(Chest. 2002;122:1938-1943.)
© 2002
American College of Chest Physicians
Advanced Presentation of Lung Cancer in Asian Immigrants*
A Case-Control Study
Geraldine A. Finlay, MD;
Brenda Joseph, CTR BS;
Cynthia R. Rodrigues, MD;
John Griffith, PhD and
Alexander C. White, MD
* From the Pulmonary and Critical Care Division and the Tupper Research Institute (Drs. Finlay, Rodrigues, and White), Department of Medicine, New England Medical Center, Tufts University School of Medicine; Medical Records Department (Ms. Joseph), New England Medical Center; and Clinical Care Research Department (Dr. Griffith), Tufts University School of Medicine, Boston, MA.
Correspondence to: Alexander C. White, MD, Pulmonary and Critical Care Division, New England Medical Center, NEMC #257, 750 Washington St, Boston MA 02111; e-mail: Awhite1{at}Lifespan.org
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Abstract
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Study objectives: To determine if Asian immigrants to the United States present with more advanced lung cancer compared to non-Asians.
Design: A 5-year retrospective case-control study (January 1, 1992, to December 31, 1996) of patients with lung cancer identified using the New England Medical Center cancer center database. A 2-year follow up was obtained in all subjects.
Setting: A tertiary level care hospital providing all levels of medical care to the local Asian population in the Boston area.
Patients: Forty-two Asian immigrants with lung cancer diagnosed over the study period were matched for age and sex with 42 non-Asian control subjects.
Results: Asians presented more frequently with advanced stage (stage III or IV) and less frequently with early stage (stage I or II) lung cancer compared with the non-Asian control group (p < 0.05). Asians were more likely to present with hemoptysis or constitutional symptoms (p < 0.01) and had a longer duration of symptoms prior to presentation (p < 0.01) compared with non-Asians. There was no difference in the length of time elapsed between diagnosis and start of treatment (approximation of workup time) between the two groups. The utilization of tests and procedures for clinical disease staging was not significantly different between the two groups. The incidence of large cell carcinoma (p < 0.05) was higher in Asians compared with non-Asians. Asians were more likely to receive radiotherapy and less likely to receive combination therapy compared with non-Asians (p < 0.05). The treatment of stage I and II lung cancer did not differ between the two groups. The median 2-year survival was significantly reduced in Asians compared with non-Asians: Asians, 7 months (95% confidence interval [CI], 3.1 to 10.9); non-Asians, 15 months (95% CI, 12.0 to 17.5) [p < 0.001].
Conclusions: Asian immigrants with lung cancer appear to present with more advanced stage of disease, have more prolonged symptomatology, and have reduced survival compared with non-Asians. These data suggest that ethnicity may play a role in the presentation and outcome of lung cancer in the Asian immigrant population.
Key Words: Asian immigrants • lung cancer • survival
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Introduction
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Lung cancer is a major cause of morbidity and mortality and is now the leading cause of cancer death in the United States.1
Racial disparities in health care exist2
and have been shown to affect lung cancer survival.3
4
For example, the resection rate of early stage lung cancer has been shown to be lower in African Americans as compared with a control group.5
Surgical resection is the most effective treatment for patients with non-small cell lung cancer, with the 5-year survival of patients following resection being closely tied to stage at presentation.6
7
Data on lung cancer outcomes in Asian immigrants living in the United States are very limited.
The number of Asian immigrants coming to the United States has been increasing over the past 5 years,8
and a significant percentage of the population of metropolitan Boston is now Asian.9
The New England Medical Center (NEMC), a tertiary referral center located in downtown Boston, provides primary through tertiary medical care to a large percentage of this local Asian population. We observed on a case-by-case basis that Asian immigrants presenting with lung cancer appeared to have more advanced stage of disease as compared with non-Asian patients. The advanced stage of lung cancer at presentation limited the treatment options available to the Asian patients, with only small numbers undergoing potentially curative resection. This observation was supported by evidence that immigrants may delay seeking medical attention for health problems in general.10
The purpose of this study was to test the hypothesis that Asian immigrants presenting with lung cancer have more advanced disease and as a result have reduced survival when compared with a non-Asian control group. We used a retrospective case-control design to study all Asian immigrant patients presenting to NEMC over a 5-year period.
