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(Chest. 2005;128:452-462.)
© 2005 American College of Chest Physicians

Clinical Features of 5,628 Primary Lung Cancer Patients*

Experience at Mayo Clinic From 1997 to 2003

Ping Yang, MD, PhD; Mark S. Allen, MD; Marie C. Aubry, MD; Jason A. Wampfler; Randolph S. Marks, MD; Eric S. Edell, MD; Stephen Thibodeau, PhD; Alex A. Adjei, MD, PhD; James Jett, MD and Claude Deschamps, MD

* From the Divisions of Epidemiology (Dr. Yang), General Thoracic Surgery (Drs. Allen and Deschamps), Anatomic Pathology (Dr. Aubry), Biostatistics (Mr. Wampfler), Medical Oncology (Drs. Marks, Adjei, and Jett), Pulmonary Medicine (Dr. Edell), and Experimental Pathology (Dr. Thibodeau), Mayo Clinic College of Medicine, Rochester, MN.

Correspondence to: Ping Yang, MD, PhD, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905; e-mail: yang.ping{at}mayo.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To improve the current understanding of the etiology and natural history of primary lung cancer, we need to study the dynamic changes of clinical presentation and prognosis among a large number of patients with newly diagnosed lung cancer. In this report, we present the clinical features and survival rates up to 5 years of a patient cohort.

Design: We identified 5,628 primary lung cancer patients between 1997 and 2002 and followed them through 2003 using multiple, complementary resources.

Measurements and results: Of the 5,628 patients, 58% were men with a mean age at lung cancer diagnosis of 66 years, and 42% were women with a mean age at diagnosis of 64 years. Ten percent were < 50 years, and 8% were > 80 years at diagnosis. A tobacco smoking history was present in 89% of patients, and 40% were smoking at the time of diagnosis. The estimated overall 5-year survival rates of patients with non-small cell lung cancer (NSCLC) by disease stage was as follows: IA, 66%; IB, 53%; IIA, 42%; IIB, 36%; IIIA, 10%; IIIB, 12%; and IV, 4%. The 5-year survival rate of patients with small cell lung cancer was 22% for limited disease and 1% for extensive disease. Approximately 50% of all patients are participants in one or more research studies, and nearly 75% of these patients have donated biological specimens for research.

Conclusion: The survival rate of this cohort of lung cancer patients was slightly improved compared with earlier reports, particularly for patients with low-stage NSCLC. Our patient and biospecimen resource has enabled us to obtain timely results from clinical and translational research of lung cancer.

Key Words: histology • lung cancer • overall survival • referral bias • TNM staging


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
In the United States, lung cancer has been a major medical and public health problem with tobacco smoking being recognized as the primary cause for more than one half of a century.1 Despite the tremendous efforts to eliminate tobacco smoking exposure in an attempt to reduce lung cancer mortality and morbidity, 50 million Americans still smoke, and 1.5 million become daily smokers each year.2 In addition, environmental tobacco smoke exposure or passive smoking alone kills > 3,000 Americans by lung cancer each year;1234 and, sadly, approximately one fourth of the children < 6 years of age are regularly exposed to environmental tobacco smoke. Unfortunately, if everyone ceased smoking today, it would take ≥ 30 years to reduce the mortality from lung cancer to the level of never-smokers.5 Consequently, it will require a century-long effort to abolish the effect of tobacco smoking on lung cancer incidence and mortality from our society.

With the changes in prevalence and types of tobacco products consumed in the population,678910 changes in lung cancer patients with regard to gender ratio, tumor histology, clinic stage, disease progression, and survival have been observed and will continue to occur. Timely and accurate data on the magnitude of these changes are important for developing better therapies and improving patient management and quality of life. We have developed the infrastructure to identify patients and recruit them in real-time for research studies without compromising medical care at our institution. This has led to a lung cancer resource that includes clinical, lifestyle, and family history information, as well as biological specimens. This report is a summary of the patients enrolled and followed between 1997 and 2003.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
In 1997, we began collecting all of the new patients who had lung cancer diagnosed or confirmed at our institution from our daily electronic pathology reporting system. This process normally takes only a few hours from the time the pathologic diagnosis is made until information becomes available for review. Each newly identified patient with primary lung cancer was invited to participate in a long-term follow-up study and was evaluated for eligibility with a baseline interview.11 Excluded from an interview were patients who do not speak English or who resided outside of North America.

