HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Traves D. Crabtree Daniel Kreisel Jennifer B. Zoole G. Alexander Patterson Bryan F. Meyers Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Veeramachaneni, N. K. Articles by Meyers, B. F. Search for Related Content PubMed Articles by Veeramachaneni, N. K. Articles by Meyers, B. F. Related Collections Lung - cancer Lung - other

J Thorac Cardiovasc Surg 2009;137:30-35
© 2009 The American Association for Thoracic Surgery

General Thoracic Surgery

A thoracic surgery clinic dedicated to indeterminate pulmonary nodules: Too many scans and too little pathology?

^a Division of Thoracic Surgery, Washington University School of Medicine, St Louis, Mo
^b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo

Received for publication May 9, 2008; revisions received August 6, 2008; accepted for publication September 1, 2008.

^_* Address for reprints: Bryan F. Meyers, MD, MPH, One Barnes-Jewish Hospital Plaza, Suite 3108 Queeny Tower, St. Louis, MO 63110-1013. (Email: meyersb{at}wustl.edu).

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Objective: Widespread application of computed tomographic scans has increased detection of asymptomatic pulmonary nodules. A dedicated clinic was established to encourage referral and manage large numbers of patients with such nodules.

Methods: Patients were evaluated periodically by a nurse practitioner with surgeon oversight, and follow-up imaging was centralized. Patients were rescanned at intervals on the basis of radiologist recommendation.

Results: A total of 414 patients, 189 male and 225 female with a median age of 60.2 years (20.7–84.1 years), were evaluated since April 2000. Median follow-up was 1.51 years (0–6.65 years). Thirty-seven percent (153/414) were older than 60 years with at least 10 pack-years of tobacco use, whereas 30% (123/414) had never smoked. A total of 286 patients completed at least 2 years of follow-up computed tomographic evaluation. After 2 years, 24.2% (69/286) were deemed in stable condition and were discharged from further follow-up, whereas 22.4% (64/286) of patients were followed up longer than 2 years owing to the development of new nodules. Forty-five percent (127/286) of patients did not complete their recommended follow-up at our clinic. Overall, 3% (13/414) of our patients have been shown to have a malignant tumor. Only 5 patients underwent curative resection of a primary lung cancer.

Conclusion: In a population of patients with indeterminate nodules in routine clinical practice, few patients required intervention and few cancers were detected. Although the benefits of a "nodule" clinic may include patient reassurance and convenience to referring physicians, a significant number of patients did not complete their follow-up in our clinic.

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
The widespread application of computed tomography (CT) scan technology has increased the detection of otherwise asymptomatic lung nodules. Unfortunately, there is no consensus as to the optimal strategy to evaluate and follow up these radiologic abnormalities. Both the Fleischner Society and the American College of Chest Physicians (ACCP) have offered guidelines as to the follow-up and frequency of repeat imaging studies, but they are not in complete agreement.^1,2 Furthermore, in a controversial recommendation, the ACCP has recommended against the use of CT scan to screen individuals at risk for lung cancer except in the context of a clinical trial. For patients with existing nodules, the ACCP has offered guidelines as to the use of adjunct studies such as fluorodeoxyglucose positron emission tomography (FDG–PET), as well as imaging and invasive procedures for tissue diagnosis based on the pretest probability of a lesion being cancer. Both the Fleischner Society and the ACCP use 2-year stability as a suggestion for a benign etiology of a pulmonary lesion.

In an effort to evaluate the growing population of patients with chest radiographic and CT abnormalities, we implemented a clinic dedicated to these patients. This study reports the outcomes of our clinic since its inception in April of 2000.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
This study is a retrospective review of patients referred to our clinic for the evaluation of chest CT abnormalities—most commonly, asymptomatic pulmonary nodules. Patients were directly referred to the nodule clinic by any referring physician. No specific guidelines or restrictions were given for patient referral, but the intention of the clinic was to centralize management of surveillance of small and indeterminate lung nodules detected on studies performed at our home institution and elsewhere. The original name for this service was the "SPIN clinic," an acronym for "Surveillance of Pulmonary Indeterminate Nodule." It was not anticipated that patients with highly suspicious lung lesions typical for cancer would be referred via this mechanism. All patients were initially evaluated by both a nurse practitioner and a thoracic surgeon. If the patient was believed to be a candidate for imaging follow-up, the patient was identified as being eligible for enrollment in the Surveillance of Pulmonary Indeterminate Nodule Clinic. If the lesion was considered to be highly suspicious for cancer on evaluation by the surgeon, the patient was not deemed eligible for inclusion in our surveillance clinic. Follow-up was arranged with a nurse practitioner dedicated to the clinic with continued oversight by the thoracic surgeon. Dedicated chest radiologists supervised and interpreted all follow-up CT studies. These studies were performed without intravenous contrast, using a low radiation dose technique with an effective tube current of 30 mA, which is approximately 3 to 4 times lower than used for CT scans performed for clinical diagnostic purposes at our institution.

