Correspondence
Management of Lung Nodules Detected by Volume CT Scanning
N Engl J Med 2010; 362:757-759February 25, 2010
- Article
To the Editor:
Van Klaveren et al. (Dec. 3 issue)1 report results of the evaluation of noncalcified pulmonary nodules according to volume and volume-doubling time among subjects at high risk for lung cancer. Although volumetric imaging appears to be more accurate for determining volume size than traditional methods are,2 I am not aware of any large studies to date verifying this. In the case of the 324 patients with nodules of concern on the first and second rounds of screening, were volume calculations that were based on diameter alone compared with those that were based on the volumetric processing algorithm? Given the large size of this observational study and the paucity of data regarding this new technology, a comparison with the current standard of care3 would be helpful for interpretation.
In addition, since the characteristics of a diagnostic test (e.g., sensitivity and specificity) depend on the precision of its measurements, it would be useful to know some additional details regarding the determination of nodule size. Did the observations between independent readers correlate well? Finally, previous studies indicate that, not surprisingly, the accuracy of nodule measurement depends on the size of the nodules.2,4 I wonder whether the reproducibility of measurements varied with size in the case of nodules that resulted in further workup (those that were 50 to 500 mm3, as compared with those that were >500 mm3), possibly affecting the test performance across different strata of nodule size.
Viswam S. Nair, M.D.
Stanford University School of Medicine, Stanford, CA
viswamnair@stanford.edu No potential conflict of interest relevant to this letter was reported.
4 References1
van Klaveren RJ ,Oudkerk M ,Prokop M , et al. Management of lung nodules detected by volume CT scanning. N Engl J Med 2009;361:2221-2229
Full Text | Web of Science | Medline2
Yankelevitz DF ,Reeves AP ,Kostis WJ ,Zhao B ,Henschke CI . Small pulmonary nodules: volumetrically determined growth rates based on CT evaluation. Radiology 2000;217:251-256
Web of Science | Medline3
Bland JM ,Altman DG . Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-310
CrossRef | Web of Science | Medline4
Goo JM ,Tongdee T ,Tongdee R ,Yeo K ,Hildebolt CF ,Bae KT . Volumetric measurement of synthetic lung nodules with multi-detector row CT: effect of various image reconstruction parameters and segmentation thresholds on measurement accuracy. Radiology 2005;235:850-856
CrossRef | Web of Science | Medline
To the Editor:
Van Klaveren et al. present only the results from the group that was screened. The results of the control group are not shown, so that the question of whether computed tomographic (CT) screening of high-risk patients is beneficial remains unanswered.
In 30 of 100 patients, cancer was diagnosed only in later rounds. Ten patients had a false negative result after the first screening round. It is surprising and controversial that seven of those patients had only bronchoscopy with bronchoalveolar lavage as the highest-level procedure to work up pulmonary nodules that were completely surrounded by lung tissue. Delayed diagnosis can lead to a change in stage and a possible decline in 5-year survival, which decreases from 77% (revised tumor–node–metastasis [TNM] classification, pT1a: ≤2 cm) to 71% (pT1b: >2 to 3 cm) and 58% (pT2a: >3 to 5 cm).1
In addition to the size at first detection and the volume-doubling time, age should be considered as a factor. The prevalence of cancer increases with increasing age (from 36% among persons <45 years of age to 96% among persons >75 years of age) and with increasing size of the lesion (from 43% when lesions are <1 cm in diameter to 78% when lesions are 1.1 to 2 cm and 94% when lesions are 2.1 to 3 cm).2
Servet Bölükbas, M.D., Ph.D.
Dr. Horst Schmidt Klinik, Wiesbaden, Germany
servet_boeluekbas@web.de Michael Eberlein, M.D., Ph.D.
National Institutes of Health, Bethesda, MDJoachim Schirren, M.D., Ph.D.
Dr. Horst Schmidt Klinik, Wiesbaden, GermanyNo potential conflict of interest relevant to this letter was reported.
2 References1
Rubins JB ,Rubins HB . Temporal trends in the prevalence of malignancy in resected solitary pulmonary lesions. Chest 1996;109:100-103
CrossRef | Web of Science | Medline2
Rami-Porta R ,Ball D ,Crowley J , et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the T descriptors in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol 2007;2:593-602
CrossRef | Web of Science | Medline
Author/Editor Response
The strategy for managing noncalcified pulmonary nodules detected by CT scanning that we used in the Dutch–Belgian randomized lung cancer screening trials (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) is based on the volume of new nodules and the volume-doubling time of existing nodules among persons 50 to 75 years of age at high risk for lung cancer. The optimal approach in the case of CT-detected nodules that are less than 1 cm in size, which comprised 98.5% of all baseline nodules detected in our study (8492 of 8623), was unknown. The only available guideline that is based on expert opinions is from the Fleischner Society.1 Therefore, a comparison with the current standard of care, as suggested by Nair, is not possible.
Volume estimates generated by our software are more accurate than estimates based on diameter because cancers are never perfectly round or spherical. Although the volume-doubling time can be estimated with the use of the modified Schwartz equation, which is based on diameters,2 this equation assumes exponential tumor growth, and growth is not always exponential. We plan to publish data on the correlation of the observations made by the two independent readers. Several articles describe the variability of software-generated volume measurements and its dependence on the size of the nodules and the attachment of the nodules to other structures (e.g., fissures and vessels).3,4 The software version that we used (Somaris/5 VA70C-W, Siemens Medical Solutions) was approved for nodules that are less than 1 cm (i.e., <500 mm3). Only participants with nodules that were larger than 500 mm3 were referred for workup and diagnosis. Therefore, it is unlikely that differences in measurement variability between nodules that were smaller than 500 mm3 and those that were larger than 500 mm3 affected the test performance across different strata of nodule size.
We agree with Bölükbas and colleagues that the diagnosis of lung cancer might have been made earlier in the seven participants with a positive baseline test result and negative findings on bronchoscopy if we had adhered to the protocol and referred them immediately for invasive diagnostic workup. We also agree that other risk factors for lung cancer in addition to size and volume-doubling time may help to differentiate between benign and malignant nodules. Therefore, we plan to examine whether using information from risk models of lung cancer that incorporate epidemiologic risk factors and biomarkers could help to reduce the rates of false positive test results and resections for benign lesions.
Rob van Klaveren, M.D., Ph.D.
Erasmus University Medical Center, Rotterdam, the Netherlands
r.j. vanklaveren@erasmusmc. nl Matthijs Oudkerk, M.D., Ph.D.
University Medical Center Groningen, Groningen, the NetherlandsHarry de Koning, M.D., Ph.D.
Erasmus University Medical Center, Rotterdam, the NetherlandsSince publication of their article, the authors report no further potential conflict of interest.
4 References1
MacMahon H ,Austin JH ,Gamsu G , et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395-400
CrossRef | Web of Science | Medline2
Schwartz M . A biomathematical approach to clinical tumor growth. Cancer 1961;14:1272-1294
CrossRef | Web of Science | Medline3
Gietema HA ,Schaefer-Prokop CM ,Mali WP ,Groenewegen G ,Prokop M . Pulmonary nodules: interscan variability of semi-automated volume measurement with multisection CT -- influence of inspiration level, nodule size, and segmentation performance. Radiology 2007;245:888-894
CrossRef | Web of Science | Medline4
Wang Y ,van Klaveren RJ ,Van der Zaag HJ , et al. Effect of nodule characteristics on variability of semi-automated volume measurements in pulmonary nodules detected in a lung cancer screening program. Radiology 2008;248:625-631
CrossRef | Web of Science | Medline
