Search

Purpose: To determine reproducibility of volume measurements of small pulmonary nodules on computed tomographic (CT) scans and to estimate critical time to follow-up CT., Materials and Methods: One hundred fifteen pulmonary nodules for which two thin-section small-field-of-view CT scans were obtained and which were stable during 2-year observation were evaluated. A standard group of 94 nodules (with no or minimal artifact) and an expanded group of 105 nodules (including those with moderate artifacts) were examined. Percentage volume change (PVC) and monthly volumetric growth index (MVGI) were computed for each nodule pair. By using estimates of the variation in PVC in stable nodules as a function of initial diameter, critical time to follow-up CT was estimated; this time is the earliest point at which growth in a nodule of a given size can be reliably identified with repeat CT., Results: The SD of PVC decreased with increasing nodule size from 18.5% in 2-5-mm nodules to 10.6% in 5-8-mm nodules and to 7.47% in 8-10-mm nodules. Inclusion of cases with moderate motion artifacts increased the SD of PVC to 27.4% in 2-5-mm nodules, to 17.1% in 5-8-mm nodules, and to 19.3% in 8-10-mm nodules. Critical time to follow-up CT for nodules detected at baseline screening was 12, 5, and 3 months and 1 month for those with initial sizes of 2, 5, 8, and 10 mm, respectively. For nodules detected at annual repeat screening, it was 4 and 3 months and 1 month for nodules that were 3, 4, and 5 mm or larger in size, respectively. Mean MVGI in 94 standard cases was 0.06%, and standard error was 0.21%., Conclusion: Factors that affect reproducibility of nodule volume measurements and critical time to follow-up CT include nodule size at detection, type of scan (baseline or annual repeat) on which the nodule is detected, and presence of patient-induced artifacts.

Purpose: To assess the frequency with which a particular, possibly optimal work-up of noncalcified nodules less than 5.0 mm in diameter identified on initial computed tomographic (CT) images at baseline screening leads to a diagnosis of malignancy prior to first annual repeat screening, compared with a possibly optimal work-up of larger nodules., Materials and Methods: Two series of baseline CT screenings in high-risk people were retrospectively reviewed. The first series (n = 1,000) was performed in 1993-1998; the second (n = 1,897), in 1999-2002. In each series, cases in which the largest noncalcified nodule detected was less than 5.0 mm in diameter and those in which it was 5.0-9 mm were reviewed to determine whether diagnostic work-up prior to first annual repeat screening showed or would have shown nodule growth and led or would have led to a diagnosis based on biopsy or surgical specimens., Results: The frequency with which malignancy was or could have been diagnosed when the largest noncalcified nodule was less than 5.0 mm in diameter was 0 of 378, whereas when the largest noncalcified nodule was 5.0-9 mm in diameter, the frequency was 13 or 14 of 238. If persons with only nodules smaller than 5.0 mm had merely been referred for first annual repeat screening without immediate further work-up, the referrals for such work-up would have been reduced by 54% (from 817 [28%] to 385 [13%] of 2,897)., Conclusion: In modern CT screening for lung cancer at baseline, detected noncalcified nodules smaller than 5.0 mm in diameter do not justify immediate work-up but only annual repeat screening to determine whether interim growth has occurred., (Copyright RSNA, 2004)

On computerized tomography (CT) screening for lung cancer within the Early Lung Cancer Action Project, both at baseline and repeat screening, we found not only solid but also subsolid nodules, which unlike solid ones do not completely obscure the lung parenchyma. We established that subsolid nodules represent approximately 20% of the nodules shown on screening and that they have a higher frequency of malignancy than solid nodules. Although we found growth of solid nodules to be a reliable indicator of malignancy, growth of subsolid nodules was more difficult to assess. On review of our results to date in screening, we have continued to refine our definition of a positive result of screening from that given in our initial publication on screening. We have also provided an updated screening regimen. It starts with the initial, low-dose CT test and for all those with positive results on this initial test, the regimen continues by specifying the work-up needed to rule-in a diagnosis of malignancy. In this regimen, we found growth assessed by high-resolution CT to be a useful indicator of malignancy and have developed image-processing tools to help in this assessment. Once growth is ascertained, we recommend fine-needle aspiration for confirmation of malignancy. It may be that once criteria for definitive growth are established and validated, fine-needle aspiration may become optional. However, in the meantime, in the context of screening, a more cautious approach is warranted.