The medical records of each patient were reviewed for data abstraction, except for < 1% of patients who denied research authorization for review of their medical records.12 Information abstracted included demographics; vital status; education; history of tobacco exposure, alcohol use, and other diseases; lung cancer histology, staging, anatomical location, and treatment; and family history of cancer and other medical conditions. Tobacco history information included current and/or previous use, duration, the average amount of cigarettes smoked per day, and the number of years since the patient quit smoking. For patients who have received medical care outside of Mayo Clinic, copies of the relevant medical records were requested. The history of COPD is determined based on explicit diagnosis13 or abnormal pulmonary function tests14 that are recorded in the medical history. Criteria for recording the treatment responses and toxicities are based on the standards used in the North Central Cancer Treatment Group as defined by the National Cancer Institute.

All of the histologic and pathologic diagnoses were confirmed in the Division of Anatomic Pathology. A pulmonary pathologist (M.C.A.) performed an independent review to adjudicate the inconsistencies and discrepancies.15 When information was insufficient for pathologic staging, the clinical stage was assigned based on results from the chest radiograph and/or CT scan, bone scan, positron emission tomography scan, and MRI, as available. Fiberoptic bronchoscopy was used to evaluate the primary tumor for most patients with suspected lung cancer. Surgical candidates underwent mediastinoscopy, mediastinotomy, thoracoscopy, and thoracotomy for resectability, as indicated. Patients with mediastinal lymphadenopathy (lymph node ≥ 1 cm in the short axis view) usually underwent transbronchoscopic needle aspiration, mediastinoscopy, and/or mediastinotomy for staging prior to a thoracotomy. Positron emission tomography scan and extensive nodal dissection have been routine diagnostic procedures in our institution. If lymph nodes were found positive for malignancy, multimodality therapy was commonly offered.

Surgery was defined as a treatment when the patient had any pulmonary resection for the primary tumor, including pneumonectomy, bilobectomy, lobectomy, segmentectomy, and wedge resection, irrespective of the status of the surgical margin. In this study, if a patient was found to be nonresectable during an exploratory thoracotomy, surgery was considered nontherapeutic and was classified as a staging procedure only. Surgical resection was the treatment of choice in early stages. For stage IIIA or higher, either or both chemotherapy and radiation therapy were given as neoadjuvant, adjuvant, or palliative according to the established clinical protocols, performance status, and eligibility criteria of these patients. When the patient received any type of diagnostic procedure and therapy elsewhere, authorization for the release of medical information was requested, and copies of the relevant medical records were requested and abstracted. All of the outside records were reviewed by a Mayo Clinic clinician.

Obtained during the patient interview were complete family history information regarding cancer and other lung disease history; vital status; cause, age, and year of death (if deceased); and cigarette smoking history for each relative. A more detailed tobacco history to confirm duration was also collected and included passive smoking or environmental tobacco smoking for each case.16 The never-smoker is defined as having smoked < 100 cigarettes during his or her lifetime, and the former smoker as having quit smoking for ≥ 6 months. Also included were occupational history and ethnic background of the paternal and maternal lineages for each subject.

All of the patients have been actively followed by mailed questionnaires, beginning 6 months after lung cancer diagnosis and then annually. Timely verification of each patient’s vital status was accomplished through the availability of the following sources of information: the Mayo Clinic registration database, next-of-kin reports, death certificates and obituary documents filed in the patient’s medical records, the Mayo Clinic Tumor Registry, and the Social Security Death Index website. For living patients, the most up-to-date information was obtained from the most recent Mayo Clinic medical record or the last follow-up questionnaire. For deceased patients, the follow-up packet was sent to the next-of-kin to obtain proxy information regarding new diseases occurring after the initial diagnosis and cause of death, changes in smoking status, body weight, appetite, dietary supplements, and updated family history of lung cancer or other cancers. All of the updates were made as of December 31, 2003, for this report.

