Japanese Journal of Clinical Oncology Advance Access originally published online on May 19, 2006
Japanese Journal of Clinical Oncology 2006 36(5):280-284; doi:10.1093/jjco/hyl015
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© 2006 Foundation for Promotion of Cancer Research
The Lung Cancer Database Project at the National Cancer Center, Japan: Study Design, Corresponding Rate and Profiles of Cohort
1 Psycho-Oncology Division, Research Center for Innovative Oncology, 2 Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba and 3 Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center Research Institute, Tokyo, Japan
For reprints and all correspondence: Yutaka Nishiwaki, Division of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Japan; E-mail: ynishiwa{at}east.ncc.go.jp
Received November 23, 2005; accepted February 6, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONMETHODSMEASUREMENTSRESULTSDISCUSSIONReferences |
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Background: The lung cancer database project was established in 1999 at the National Cancer Center Hospital East, Japan, as an ongoing project to integrate data on various factors in lung cancer patients. The aim of the project was to construct a large-scale cancer registry for lung cancer that would contribute to basic research and clinical research in the future.
Methods: Between July 1999 and July 2004, consecutive lung cancer patients were recruited into this project. The baseline survey consisted of self-administered questionnaires concerning various demographic data, health habits and psychological factors. Medical information was obtained from the patients' medical charts. Urine specimens and blood samples were collected, and DNA was extracted from blood lymphocytes.
Results: Out of the 2506 patients who were asked to participate in the project, 2036 (81%) patients with newly diagnosed, untreated primary lung cancer were enrolled. The final analytic cohort consisted of 1995 patients. Virtually all of the 1995 patients (corresponding rate, 99%) completed the questionnaires on demographic data and health habits. The corresponding rates for the questionnaires on psychological factors and dietary habits were 99 and 94%, respectively. In a follow-up survey conducted to determine vital status as of December 2004, a total of 1051 patients (53%) had died and 44 patients (2%) were lost to follow-up.
Conclusions: This paper overviews the rationale for initiating the lung cancer database project, Japan. This database should prove useful for researchers examining the pathogenesis of lung cancer and may contribute to the formulation of a framework for cancer treatment.
Key Words: follow-up survey • health habits • large-scale cancer registry • lung cancer • psychological factors
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INTRODUCTION |
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Lung cancer is the most common form of cancer and the most common cause of cancer-related deaths throughout the world (1,2). In Japan, lung cancer is the leading cause of death from cancer among men and women, and the incidence of lung cancer has been increasing in recent years (3). In 2003, the number of lung cancer deaths reached 41 615 (22% of all cancer-related deaths) in men and 15 086 deaths (12% of all cancer-related deaths) in women (3). Lung cancer is often resistant to treatment, so research programs designed to share epidemiologic, psychosocial and molecular biology data are needed to improve treatment efficacy and patient outcome. It is difficult to determine the factors associated with lung cancer outcome because of the marked clinical heterogeneity of patients. In earlier reports, various individual characteristics like age, sex, pathologic stage, performance status, co-morbidity, molecular biological markers, marital status, psychological factors and smoking status have all been implicated to contribute to the survival rate in lung cancer (4–7). Further clarification of the factors contributing to survival from lung cancer is needed.
Approximately 400 newly diagnosed primary lung cancer patients visit the National Cancer Center Hospital East (NCCHE), Japan, for treatment each year. In 1999, the Lung Cancer Database Project was initiated as an ongoing project to integrate information on various factors in lung cancer patients. The aim of the project was to construct a large-scale cancer registry for lung cancer that would contribute to basic research and clinical research in the future. In addition, by investigating the factors that influence the outcome of patients with lung cancer, we hoped to clarify several specific points related to cancer treatment in order to improve patient outcome.
This paper describes the epidemiological background and the study design, the questionnaire corresponding rates, the cohort profile and the survival rates obtained in a follow-up survey of patients in the Lung Cancer Database Project.
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METHODS |
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STUDY SETTING
The NCCHE was founded in the city of Kashiwa in suburban eastern Japan on July 1, 1992. The NCCHE has 425 beds and consists of 9 clinical divisions. As of January 1, 2005, the hospital staff included 73 physicians, 17 pharmacists and 268 nurses. During 2004, this hospital took care of 146 802 outpatients, including 7706 newcomers and 7506 inpatients.
