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Ann Thorac Surg 2002;74:1004-1007
© 2002 The Society of Thoracic Surgeons

Original article: general thoracic

Surgical resection of lung cancer in patients with underlying interstitial lung disease

Emmanuel Martinod, MD*a, Jacques F. Azorin, MDa, Danielle Sadoun, MDb, Marie-Dominique Destable, MDa, Philippe Le Toumelin, MDb, Elisabeth Longchampt, MDc, Marianne Kambouchner, MDc, Loïc Guillevin, MDd, Dominique Valeyre, MDb

a Department of Thoracic and Vascular Surgery, Hôpital Avicenne, Assistance Publique—Hôpitaux de Paris and UFR SMBH, Bobigny, Université Paris XIII, France
b Department of Pneumology, Hôpital Avicenne, Assistance Publique—Hôpitaux de Paris and UFR SMBH, Bobigny, Université Paris XIII, France
c Department of Pathology, Hôpital Avicenne, Assistance Publique—Hôpitaux de Paris and UFR SMBH, Bobigny, Université Paris XIII, France
d Internal Medicine, Hôpital Avicenne, Assistance Publique—Hôpitaux de Paris and UFR SMBH, Bobigny, Université Paris XIII, France

Accepted for publication May 14, 2002.

* Address reprint requests to Dr Martinod, Service de Chirurgie Thoracique et Vasculaire, Hôpital Avicenne, 125 rue de Stalingrad, 93009 Bobigny, France
e-mail: emartinod{at}wanadoo.fr


   Abstract
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 Abstract
Introduction
 Material and methods
 Results
 Comment
 References
 
Background. The association between interstitial lung disease (ILD) and an increased risk of developing lung cancer has been reported. The goal of this retrospective study was to determine the outcome of lung cancer resection among patients with ILD.

Methods. Between January 1979 and March 1999, 27 patients with both lung cancer and ILD were identified. Seven patients with poor pulmonary function tests or distant metastases underwent medical treatment and were excluded from this study. Twenty patients treated by surgical resection were analyzed.

Results. Various types of ILD such as sarcoidosis (n = 7), idiopathic interstitial pneumonia (n = 4), histiocytosis X (n = 4), pneumoconiosis (n = 4), and amiodarone-induced ILD (n = 1) were observed. Tumors were located in the peripheral part of the lung in 16 cases. The most frequent tumor cell types were squamous and adenocarcinoma. The resections consisted of lobectomy (n = 16), bilobectomy (n = 1), and pneumonectomy (n = 3). Most cancers were stage I (n = 10) or II (n = 6). There was no postoperative death. The postoperative course was uneventful in 16 cases. The majority of patients (70%) did not experience respiratory insufficiency during the follow-up period. The actuarial 2-year and 5-year survival rates were, respectively, 83.5% and 66.4%.

Conclusions. In this series, the long-term survival of patients who had lung cancer resection appeared to be not affected by the association with ILD. This could be explained by an adequate preoperative selection based on pulmonary function tests and a preferential choice for lobectomies. Thus, surgical resection should be offered to properly selected patients with lung cancer and underlying ILD.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 References
 
The association between interstitial lung disease (ILD) and an increased risk of primary lung cancer (LC) has been previously reported [1]. However, the prognosis after surgical resection remains poorly documented in this patient population. The goal of this retrospective study was to report our experience with surgical resection of LC associated with ILD and to determine if surgical treatment should be recommended in patients with both ILD and LC.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 References
 
Between January 1979 and March 1999, 27 patients with both primary LC and ILD were identified from the Department of Respiratory Diseases and Thoracic Surgery. After an extensive preoperative workup, 7 of these patients with poor pulmonary function tests or distant metastases underwent medical treatment and were excluded from this retrospective study. Twenty patients treated by surgical resection were analyzed. A detailed retrospective chart review was performed, and the following items were recorded for each patient: (1) medical history, smoking habit, and clinical status, (2) preoperative workup including chest radiograph, computed tomographic scan, bronchoscopy with pathologic examinations, pulmonary function tests, and appropriate cardiac evaluation, (3) surgical procedure, (4) type of ILD, (5) histologic subtype of LC and pTNM status, (6) postoperative course, (7) progression of LC, (8) evolution of pulmonary function, and (9) disease status at last follow-up. Information on follow-up was obtained by chart review or by direct communication with the referring physician. Actuarial survival curves were performed using the Kaplan-Meier method.