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Materials and Methods
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All patients with diagnosed lung cancer (International Classification of Diseases codes 162.0–162.9) between January 1, 1992, and December 31, 1996, were identified from the NEMC cancer center database. An Asian patient was defined as one who was born in the continent of Asia and had immigrated to the United States. Ninety-five percent of the Asian patients with lung cancer identified in this study had emigrated to the United States from China. Each Asian patient with lung cancer (case) was matched for age and sex with a non-Asian patient with lung cancer who also received a diagnosis of lung cancer in the same 5-year period (control). To reduce selection bias, each case was randomly matched using a computerized randomization program with one of five potential controls identified by the matching process. The following data were abstracted from the medical record (both paper and electronic) of each case or control by two of the authors (G.A.F. or A.C.W.): age, sex, the presence of pulmonary symptoms (ie, cough, dyspnea, hemoptysis, or chest pain), constitutional symptoms (ie, weight loss, anorexia, night sweats, fever, and fatigue), smoking history, time elapsed from diagnosis to start of treatment, testing utilized as part of staging (CT of chest, abdomen, and head; mediastinoscopy; bone scan; MRI of the head or spine; thoracentesis; and pleural biopsy), lung cancer histology, treatment course (surgery alone, chemotherapy alone, local radiation, and combination therapy or no treatment), survival from time of diagnosis to January 1999 (recorded in months), FEV1 (obtained within 1 month of diagnosis), serum albumin and protein concentrations, country of birth, and need for interpreter. Spirometry was performed using a SensorMedics 2450 spirometer (SensorMedics; Yorba Linda, CA). The TNM staging classification for lung cancer in use during the study period was used to stage lung cancer.6
We used the older TNM staging classification, as it was in use during the period of time used for the study and therefore determined patient treatment. For each patient, the clinical stage at presentation was identified from the database and was confirmed by analysis of chest CT scans. Pathologic stage data were obtained in all patients who underwent surgical resection of lung cancer. Outcome data were obtained from either the patient’s medical records or from the Registry of Vital Records in the City of Boston.
All results are expressed as mean ± SD. Values for survival are expressed as the median survival in months. Statistical analysis was performed using SPSS software (SPSS; Chicago, IL). The 
2 test was used to evaluate group comparisons. The Fisher exact test was used for comparing the testing used for clinical staging. Kaplan-Meier curves and log-rank statistics were used to assess differences in survival between the groups. Statistical significance was assumed at a p value < 0.05.
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Results
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Demographic Data
A total of 84 patients with lung cancer were identified (42 Asian cases) and 42 non-Asian control patients) over the 5-year period. Of the 42 Asian cases evaluated, 95% (n = 40) were Chinese and 5% (n = 2) were Vietnamese. The non-Asian control patients were all born in the United States. Hospital interpreter services were used to obtain a history in 81% of the Asians and in none of the non-Asians. In 9.3% of the Asians, it was not possible to determine from the record if interpreter services had been used.
All demographic and histologic data are shown in Table 1
. There was no difference in the number of smoking pack-years between the two groups. However, a smaller percentage of Asians were smokers (current or ex-smokers) compared to non-Asians (Asians, 76%; non-Asians, 97%; p < 0.01). All female patients in the non-Asian group had a history of smoking compared with only one female patient in the Asian group (p < 0.001). Large cell carcinoma was diagnosed more frequently in Asians compared with non-Asians (Asians, 35.7%; non-Asians, 11.9%; p < 0.05).
Presentation and Stage
Symptoms at presentation are compared in Table 2
. Hemoptysis and constitutional symptoms were more common in Asians (p < 0.01). In addition, overall symptom duration, measured in months, was longer in the Asian group compared with non-Asians (p < 0.01).
Comparison of lung cancer stage at presentation showed that Asians presented more frequently with stage IV disease (Asians, 50%; non-Asians, 38.1%; p < 0.05) and less frequently with stage I disease (Asians, 11.9%; non-Asians, 23.8%; p < 0.05) [Fig 1
]. Similar differences were seen in stage II and III disease, with fewer Asians presenting with stage II disease and more presenting with stage III disease. The advanced stage of presentation of the Asian group was more apparent when the stage data were combined as two new groups, stage I and II vs stage III and IV (p < 0.01), as shown in Figure 2
.
There was no significant difference in time elapsed from diagnosis to start of treatment (a measure of workup time) between Asians and non-Asians (Asians, 31 ± 32 days; non-Asians, 26 ± 21 days). There was no significant difference in the type or number of tests performed for staging among cases or controls as shown in Table 3
.