Even non-scientific people are generally aware of, and commonly also personally affected by, the confusion and debates that arose from two recent systematic reviews and their associated meta-analyses of the published randomized controlled trials (RCTs) that had been designed to assess the usefulness of screening for breast cancer. With nothing about the principles of research on cancer screening learned from this debacle, an RCT on screening for lung cancer has just been launched in the same 'gold standard' framework; and so in about 10 years, and upon expenditure of hundreds of millions of dollars, we are said to be able to learn whether the screening saves lives and whether it thereby is justifiable as a matter of public policy. We here examine the core tenets and precepts in this 'gold standard' line of thinking, and we argue that they are matters of belief at variance with the dictates of reason.

Background: The pattern of results in the Mayo Lung Project (MLP), which is the basis for the prevailing recommendations against radiographic screening for lung carcinoma, has led to the assertion that up to 50% of the diagnosed cases of early-stage disease in that trial may have represented overdiagnosed, indolent cases. This finding suggests the possibility of such a high frequency of overdiagnosis in chest radiographic lung carcinoma screening in general. In the current study, the authors analyzed data from the MLP and its counterpart study at Memorial Sloan-Kettering Cancer Center (MSK) to estimate the frequency of overdiagnosis in these studies., Methods: For the cases diagnosed as Stage I in the MLP and the MSK studies, the doubling times of tumor volumes were calculated. The calculations were based on size measurements recorded by the original investigators from chest radiographs taken during the course of each study., Results: The median doubling times were 101 days in the MLP and 144 days in the MSK, times that are somewhat shorter than those reported in published series of adenocarcinoma cases diagnosed outside screening, and only 5% had doubling times exceeding 400 days., Conclusions: The hypothesis that early-stage lung tumors diagnosed on chest radiography during lung carcinoma screening may frequently be overdiagnosed, indolent cases needs to be rejected., (Copyright 2003 American Cancer Society.)

Purpose: To assess the genuineness and curability of diagnosed cases of Stage IA non-small-cell lung cancer of diameter 6-15 mm, with a view to screen-diagnosed asymptomatic cases., Methods: We identified all cases of diagnosed Stage IA (T1N0M0) primary non-small-cell lung cancer documented in the Surveillance, Epidemiology, and End Results (SEER) registry in 1988-1994. There were 885 such cases of diameter 6-15 mm, 33 of them unresected, 1659 of diameter 16-25 mm, and 782 of diameter 26-30 mm. We determined the 8-year cumulative lung-cancer death rates adjusted for competing causes of death, separately for untreated and fully resected cases. Given the relative underdetection of lymph node metastases of the untreated cases, we also documented the case-fatality rates for the resected with inclusion of those with detected intra-pulmonary, hilar or ipsilateral mediastinal lymph node metastases., Results: The 8-year fatality rate for the diagnosed but untreated cases of lung cancer 6-15 mm in diameter was 87%, for 16-25 mm it was 94%, and for 26-30 mm it was 88%. The corresponding estimates of cure rates with resection were 71, 67, and 55%, respectively. The cure rate estimate for the smallest cancers was 66% when adding those with detected lymph node metastases to the resected series, for those 16-25 mm in diameter it was 65%, and for those 26-30 mm in diameter it was 51%., Conclusion: Almost all diagnosed cases of Stage IA lung cancer as small as 10 mm in diameter have a malignant natural course, fatal if not treated, thus representing genuine cancer. Most of these cases are curable by resection.

The Early Lung Cancer Action Project (ELCAP) recently demonstrated that earlier diagnosis of lung cancer can be achieved with CT, and these results have led to considerable demand for CT screening. The advisability of screening seems obvious, as screening has been shown to provide for lung cancer treatment at a relatively early stage, leading to a better chance to avert death from lung cancer than when treatment is prompted by symptoms and/or signs. There are, however, countervailing ideas that CT lung cancer screening has not yet been demonstrated to 'save lives.' Further, it has been stated that CT screening has a notable problem of "overdiagnosis," meaning that screening finds lesions that are not life threatening, leading to unnecessary surgery. These concerns have led to the argument that assessing 'lives saved,' as well as the effects of overdiagnosis, can only be achieved with a randomized, controlled trial comparing CT screening with no screening, using a mortality endpoint. To this end, the National Lung Screening Trial (NLST) has been funded. This randomized, controlled trial is the most expensive screening study ever proposed. It compares CT screening with chest X-ray screening, and its designers envision that it will provide an answer about the benefit of CT screening, or lack thereof, in about 10 years. We do not question the value of the randomized design of 'treatment' trials for comparing competing interventions (treatments), but we have serious concerns about the use of randomization in the evaluation of a diagnostic test, such as CT. We feel that randomization is not necessary for evaluating a diagnostic test and may generate misleading results. Rather, we feel that the desired information is how often and how early is the disease diagnosed using that test. The purpose of this article is to raise the general level of concern about the underpinnings of such randomized 'screening' trials, and to convey some of the evidence that led to our pessimism about the NLST.