   Results
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 Abstract
 Introduction
 Material and methods
 Results
Comment
 References
 
Twenty patients underwent surgical resection for LC associated with ILD between January 1979 and March 1999. There were 16 male and 4 female patients. Age ranged from 38 to 72 years with a mean of 58 years. Smoking history was reported in all patients and was greater than 20 pack-years in 19 of them. Interstitial lung disease was diagnosed before LC resection in 15 patients by pathologic features (n = 13) or clinical and radiologic criteria (n = 2). In other patients (n = 5), ILD was discovered on histologic examinations after surgical resection.

Various types of ILD such as sarcoidosis (n = 7), idiopathic interstitial pneumonia (n = 4), histiocytosis X (n = 4), pneumoconiosis (n = 4), and amiodarone-induced ILD (n = 1) were observed. There were three subtypes of idiopathic interstitial pneumonia including usual interstitial pneumonia (n = 2), desquamative interstitial pneumonia (n = 1), and respiratory bronchiolitis ILD (n = 1).

Lung cancer was revealed by new complaints in 12 patients (worsening dyspnea, n = 6; hemoptysis, n = 2; cough, n = 1; chest pain, n = 1; weight loss, n = 1; or asthenia, n = 1) or by new abnormalities observed on systematic chest radiograph in 8 patients without symptoms or with stable respiratory function. Tumor characteristics on chest computed tomographic scan are summarized in Table 1. The diagnosis of LC was confirmed by bronchoscopy with histologic examinations in 5 patients and by thoracotomy for the remaining patients.


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  		Table 1. Characteristics of Tumors on Chest Computed Tomographic Scan

 
Preoperative pulmonary function tests are presented in Table 2. Forced expiratory volume in 1 s (FEV1, percent predicted) was superior or equal to 60% in all patients but 3. Forced vital capacity (percent predicted) was superior to 60% in all patients. Diffusing capacity of the lung for carbon monoxide (percent predicted) was superior to 40% in all cases.


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  		Table 2. Preoperative Pulmonary Function Testsa

 
Surgical procedure, histologic type of both ILD and LC, stage, and pTNM status are detailed in Table 3. Surgical resection was complete microscopically in all patients. There was no postoperative death. The postoperative course was uneventful for 16 patients. Postoperative morbidity consisted of pneumonia (n = 2), minor regressive chylothorax (n = 1), and bleeding that required surgical hemostasis (n = 1). The mean hospital stay was 11.9 days (range, 7 to 22 days). The median length of follow-up was 43.1 months (range, 1 to 243 months). Fifteen patients were alive and 5 patients were dead at last follow-up. The cause of death was tumor progression (n = 3) or respiratory insufficiency (n = 2). In the subgroup of 15 alive patients, 3 had tumor recurrence, 3 had respiratory insufficiency, 1 had both, and 8 remained stable. Only 1 of 4 patients who had a pneumonectomy (n = 3) or a bilobectomy (n = 1) was stable at the last follow-up. Only 1 of 3 patients with an FEV1 value less than 60% had a stable condition at the last follow-up. Disease status at last follow-up is detailed in Table 4. The actuarial 2-year and 5-year survival rates were 83.5% and 66.4%, respectively (Fig 1).


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  		Table 3. Histologic Type of Interstitial Lung Disease and Lung Cancer, Surgical Resection, Stage, and pTNM Status

 

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  		Table 4. Disease Status at Last Follow-Upa

 


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  		Fig 1. Survival rate after surgical resection of lung cancer in patients with underlying interstitial lung disease.

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
References
 
In this report, 27 patients with both LC and ILD were identified during a 20-year period. According to the usual guidelines of preoperative selection for patients with LC, 7 patients with poor pulmonary function or distant metastases underwent medical treatment. As a result, surgical resection was indicated in 20 patients. Interestingly, there were no postoperative deaths, and we observed a low postoperative morbidity. Furthermore, no respiratory insufficiency was demonstrated in the majority of cases (70%) during the follow-up period. In addition, long-term survival rate appeared to be not affected by the presence of ILD. These results could be explained by (1) a rigorous preoperative patient selection, which was particularly focused on pulmonary function tests, (2) the majority of patients (80%) who had a lobectomy because of the peripheral localization of LC, (3) the low proportion of patients (10%) with usual interstitial pneumonia or idiopathic pulmonary fibrosis that is commonly associated with a poor long-term prognosis, and (4) the predominance of sarcoidosis (35%) and histiocytosis X (20%) commonly associated with a better prognosis.