For inclusion in this study, all patients must have presented with an initial chest CT scan. For patients presenting with more than one nodule, we identified, for the purposes of this review, the nodule on the initial scan and first follow-up scan having features most concerning for malignancy as the "index" nodule and tracked the changes of this nodule on subsequent scans.

Follow-up recommendations were based on clinical evaluation and CT findings. Follow-up appointments were made for the patient at the end of each clinic visit, and a letter was sent to the referring physician detailing our recommendations. The patient would receive a telephone call before the next scheduled visit as a reminder. Follow-up and outcomes were determined by review of clinic notes and imaging studies. The conduct of this study was approved by the Washington University School of Medicine Human Research Protection Office.

Categorical data are expressed as counts and proportions. Descriptive statistics are expressed as mean ± standard deviation and median (range) unless otherwise specified. Comparisons are done with independent samples t tests for means of normally distributed continuous variables, and Fisher's exact test was used to analyze differences among the categorical data. All data analysis was performed with SPSS software (SPSS 11.0 for Windows; SPSS Inc, Chicago, Ill).

	Results

Top Abstract Introduction Methods Results Discussion References

 
A total of 414 patients, 189 male and 225 female with a median age of 60.2 years (20.7–84.1 years), were evaluated since April 2000. The initial CT scan of the chest that led to referral for this service was obtained because of an abnormal chest x-ray film in 20.3% (84/414), enrollment in the National Lung Screening Trial (http://www.cancer.gov/NLST) in 27.3% (113/414), incidental findings on CT scans done for other reasons in 51.4% (123/414), and direct patient referral or primary care physician order in 1% (4/414).

Whereas 30% (123/414) of our patients were never smokers, the remainder were former (40%; 166/414) or active smokers (30%; 125/414). Of these former and active smokers, 92% (269/291) had more than a 10 pack-year smoking history. Ten percent (38/414) of patients in our series presented with a diagnosis of chronic obstructive pulmonary disease.

Only a minority of patients in our cohort had a single CT abnormality. Review of the first follow-up CT scan done on admission to our clinic revealed resolution of the CT abnormality in 4% (16/414), 1 nodule in 23% (97/414), 2 nodules in 16% (67/414), and more than 2 nodules in 50% (206/414) of patients. In the remaining 28 patients, no data are available as 6 patients were discharged from the clinic without further follow-up, 6 are awaiting their first follow-up scan, 9 patients declined further follow-up in our clinic or chose to continue their care with their referring physician, 1 patient died before follow-up, and the remaining 6 patients were lost to follow-up.

The median initial nodule size was 0.6 cm (0.2–4.3 cm). Seven patients in our series presented with masses greater than 3 cm in size. On review of the clinical notes and radiology reports, the cause of these largest lesions was attributed to infectious etiology in 4 of 7, and 1 patient was given a diagnosis of silicosis of the lung. In 1 patient the mass demonstrated a benign pattern of calcification, and in the remaining patient ground-glass opacity requiring further evaluation was noted.

Median follow-up was 1.51 years (0–6.65 years). At least 1111 CT scans were performed in the entire cohort of patients. A total of 286 patients received their initial scan at least 2 years before the preparation of this report and would therefore have been eligible for discharge on the basis of CT stability. Of these eligible patients, only 55% (159/286) completed 2 years of clinic follow-up. Forty-five percent (127/286) of patients did not return for all of the scheduled follow-up visits. After at least 2 years, 24.2% (69/286) were deemed in stable condition on CT and were discontinued from further follow-up. Despite stability of the index nodule, 22.4% (64/286) of patients were followed up longer than 2 years owing to the development of new nodules. Of the remaining 26 patients who completed 2 years of follow-up, 2 were discharged after further imaging studies, 17 patients continued to be observed, and 7 patients were lost to follow-up. In the patients who had completed at least 2 years of follow-up, the mean number of scans was 4, with a time interval between CT scans of 266 days.

Forty-two (10.1%) of 414 patients underwent FDG–PET imaging, which suggested malignancy in 8 of the 42 scanned patients. Measurements of standardized uptake value were not uniformly reported by the radiologists and therefore not reportable here. In 67% (28/42) of PET-screened patients, the PET imaging was used within the first two clinic visits. However, FDG–PET was not consistently used before invasive procedures for tissue diagnosis in all patients. Of the 20 patients undergoing an invasive procedure for pathologic diagnosis, 11 had preliminary FDG–PET imaging and 9 went directly to biopsy or resection without FDG–PET.

