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Biomedical subjects

David F Yankelevitz

Publications and source records attributed to David F Yankelevitz.

At least 19 recordsLinked to original sources
PubMed2006

Survival of patients with stage I lung cancer detected on CT screening.

BACKGROUND: The outcome among patients with clinical stage I cancer that is detected on annual screening using spiral computed tomography (CT) is unknown. METHODS: In a large collaborative study, we screened 31,567 asymptomatic persons at risk for lung cancer using low-dose CT from 1993 through 2005, and from 1994 through 2005, 27,456 repeated screenings were performed 7 to 18 months after the previous screening. We estimated the 10-year lung-cancer-specific survival rate among participants with clinical stage I lung cancer that was detected on CT screening and diagnosed by biopsy, regardless of the type of treatment received, and among those who underwent surgical resection of clinical stage I cancer within 1 month. A pathology panel reviewed the surgical specimens obtained from participants who underwent resection. RESULTS: Screening resulted in a diagnosis of lung cancer in 484 participants. Of these participants, 412 (85%) had clinical stage I lung cancer, and the estimated 10-year survival rate was 88% in this subgroup (95% confidence interval [CI], 84 to 91). Among the 302 participants with clinical stage I cancer who underwent surgical resection within 1 month after diagnosis, the survival rate was 92% (95% CI, 88 to 95). The 8 participants with clinical stage I cancer who did not receive treatment died within 5 years after diagnosis. CONCLUSIONS: Annual spiral CT screening can detect lung cancer that is curable.

Adult↗
PubMed2006

Diagnostic percutaneous transthoracic needle biopsy does not affect survival in stage I lung cancer.

RATIONALE: Lung cancer dissemination has been cited as a potential adverse consequence of diagnostic percutaneous transthoracic needle biopsy (PTNB) of lung nodules. Despite multiple reports in the literature of malignant spread along the needle track, the potential effect of lung cancer dissemination after PTNB on survival is unknown. OBJECTIVE: To evaluate whether diagnostic PTNB is associated with increased risk of lung cancer death. METHODS: This study included 8,607 cases of surgically resected stage I non-small cell lung cancer diagnosed between 1991 and 1999 from the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare records. Overall and lung cancer-specific survival of patients who had and did not have PTNB was compared using Kaplan-Meier curves. Stratified survival analyses and Cox regression were used to compare survival with adjustment for potential confounders. RESULTS: Approximately 36% of patients underwent diagnostic PTNB. Overall and lung cancer-specific survival did not differ in patients that underwent PTNB as part of their cancer diagnostic work-up and those who did not (p = 0.57 and 0.46, respectively). In stratified and multivariate analysis, PTNB was not associated with an increased risk of death after controlling for age, race, income, access to care, comorbidities, tumor histology and size, and type of treatment received. CONCLUSIONS: In this large national sample, preoperative PTNB was not associated with increased risk of death. These data suggest that PTNB can be safely used for the work-up of pulmonary nodules when there is a suspicion of lung cancer.

Aged↗
PubMed2006

Computed tomographic screening for lung cancer: the relationship of disease stage to tumor size.

BACKGROUND: The relationship of lung cancer stage to tumor diameter has been identified as a prognostic indicator. We report on the stage-size relationship of these asymptomatic, latent lung cancer cases diagnosed by computed tomographic screening. METHODS: Baseline and repeat screening of 28 689 people following the International Early Lung Cancer Action Program regimen of screening has resulted in 464 diagnoses of lung cancer. Each case was characterized according to tumor diameter, consistency (solid, part solid, or nonsolid), and the presence or absence of identifiable metastases (N0 M0) at the time of diagnosis, regardless of whether it was delayed. RESULTS: For the 436 non-small cell carcinomas, the percentages of cases with no metastases (N0 M0) were 91%, 83%, 68%, and 55% for the categories 15 mm or less, 16 to 25 mm, 26 to 35 mm, and 36 mm or greater, respectively. The gradients in the successive percentages of N0 M0 cases were significantly different (P = .02, 1-sided), except between the last 2 categories, and held for solid nodules, were suggestive for part-solid ones, but were not suggestive for nonsolid ones. For the 28 small cell carcinomas, the percentages of N0 M0 cases were 67% and 23% (P = .01, 1-sided), respectively, for those 25 mm or less compared with those greater than 25 mm. CONCLUSIONS: Lymph node status has a strong relationship to tumor diameter for non-small cell and small cell cancers. The percentages of N0 M0 cases in screen-diagnosed lung cancers are much higher than previously reported in the Surveillance, Epidemiology, and End Results registry. These results provide direct evidence of a stage-size relationship in a screened population.