In this series, various types of ILD including sarcoidosis (n = 7), idiopathic interstitial pneumonia (n = 4), histiocytosis X (n = 4), pneumoconiosis (n = 4), and amiodarone-induced ILD (n = 1) were observed. It is well established that chronic lung diseases such as asbestosis, silicosis, and idiopathic pulmonary fibrosis increased the risk of developing LC [1–7]. Turner-Warwick and colleagues [4] have reported a relative risk for LC of 14.1 among patients with pulmonary fibrosis compared with the general population. In other types of ILD such as histiocytosis X, some authors have suggested that smoking represents the most significant offending agent in the pathogenesis of LC [8]. In the present series, all patients but one were heavy smokers (>20 pack-years). In 3,712 consecutive autopsy cases, Matsushita and colleagues [6] have demonstrated that heavy smoking is one of the most important risk factors in developing LC in usual interstitial pneumonia.

Tumors were located most commonly in the peripheral part of the lung (16 of 20 patients). In a chest computed tomographic scan study, Lee and colleagues [9] have shown that LC associated with idiopathic pulmonary fibrosis usually developed in the peripheral area where the most advanced fibrosis was situated. Diagnosis of LC was confirmed preoperatively by bronchoscopic biopsies in the minority of patients (5 of 20 patients) because of the distal situation of tumors. The most frequent tumor cell types were squamous (10 of 20 patients) and adenocarcinoma (8 of 20 patients) as is usually observed in large series of primary LC. This may support the hypothesis that, in case of ILD, smoking habits in addition to underlying lung scars could play an important pathogenic role in the formation of LC. Contrary to our results, some studies have shown that LC associated with ILD, especially in case of idiopathic pulmonary fibrosis, was mainly located in the lower lobe [9, 10]. This difference could be the direct consequence of the variety of ILD with a low proportion of idiopathic interstitial pneumonia. In a retrospective study, Mizushima and Kobayashi [10] reviewed 154 patients with both LC and idiopathic pulmonary fibrosis. Twenty-three had synchronous multiple LC associated with some clinical characteristics such as small cell carcinoma histologic type, with lower lobe and peripheral localization.

Preoperative selection of patients was made on the basis of pulmonary function tests including FEV1, forced vital capacity, and diffusing capacity of the lung for carbon monoxide. In case of LC with underlying ILD, special attention to the measurement of diffusing capacity of the lung for carbon monoxide or the transfer factor for carbon monoxide must be advised. Usually, patients with estimated postoperative FEV1 or transfer factor for carbon monoxide value less than 40% should not be proposed for surgical resection [11, 12]. Furthermore, both FEV1 and transfer factor for carbon monoxide seem to be independent prognostic factors [13]. In this series, values of FEV1, forced vital capacity, and diffusing capacity of the lung for carbon monoxide have been especially considered as predictors of surgical risk. As a result, no patient with a diffusing capacity of the lung for carbon monoxide value less than 40% predicted and only 3 patients with a FEV1 value less than 60% predicted were offered to undergo surgical resection. In addition, all patients had a forced vital capacity value greater than 60% predicted.

Lobectomy was the most common lung resection (16 of 20 patients) based on the predominance of peripherally located tumors. Only three pneumonectomies were performed for central LC. A posterolateral or lateral thoracotomy was used in most cases (17 of 20 patients). Video-assisted thoracic surgery was proposed for 3 patients with peripheral cancer. This still controversial technique has produced interesting results and could be an alternative to thoracotomy for selected patients with T1 or T2 LC [14, 15]. In our opinion, minimally invasive surgery could represent an attractive option to avoid major postoperative pulmonary function impairment in patients with underlying ILD. In the present study, the preoperative selection of patients and the high proportion of lobectomies performed could explain the low postoperative mortality and morbidity rate. Lobectomy is commonly associated with a lower mortality rate (2% to 4%) compared with pneumonectomy (6% to 8%) [12]. Brutsche and colleagues [16] have demonstrated that the extent of lung resection is clearly a major predictor of surgical risk in patients with LC. In addition, operative morbidity may be increased by other factors such as advanced age, heart ischemia, right-sided pneumonectomy, preoperative chemoradiotherapy, poor performance status, and impaired respiratory function [12]. According to the revised classification of the American Joint Committee (1997), most cancers were stage IA (n = 4), IB (n = 6), IIA (n = 2), and IIB (n = 4). Only four tumors were stage IIIA. Postoperative radiotherapy was not used to avoid additional risk of chronic lung toxicity [17].

During the follow-up period, 5 patients died secondary to tumor recurrence in 3 cases or respiratory insufficiency in 2 cases. The majority of survivors remained stable. Only 1 of 4 patients who had a pneumonectomy (n = 3) or a bilobectomy (n = 1) was stable at the last follow-up. Only 1 of 3 patients with an FEV1 value less than 60% had a stable condition at the last follow-up. This confirms that preoperative pulmonary function tests and the extent of lung resection are the main predictors of long-term survival in patients with both LC and ILD. No large series evaluating the long-term survival of patients with ILD who had LC resection has been published to date. The results of the present series have to be analyzed with caution because of the small number of patients included (n = 20). However, the actuarial 2-year and 5-year survival rates observed in the present series appeared to be similar to those found in major series of patients with LC. In a recent retrospective analysis of 1,905 patients with LC treated by surgical resection, Fang and colleagues [18] reported a 5-year survival rate of 49.5% in the group in which a complete resection was performed. Furthermore, the 5-year survival rate reported by Fang and coworkers [18] was 72.0% in stage IA, 61.0% in stage IB, 32.9% in stage IIA, and 34.5% in stage IIB.

