Elsevier

Lung Cancer

Volume 67, Issue 3, March 2010, Pages 306-310
Lung Cancer

Structural lung damage after chemotherapy: Fact or fiction?

https://doi.org/10.1016/j.lungcan.2009.04.013Get rights and content

Abstract

Background

The hypothesis that chemotherapy increases morbidity after pneumonectomy remains under debate, as the results of previous surgical series remain controversial. The hypothesis of the study is that patients who received preoperative chemotherapy may have subclinical parenchymal damage, increasing their risk of respiratory complications.

Methods

The study population was composed of 10 patients who underwent pneumonectomy after chemotherapy for lung cancer (cisplatin + gemcitabine) randomly selected from our database and compared with 10 matched patients who underwent pneumonectomy without previous chemotherapy during the same period. Healthy lung tissue was obtained from surgical specimens, processed according to standard methods and evaluated on ematossilin and eosin-stained sections. Two pathologists without information on the preoperative treatment were asked to review the slides in order to reach a consensus on the type and extent of lung damage. Relevant information was then compared with functional tests and postoperative outcome.

Results

Severe and diffuse (more than 50% of lung parenchyma) interstitial alterations were detected in the lungs of eight patients, seven of which belonged to the chemotherapy group (70%, p 0.02). Six of these patients developed postoperative respiratory complications.

In the chemotherapy group, patterns of interstitial involvement were variable interstitial inflammation and fibrosis associated with obliterative bronchiolitis [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885–8], bronchiolitis obliterans-organizing pneumonia [Leo F, Solli P, Veronesi G, et al. Does chemotherapy increase the risk of respiratory complications after pneumonectomy? J Thorac Cardiovasc Surg 2006;132:519–23], diffuse alveolar damage [Novoa N, Varela G, Jimenez MF. Morbidity after surgery for non-small cell lung carcinoma is not related to neoadjuvant chemotherapy. Eur J Cardiothor Surg 2001;20:700–4], DIP (desquamative interstitial pneumonia)-like reaction [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885–8] and UIP (usual interstitial pneumonia)-like changes [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885–8]. The only preoperative clinical predictor of severe diffuse damage was preoperative diffusion by carbon monoxide (Dlco).

Conclusions

Preoperative chemotherapy is associated with an increased risk of severe and diffuse pulmonary disease even in the presence of normal spirometric parameters. These alterations may play an important role in the occurrence of postoperative respiratory complications.

Introduction

The impact of induction chemotherapy on the postoperative outcome of patients undergoing lung resection is a matter of controversy [1], [2]. In terms of overall postoperative complications, no significant difference has been clearly demonstrated in patients receiving neoadjuvant treatment. On the other hand, an increased risk of respiratory complications has been recorded when platinum-based chemotherapy preceeds pneumonectomy [3], [4].

Lung impairment due to chemotherapy is an event that ranges from acute toxicity to subclinical modifications. Acute lung toxicity is a very rare event in patients receiving chemotherapy for lung cancer (<1%), being more frequent in older patients, current smokers with pre-existing interstitial lung disease, in cases of poor performance status and in patients receiving Gefitinib [5]. On the contrary, functional impairment at the level of the alveolo-capillary membrane is a frequent event (80%) which is asymptomatic and detected only by diffusion of carbon monoxide assessment (Dlco) [6].

One of the explanations for both these effects is the occurrence of parenchymal pulmonary damages (PPD) which may predispose patients to pulmonary toxicity in the case of further treatments, such as surgery or radiotherapy. The hypothesis of this retrospective study is that PPD due to chemotherapy may be detected at the time of surgery by analyzing lung tissue spared by the tumor.

Section snippets

Population

The data of patients who underwent pneumonectomy for lung cancer was extracted from the clinical database of the Thoracic Surgery Department of the European Institute of Oncology. After eliminating cases with: respiratory symptoms at the time of admission, preoperative radiotherapy, patients with previous history of interstitial lung disease and pulmonary fibrosis and those with radiological signs of atelectasis, the records of 10 patients operated between 2000 and 2007 after having completed

Results

The matching process was successful, as no differences were detected between the two patient groups in terms of age, sex, side of surgery and preoperative FEV1. Clinical information on chemotherapy and control patients is given in Table 1. Severe and diffuse interstitial alterations were detected in the lungs of eight patients, seven of which belonged to the chemotherapy group (70% vs. 10% in the control group, p = 0.020).

In the chemotherapy group, patterns of severe and diffuse interstitial

Discussion

Results from this study have provided three useful indicating factors in clinical practice: (1) a certain proportion of candidates for pneumonectomy presented diffuse parenchymal damage at the time of surgery (40%); (2) diffusion of carbon monoxide was impaired in patients with diffuse pulmonary alterations (3) such extensive pulmonary damage was significantly more frequent in patients who received preoperative chemotherapy as compared to patients without induction treatment (70% vs. 10%).

Acknowledgments

The authors declare that they have no conflict of interest to disclose.

This paper was presented at the 2008 ESTS (European Society of Thoracic Surgeons) meeting in Bologna, Italy, on the 9th of June 2008.

The authors give their thanks to Ms Kendall Katze for editing the manuscript.

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