Correspondence
Staging of Non–Small-Cell Lung Cancer with Positron-Emission Tomography
N Engl J Med 2000; 343:1571-1573November 23, 2000
- Article
To the Editor:
In their study of the value of positron-emission tomography (PET) in the preoperative staging of non–small-cell lung cancer, Pieterman et al. (July 27 issue)1 found that PET was more sensitive and specific than computed tomography (CT) in detecting mediastinal metastases and that PET identified distant metastases that had not been found by standard methods in 11 of 102 patients. Of 29 “hot spots” potentially representing distant metastases, 9 were considered to be false positive results; the evaluation of such false positive findings may result in complications, increased costs, and delayed treatment.
Experience with the use of imaging tests to identify distant metastasis in patients with lung cancer has demonstrated that accuracy depends on the pretest probability of metastatic disease. A relatively simple and inexpensive clinical evaluation consisting of a history taking, physical examination, and laboratory examinations has a high negative predictive value (92 to 97 percent) with respect to the identification of metastatic disease on CT or radionuclide scanning.2 In the light of these findings, the American Thoracic Society (ATS) and the European Respiratory Society have recommended that an extensive search for metastatic disease not be carried out in patients with negative findings on clinical evaluation3: the absence of weight loss, bone pain, and neurologic symptoms; the absence of neurologic findings, lymphadenopathy, hoarseness, the superior vena cava syndrome, hepatomegaly, a soft-tissue mass, and bone tenderness; and the finding of a normal hematocrit, liver function, and calcium levels. Whether PET scanning will be useful in detecting distant metastases in patients with negative findings on clinical evaluation is an important issue that was not addressed in the study by Pieterman et al., nor were the clinical criteria the investigators used to identify potential instances of metastatic disease defined.
3 ReferencesYork E. Miller, M.D.
Denver Veterans Affairs Medical Center, Denver, CO 80220-38031
Pieterman RM ,van Putten JWG ,Meuzelaar JJ , et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000;343:254-261
Full Text | Web of Science | Medline2
Silvestri GA . Staging strategies for patients with newly diagnosed bronchogenic carcinoma: the importance of the clinical evaluation. Semin Respir Crit Care Med 1996;17:343-348
CrossRef | Web of Science3
Pretreatment evaluation of non-small-cell lung cancerAm J Respir Crit Care Med 1997;156:320-332
Web of Science | Medline
To the Editor:
We disagree with the system of mediastinal lymph-node mapping used by Pieterman et al. in their assessment of the value of PET in the staging of non–small-cell lung cancer. Their classification of lymph-node levels is misleading, because it alters the universally accepted approach described by Naruke et al.1 and accepted by the ATS.2 As defined by Pieterman et al., level 1 is pretracheal and is equivalent to level 3 in the ATS system. Moreover, the numbering in general is confusing because paratracheal lymph-node areas recognized by the ATS system are combined in new areas. In addition, the subaortic and paraaortic areas included in level 4 by Pieterman et al. correspond to a level of 5 in the ATS system, whereas in the ATS system, level 4 is divided into level 4R, which includes the right-sided lower paratracheal nodes between the cephalic border of the azygos vein and the intersection of the caudal margin of the brachiocephalic artery with the right side of the trachea, and level 4L, which includes the left-sided lower paratracheal nodes between the top of the aortic arch and the level of the carina, medial to the ligamentum arteriosum.
Furthermore, Pieterman et al. divide the lower mediastinum differently; they consider the paraesophageal area and the pulmonary ligament (equivalent to ATS levels 8 and 9, respectively) together and instead differentiate between the left side (their level 6) and the right side (their level 7) of this region. Instead of including the left side of the paraesophageal area and pulmonary ligament, level 6 of the ATS system includes the nodes anterior to the ascending aorta or the innominate artery, and level 7 includes subcarinal nodes arising caudal to the carina of the trachea.
The extrapulmonary locations of the intrathoracic lymph nodes in humans were described by Rouvière3 in 1938, and the intrapulmonary lymphatic anatomy and its interconnecting network were summarized in 1952 by Borrie,4 who elucidated the patterns of dissemination of lung cancer in the intrapulmonary lymphatics of resected specimens. Since then, the system of lymph-node mapping proposed by Naruke et al.1 and accepted by the ATS2 has guided the techniques of lymph-node sampling and dissection. If Pieterman et al. want to propose a new system of lymph-node mapping, they should take care to eliminate the inconsistencies I have pointed out, so that their system will conform to the generally accepted classification. Otherwise, their system will only lead to unnecessary confusion on the part of thoracic surgeons, pathologists, and oncologists.