STUDY COHORT
The project was approved by the Institutional Review Board and the Ethics Committee of the National Cancer Center, Japan (in March, 1999). The Japanese Ministry of Health, Labour and Welfare established the two guidelines that follow [‘the Ethical Guidelines Concerning Human Genome and Gene Analysis’ (in March, 2001) and ‘the Ethical Guidelines Concerning Epidemiologic Study’ (in June, 2002)]. (http://www.mhlw.go.jp/general/seido/kousei/i-kenkyu/ekigaku/dl/shinkyu.pdf http://www.mhlw.go.jp/general/seido/kousei/i-kenkyu/genome/dl/shinkyu.pdf).
When we planned a new study based on this project, the study needed to be approved by the Institutional Review Board and the Ethics Committee of the National Cancer Center, Japan. Moreover, the study followed two guidelines by the Japanese Ministry of Health, Labour and Welfare.
Data from subjects who participated in the Lung Cancer Database Project at the NCCHE and at the National Cancer Center Research Institute East were used in this study. We distributed two self-administered questionnaires to the patients before the start of cancer treatment (at baseline). The first questionnaire included questions on various demographic data, health habits and psychological factors (including the Mental Adjustment to Cancer Scale, the Eysenck Personality Questionnaire-Revised and the Hospital Anxiety and Depression Scale), and the second was on dietary habits (the Food Frequency Questionnaire). Medical information was obtained from the patients' medical charts. After admission but before cancer treatment, urine specimens and blood samples were collected, and DNA was extracted and collected from blood lymphocytes. These samples were stored at –80°C until further use. We previously reported part of the information in a project (8).
The subjects enrolled in this study were all newly diagnosed primary lung cancer patients, who had visited the Division of Thoracic Oncology of the NCCHE, Japan. Patients were included in this database study if they met all of the following criteria: knowledge of their lung cancer diagnosis; new diagnosis of primary lung cancer; physically capable of completing the questionnaires; absence of cognitive impairment (i.e. dementia, delirium); ability to provide written consent; and no problems regarding the patients' participation in this project, as judged by their physicians.
STUDY PROCEDURE
In the initial study plan, the sample size and accumulation period were decided as 1500 patients and 5 years, respectively. Approximately 400 newly diagnosed patients with primary lung cancer visit the NCCHE each year. We estimated that the rate of ineligible patients and/or patients who would refuse to participate in the project would be 25%.
Between July 1999 and July 2004, consecutive patients eligible for the project were recruited after disclosure of their diagnosis by their attending physician. The patients completed the questionnaires during the waiting period before admission, and the questionnaires were collected after the patients were admitted. All patients provided their written informed consent prior to enrolment in this project.
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MEASUREMENTS |
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DEMOGRAPHIC DATA AND MEDICAL INFORMATION
Demographic factors (age at time of cancer diagnosis, sex, education level, marital status, smoking history, past history of cancer and family history of cancer) and medical information (histology, clinical stage, pathologic stage, cancer treatment of first line, performance status and symptoms) were obtained from the self-administered questionnaires and the patients' medical charts. Performance status (PS) was assessed by each attending physician using the Eastern Cooperative Oncology Group criteria (9).
FAGERSTRÖM TOLERANCE QUESTIONNAIRE [FTQ]/FAGERSTRÖM TEST FOR NICOTINE DEPENDENCE
Nicotine dependence was evaluated using the Fagerström Tolerance Questionnaire (FTQ) and the Fagerström Test for Nicotine Dependence (FTND). In 1978, Fagerström developed a self-rating scale (the FTQ) to assess nicotine dependence and used the questionnaire in a smoking cessation clinic (10). As a revised version of the FTQ, the FTND was developed by Heatherton et al. in 1991 (11). The Japanese version of the FTND is a reliable and valid measure of nicotine dependence in patients with smoking-related cancers (12).
