Correspondence

Staging of Non–Small-Cell Lung Cancer with Integrated PET and CT

N Engl J Med 2003; 349:1188-1190September 18, 2003

Article

To the Editor:

Lardinois et al. (June 19 issue)1 state that the accuracy of positron-emission tomography (PET) in lymph-node staging is only 49 percent. At least 15 patients had N0 disease on tumor–node–metastasis staging (i.e., IA or IB disease). If it is assumed that at least in these patients, the findings were correctly interpreted as negative, then apparently the PET evaluation was correct in only 3 of the remaining 22 node-positive patients, whereas the findings in most of the node-positive patients were interpreted as equivocal. This poor accuracy of PET in nodal staging contrasts with the results of all previous studies.2,3 The authors do not explain these discrepancies with the literature.

Holger Schirrmeister, M.D.
University Kiel, 24105 Kiel, Germany
hschirrmeister@wkk-hei.de

Martin Hetzel, M.D.
Andreas Buck, M.D.
University Ulm, 89081 Ulm, Germany

3 References

1. 1

   Lardinois D, Weder W, Hany TF, et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003;348:2500-2507
   Full Text | Web of Science | Medline

2. 2

   Pieterman RM, van Putten WG, Mezelaar 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 | Medline

3. 3

   Dwamena BA, Sonnad SS, Angobaldo JO, Wahl RL. Metastases from non-small cell lung cancer: mediastinal staging in the 1990s -- meta-analytic comparison of PET and CT. Radiology 1999;213:530-536
   Web of Science | Medline

To the Editor:

The research by Lardinois et al. represents an excellent use of modern technology for an understanding of lung-cancer staging and treatment. I would like to raise two points. First, the reviewers on Review Board A were not provided with the integrated computed tomographic (CT)–PET images, as were those on Review Board B, leading to a potential bias in staging. It would have been interesting if a third group had reviewed the integrated CT–PET images without knowledge of the findings on the CT and attenuation-corrected PET scans.

Second, were the patients made aware of the radiation exposure they would sustain in undergoing CT, PET, and integrated CT–PET scanning? With a typical CT scan of the chest, the dose of radiation is approximately 8 mSv, and with a PET scan of the chest, it is approximately 7 mSv, as compared with 0.02 mSv when a plain-film radiograph of the chest is obtained.1 I hope this exposure level could be indisputably justified on the basis of the perceived benefits.

Egbert Pravinkumar, M.R.C.P.
University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom
e.pravinkumar@abdn.ac.uk

1 References

1. 1

   Making the best use of a department of clinical radiology: guidelines for doctors. 4th ed. London: Royal College of Radiologists, 1998.
   

To the Editor:

Lardinois et al. are to be commended for their work demonstrating the improved accuracy of lung-cancer staging that is achievable with integrated PET–CT. However, it is also important to demonstrate that improved diagnostic accuracy translates into improved clinical management and outcomes. Unfortunately, the format in which Lardinois et al. present their data does not allow any assessment of the effect of PET–CT on clinical management, because the changes in clinical tumor stage afforded by PET–CT are not described. Clearly, a change in the apparent stage from IIB to IIIB would have a substantial effect on management, probably leading to the selection of radiotherapy, whereas a change from stage I to stage II would have little effect, since surgery would be the likely option in either case. The work of Lardinois et al. suggests great promise for PET–CT but leaves us needing more information before we can fully embrace this exciting new technology.

Kenneth A. Miles, M.D.
Brighton and Sussex Medical School, Brighton BN1 9PH, United Kingdom
k.a.miles@bsms.ac.uk

To the Editor:

Lardinois et al. found that PET–CT was more accurate than visual correlation of PET and conventional CT for the staging of non–small-cell lung cancer. The rapid introduction of PET–CT into clinical use underscores the importance of this study. During PET acquisition, however, the movement of lung lesions due to breathing is inevitable.1 In addition, PET overestimates lesion size (because of the 1-to-2-mm penetration of positrons in tissue). It is not clear how the authors corrected for these inaccuracies in tumor staging. Finally, with a 22-second period of breath holding, some acquisitions will be suboptimal or will fail. Because the study was not conducted in consecutive patients, the rate of technical failure should be reported.