Mayo Clinic is a tertiary medical center located in Olmsted County, MN, that serves the county residents as a major primary care hospital. Although cause-of-death information was not available for the majority of the referral cases, this information has been routinely and actively sought for all of the Olmsted County residents through death certificates, autopsy records, and physician reports.17 We have assessed the lung cancer-related and nonlung cancer-related deaths of patients who were residents of Olmsted County.

A peripheral blood sample (for collecting and storing DNA, RNA, plasma, and serum) was obtained from each consenting patient. Fresh tissue samples (tumor and adjacent normal) have been procured whenever available after pathologic diagnosis from patients undergoing surgical resection.

We conducted primarily descriptive analyses on patient characteristics, clinical features of disease, and postdiagnosis survival. Selected comparative analyses were performed using a {chi}2 test, Fisher exact test, or Wilcoxon rank sum tests, as appropriate. When multiple comparisons were needed, Bonferroni-adjusted p values were used.18 Survival was defined as the time from lung cancer diagnosis to death or the last known date that the patient was reported to be alive. Patients known to be alive at last contact were censored. Survival rate estimates were calculated at yearly increments using the Kaplan-Meier method. We have also compared all of the clinical patients with a population-based lung cancer cohort of Olmsted County residents. We estimated the overall survival rate among Olmsted County lung cancer patients and evaluated the potential referral bias of the patients from outside the county. All of the analyses were done using computer software (SAS, version 8.12; SAS Institute; Cary, NC).

All of the procedures in case identification for research purposes are in compliance with regulations under the Health Insurance Portability and Accountability Act of 1996. All of the patient contact materials, biological specimen collection, storage protocol, and follow-up questionnaires were approved by the Mayo Foundation Institutional Review Board.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Between 1997 and 2002, 6,077 primary lung cancer patients were identified; 5,759 patients received a new lung cancer diagnosis, and 318 patients had an initial lung cancer diagnosis before 1997. Among the 5,759 new patients, 5,717 patients (99%) gave permission to use their medical records for research. Eighty-nine patients (1.5%) were excluded because they were from outside of North America, leaving 5,628 patients for analysis.

Overall, women who received a lung cancer diagnosis were 2 years younger than men (p < 0.001) [Table 1 ]. Of the patients with known smoking status, 18% of the women and 7% of the men were never-smokers. Current smokers were the youngest patients at lung cancer diagnosis, and former smokers were the oldest (p < 0.001). Among smokers, women smoked nearly 11 pack-years less than men (mean pack-years, 46 vs 57, respectively; p < 0.001). Former smokers were more likely to have used other tobacco products (19.1%) than never-smokers (7.2%) and current smokers (8.5%; p < 0.001 between former and never-smokers or current smokers).


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  		Table 1. Demographic and Clinical Information by Cigarette Smoking Status of 5,628 Patients in Whom Primary Lung Cancer Was Diagnosed Between 1997 and 2002 at Mayo Clinic*

 
Tumor Histopathology and Disease Stage
Eighty-nine percent of all patients had non-small cell lung cancer (NSCLC), and 11% had small cell lung cancer (SCLC). Virtually all of the never-smokers had NSCLC, and the few who developed SCLC were all exposed to extensive second-hand smoke.16 Adenocarcinoma was the most frequent tumor subtype, irrespective of smoking status, however, showing a progressive decrease of prevalence in the different groups ranging from 63% in never-smokers, 47% in former smokers, and 39% in current smokers. This decrease corresponded with an associated increase in the prevalence of squamous cell and small cell carcinomas.

The majority of patients (65%) with NSCLC presented with late-stage disease. Never-smokers or former smokers were more likely to present with stage I disease than current smokers (p < 0.001).