MENTAL ADJUSTMENT TO CANCER (MAC) SCALE
The patients' psychological response to their cancer diagnosis was measured using the Japanese version of the MAC scale, a 40-item, self-rating scale developed in England (13). The scale consists of five subscales: fighting spirit (16 items), anxious preoccupation (9 items), fatalism (8 items), helplessness/hopelessness (6 items) and avoidance (1 item). The respondents were asked to read a number of statements that might describe their reactions to having cancer and to circle the number indicating the degree to which each statement applied to them. Each item was rated on a scale of 1–4, ranging from ‘definitely does not apply to me’ to ‘definitely applies to me’. Previous studies have revealed that the MAC scale is adequately valid and reliable (14).
EYSENCK PERSONALITY QUESTIONNAIRE-REVISED
Personality was evaluated using the Eysenck Personality Questionnaire-Revised (EPQ-R). The Japanese translation of the original English version of the EPQ-R Short Form is one of a series of personality inventories developed by Eysenck and colleagues (15). It contains 48 questions with dichotomized responses (yes or no); there are 12 questions for each of the four subscales (extraversion, neuroticism, psychoticism and lie). The scores on each subscale ranged from 0 to 12, with higher scores indicating a greater tendency to possess the personality trait represented by each subscale. Extraversion represents sociability, liveliness and assurgency; neuroticism represents emotional instability and anxiousness; psychoticism represents tough-mindedness, aggressiveness, coldness and egocentricity; and lie represents unsophisticated dissimulation and social naivety or conformity (16). Previous studies have revealed that the EPQ-R is adequately valid and reliable (17).
HOSPITAL ANXIETY AND DEPRESSION SCALE
Anxiety and depression symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS). The HADS (18) consists of a 7-item anxiety subscale and a 7-item depression subscale to assess symptoms of anxiety and depression during the preceding week in medically ill patients. The HADS has been used as a reliable and valid method of screening for depression in patients with cancer. Each item is rated on a scale of 0–3, with higher scores denoting a greater mood disturbance. The reliability and validity of the Japanese version of this questionnaire has been established in Japanese cancer patients (19).
FOOD FREQUENCY QUESTIONNAIRE
Dietary habits were assessed using the semiquantitative Food Frequency Questionnaire (FFQ), which was constructed for a population-based prospective study in Japan (20) and contains questions regarding 138 foods. For each food item, the participants reported the usual serving size. When the patient's dietary habits changed following the appearance of symptom(s) resulting in hospitalization, the dietary habits before the appearance of the symptom(s) was reported. Nine responses were possible for each food item, ranging from ‘never’ to ‘7 or more times per day’. The average daily intake of nutrients was calculated by multiplying the frequency of the consumption of each item by its nutrient content per serving and totaling the nutrient intake for all food items. The method used to calculate the average daily intake of each food and nutrient based on the FFQ responses has been described elsewhere (21).
URINE SPECIMENS
Urine specimens (20 ml) were collected after admission but before treatment, and stored at –80°C until further use.
BLOOD SAMPLES
Blood samples (20 ml) were collected after admission but before treatment. After storing the samples for about 2 h at 4°C, the serum was separated by centrifugation (1870 g, 10 min) and stored at –80°C until further use.
DNA
Peripheral blood samples (3 ml) were collected after admission. DNA was extracted from the blood lymphocytes by a specialist at the Division of Thoracic Oncology, NCCHE, Japan, and strictly stored at –80°C until further use.
Patients' DNA samples were analyzed after deleting their names and addresses. When we analyzed their DNA samples in planning a new study, these samples were labeled again with new identification numbers which could be linked to patients' information only by the specialist. Patients' DNA samples were strictly kept at the NCCHE, Japan. This project created the system concerning DNA sampling and reservation.
FOLLOW-UP METHOD
To assess vital status as part of a follow-up study, survival was confirmed by referring to the medical records, by normal postal mail, or using municipality registration data. Follow-up surveys were conducted once a year between July 1999 and December 2004 by members of our co-medical staff.
In order to protect patients' personal information, we planned a new study based upon this project, which needed to be approved by the Institutional Review Board and the Ethics Committee of the National Cancer Center, Japan. Each patient's information was analyzed after deleting his/her name and address. When we analyzed their information, we labeled again with new identification numbers which could be linked to patients' information. The clinical data included in this project was carefully managed by the researcher and the research secretariat.