Treatment and Survival
The treatment for lung cancer was significantly different between the two groups (p < 0.05). Asians were more likely to receive radiation therapy alone compared to the control population (Asians, 57.2%; non-Asians, 26.1%; p < 0.05) and less likely to receive combination therapy (defined as any combination of surgery, radiation or chemotherapy) [Asians, 9.6%; non-Asians, 35.7%; p < 0.05]. There was no difference between Asians and non-Asians for all other treatment regimens used. Treatment modalities used for each stage of lung cancer are compared in Table 4
. The individual group numbers were too low to allow statistical analysis but a number of observations can be made. Asians with stage III or IV lung cancer were at least three times more likely to receive radiation therapy compared with non-Asians with same stage disease. In contrast, non-Asian patients were three times more likely to receive combination therapy for stage III or IV disease compared to Asians at the same stage of lung cancer. There was no difference noted between Asians and non-Asians in the treatment modalities used to treat stage I and II lung cancer.
Complete data were available for a comparison of 2-year Kaplan-Meier survival curves for Asians and non-Asians (Fig 3
). Survival at 2 years was significantly reduced in the Asians compared with non-Asians (Asians, 14.3%; non-Asians, 42.9%; p < 0.01). Overall median survival at 2 years was 15 months in non-Asians (95% confidence interval [CI], 12.0 to 17.5), compared to 7 months (95% CI, 3.1 to 10.9) in the Asian group (cases) [p < 0.001]. When grouped into stage I and II vs stage III and IV, there was no statistical difference observed in the median 2-year survival between Asians and non-Asians for stages I and II (Asians, 20 months [95% CI, 14.9 to 23.5]; non-Asians, 20 months [95% CI, 15.4 to 22.5]; p > 0.05). However, a statistically significant difference in survival was seen for stage III and IV (Asians, 5 months [95% CI, 2.6 to 7.4]; non-Asians, 8 months [95% CI, 4.1 to 11.9]) [p < 0.05].
Albumin, Total Protein, and FEV1
Albumin and total protein values were available for 86% of Asians and 64% of non-Asians. The mean albumin value was 2.9 ± 0.8 mg/dL in Asians compared with 3.1 ± 0.9 mg/dL in the non-Asian group, and the mean total protein value was 6.5 ± 0.7 mg/dL in Asians compared with 6.1 ± 1 mg/dL in non-Asians (differences not significant [NS]). The mean FEV1 in the Asians was 1.6 ± 0.6 L (n = 17), compared to 2.2 ± 0.8 L (n = 13) in non-Asians (p < 0.05).
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Discussion
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This study demonstrates that Asian immigrants living in the metropolitan Boston area present with lung cancer at a more advanced stage when compared with a non-Asian control group. Furthermore, the Asian group had reduced survival when compared with a non-Asian control group. These findings are consistent with recent reports of an effect of ethnicity on lung cancer presentation and outcome.2
5
11
12
A 1998 study showed that African Americans were less likely to present with "localized" lung cancer when compared with other ethnic groups.13
A predominance of advanced stage lung cancer has also been reported in China.14
Here, we observed differences in presentation in both the early and late stages of lung cancer between Asian immigrants and non-Asian control patients. The percentage of patients with stage I disease was lower in the Asians (11.9%) compared with non-Asians (23.8%). This difference was striking and probably a major factor in the reduced survival seen in the Asian group. In order to exclude stage migration as a confounding variable affecting stage, we analyzed the staging techniques used in each group and compared the results. We were unable to show any significant difference in the utilization of diagnostic and staging techniques between the two groups. Therefore, stage migration does not appear to have been a factor in explaining the differences in presentation.
The presenting symptoms differed between the two groups with Asians having a higher incidence of hemoptysis and constitutional symptoms as compared with non-Asians. In addition, symptom duration prior to presentation was more prolonged in the Asian group. These observations raise the possibility that Asian patients with lung cancer delay seeking medical attention despite having serious symptoms.10
15
A delay of this nature may help explain why the Asian group presented with more advanced lung cancer stage.
Language is an important potential barrier to effective health care.15
16
More than 80% of Asian patients in this study required an interpreter, raising the possibility that a language barrier caused a delay in access to medical care. A more prolonged evaluation time, which may be due in part to a language barrier, may also delay diagnosis and treatment. We used time elapsed from presentation to first treatment as an estimate of evaluation time and did not find any difference between the two groups. Other possible causes of delay include a cultural reluctance to accept western-style medical care10
16
or a reliance on traditional Asian methods of treatment.17
We were unable to address these issues given the retrospective design of the study. A prospective analysis would help determine why Asian immigrant patients appear to ignore serious symptoms and present with late stage lung cancer.
