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Rebecca M. Lindell, MD
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From the Department of Radiology, Mayo Clinic.

Correspondence to: Rebecca M. Lindell, MD, Mayo Clinic, Charlton 2-290, 200 1st St SW, Rochester, MN 55905; e-mail: lindell.rebecca@mayo.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 (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(4):1003-1004. doi:10.1378/chest.10-0086
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To the Editor:

I would like to thank Quint el al and Kakinuma et al for their letters and making us aware of the article by Quint et al titled “Lung Lesion Doubling Times: Values and Variability Based on Method of Volume Determination.”1 Their article’s focus was on volume determination methods, whereas our article in a recent issue of CHEST (December 2009)2 was on the lack of exponential growth of a subset of lung cancers as shown by growth curves and the implications that this could have on prior studies that advocated using two volume measurements to determine volume doubling time. While their study did include growth curves for 20 lesions, only 13 of those were lung cancers, and although it is difficult to be sure from their growth curves, it appears that most, if not all, of their lung cancers were followed with only three CT scan exams. An early criticism of our manuscript during peer review was that it would be difficult to prove or exclude exponential growth based on only three data points, and it was recommended that we include only cases with at least four CT scan exams. Therefore, although Quint and colleagues did generate growth curves, it is our position that based on peer review feedback they did not plot growth curves that were analogous to the curves we plotted. We did perhaps err in not referencing the paper and explaining our reasoning. We do agree with their conclusion that “given the very slow growth of some lung cancers, short term follow-up CT may not always be capable of detecting volume changes indicative of malignancy. Therefore, stability on short term follow-up exams should be interpreted with caution.” However, based on our study we would expand on that to caution that even using a volume doubling equation based on two exams could potentially be misleading since the assumption of exponential growth has been called into question.

The differing results regarding exponential growth are interesting but perhaps somewhat explainable by our prospective screening method and different inclusion criteria. Compared with their study, our study’s criteria resulted in a population of lung cancers with a smaller initial size (none > 8 mm vs a mean of 11-17 mm) and slower growth (volume doubling time mean of 771 days vs a mean range of 58-128 days) that were followed on more CT scan exams for a longer period of time (mean 1,025 days, median 1,051 days, range 404-1,666 days, or 55.5 months if assuming 30 d/mo, vs a mean of 227 days, median 154 days, range 6 days-34.5 months). Since their study was retrospective and only included lesions with a histologic diagnosis, they selected for a different set of cancers. Cancers with a slower growth rate may not have changed sufficiently during the course of their study to have undergone resection and were therefore not included.

Regarding the letter from Quint et al, the “Discussion” section in our article acknowledges that volume calculation based on two-dimensional measurements may be less accurate than an automated volumetric measurement; however, it is more likely to reflect clinical practice. We agree that CT scan-based growth rates are more accurate than the older rates based on prior radiographic studies.

The letter from Kakinuma et al points out an interesting case report3 of a small cell carcinoma that exhibited latent growth, but our report focused on non-small cell lung cancers. Regarding the other articles,4,5 we already acknowledged in our article’s discussion that prior studies have reported decreases in lung cancer size prior to treatment. However, to our knowledge, no article had used growth curves generated from multiple CT scan exams to show a lack of exponential growth, and inference of a potential finding is different from actual data. Reviewing those articles, we still feel that our paper provides unique information by plotting growth curves of screening-detected lung cancers and comparing them to histologic data, CT scan attenuation, stage, survival, and size.

Quint LE, Cheng J, Schipper M, Chang AC, Kalemkerian G. Lung lesion doubling times: values and variability based on method of volume determination. Clin Radiol. 2008;631:41-48. [CrossRef] [PubMed]
 
Lindell RM, Hartman TE, Swensen SJ, Jett JR, Midthun DE, Mandrekar JN. 5-year lung cancer screening experience: growth curves of 18 lung cancers compared to histologic type, CT attenuation, stage, survival, and size. Chest. 2009;1366:1586-1595. [CrossRef] [PubMed]
 
Nakamura H, Kawasaki N, Taguchi M, Kitamura H. A minute small-cell lung cancer showing a latent phase early in growth. Ann Thorac Cardiovasc Surg. 2007;134:254-257. [PubMed]
 
Takashima S, Maruyama Y, Hasegawa M, et al. CT findings and progression of small peripheral lung neoplasms having a replacement growth pattern. AJR Am J Roentgenol. 2003;1803:817-826. [PubMed]
 
Kakinuma R, Ohmatsu H, Kaneko M, et al. Progression of focal pure ground-glass opacity detected by low-dose helical computed tomography screening for lung cancer. J Comput Assist Tomogr. 2004;281:17-23. [CrossRef] [PubMed]
 

Figures

Tables

References

Quint LE, Cheng J, Schipper M, Chang AC, Kalemkerian G. Lung lesion doubling times: values and variability based on method of volume determination. Clin Radiol. 2008;631:41-48. [CrossRef] [PubMed]
 
Lindell RM, Hartman TE, Swensen SJ, Jett JR, Midthun DE, Mandrekar JN. 5-year lung cancer screening experience: growth curves of 18 lung cancers compared to histologic type, CT attenuation, stage, survival, and size. Chest. 2009;1366:1586-1595. [CrossRef] [PubMed]
 
Nakamura H, Kawasaki N, Taguchi M, Kitamura H. A minute small-cell lung cancer showing a latent phase early in growth. Ann Thorac Cardiovasc Surg. 2007;134:254-257. [PubMed]
 
Takashima S, Maruyama Y, Hasegawa M, et al. CT findings and progression of small peripheral lung neoplasms having a replacement growth pattern. AJR Am J Roentgenol. 2003;1803:817-826. [PubMed]
 
Kakinuma R, Ohmatsu H, Kaneko M, et al. Progression of focal pure ground-glass opacity detected by low-dose helical computed tomography screening for lung cancer. J Comput Assist Tomogr. 2004;281:17-23. [CrossRef] [PubMed]
 
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