Emile F. Comans, M.D., Ph.D.
Vrije Universiteit Medical Center, 1007 MB Amsterdam, the Netherlands
efi.comans@vumc.nl

1 References

1. 1

   Cohade C, Osman M, Marshall LM, Wahl RN. PET-CT: accuracy of PET and CT spatial registration of lung lesions. Eur J Nucl Med Mol Imaging 2003;30:721-726
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Schirrmeister and colleagues question our results with the use of PET for lymph-node staging. The sensitivity and specificity of CT alone and of PET alone for diagnosing lung cancer are well known. By superimposing the two techniques, we did not expect that the sensitivity and specificity would change. We undertook this study to determine whether integrated PET–CT provides additional information. The precise localization of lesions resulted in many equivocal interpretations with PET alone. We used “diagnostic accuracy” for the exact definition of tumor stage but not “statistical accuracy,” which could have led to misunderstanding.

Dr. Pravinkumar warns that the review by two independent boards may have led to a potential bias in staging. The study was designed to evaluate conventional correlation of PET alone and CT alone in comparison with the new method of integrated PET–CT. To avoid a potential bias, the members of Review Board A did not interpret integrated PET–CT images. We do not believe that the use of a third reviewer group would have changed the message of the study; instead, it might have provided information on interobserver variability.

Dr. Pravinkumar also inquires about radiation exposure. In an integrated PET–CT examination, CT and PET are performed sequentially. Because of the fixed, in-line arrangement of the dual-modality scanner, the CT and PET images are inherently coregistered. To minimize radiation exposure, we used low-dose CT for the integrated PET–CT examination, resulting in a total dose of between 12 and 13 mSv.1 As stated in the article, all the patients gave written informed consent.

We agree with Dr. Miles that increased precision in staging could influence treatment decisions. Our first objective was to evaluate the diagnostic accuracy of integrated PET–CT in comparison with conventional methods. In an ongoing study, we are analyzing the effect of integrated PET–CT on clinical management. Patients' outcomes are dependent not only on accurate staging and treatment decisions but also on risk factors and associated diseases. The direct effect of integrated PET–CT on outcomes will therefore be difficult to determine.

In response to Dr. Comans: consecutive patients were enrolled in our study. For integrated PET–CT imaging, breathing protocols were developed to reduce the possibility of misregistration of pulmonary lesions.2,3 We found that acquiring CT images during normal expiration and acquiring PET images during shallow breathing resulted in the best matching of lung lesions on coregistered PET–CT images. However, misregistration may occur in some patients, most often in the lower part of the lungs.4,5

Didier Lardinois, M.D.
Walter Weder, M.D.
Hans C. Steinert, M.D.
University Hospital of Zurich, 8091 Zurich, Switzerland
hans.steinert@dmr.usz.ch

5 References

1. 1

   Kneifel S. Radiation doses and radiation protection. In: Von Schulthess GK, ed. Clinical molecular anatomic imaging: PET, PET/CT, and SPECT/CT. Philadelphia: Lippincott Williams & Wilkins, 2003:68-71.
   

2. 2

   Goerres GW, Kamel E, Seifert B, et al. Accuracy of image coregistration of pulmonary lesions in patients with non-small cell lung cancer using an integrated PET/CT system. J Nucl Med 2002;43:1469-1475
   Web of Science | Medline

3. 3

   Beyer T, Antoch G, Blodgett T, Freudenberg LF, Akhurst T, Mueller S. Dual-modality PET/CT imaging: the effect of respiratory motion on combined image quality in clinical oncology. Eur J Nucl Med Mol Imaging 2003;30:588-596
   CrossRef | Web of Science | Medline

4. 4

   Goerres GW, Burger C, Kamel E, et al. Respiration-induced attenuation artifact at PET/CT: technical considerations. Radiology 2003;226:906-910
   CrossRef | Web of Science | Medline

5. 5

   Cohade C, Osman M, Marshall LT, Wahl RN. PET-CT: accuracy of PET and CT spatial registration of lung lesions. Eur J Nucl Med Mol Imaging 2003;30:721-726
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Otto S. Hoekstra, Harm van Tinteren, Egbert F. Smit. (2006) Evaluation of Cost-effectiveness of FDG-PET in Non–Small Cell Lung Cancer. PET Clinics 1:4, 329-337
   CrossRef