We observed a higher incidence of large cell carcinoma in the Asian group compared with the non-Asians. Data suggest that ethnic differences in lung cancer presentation and outcome may reflect an interaction between genetic makeup and environmental exposure.18
For example, polymorphisms in the NAD(P)H:quinone oxidoreductase (NQO1) enzyme19
and in the microsomal epoxide hydrolase gene may be risk factors for smoking-associated lung cancer in Asia.20
In addition, occupational or environmental carcinogen exposure may differ between Asians and non-Asians.21
Genetic or environmental effects such as these may explain the higher incidence of large cell carcinoma we observed in the Asian group. Smoking remains the major cause of lung cancer in the male Asian population and accounts for approximately 25% of lung cancers in Asian female subjects.22
We did not expect to find a smaller percentage of smokers in the Asian (76%) compared with the non-Asian (97%) population. However, smoking habits may not be accurately recorded in the chart, and self-reported smoking status has been shown to underestimate true smoking status in Asian immigrants.23
Smoking is likely to continue to be the major cause of lung cancer in the Asian immigrant population, as there is evidence that public education programs are not effective in educating Asian Americans about the risks of smoking.24
An effect of ethnicity on lung cancer survival has been reported. Increased mortality rates have been reported for both Asian Americans25
and African Americans13
with lung cancer compared with Americans of European descent. Data have also shown lower resection rates and reduced survival for early stage lung cancer among different ethnic groups.5
26
We did not find any difference in the resection rates for early-stage lung cancer between the Asians and non-Asians. We did observe differences in the treatment regimens administered to patients with more advanced stage lung cancer. We suspect these differences reflect patient treatment preferences rather than an effect of ethnicity on delivered medical care.
The increase in mortality that was observed in the Asian group is most likely due to the higher percentage of patients presenting with advanced stage lung cancer. Lead-time bias may be a factor in mortality in the Asian group, as they delayed seeking medical attention. Cancer mortality in different populations may be confounded by comorbid diseases.27
Based on the available serum albumin data, nutritional status was similar between the two groups. There was a significant reduction in FEV1 in the Asian compared with the non-Asian group, but the implications of this observation on lung cancer mortality are unclear, as a 2000 study has shown lower-than-average values for FEV1 in Asian Americans compared to European Americans.28
The lower FEV1 in the Asian group did not reduce the rate of surgical resection for stages I and II lung cancer in this group compared with the non-Asian group. A prospective study is needed to better determine the impact of comorbid disease such as COPD on lung cancer survival in the Asian population.
This study has a number of relevant limitations. The small sample size limits both the statistical power of the study and the ability to make inferences to the immigrant Asian lung cancer population in general. Referral bias needs to be considered as an explanation for the difference in lung cancer stage, as it may have a confounding effect on one ethnic group and not on others. A number of patients with lung cancer in community hospitals in the greater Boston area are referred to downtown medical centers for evaluation and treatment. A referral pattern of this nature may have a greater effect on one ethnic group compared with others depending on the demographics of the referring town. Conversely, Asian immigrant patients living in the metropolitan Boston area may be more likely to receive all levels of medical care at downtown medical centers and therefore may not be subject to this type of referral bias.
In summary, Asian immigrants have a delayed presentation of lung cancer and have more advanced stage of disease at the time of diagnosis when compared with age- and sex-matched non-Asian control patients. Outreach programs targeting the immigrant Asian population may help improve lung cancer outcomes in this group.
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Footnotes
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Abbreviations: CI = confidence interval; NEMC = New England Medical Center; NS = not significant
Received for publication June 19, 2000.
Accepted for publication July 17, 2002.
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References
|
|---|
- Recent trends in mortality rates for four major cancers, by sex and race/ethnicity–United States, 1990–1998. MMWR Morb Mortal Wkly Rep 2002;51,49-53[Medline]
- Epstein, AM, Ayanian, JZ Racial disparities in medical care. N Engl J Med 2001;344,1471-1473[Free Full Text]
- Groeger, AM, Odocha, O, Mueller, MR, et al Racial variation in lung cancer. Anticancer Res 1997;17,2843-2848[ISI][Medline]
- Groeger, AM, Mueller, MR, Odocha, O, et al Ethnic variations in lung cancer. Anticancer Res 1997;17,2849-2857[ISI][Medline]
- Bach, PB, Cramer, LD, Warren, JL, et al Racial differences in the treatment of early-stage lung cancer. N Engl J Med 1999;341,1198-1205[Abstract/Free Full Text]
- Mountain, CF Lung cancer staging classification. Clin Chest Med 1993;14,43-53[ISI][Medline]
- Mountain, CF Revisions in the International System for Staging Lung Cancer. Chest 1997;111,1710-1717[Abstract/Free Full Text]
- US Bureau of the Census.. Statistical abstract of the United States 16th ed. 1996 US Government Printing Office Washington, DC.
