.4%), and stage 1 (2.1%). A significantly greater proportion of young patients were diagnosed with metastatic disease, compared to the older age group (41.7% vs. 25.4%, P = 0.009).

A significantly greater proportion of patients of young age group received combined modality treatment as compared to older patients (66.7% vs. 45.6%, respectively, P = 0.001).

The median survival was 14 months (range of 3–51 months) for the total 780 patients, which was found significantly greater for the younger compared to the older NSCLC patients (18 months vs. 15 months, respectively, P = 0.047) [Figure 1].{Figure 1}

Multivariate analysis was performed (P < 0.05 and 95% confidence interval), which revealed that the factors affecting survival in the present study were age, performance status, comorbidities such as DM-2, asthma/COPD, HTN, histopathology (squamous histology had better survival than adenocarcinoma), stage, and treatment modalities [Table 2].{Table 2}

 Discussion



NSCLC commonly represents a disease of the older population. A smaller, but not insignificant proportion of patients with NSCLC are younger than 50. The present study was aimed to evaluate the trends in incidence, clinicopathologic characteristics, treatment profile, and survival outcome of NSCLC in two different age groups (<50 vs. ≥50 years). The younger NSCLC patients were found to have unique clinical, pathological, treatment profile, as well as survival outcomes, when compared with older NSCLC patients.

Younger age group (<50 years) represented 6.2% of the total NSCLC patients in the present study. This cohort constituted a greater proportion of female patients and lesser proportions of smokers compared to the elderly cohorts. The above findings were in concordance with previous studies.[2],[13],[14]

Younger NSCLC patients were found to have better performance status during diagnosis, more positive family history of lung cancer, and adenocarcinoma as the most common histopathology, whereas it was squamous cell carcinoma among the elderly patients. The above findings of the present study were in concordance with previous studies.[15],[16]

A previous study has reported older NSCLC patients to be more likely diagnosed with other comorbidities.[17] Similarly, in the present study, comorbid illnesses such as Type-2 DM, HTN, BA/COPD, and tuberculosis were found in significantly higher proportion among older NSCLC patients.

Metastatic disease during initial diagnosis was reported to be higher among younger NSCLC patients compared to the older NSCLC patients.[2] Similarly, in the present study, majority of the patients in all age groups were diagnosed in Stage II or III, whereas metastatic disease during initial diagnosis was found significantly higher among young patients.

Existing literature supports the concept that combined modalities of treatments in NSCLC results in better survival outcomes as compared to single-modality treatment or supportive care even in elderly cohorts or poor performance status.[18],[19] On the contrary, the advancement of age has been reported to be associated with increased comorbidities, decreased physiological functions, decreased functional reserve of body organs, and increased likely hood of polypharmacy.[20],[21],[22],[23],[24] Because of the above changes associated with advancement in age, the body tolerability to active anticancer treatment decreases. As a result of which, the treatment toxicity becomes a major limiting factor for surgery or combined chemotherapy in this cohort. In the present study, a significantly higher proportion of patients among elderly NSCLC patients did not receive any combined modality treatment or first-line chemotherapy, whereas received first-line tyrosine kinase inhibitor therapy or supportive care only, which was in concordance with the previous study,[25] whereas the proportion of patients received combined modality treatment was significantly higher among younger NSCLC patients compared to the elderly counterparts, as reported by the previous studies, where the stage-wise treatment plans were significantly affected by the presence of comorbidities.[16],[26]

Comorbidities affect the stage-wise treatment selection and the overall survival, and the advancing age is an independent negative predictor of treatment outcome irrespective of comorbidities and disease stage.[26],[27] Patient's performance status plays an important role in treatment selection and consequently affects the survival outcome. Low-performance status of patients makes them unfit for combined modality treatment, which results in inferior overall survival.[28],[29] In the present study, elderly lung cancer patients were more associated with poor performance status, greater comorbidities, lesser proportions of patients received combined modality anticancer treatment, and lesser overall survival as compared to the patients of younger age NSCLC. After multivariate analysis (P < 0.05 and confidence interval of 95%), it was confirmed that poor performance status, comorbidities such as DM-2 and BA/COPD, and smokers were associated with poor overall survival. Although the previous Indian studies have reported no difference in survival between older and younger age lung cancer patients,[13],[14] the median overall survival of younger NSCLC patients in the present study was found greater (18 months) compared to the older NSCLC patients (15 months).

 Conclusions



The present study found NSCLC to be a disease of the elderly population with a median age of 65 years at diagnosis. Younger NSCLC cases constituted 6.2% of the total NSCLC cases, which was found to be associated with greater proportion of female patients, more positive family history, better performance status, lesser proportion of smokers, adenocarcinoma as the most common histopathology subtype, aggressive and more likely to have metastatic disease at diagnosis, lesser rate of comorbidities, more likely to receive surgery and combine modality treatment, and better overall survival, whereas elderly NSCLC patients were found to be diagnosed with poor performance status, squamous cell carcinoma as most common histopathology subtype, more likely associated with comorbidities, less likely to be fit to undergo surgery, or to receive combined chemotherapy treatment, associated with poor overall survival compared to the young NSCLC.

Better survival with combined modality treatment in younger NSCLC patients in spite of advanced stage at diagnosis encourages this age group for aggressive treatment.