Comorbid Conditions
The histories of selected medical (or comorbid) conditions by smoking status at the time of lung cancer diagnosis are shown in the bottom portion of Table 1. Former smokers had the highest prevalence of other cancers and heart diseases. All of the smokers had a higher prevalence of nonneoplastic lung diseases than the never-smokers, except for asthma.

Treatment
Thirty-seven percent of the patients underwent surgery; 11% had received only chemotherapy, 8% only received radiotherapy, 13% received a combination of surgery and chemotherapy or radiotherapy, and 14% received both chemotherapy and radiotherapy. Two percent of the patients underwent other forms of treatment (photodynamic, laser, talc pleurodesis, hormone therapy, resection, or radiation to other tumor locations), and 15% received no treatment during our follow-up period. Although the majority of the surgical resections (86%) were performed at Mayo Clinic, more than one half of the patients (57%) received their initial chemotherapy or radiotherapy elsewhere.

Approximately 93% of all of the patients with stage I disease underwent surgical resection, and 10% of them had radiation and/or chemotherapy. Among stage II patients, 87% underwent surgical resection, and 27% of them had radiation and/or chemotherapy. Among stage III patients, 52% and 24%, respectively, were surgically resected for stage IIIA and IIIB disease; 66% received radiation and/or chemotherapy; and 15% were not treated. Among stage IV patients, 27% did not receive any treatment; approximately 64% received radiation and/or chemotherapy (32% each), and 11% received surgical resection. For stage IV patients who received surgical treatment, 36% was for multiple lung nodules without distant metastasis, 30% was for other-organ metastasis (brain, adrenal, bone, eye, and other) without nodal involvement, and the rest (34%) were for miscellaneous metastases with nodal involvement.

Cause of Death
The cause of death information, confirmed by death certificates and medical records, was complete for the Olmsted County patients (n = 310). Based on 179 deceased patients in the study period, 92.7% died of lung cancer, with little variation across smoking status at their diagnosis. Other causes of death included other cancer, respiratory insufficiency or failure, COPD, pneumonia, internal hemorrhaging, and others.

Observed Survival Rates
The median survival time and the annual survival rate (with 95% confidence intervals [CIs]) after diagnosis were estimated with regard to disease stage and place of treatment (Table 2 ). The overall median survival time was 1.24 years (NSCLC patients, 1.32 years; SCLC patients, 1.00 year). Among NSCLC patients, except for those with stage IB and IIA disease, patients with an earlier stage of disease had a significantly better survival time than those with the disease stage immediately after (all with p < 0.001). Eliminating the 39 patients who died within 30 days of diagnosis and 155 patients with carcinoid tumors did not change the survival outcome significantly.


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  		Table 2. Lung Cancer Survival by Stage and by Place of Treatment Among Patients in Whom Lung Cancer Was Diagnosed Between 1997 and 2002 at Mayo Clinic*

 
Stage-specific annual survival rates were significantly better for NSCLC patients who received their initial or entire treatment at Mayo Clinic compared with those who were treated elsewhere (p < 0.001). The opposite was observed for patients with extensive-stage SCLC (p < 0.001). Table 3 compares the 5-year survival rates (and 95% CI) among four subgroups of patients defined by whether or not they received a lung cancer diagnosis and were treated at Mayo Clinic. Note that the patients who were initially treated for extensive SCLC before coming to our institution were, on average, 11 years younger than other patients with the same stage of disease (p < 0.001).


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  		Table 3. 5-Year Survival Rates by Place of Diagnosis and Treatment Among Patients in Whom Lung Cancer Was Diagnosed Between 1997 and 2002 at Mayo Clinic*

 
Survival time by TNM staging for NSCLC is presented in Table 4 , providing detailed subgroup-specific survival information within each stage. There was no difference in survival time among the stage IIB and IIIB TNM subgroups, whereas a significant difference was observed among the TNM subgroups within stage IIIA or IV disease (p < 0.01 for both). However, there was no significant difference between IIB and T3N1N0 (a subgroup of IIIA; p = 0.80). One hundred sixty-nine stage IIIB patients had T4N0M0 disease (satellite lesions, invasion of major vessels, trachea, carina, vertebral body, or malignant pleural effusions), with a median survival time of 1.63 years, which is significantly longer than other stage IIIB patients (0.85 year; p < 0.001). Forty-five stage IV patients had lung metastasis (T4N0M1) with a median survival time of 1.62 years, which is significantly longer than that for other stage IV patients (0.71 year; p = 0.008). Incomplete T and N data were found in < 1% of all of the NSCLC patients with M0 disease and in 64% with M1 disease.