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RESULTS |
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Questionnaires concerning psychological factors and dietary habits achieved the target of 1500 participants within 4 years, and the questionnaires were completed in July 2003. The questionnaire on demographic variables was distributed for 5 years, and was completed in July 2004. In total, the project was explained to 2506 patients, of whom 2036 (81.3%) patients with newly diagnosed, untreated primary lung cancer were enlisted during the enrollment phase. A total of 470 cases were ineligible for the following reasons: could not be contacted (49 cases), lung cancer diagnosis not confirmed at time of admission (175 cases), non-lung cancer (120 cases), poor physical symptoms (77 cases), refusal to participate in the project (43 cases), treated for lung cancer at another hospital (5 cases), or not yet informed of their diagnosis (1 case). In 40 of the 2036 patients, written informed consent could not be confirmed, and one patient withdrew consent during the follow-up period. Finally, the analytic cohort consisted of 1995 patients.
For the corresponding rate according to baseline assessments among the patient, virtually all of the 1995 patients (corresponding rate, 99%) completed the questionnaires on demographic data and health habits. The corresponding rates for the questionnaires on psychological factors and dietary habits were 99 and 94%, respectively.
The demographic data and medical information is summarized in Table 1. Most of the patients were in their sixth decade at the time of their lung cancer diagnosis (38%), and there were more men than women (71 versus 29%, respectively). As for clinical stage, most of the patients (27%) had stage IV lesions, followed in descending order by IA (24%), IIIB (18%) and IB (14%). Histological classification revealed adenocarcinoma to be the most common lesion (58%), followed in descending order by squamous cell carcinoma (21%) and small cell carcinoma (11%). Most of the patients (44%) underwent surgery as their first-line treatment, followed in descending order by chemotherapy (37%) and chemotherapy plus radiotherapy (11%). Most of the patients were either PS 1 (50%) or PS 0 (44%).
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For the vital status among this patient as of December 2004, out of the 1995 patients, 1051 patients had died (52.7%) and 44 patients had been lost to follow-up (2%). The proportion of patients lost to follow-up was low, ranging from 1 to 17%.
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DISCUSSION |
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TOPAbstractINTRODUCTIONMETHODSMEASUREMENTSRESULTSDISCUSSIONReferences |
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This paper overviews the rationale for initiating the Lung Cancer Database Project at the National Cancer Center, Japan. Few previous studies have analyzed such a wide variety of factors among lung cancer patients, making this a valuable clinical observation project.
The advantages of this cohort study were as follows: (1) as the corresponding rates to the baseline questionnaires on demographics, health habits, psychological factors and dietary habits were satisfactorily high, the data can be regarded as being representative of the subject; (2) because not only medical information but a variety of health habits and psychological factors were assessed using standardized questionnaires, valid evaluations of associations in the pathogenesis of lung cancer can be made; (3) urine specimens, blood samples and DNA were collected from all patients so that when important new biomarkers are discovered, studies utilizing the database will be able to be promptly performed, hopefully leading to greater treatment efficacy in the future; and (4) the follow-up rate was satisfactorily high. The corresponding rate was high, despite the numerous questions on demographic data, health habits and psychological factors that were asked. For this reason, the research assistants reinvestigated patients who did not completely respond to the questionnaires.
The project had some limitations. First, a sampling bias existed because the project was conducted from only one institution, a teaching cancer center hospital in Japan. Care should be taken when generalizing the results of this project and applying them to other oncology settings. Second, we distributed the questionnaire on psychological variables and health habits only once before the patients underwent cancer treatment. Therefore, possible changes in these variables after cancer treatment remain unclear.
In summary, this project constructed a large-scale cancer registry containing data on the demographics, health habits, psychological factors and medical information on lung cancer patients. This database should prove useful for researchers examining the pathogenesis of lung cancer, and may contribute to the formulation of a framework for cancer treatment.
PARTICIPATING INSTITUTIONS
Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center Research Institute, Tokyo, Japan; Psycho-Oncology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
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Acknowledgments |
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This study was supported by the Awardees of Research Resident Fellowship from the Foundation for the Promotion of Cancer Research (Japan) for the 3rd Term Comprehensive Control Research for Cancer. We would like to express special thanks to Toyoko Matsumoto and Fumiko Koh for the collecting and filing the data for this project. We also wish to thank Yuko Kojima, Nobue Taguchi and Ryoko Katayama of the Psycho-Oncology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan, for their research assistance.