This article reviews the current state of knowledge regarding computed tomography (CT) screening for lung cancer. The initial 3 studies have demonstrated the superiority of CT-based screening for lung cancer over traditional radiography. Furthermore, false-positive tests common on baseline screening were manageable without notable excess of biopsies or thoracotomies. Differences and similarities of various screening regimens are discussed in relation to reported study results. When comparing the various studies, the focus should be placed on the diagnostic distribution achieved under annual repeat screening, as it is this distribution which is obtained year after year of repeat screening and this distribution and the curability of these repeat screen-diagnosed lung cancer which determine the usefulness of the screening regimen. To date, these studies demonstrate a consistent shift to over 80% of the cancer being diagnosed in Stage IA. This marked shift suggest that the curability of screen-detected lung cancers will be markedly improved.

Objective: In the Early Lung Cancer Action Project (ELCAP), we found not only solid but also part-solid and nonsolid nodules in patients at both baseline and repeat CT screening for lung cancer. We report the frequency and significance of part-solid and nonsolid nodules in comparison with solid nodules., Materials and Methods: We reviewed all instances of a positive finding in patients at baseline (from one to six noncalcified nodules) and annual repeat screenings (from one to six newly detected noncalcified nodules with interim growth) to classify each of the nodules as solid, part-solid, or nonsolid. We defined a solid nodule as a nodule that completely obscures the entire lung parenchyma within it. Part-solid nodules are those having sections that are solid in this sense, and nonsolid nodules are those with no solid parts. Chi-square statistics were used to test for differences in the malignancy rates., Results: Among the 233 instances of positive results at baseline screening, 44 (19%) involved a part-solid or nonsolid largest nodule (16 part-solid and 28 nonsolid). Among these 44 cases of positive findings, malignancy was diagnosed in 15 (34%) as opposed to a 7% malignancy rate for solid nodules (p = 0.000001). The malignancy rate for part-solid nodules was 63% (10/16), and the rate for nonsolid nodules was 18% (5/28). Even after standardizing for nodule size, the malignancy rate was significantly higher for part-solid nodules than for either solid ones (p = 0.004) or nonsolid ones (p = 0.03). The malignancy type in the part-solid or nonsolid nodules was predominantly bronchioloalveolar carcinoma or adenocarcinoma with bronchioloalveolar features, contrasting with other subtypes of adenocarcinoma found in the solid nodules (p = 0.0001). At annual repeat screenings, only 30 instances of positive test results have been obtained; seven of these involved part-solid or nonsolid nodules., Conclusion: In CT screening for lung cancer, the detected nodule commonly is either only part-solid or nonsolid, but such a nodule is more likely to be malignant than a solid one, even when nodule size is taken into account.

The development of CT technology reopened the lung cancer screening debate. Computed tomography screening for lung cancer certainly meets all the criteria required for an appropriate screening test. First and perhaps most importantly, the disease for which the screening is being performed should have a significant prevalence in the population being studied and be a significant health risk for those afflicted with it. Lung cancer is the leading cause of cancer death in both men and women, and one of the most lethal of all cancers.

Objective: As bronchioloalveolar carcinoma (BAC) is noninvasive but, in its later stages, has a worse prognosis than adenocarcinoma with bronchioloalveolar features (ACB), early identification and differentiation is important for therapeutic and prognostic purposes. We wanted to identify features of BAC, which differentiated it from ACB when both presented as ground-glass opacities (GGOs) on CT., Materials and Methods: We reviewed all pathologic specimens of patients who were diagnosed with BAC and ACB in the lung from 1991 to 1999 in our institution and whose malignancy presented as a GGO on CT. This yielded 29 patients, 15 with BAC and 14 with ACB with GGOs on CT. Both univariate frequency table and multivariate logistic regression approaches were used to analyze the CT characteristics of these GGOs (location, GGO pattern, size, shape, margin, presence and type of air bronchogram and pseudocavitation)., Results: BAC most frequently had a "GGO halo" around a solid opacity, often was a GGO "mixed with consolidation" with the smallest BACs being "pure GGO." Air bronchograms were frequently present in the largest GGOs. Pseudocavitations were rare. ACB, on the other hand, most frequently presented as a GGO "mixed with consolidation," less frequently with a "GGO halo" and rarely with "superimposed lymphangitis." The air bronchograms, frequently present, were usually tortuous and ectatic. Pseudocavitation was present in about one-third of the cases. The most useful CT features of GGO in separating those due to BAC from those due to ACB were pure (uniform) ground-glass attenuation and absence of lymphangitis., Conclusion: The CT features of BAC and ACB presenting as GGO reflect the histologic descriptions of these carcinomas.