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  		Table 4. NSCLC Survival by TNM Stage Among Patients in Whom Lung Cancer Was Diagnosed Between 1997 and 2002 at Mayo Clinic*

 
Survival rate by other characteristics of patients is presented in Table 5 , including tumor histology and grade, smoking status and intensity, and region of residence. Survival time varied significantly among the histologic subgroups, and was highest for typical carcinoids and salivary gland tumors and lowest for small cell and carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements. Notably, 8% of all of the cases had nongraded tumors that included, mainly, advanced-stage NSCLC with no gradable tissue (mostly cytology only specimens) and rare histologic types that do not follow the existing grading system. Patients in the nongraded group had the shortest median survival time.


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  		Table 5. Lung Cancer Survival by Other Factors Among Patients Diagnosed Between 1997 and 2002 at Mayo Clinic*

 
We compared our results with the published survival data based on the 5,319 patients who were treated between 1972 and 1988 as reported in a series by Mountain,19 by estimated 99% CIs from patients who were treated at Mayo Clinic between 1997 and 2003 (Fig 1 ). Lung cancer stage was primarily assigned pathologically and supplemented by clinical staging when necessary. The survival rates are considered similar when the point estimation from the reference is within the CI derived from our study. Taking the 5-year survival rate of stage IA as an example, 64% was reported from the series by Mountain,19 and 66% was observed in our cohort; however, the 99% CI for our point estimate was 59 to 73%, which includes 64%. Our data show a slightly but significantly better survival rate for patients with stage IIIB and IV NSCLC than that in the series by Mountain.19



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  		Figure 1. Five-year survival rates and 99% CIs of Mayo Clinic NSCLC patients compared with a reference. {square}, average survival rates for each disease stage based on the series by Mountain19 estimated by proportions of the patients with clinical or pathologic staging. {circ} with lines, estimated survival rates and 99% CIs for the Mayo Clinic series in the current study.

 
Differences Between Olmsted County (Local) and Referral Patients
Forty-four percent of all of the patients received a lung cancer diagnosis before their referrals to Mayo Clinic. More than one third of the patients (38%) were from Minnesota, 49% were from other Midwestern states (North Dakota, South Dakota, Nebraska, Kansas, Missouri, Iowa, Wisconsin, Illinois, Indiana, and Michigan), 12% were from other states across the United States, and the remaining 1% were from Canada and Mexico. Nearly 6% of the patients were local residents in Olmsted County, with a population of 116,000. As shown in Table 5, patients who received an initial lung cancer diagnosis at Mayo Clinic, regardless of whether they were from the local population or were referred from outside of Olmsted County, experienced very similar survival rates, with 5-year survival rates of 23% and 24%, respectively.

A significant difference was observed between the local and referral patients, and the later was over-represented by never-smokers and early stage disease (p = 0.01 for both), although the gender ratio was similar. Tumor histology distribution by gender differed significantly: more adenocarcinomas and fewer squamous cell carcinomas were observed in women than in men (p < 0.001) for referral patients, but there was not a significant difference for the local patients. The histology distribution of referred women differed from that of local women (p = 0.01), but it was similar among men. The distribution of adenocarcinoma, squamous cell, and small cell carcinoma by smoking status at diagnosis between men and women for both the local and referral patients are depicted in Figure 2 . There were fewer never-smokers and more former smokers in men than in women for adenocarcinoma and squamous cell carcinoma, and there were no never-smokers among local patients who developed SCLC (Fig 2, bottom left, C, and bottom right, D). The female adenocarcinoma patients were evenly distributed across smoking status, whereas very few female squamous cell and small cell carcinoma patients were never-smokers (Fig 2, top right, B and bottom right, D).