A pathologic diagnosis was made by CT-guided fine-needle aspiration in 3 patients and by operative procedure in 17 patients. Seven (7/20) of the patients having a biopsy underwent a surgical procedure for what turned out to be a diagnosis of an infectious or inflammatory process. In 3 patients with a benign diagnosis, a thoracotomy was required to obtain tissue diagnosis. Overall, 3% (13/414) of our patients have been proven to have cancer. Nine patients had non–small cell lung cancer, 1 patient had small cell lung cancer, 1 patient had lymphoma, and 2 patients had lung metastasis of a distant tumor. All 10 patients with lung cancer underwent a biopsy procedure owing to change in the nodule from baseline size and appearance on follow-up CT scan. There was considerable variability in the length of follow-up before pathologic diagnosis. Forty-six percent of patients (6/13) were followed up by radiologic imaging for at least 2 years before the diagnosis of a cancerous lesion. In 9 of 13 patients with cancer, at least 4 follow-up scans were obtained before the diagnosis of malignancy, and in 2 patients, tissue diagnosis was obtained after 8 follow-up CT scans. In those patients followed up for more than 2 years, the index nodule began as a lesion 1 cm or less in size and was often accompanied by multiple other small nodules. Development of new small subcentimeter lesions in these cases prompted continuation of CT surveillance beyond the 2-year period originally intended for the index nodule.

Among the 10 patients with lung cancer, the median age was 64 years (58.0–78.0 years) with a mean smoking history of 57.3 ± 30.8 pack-years. There was no difference in age (P = .173), gender (P = .406), or smoking history (P = .063) between these 10 patients diagnosed with primary lung cancer and the entire cohort. The patient with a diagnosis of small cell lung cancer did not undergo surgical resection but was offered chemotherapy and radiation. Of the 9 patients with non–small cell lung cancer, 1 patient was not offered surgery owing to discovery of asymptomatic metastatic disease and 1 patient underwent thoracotomy only to discover extensive multistation N2 disease resulting in wedge resection and lymph node sampling being performed. Two patients believed not to be operative candidates owing to poor pulmonary function were treated with stereotactic radiation, and the remaining 5 patients underwent resection of node-negative lung cancer (3 patients with T1 N0, 1 patient with T2 N0, and 1 patient with T4 N0).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Our clinic was designed to facilitate the follow-up and evaluation of patients with pulmonary indeterminate nodules. The original intent was to provide a streamlined service for our patients and their referring physicians. This report is a retrospective review of our experience. Although we are unable to offer conclusions as to the rationale and utility of current recommendations for the imaging evaluation and clinical testing of patients with indeterminate pulmonary nodules, we are able to provide an overview of the experience of a busy thoracic surgery service at a large tertiary referral hospital in the United States.

Both the Fleischner Society and the ACCP recommend 2 years of surveillance to deem a lesion stable.^1,2 Using the 2 years of imaging follow-up as the benchmark for discharge from our clinic, surprisingly few patients met the criterion. We do not have data on why patients did not follow up in our clinic over the recommended 2-year period. We did contact a subset (n = 16) of patients who did not return for the first recommended follow-up. Of these 16 patients, 1 died of unrelated illness, 9 declined further follow-up in our clinic and chose to continue care with their referring physician, 1 patient declined follow-up owing to his own opinion that the nodules were not a health care issue, 1 patient had insurance deny further follow-up at our center, and the remaining 4 were unable to be contacted. We speculate that a significant reason for patient attrition may be the wide region of referral to our center. After reassurance from the initial visits that no immediate surgical intervention was needed, patients may have elected to follow up with their own local physicians owing to the difficulties associated with prolonged travel times to our clinic. At the implementation of this clinic, we did not undertake any formal assessment to study the psychosocial impact of patients being evaluated in a clinic dedicated to chest CT abnormalities. However, from patient and family interaction, it is clear that many patients find reassurance from periodic evaluation by a thoracic surgeon for their CT abnormalities. Referring physicians were also kept continually informed of the progress of their patients and our decision-making process, facilitating long-term care by the referring physician.

