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Nodule Volume MeasurementNodule Volume Measurement: Pushing the Pendulum: Pushing the Pendulum FREE TO VIEW

Douglas A. Arenberg, MD, FCCP
Author and Funding Information

From the Department of Internal Medicine, Division of Pulmonary & Critical Care Medicine, University of Michigan Medical School.

Correspondence to: Douglas A. Arenberg, MD, FCCP, University of Michigan Medical School, 1150 W Medical Ctr Dr, 6301 MSRB III, Ann Arbor, MI 48109-5642; e-mail: darenber@umich.edu


Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(3):440-442. doi:10.1378/chest.13-1964
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In 2005, when the original Fleischner Society recommendations for the management of indeterminate solitary pulmonary nodules was published, it was evident that incidental nodules were a growing clinical challenge.1 There is a reason that the Fleischner criteria paper1 is among the most commonly cited reference in the radiologic literature. We do more CT scans, for more reasons, with better and better resolution. We read scans on high-resolution screens often with > 500 images instead of films with 50 to 60 images. We are flush with nodules, and the role of the “oncopulmonologist” is to prove they are benign.

We have three tools in our kit for obtaining proof: benign patterns of fat or calcification, surgical resection, and time. A biopsy specimen is better at proving something is cancer than at providing definitive proof of benignity. Given that few calcified nodules ever result in referral to a specialist, proof of benignity boils down to referral for surgery or serial observation. We decide among these polar opposite strategies of surgery and observation on the basis of pretest estimates of the probability of malignancy, aided by the use of fluorodeoxyglucose-PET scans. We use clinical intuition to push a pendulum toward a high or low probability of malignancy, and the features we use to generate this intuition are largely based on the patient’s risk for cancer (prior history of cancer and tobacco use) and the characteristics of the nodule (eg, size, density, and border characteristics). Nobody should want to diagnose a benign nodule with surgical resection.

The American College of Chest Physicians recommendations advocate that the first step in the evaluation of any nodule is to estimate the pretest probability of malignancy.2 In this setting we teach one of two approaches: clinical intuition or models using clinically available information to mathematically describe our intuition. The most frequently used model was published by Swensen et al3 in 1997, and though it was largely developed based upon nodules detected by chest radiography, it remains useful to this day, perhaps due to its simplicity.4 Despite the usefulness of these models, astute investigators continue to ask important questions such as whether we have mined the radiologic characteristics of nodules for all of their predictive ability. In this edition of CHEST (see page 464), Mehta et al5 publish a report that took the existing Swensen model and added volumetric nodule measurements to determine whether there is incremental predictive value in measuring lung nodule volume for detecting (or, conversely, excluding) cancer. The authors used the Swensen model to determine the probability of malignancy in 230 nodules (221 consecutive subjects). Clinical data and nodule characteristics were combined with volume measurements that were calculated using a commercially available product. Subjects were prospectively followed and a definitive diagnosis was established either by resection, biopsy specimen, or size stability for at least 2 years on serial CT scans. The investigators incorporated volume as a variable into the Swensen model in three separate ways: nodule volume (model 1), the ratio of volume to diameter (model 2), or sphericity index (model 3)—a metric defined as the ratio of measured nodule volume to the volume of a perfect sphere with a diameter equal to that of the nodule. Using a 0.5 probability of malignancy as a cutoff, they determined that models 1 (83%), 2 (88%), and 3 (88%) correctly classified more nodules than Swensen’s base model (67%). It should be emphasized that the main improvement in accuracy of the models incorporating volume measurements was the increased recognition of malignant nodules beyond what the Swensen model would predict. Volume measurements were, thus, better at pushing the pendulum toward cancer than toward benignity. Their inclusion of only subjects with nodules of < 15 mm diameter makes this particularly relevant to clinical practice, since larger nodules pose very little management dilemma.