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  		Figure 2. Adenocarcinoma, squamous cell, and small cell carcinoma distribution by cigarette smoking status of primary lung cancer patients diagnosed between 1997 and 2002 at the Mayo Clinic. Top left, A: male referral patients (n = 2,090). Top right, B: female referral patients (n = 1,536). Bottom left, C: Olmsted County male patients (n = 140). Bottom right, D: Olmsted County female patients (n = 116).

 
For NSCLC, similar distributions of smoking status across the stages were observed between the local and referral patients, except for stage IV, where more never-smokers and fewer current smokers were seen among the referral patients than among the local patients (p = 0.04). For SCLC, similar patterns were seen between men and women among the referral patients, but dissimilar patterns were seen among local patients with extensive stage, which could be attributable to the small number of patients in this group (data not shown).

Resources Available for Clinical and Basic Science Studies
We have also obtained comprehensive data from patients beyond the ordinary demographic and clinical information at the time of diagnosis. These data were collected through patient interviews and periodic follow-up. For example, ethnicity background was obtained based on self-reported country-of-origin of a patient’s four grandparents.

Table 6 presents the patients with special characteristics. For example, 16% of the patients had at least one first-degree relative with lung cancer, 16% had at least two first-degree relatives with other cancers, 10% were never-smokers, 11% received a lung cancer diagnosis at < 50 years of age (2% received a lung cancer diagnosis while < 40 years of age), 8% were > 80 years of age, and 11% had an uncommon tumor type or subtype (eg, bronchioloalveolar carcinoma, pleomorphic/sarcomatoid, mucoepidermoid, salivary-gland type, and carcinoids). Numerous research projects have been initiated utilizing these special patient groups, and the patient participation rate and biological sample availability are also provided in Table 6.


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  		Table 6. Selected Characteristics of Primary Lung Cancer Patients in a Comprehensive Resource for Research at the Mayo Clinic*

 
Information regarding second-hand smoke and other environmental exposures was also collected for research purposes. For example, among the 246 male and 120 female never-smokers with other exposure information, 74% of the men and 78% of the women were exposed to second-hand smoke. More than 70% of men who did not report a second-hand smoking history had extensive exposure to petroleum and farm chemicals, in contrast with < 30% of men who were passive smokers and who had such exposures (p = 0.002).


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
From 5,628 patients with newly diagnosed primary lung cancer, we observed that the ratio of men to women was 1.4, and men were 2 years older than women. A higher proportion of women than men had never smoked, and, among smokers, women smoked much less compared with men. Adenocarcinoma was the most frequent histologic subtypes regardless of the patient’s gender or smoking status, and former smokers were more likely to have suffered from other cancers and heart diseases than never-smokers and current smokers. We have elaborated on these patient characteristics in other reports.1617181920 One of the most significant findings from our study is the 5-year survival rates of patients. The 5-year survival rates of our patient cohort were largely comparable with the currently cited data.19

In a stage-by-stage comparison with the expected 1-year survival rate to the 5-year survival rate, as reported by Mountain,19 a significant improvement was observed if we compared only patients who received their initial or entire treatment in our institution. A noted difference is that the series by Mountain19 excluded patients who died within 30 days of diagnosis, and our series included them. These comparative results may be artificial because of confounding factors and referral differences between medical centers, although they may reflect improvements in lung cancer treatment and patient management in the recent decade across similar medical centers.

Three major advantages of developing a comprehensive lung cancer resource, as we currently report, are as follows: (1) to learn in a timely way about changes in outcomes; (2) to recruit living patients with newly diagnosed lung cancer for unbiased investigations in disease etiology and prognosis; and (3) to obtain biological specimens for developing the most sensitive and specific tools in accurate risk assessment, disease detection, treatment planning, and survival prediction for each individual. This resource will undoubtedly foster multidisciplinary research investigations and accelerate the translation and application of study findings.