Optimum treatment strategy in NSCLC in elderly patients is not yet standardized, which needs multiinstitutional randomized studies on this cohort to establish a standardized treatment protocol.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
2Thomas A, Chen Y, Yu T, Jakopovic M, Giaccone G. Trends and characteristics of young non-small cell lung cancer patients in the United States. Front Oncol 2015;5:113.
3Ramalingam S, Pawlish K, Gadgeel S, Demers R, Kalemkerian GP. Lung cancer in young patients: Analysis of a Surveillance, Epidemiology, and End Results database. J Clin Oncol 1998;16:651-7.
4Nugent WC, Edney MT, Hammerness PG, Dain BJ, Maurer LH, Rigas JR. Non-small cell lung cancer at the extremes of age: Impact on diagnosis and treatment. Ann Thorac Surg 1997;63:193-7.
5Bryant AS, Cerfolio RJ. Differences in outcomes between younger and older patients with non-small cell lung cancer. Ann Thorac Surg 2008;85:1735-9.
6Sacher AG, Dahlberg SE, Heng J, Mach S, Jänne PA, Oxnard GR. Association between younger age and targetable genomic alterations and prognosis in non-small-cell lung cancer. JAMA Oncol 2016;2:313-20.
7Bourke W, Milstein D, Giura R, Donghi M, Luisetti M, Rubin AH, et al. Lung cancer in young adults. Chest 1992;102:1723-9.
8Tas F, Ciftci R, Kilic L, Karabulut S. Age is a prognostic factor affecting survival in lung cancer patients. Oncol Lett 2013;6:1507-13.
9Arnold BN, Thomas DC, Rosen JE, Salazar MC, Blasberg JD, Boffa DJ, et al. Lung cancer in the very young: treatment and survival in the national cancer data base. J Thorac Oncol 2016;11:1121-31.
10Sekine I, Nishiwaki Y, Yokose T, Nagai K, Suzuki K, Kodama T. Young lung cancer patients in Japan: Different characteristics between the sexes. Ann Thorac Surg 1999;67:1451-5.
11Mahesh PA, Archana S, Jayaraj BS, Patil S, Chaya SK, Shashidhar HP, et al. Factors affecting 30-month survival in lung cancer patients. Indian J Med Res 2012;136:614-21.
12Murali AN, Radhakrishnan V, Ganesan TS, Rajendranath R, Ganesan P, Selvaluxmy G, et al. Outcomes in lung cancer: 9-year experience from a tertiary cancer center in India. J Glob Oncol 2017;3:459-68.
13Akcay O, Kaya SO, Ceylan KC. Does age have an impact on lung cancer survival? Eurasian J Pulmonol 2018;20:162-6.
14Jemal A, Miller KD, Ma J, Siegel RL, Fedewa SA, Islami F, et al. Higher lung cancer incidence in young women than young men in the United States. N Engl J Med 2018;378:1999-2009.
15Radzikowska E, Roszkowski K, Głaz P. Lung cancer in patients under 50 years old. Lung Cancer 2001;33:203-11.
16Rich AL, Khakwani A, Free CM, Tata LJ, Stanley RA, Peake MD, et al. Non-small cell lung cancer in young adults: Presentation and survival in the English National Lung Cancer Audit. QJM 2015;108:891-7.
17Dima S, Chen KH, Wang KJ, Wang KM, Teng NC. Effect of comorbidity on lung cancer diagnosis timing and mortality: a nationwide population-based cohort study in Taiwan. Biomed Res Int 2018;2018:1252897.
18Gajra A, Jatoi A. Non–small-cell lung cancer in elderly patients: A discussion of treatment options. J Clin Oncol 2014;32:2562-9.
19Santos FN, de Castria TB, Cruz MR, Riera R. Chemotherapy for advanced non-small cell lung cancer in the elderly population. Cochrane Database Syst Rev 2015;2015:CD010463.
20Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL Jr., Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 2004;291:2441-7.
21Lees J, Chan A. Polypharmacy in elderly patients with cancer: Clinical implications and management. Lancet Oncol 2011;12:1249-57.
22Young A. Ageing and physiological functions. Philos Trans R Soc Lond B Biol Sci 1997;352:1837-43.
23Balducci L. Aging, frailty, and chemotherapy. Cancer Control 2007;14:7-12.
24Leduc C, Antoni D, Charloux A, Falcoz PE, Quoix E. Comorbidities in the management of patients with lung cancer. Eur Respir J 2017;49:1601721.
25Hsu CL, Chen JH, Chen KY, Shih JY, Yang JC, Yu CJ, et al. Advanced non-small cell lung cancer in the elderly: The impact of age and comorbidities on treatment modalities and patient prognosis. J Geriatr Oncol 2015;6:38-45.
26Gould MK, Munoz-Plaza CE, Hahn EE, Lee JS, Parry C, Shen E. Comorbidity profiles and their effect on treatment selection and survival among patients with lung cancer. Ann Am Thorac Soc 2017;14:1571-80.
27Blanco R, Maestu I, de la Torre MG, Cassinello A, Nuñez I. A review of the management of elderly patients with non-small-cell lung cancer. Ann Oncol 2015;26:451-63.
28Wang S, Wong ML, Hamilton N, Davoren JB, Jahan TM, Walter LC. Impact of age and comorbidity on non-small-cell lung cancer treatment in older veterans. J Clin Oncol 2012;30:1447-55.
29Tabchi S, Kassouf E, Florescu M, Tehfe M, Blais N. Factors influencing treatment selection and survival in advanced lung cancer. Curr Oncol 2017;24:E115-22.