The study’s findings are important for more reasons, and the most notable of these may not be the most obvious. Mehta et al5 recognized first and foremost that there is untapped potential in single CT scans; that is, CT scans contain additional important information that can inform us about the likelihood of malignancy in incidental or screen-detected nodules. In addition to volumetric measurements, there are almost certainly other features of nodules that can be determined on CT scan that improve our ability to discriminate malignant from benign. Some of these fall under the category of low hanging fruit, such as the perifissural location and angular shape of some small nodules, which is almost always predictive of a benign nature.6 Other possibilities include the potential to define the border more precisely. Can higher-resolution images detect spiculation that we might otherwise have overlooked? Certainly ground-glass character is recognized as a two-edged sword that predicts both a higher likelihood of malignancy yet a lower likelihood of invasiveness (in situ carcinoma). In an era in which nodule detection is likely to increase even more, we should continue to seek ways to move the pendulum toward the extremes and inform the decision-making process for anxious patients.

So what have we learned? I would congratulate the investigators for showing us that (1) we are not at the end of the line in terms of what CT scans can tell us about a nodule; (2) diameter matters, but so does volume and other characteristics not addressed in this article; and (3) nodule evaluation is a moving target, and we will have to use all the tools at our disposal to define, develop, test, validate, and compare models.

What additional challenges can we focus on? The issue of overdiagnosis is not going to go away. Can we recognize clinically insignificant nodules and avoid treating indolent, nonprogressing cancer? Recognition of the in situ nature of pure ground-glass nodules may provide an opportunity to answer this question. How do we communicate the risk of overdiagnosis and its harm to anxious patients who have been indoctrinated in and convinced of the value of early detection? Early detection is necessary, but not sufficient for a screening program. Only a mortality benefit can prove the value of early detection. How do we use measurements of nodule volume in a screened population? We cannot necessarily extrapolate data from this study of incidentally detected nodules to a population of subjects being screened for cancer. The Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trial may teach us how to incorporate nodule volume measurement in a screening setting to reduce use of unnecessary imaging and biopsy procedures.7

References

MacMahon H, Austin JHM, Gamsu G, et al; Fleischner Society. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology. 2005;237(2):395-400. [CrossRef] [PubMed]
 
Gould MK, Donington J, Lynch WR, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5_suppl):e93S-e120S. [CrossRef] [PubMed]
 
Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. 1997;157(8):849-855. [CrossRef] [PubMed]
 
Swensen SJ, Silverstein MD, Edell ES, et al. Solitary pulmonary nodules: clinical prediction model versus physicians. Mayo Clin Proc. 1999;74(4):319-329. [CrossRef] [PubMed]
 
Mehta HJ, Ravenel JG, Shaftman SR, et al. The utility of nodule volume in the context of malignancy prediction for small pulmonary nodules. Chest. 2014;145(3):464-472.
 
de Hoop B, van Ginneken B, Gietema H, Prokop M. Pulmonary perifissural nodules on CT scans: rapid growth is not a predictor of malignancy. Radiology. 2012;265(2):611-616. [CrossRef] [PubMed]
 
van Klaveren RJ, Oudkerk M, Prokop M, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009;361(23):2221-2229. [CrossRef] [PubMed]
 

Figures

Tables

References

MacMahon H, Austin JHM, Gamsu G, et al; Fleischner Society. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology. 2005;237(2):395-400. [CrossRef] [PubMed]
 
Gould MK, Donington J, Lynch WR, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5_suppl):e93S-e120S. [CrossRef] [PubMed]
 
Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. 1997;157(8):849-855. [CrossRef] [PubMed]
 
Swensen SJ, Silverstein MD, Edell ES, et al. Solitary pulmonary nodules: clinical prediction model versus physicians. Mayo Clin Proc. 1999;74(4):319-329. [CrossRef] [PubMed]
 
Mehta HJ, Ravenel JG, Shaftman SR, et al. The utility of nodule volume in the context of malignancy prediction for small pulmonary nodules. Chest. 2014;145(3):464-472.
 
de Hoop B, van Ginneken B, Gietema H, Prokop M. Pulmonary perifissural nodules on CT scans: rapid growth is not a predictor of malignancy. Radiology. 2012;265(2):611-616. [CrossRef] [PubMed]
 
van Klaveren RJ, Oudkerk M, Prokop M, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009;361(23):2221-2229. [CrossRef] [PubMed]
 
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