Roche Diagnostics提供部分資助予本研究。van Klaveren博士報告接受Eli Lilly、Roche Pharmaceuticals與Roche Diagnostics等的諮詢費用、演講費用以及資金支持。Mulshine醫師報告接受Savara Pharmaceutical的顧問費用；Optical Society of America — Kitware的資金支持；和部份與肺癌診斷之分子方法有關的專利費用。
N Engl J Med. 2009;361:2221-2229, 2281-2282.
Is That CT-Detected Noncalcified Nodule Lung Cancer or Not?
By Nick Mulcahy
Medscape Medical News
December 4, 2009 — It is not yet known whether lung cancer screening with computed tomography (CT) provides a mortality benefit. A number of clinical trials are ongoing to address that unknown.
Investigators from one of those trials, from the Netherlands and Belgium, report not on mortality benefit, but on a clinical challenge presented by the technology: how to proceed with patients in whom noncalcified pulmonary nodules are detected.
The investigators, in a report published in the December 3 issue of the New England Journal of Medicine, explain that the use of a "volume-doubling time" measurement is a highly accurate method for determining which of these nodules can be categorized as a "negative" scan result and not a clinically significant lung cancer.
This volumetric measurement, which is made with the help of nonproprietary software that can be used with any CT system, helped provide a negative predictive value of 99.7% (95% confidence interval, 99.6 to 99.8) among the negative scans in the study, report the investigators from the Nederlands-Luevens Longanker Screening Onderzoek (NELSON) trial.
Volume-doubling time refers to the estimated amount of time it takes for a nodule to double its volume.
In this study of 7557 high-risk lung cancer patients who underwent CT screening, a nodule with a doubling time of more than 400 days was considered slow and, therefore, the scan was considered negative; scans that showed no nodules were also considered negative.
Among the 7361 negative CT scans detected by an initial round of scanning of these high-risk patients, only 20 lung cancers were detected during 2 years of follow-up — yielding the high negative predictive value.
"The chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively," note the authors, led by Rob J. van Klaveren, MD, PhD, from the Erasmus Medical Center in Rotterdam, the Netherlands.
Potential Pain and Money Saver
In an editorial that accompanies the study, a pair of American lung cancer experts were impressed by helpfulness of the volumetric measurements.
"The results suggest that the efficiency of the diagnostic workup for lung cancer can be improved by integrating the measurement of volume growth of lung nodules as an indicator of clinically significant lung cancer while limiting the need for additional costly or potentially harmful diagnostic procedures," write James L Mulshine, MD, from the Rush University Medical Center in Chicago, Illinois, and David M. Jablons, MD, from the University of California, San Francisco Cancer Center.
Referral for additional diagnostic evaluation — which potentially includes a lung biopsy — is the current practice when clinicians find a noncalcified nodule larger than 5 mm in diameter in this setting, write the study authors.
By measuring volume and volume-doubling time, the investigators write, they were able "to provide an inexpensive and simple follow-up process without increasing the false-negative rate of the screening test."
As the editorialists point out, volume growth of a nodule has been previously proposed as a criterion for malignancy (Radiology. 2000;217:251-256). The contribution of this study is to validate a methodology for this CT-screening workup, say the editorialists. This approach must be further validated in the setting of routine clinical practice, they add.
Study Details
The purpose of the multicenter NELSON trial is to determine whether or not, at 10 years after randomization, CT screening will have reduced mortality from lung cancer by at least 25%, compared with no screening, say the study authors.
The randomized participants, all at high risk for lung cancer, undergo either no screening or screening at baseline (the first round), 1 year, and 3 years from baseline. LungCare software was used to determine the volume and then the volume-doubling time of any noncalcified lung nodule.
Growth of a nodule was defined as an increase in volume of at least 25% between 2 scans. The first round of screening was considered negative "if the nodule volume was less than 50 mm3, if it was 50 to 500 mm3 but had not grown by the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was [an estimated] 400 days or more," they write.
Among the 7557 participants who underwent screening, a noncalcified nodule between 50 mm3 and 500 mm3 was found in 1451 individuals at baseline. Among those, 518 had nodules with an estimated volume-doubling time of more than 400 days according to the follow-up scan at 3 months.
The participants with these slow volume-doubling times were grouped with those who had negative scans at the baseline screening. The combined group was followed for 2 years and, as noted above, 20 lung cancers were subsequently detected.
The study was partly funded by a grant from Roche Diagnostics. Dr. van Klaveren reports receiving advisory board fees, lecture fees, and grant support from Eli Lilly, Roche Pharmaceuticals, and Roche Diagnostics. Dr. Mulshine reports receiving consulting fees from Savara Pharmaceutical; grant support from the Optical Society of America — Kitware; and royalties from patents, some of which involve with molecular methods of lungncancer diagnosis.