Of the patients eligible for 2 years of follow-up, 22.4% had a new nodule develop, leading to recommendation for further imaging. The development of new nodules is expected in patients with smoking history. In the Early Lung Cancer Action Program (ELCAP) study, 23% of patients had a nodule on the initial screening, and an additional 5% had a new nodule develop during the follow-up period.³ The highest prevalence of lung cancer reported in any trial of CT scanning has been the 2.7% reported by the ELCAP investigators.⁴ The variability of tumor doubling times further affects recommendations for duration of follow-up. At presentation, a very small nodule may take considerably longer to become clinically relevant than a larger nodule with the same doubling time. Given the lengthy time interval from initial presentation to pathologic diagnosis demonstrated in our series, it is unclear what implication this has for the numerous other patients who were discharged from our clinic because of stable imaging findings with 2 years of follow-up. A longer period of follow-up may be necessary.

In another large prospective study of the role of CT screening studies, investigators at the Mayo Clinic reported that 847 new nodules were detected in their cohort of 1520 patients followed up for 5 years with annual CT scan.⁵ In fact, 56% of patients presented with a malignancy not found on the initial CT scan.⁵ The development of new indeterminate nodules raises the question of when to stop screening patients. Given the lack of compelling data, we would not offer continued screening CT scans outside the setting of a clinical trial.

Few patients required surgical intervention. From our clinic's evaluation process, 3 patients were referred to the radiology service for CT-guided biopsy, and 17 operative procedures were performed. Of these procedures, the majority were bronchoscopy or mediastinoscopy. Only 3 thoracotomies were performed for what was ultimately deemed a benign process. Participation in our clinic, with early involvement of a thoracic surgeon, may have prevented unnecessary procedures. Whereas 5% (20/414) of patients in our series underwent a diagnostic procedure, the International Early Lung Cancer Action Program Investigators reported nearly double the rate of diagnostic procedures—9.4% (535/5646 patients with nodules).³

We were able to identify 10 patients with primary lung cancer. Unfortunately, only 5 patients underwent curative resection. Early detection and frequent follow-up did not lead to curative resection in the other 5 patients. In fact, 3 of the 5 patients who underwent curative resection required more than 2 years of follow-up before a clinical decision was made to perform a procedure for tissue diagnosis. The need for prolonged follow-up was not due to change in the initial index lesion, but to the development of new subcentimeter lesions, with subsequent recommendations for continued follow-up.

The management and follow-up of patients with asymptomatic pulmonary nodules remains an important and challenging clinical problem. Although a number of professional societies provide recommendations to guide the care of these patients, our experience with this group of patients has not been straightforward. We were not able to centralize the care of these patients at our institution, and close to half of patients enrolled in our clinic did not complete 2 years of follow-up at our center. Well over 1000 CT scans were performed at our center in a cohort of 414 patients. Whereas a diagnosis of primary lung cancer was made in 10 patients, only 5 of these patients could be definitively treated with surgery. At the time of this report, our formal clinic for the evaluation and follow-up of patients with indeterminate nodules has been disbanded owing to cutbacks in advanced nurse practitioner personnel. We believe that further prospective investigation is required to evaluate the optimal treatment strategy for patients with indeterminate pulmonary nodules and to determine the long-term benefits of early detection.

	Acknowledgments

 
We are grateful for the efforts of Dr Joel Cooper for the design and inception of this clinic.

	Footnotes

 
Read at the Eighty-eighth Annual Meeting of The American Association for Thoracic Surgery, San Diego, California, May 10–14, 2008.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Gould MK, Fletcher J, Iannettoni, MD, Lynch WR, Midthun DE, Naidich DP, et al. American College of Chest Physicians. Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132:108S-130S.[Abstract/Free Full Text]
   
2. MacMahon H, Austin JH, Gamsu G, Herold CJ, Jett JR, Naidich DP, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395-400.[Abstract/Free Full Text]
   
3. Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006;355:1763-1771.[Medline]
   
4. Diederich S, Wormanns D. Impact of low-dose CT on lung cancer screening. Lung Cancer 2004;45(Suppl 2):S13-S19.[Medline]
   
5. Swensen SJ, Jett JR, Hartman TE, Midthun DE, Mandrekar SJ, Hillman SL, et al. CT screening for lung cancer: five-year prospective experience. Radiology 2005;235:259-265.[Abstract/Free Full Text]
   

This article has been cited by other articles:

				D. S. Ettinger, W. Akerley, G. Bepler, M. G. Blum, A. Chang, R. T. Cheney, L. R. Chirieac, T. A. D'Amico, T. L. Demmy, A. K. P. Ganti, et al. Non-Small Cell Lung Cancer J Natl Compr Canc Netw, July 1, 2010; 8(7): 740 - 801. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Traves D. Crabtree Daniel Kreisel Jennifer B. Zoole G. Alexander Patterson Bryan F. Meyers Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Veeramachaneni, N. K. Articles by Meyers, B. F. Search for Related Content PubMed Articles by Veeramachaneni, N. K. Articles by Meyers, B. F. Related Collections Lung - cancer Lung - other