The immediate utilization of such a resource includes a wide range of clinical prognosis research; for example, the effects on survival of treatment modalities,21 gender,22 history and continued use of tobacco products,5 vitamin and mineral intake,23 and dietary patterns and physical activities.24 The long-term utilization of our comprehensive database of patients and biospecimen resources includes multidisciplinary investigations in etiology and mechanisms of lung cancer development,11162526 in patient quality of life,2728 and in gene-environment interactions of lung cancer progression.2930

The major purposes of all research, patient-oriented or bench-based, as exemplified above, are either testing existing hypotheses or generating new hypotheses. The ultimate goals of research are to produce results that will be useful in developing individualized risk assessment systems, early and accurate detection and diagnosis tools, new effective therapies, personalized treatment plans, and high quality of life.

There are several limitations in our efforts. First, although all of the patients had their lung cancer pathologically diagnosed, not all of the patients could be assigned a pathologic stage. This was particularly relevant to M1 disease, where T and N were not routinely staged as vigorously as M0 disease. Some patients could only be staged clinically, and we included all of the patients in our results as a complete clinical description of lung cancer from a tertiary medical center.

The second limitation is the self-selected patient population in our institution. To rapidly capture the dynamic changes of clinical features and outcomes, we relied mostly on referral patients. Therefore, we need to carefully evaluate the potential bias attributable to referral practice and self-selection of study subjects by comparing our results with those of other hospital-based and population-based studies. A properly designed metaanalysis of the survival according to the treatment and stage of the disease, as well as the performance scores of the patients, is warranted.

Taking advantage of the patients from the Olmsted County population, a subset of our entire patient population, we were able to compare the referral and local patients whose lung cancer was diagnosed and treated during the same time period and in the same institution. Aside from some demographic differences in smoking status and disease stage at diagnosis, the majority of our patients, local or referral, were Caucasians of European origin. The experience of survival for 1 to 5 years was very similar between the local and referral patients who received their initial or entire treatment at Mayo Clinic.

The third limitation is the incompleteness of patient enrollment in the comprehensive resource to obtain interview information and biological specimens, mainly because of a systematic loss of patients with fatal diseases shortly after lung cancer diagnosis and self-elected decline to be study participants. However, we could feasibly assess the potential selection bias between participants and nonparticipants using information on demographic and clinical features that are available for all of the patients.

In conclusion, our timely reporting of characteristics of a large volume of lung cancer patients from a medical center will be useful for the identification of changes in clinical course and outcome of this deadly disease, including treatment responses, disease recurrence, new primary tumors, comorbid conditions, and survival rates (overall and cause-specific). These changes may, in turn, lead to modifications in patient management and discoveries of improved treatment modalities.

Our patient database is a valuable resource for investigating the mechanisms of lung cancer development and progression. Our timely information on the clinical features of the most recent patients will provide important clues for both improved patient management and translational research of causes, progression, prevention, and treatment of lung cancer.


   Acknowledgements
 
We thank Aaron O. Bungum, Stephen D. Cassivi, Jon O. Ebbert, Chiaki Endo, Erin E. Finke, Aminah Jatoi, Rebecca L. Meyer, Daniel L. Miller, David E. Midthun, Francis C. Nichols, Scott H. O’Kuno, Peter C. Pairolero, Hiroshi Sugimura, Zhifu Sun, Shawn M. Stoddard, Victor F. Trastek, Antonio L. Visbal, and Brent A. Williams for their work at various stages of the study including patient identification, information and material collection, and data verification. Additionally, we thank Susan M. Ernst for technical support.


   Footnotes
 
This study was supported by National Institutes of Health grants CA77118, CA80127, and CA84354.

Abbreviations: CI = confidence interval; NSCLC = non-small cell lung cancer; SCLC = small cell lung cancer.

Received for publication September 13, 2004. Accepted for publication January 27, 2005.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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