4 ReferencesRafael Rosell, M.D.
Hospital Germans Trias i Pujol, 08916 Badalona, Spain1
Naruke T ,Suemasu K ,Ishikawa S . Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg 1978;76:832-839
Web of Science | Medline2
Clinical staging of primary lung cancerAm Rev Respir Dis 1983;127:659-664
Web of Science | Medline3
Rouvière H. Anatomy of the human lymphatic system. Tobias MJ, trans. Ann Arbor, Mich.: Edwards Brothers, 1938:83.
4
Borrie J . Primary carcinoma of the bronchus: prognosis following surgical resection (a clinico-pathological study of 200 patients). Ann R Coll Surg Engl 1952;10:165-186
Web of Science | Medline
To the Editor:
Pieterman et al. demonstrated the excellent sensitivity of PET with 18F-fluorodeoxyglucose for the detection of metastases of non–small-cell lung cancer. In their editorial, Berlangieri and Scott1 ascribe the problems of sensitivity in detecting small pulmonary lesions to respiratory motion and the limits of PET resolution. In addition, we want to stress that the type of tumor may have a role. The results of PET with 18F-fluorodeoxyglucose may be falsely negative in patients with bronchioloalveolar carcinomas and carcinoid tumors.2,3 Consequently, a negative result on PET with 18F-fluorodeoxyglucose may also provide information about the nature of lung cancer, especially lung tumors that induce ectopic secretion of corticotropin. In patients with this condition, a negative result strongly suggests a carcinoid tumor rather than a small-cell lung carcinoma as the cause of ectopic secretion of corticotropin.
3 ReferencesJulian E. Donckier, M.D., Ph.D.
Véronique Roelants, M.D.
Jean-Michel Pochet, M.D.
Université Catholique de Louvain at Mont-Godinne, B-5530 Yvoir, Belgium1
Berlangieri SU ,Scott AM . Metabolic staging of lung cancer. N Engl J Med 2000;343:290-292
Full Text | Web of Science | Medline2
Higashi K ,Ueda Y ,Seki H , et al. Fluorine-18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 1998;39:1016-1020
Web of Science | Medline3
Rege SD ,Hoh CK ,Glaspy JA , et al. Imaging of pulmonary mass lesions with whole-body positron emission tomography and fluorodeoxyglucose. Cancer 1993;72:82-90
CrossRef | Web of Science | Medline
Author/Editor Response
Dr. Groen replies:
To the Editor: Dr. Miller asks which clinical criteria we used to identify potential instances of metastatic disease. At the time of preoperative staging and during follow-up after thoracotomy, patients were clinically evaluated for symptoms and signs suggestive of metastatic disease in the way Dr. Miller suggested. I agree that the pretest probability of metastatic disease determines the accuracy of PET. Indeed, not all hot spots identified on PET were diagnosed as malignant disease. In the colon, hot spots and, more often, linear areas of increased uptake of 18F-fluorodeoxyglucose on PET were diagnosed as Crohn's disease or ulcerative colitis in patients with only marginal symptoms.
Although false positive results of PET require further evaluation, in our study, PET identified distant metastases that had not been found with traditional methods in 11 percent of our patients. In these patients, thoracotomy could have been avoided. Randomized studies of PET are being performed in the Netherlands to determine whether PET is cost effective with regard to the number of diagnostic tests and to what extent the use of PET as an early diagnostic test for lung cancer obviates the need for invasive procedures.
Dr. Rosell disagreed with the system of classification of mediastinal lymph nodes that we used. By our use of this system we did not mean to imply that the ATS system should be changed; rather, we wanted to compare the results of various imaging techniques with those of histopathological examinations of dissected mediastinal lymph nodes that were labeled according to the classification of Mountain and Dresler.1 Because of the limited anatomical resolution of PET, the use of a broader lymph-node category was necessary for an adequate comparison of PET, CT, and surgical lymph-node mapping. The numbering of the lymph-node categories has no relation to that of the ATS system.
I agree with Donckier et al. that not all lung tumors have increased uptake of 18F-fluorodeoxyglucose. Recently, we found no pulmonary hot spots at all in four patients with bronchioloalveolar carcinoma and one patient with bronchial adenocarcinoma.
1 ReferencesHarry J.M. Groen, M.D., Ph.D.
University Hospital Groningen, 9700 RB Groningen, the Netherlands1
Mountain CF ,Dresler CM . Regional lymph node classification for lung cancer staging. Chest 1997;111:1718-1723
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Ching-Fei Chang, Afshin Rashtian, Michael K. Gould. (2011) The Use and Misuse of Positron Emission Tomography in Lung Cancer Evaluation. Clinics in Chest Medicine 32:4, 749-762
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