- US Bureau of the Census.. Statistical abstract of the United States: 2001 121st ed. 2001 US Government Printing Office Washington DC. Library of Congress Card No. 4-18089; 38
- Hoang, GN, Erickson, RV Cultural barriers to effective medical care among Indochinese patients. Annu Rev Med 1985;36,229-239[CrossRef][ISI][Medline]
- Cooley, ME, Jennings-Dozier, K Lung cancer in African Americans: a call for action. Cancer Pract 1998;6,99-106[CrossRef][ISI][Medline]
- Gadgeel, SM, Severson, RK, Kau, Y, et al Impact of race in lung cancer: analysis of temporal trends from a surveillance, epidemiology, and end results database. Chest 2001;120,55-63[Abstract/Free Full Text]
- Landis, S, Murray, T, Bolden, S, et al Cancer statistics, 1998. CA Cancer J Clin 1998;48,6-29[Abstract]
- Liao, ML, Yang, ZP, Ling, ZQ, et al Current status of lung cancer diagnosis and treatment in Shanghai. Lung Cancer 1994;10,333-338[CrossRef][ISI][Medline]
- Choy, J, Foote, D, Bojanowski, J, et al Outreach strategies for Southeast Asian communities: experience, practice, and suggestions for approaching Southeast Asian immigrant and refugee communities to provide thalassemia education and trait testing. J Pediatr Hematol Oncol 2000;22,588-592[CrossRef][ISI][Medline]
- Muecke, MA Caring for Southeast Asian refugee patients in the USA. Am J Public Health 1983;73,431-438[Abstract/Free Full Text]
- Buchwald, D, Panwala, S, Hooton, TM Use of traditional health practices by Southeast Asian refugees in a primary care clinic. West J Med 1992;156,507-511[ISI][Medline]
- Gu, J, Spitz, MR, Yang, F, et al Ethnic differences in poly(ADP-ribose) polymerase pseudogene genotype distribution and association with lung cancer risk. Carcinogenesis 1999;20,1465-1469[Abstract/Free Full Text]
- Lin, P, Wang, HJ, Lee, H, et al NAD(P)H quinone oxidoreductase polymorphism and lung cancer in Taiwan. J Toxicol Environ Health 1999;58,187-197[CrossRef][ISI][Medline]
- Yin, L, Pu, Y, Liu, TY, et al Genetic polymorphisms of NAD(P)H quinone oxidoreductase, CYP1A1, and microsomal epoxide hydrolase and lung cancer risk in Nanjing, China. Lung Cancer 2001;33,133-141[CrossRef][ISI][Medline]
- Liu, Y, Zhang, P, Yi, F Asbestos fiber burdens in lung tissues of Hong Kong Chinese with and without lung cancer. Lung Cancer 2001;32,113-116[CrossRef][ISI][Medline]
- Gao, YT, Blot, WJ, Zheng, W, et al Lung cancer and smoking in Shanghai. Int J Epidemiol 1988;17,277-280[Abstract/Free Full Text]
- Wewers, ME, Dhatt, RK, Moeschberger, ML, et al Misclassification of smoking status among southeast Asian Adult Immigrants. Am J Respir Crit Care Med 1995;152,1917-1921[Abstract]
- Chung, M Re-evaluating the smoking habits of Asian Pacific Americans. Asian Am Policy Rev 1998;8,44-49
- Fraumeni, JF, Jr, Mason, TJ Cancer mortality among Chinese Americans, 1950–69. J Natl Cancer Inst 1974;52,659-665[ISI][Medline]
- Greenwald, HP, Polissar, NL, Borgatta, EF, et al Social factors, treatment, and survival in early-stage non-small cell lung cancer. Am J Public Health 1998;88,1681-1684[Abstract/Free Full Text]
- Bach, PB, Schrag, D, Brawley, OW, et al Survival of blacks and whites after a cancer diagnosis. JAMA 2002;287,2106-2113[Abstract/Free Full Text]
- Korotzer, B, Ong, S, Hansen, JE Ethnic differences in pulmonary function in healthy nonsmoking Asian-Americans and European-Americans. Am J Respir Crit Care Med 2000;161(4 pt 1),1101-1108[Abstract/Free Full Text]
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Abstract
Introduction