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References |
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1 Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999;80:827–41.[CrossRef][Web of Science][Medline]
2 Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 1999;83:18–29.[Web of Science][Medline]
3 Statistics and Information Department, Minister's Secretariat, Ministry of Health, Labour and Welfare. Vital Statistics of Japan 1950–2003. Tokyo: Health and Welfare Statistics Association; 1952–2005.
4 Brundage MD, Davis D, Mackillop WJ. Prognostic factors in non-small cell lung cancer: a decade of prognosis. Chest 2002;122:1037–57.[CrossRef][Medline]
5 Yip D, Harper PG. Predictive and prognostic factors in small cell lung cancer: current status. Lung Cancer 2000;28;173–85.[CrossRef][Web of Science][Medline]
6 Buccheri G. Depressive reactions to lung cancer are common and often followed by a poor outcome. Eur Respir J 1998;11:173–8.
7 Faller H, Bülzebruck H, Drings P, Lang H. Coping, distress, and survival among patients with lung cancer. Arch Gen Psychiatry 1999;56:756–62.
8 Suzuki S, Akechi T, Kobayashi M, Taniguchi K, Goto K, Sasaki S, et al. Daily omega-3 fatty acid intake and depression in Japanese patients with newly diagnosed lung cancer. Br J Cancer 2004;90:787–93.[Medline]
9 Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–55.[Web of Science][Medline]
10 Fagerström KO. Measuring degree of physical dependence to tobacco smoking with reference to individualization of treatment. Addict Behav 1978;3:235–41.[CrossRef][Web of Science][Medline]
11 Heeatherton T, Kozlowski K, Frecker R, Fagerström KO. The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. Br J Addict 1991;86:1119–27.[CrossRef][Web of Science][Medline]
12 Mikami I, Akechi T, Kugaya A, Okuyama T, Nakano T, Okamura H, et al. Screening for nicotine dependence among smoking-related cancer patients. Cancer Sci 1999;90:1071–5.[CrossRef][Web of Science][Medline]
13 Greer S, Moorey S, Watson M. Patients' adjustment to cancer: the Mental Adjustment to Cancer (MAC) scale vs clinical ratings. J Psychosom Res 1989;33:373–7.[CrossRef][Web of Science][Medline]
14 Akechi T, Fukue-Saeki M, Kugaya A, Okamura H, Nishiwaki Y, Uchitomi Y. Psychometric properties of the Japanese version of the Mental Adjustment to Cancer (MAC) scale. Psychooncology 2000;9:395–401.[CrossRef][Medline]
15 Eysenck HJ, Eysenck SBG. Manual of the Eysenck Personality Questionnaire (adult and junior). London: Hodder & Stoughton; 1975.
16 Eysenck HJ, Eysenck SBJ. Manual of the Eysenck Personality Scales. (EPS Adult). London (UK): Hodder & Stoughton; 1991.
17 Hosokawa T, Ohyama M. Reliability and validity of the Japanese version of the short form Eysenck Personality Questionnaire-Revised. Psychol Rep 1993;72:823–32.
18 Zigmond AS, Snaith RP. The hospital and depression scale. Acta Psychiatr Scand 1983;67:361–70.[Web of Science][Medline]
19 Kugaya A, Akechi T, Okuyama T, Okamura H, Uchitomi Y. Screening for psychological distress in Japanese cancer patients. Jpn J Clin Oncol 1998;28:333–8.
20 Tsugane S, Kobayashi M, Sasaki S. Validity of the self-administered frequency questionnaire used in the 5-year follow-up survey of the JPHC Study Cohort I: comparison with dietary records for main nutrients. J Epidemiol 2003;13(Suppl. 1):S51–6.[Web of Science][Medline]
21 Sasaki S, Kobayashi M, Ishihara J, Tsugane S. Self-administered food frequency questionnaire used in the 5-year follow-up survey of the JPHC study: questionnaire structure, computation algorithms, and area-based mean intake. J Epidemiol 2003;13(Suppl. 1):S13–22.[Web of Science][Medline]
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