In conclusion, the postoperative follow-up and long-term survival of patients who underwent resection for LC seemed to be not affected by the presence of underlying ILD. With an adequate preoperative patient selection and surgical approach, ILD did not appear to be associated with an increased mortality and morbidity rate after surgical LC resection. Thus, surgical resection should be offered to properly selected patients with LC and underlying ILD.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

  1. Samet J.M. Does idiopathic pulmonary fibrosis increase lung cancer risk ?. Am J Respir Crit Care Med 2000;161:1-2.[Free Full Text]
  2. Stack B.H.R., Choo-Kang Y.F.J., Heard B.E. The prognosis of cryptogenic fibrosing alveolitis. Thorax 1972;27:535-542.[Abstract/Free Full Text]
  3. Fraire A.E., Greenberg S.D. Carcinoma and diffuse interstitial fibrosis of lung. Cancer 1973;31:1078-1086.[Medline]
  4. Turner-Warwick M., Lebowitz M., Burrows B., Johnson A. Cryptogenic fibrosing alveolitis and lung cancer. Thorax 1980;35:496-499.[Abstract/Free Full Text]
  5. Kawai T., Yakumaru K., Suzuki M., Kageyama K. Diffuse interstitial pulmonary fibrosis and lung cancer. Acta Pathol Jpn 1987;37:11-19.[Medline]
  6. Matsushita H., Tanaka S., Saiki Y., et al. Lung cancer associated with usual interstitial pneumonia. Pathol Int 1995;45:925-932.[Medline]
  7. Hubbard R., Venn A., Lewis S., Britton J. Lung cancer and cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 2000;161:5-8.[Abstract/Free Full Text]
  8. Sadoun D., Vaylet F., Valeyre D., et al. Bronchogenic carcinoma in patients with pulmonary histiocytosis X. Chest 1992;101:1610-1613.[Abstract/Free Full Text]
  9. Lee H.J., Im J.G., Ahn J.M., Yeon K.M. Lung cancer in patients with idiopathic pulmonary fibrosis: CT findings. J Comput Assist Tomogr 1996;20:979-982.[Medline]
  10. Mizushima Y., Kobayashi M. Clinical characteristics of synchronous multiple lung cancer associated with idiopathic pulmonary fibrosis. A review of Japanese cases. Chest 1995;108:1272-1277.[Abstract/Free Full Text]
  11. Markos J., Mullan B.P., Hillman D.R., et al. Preoperative assessment as a predictor for mortality and morbidity after lung resection. Am Rev Respir Dis 1989;139:902-909.[Medline]
  12. BTS guidelines. Guidelines on the selection of patients with lung cancer for surgery. Thorax 2001;56:89-108.[Free Full Text]
  13. Pierce R.J., Copland J.M., Sharpe K., et al. Preoperative risk evaluation for lung cancer resection: predicted postoperative product as a predictor of surgical mortality. Am J Respir Crit Care Med 1994;150:947-955.[Abstract]
  14. Giudicelli R., Thomas P., Lonjon T., et al. Video-assisted minithoracotomy versus muscle-sparing thoracotomy for performing lobectomy. Ann Thorac Surg 1994;58:712-717.[Abstract]
  15. Nakata M., Saeki H., Yokoyama N., Kurita A., Takiyama W., Takashima S. Pulmonary function after lobectomy: video-assisted thoracic surgery versus thoracotomy. Ann Thorac Surg 2000;70:938-941.[Abstract/Free Full Text]
  16. Brutsche M.H., Spiliopoulos A., Bolliger C.T., Licker M., Frey J.G., Tschopp J.M. Exercise capacity and extent of resection as predictors of surgical risk in lung cancer. Eur Respir J 2000;15:828-832.[Abstract]
  17. Griffin J.P. Interstitial pulmonary fibrosis and lung cancer. Chest 1995;108:1193.[Free Full Text]
  18. Fang D., Zhang D., Huang G., Zhang R., Wang L., Zhang D. Results of surgical resection of patients with primary lung cancer: a retrospective analysis of 1905 cases. Ann Thorac Surg 2001;72:1155-1159.[Abstract/Free Full Text]



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