Adenocarcinoma↗
PubMed2006

Evaluation of lung MDCT nodule annotation across radiologists and methods.

RATIONALE AND OBJECTIVES: Integral to the mission of the National Institutes of Health-sponsored Lung Imaging Database Consortium is the accurate definition of the spatial location of pulmonary nodules. Because the majority of small lung nodules are not resected, a reference standard from histopathology is generally unavailable. Thus assessing the source of variability in defining the spatial location of lung nodules by expert radiologists using different software tools as an alternative form of truth is necessary. MATERIALS AND METHODS: The relative differences in performance of six radiologists each applying three annotation methods to the task of defining the spatial extent of 23 different lung nodules were evaluated. The variability of radiologists' spatial definitions for a nodule was measured using both volumes and probability maps (p-map). Results were analyzed using a linear mixed-effects model that included nested random effects. RESULTS: Across the combination of all nodules, volume and p-map model parameters were found to be significant at P < .05 for all methods, all radiologists, and all second-order interactions except one. The radiologist and methods variables accounted for 15% and 3.5% of the total p-map variance, respectively, and 40.4% and 31.1% of the total volume variance, respectively. CONCLUSION: Radiologists represent the major source of variance as compared with drawing tools independent of drawing metric used. Although the random noise component is larger for the p-map analysis than for volume estimation, the p-map analysis appears to have more power to detect differences in radiologist-method combinations. The standard deviation of the volume measurement task appears to be proportional to nodule volume.

Artificial Intelligence↗
PubMed2006

Pathologic findings of lung tumors diagnosed on baseline CT screening.

Sixty-five people had a resection of their baseline screen-diagnosed lung cancers in the Early Lung Cancer Action Program. Forty-nine of the carcinomas were solitary, and 42 of these were adenocarcinomas. More than 1 carcinoma was found in 16 patients after pathologic examination of the lobectomy specimen; 15 of the 16 second carcinomas were adenocarcinomas, mixed subtype. Eighteen cases were submitted by local pathologists as Bronchioloalveolar carcinomas but were found to be invasive adenocarcinomas according to the World Health Organization classification by the Pathology Review Panel. Of the 65 resected cases, 57 were N0, 7 were N1, and 1 was N2. Upon careful review of the lobectomy specimens, 49 cases had solitary malignancies, 30 were Stage IA, 13 Stage IB, 3 Stage IIA, 2 Stage IIB, and 1 Stage IIIA on the basis of the American Joint Committee on Cancer/International Union for Cancer Control criteria. In the 16 cases found to have multiple malignancies, 6 had histologically different carcinomas and the remaining 10 had histologically identical malignancies. Eighty-three percent (76/92) of the carcinomas invaded the stroma with destruction of normal lung, and 21% (19/92) also showed either pleural or angiolymphatic invasion, even though 88% (57/65) of the carcinomas were free of lymph node metastases. This report describes the pathologic findings of the resected cases. Histopathologic distinctions among atypical adenomatous hyperplasia, bronchioloalveolar carcinomas, and invasive adenocarcinoma are described in detail.

Aged↗
PubMed2006

On measuring the change in size of pulmonary nodules.

The pulmonary nodule is the most common manifestation of lung cancer, the most deadly of all cancers. Most small pulmonary nodules are benign, however, and currently the growth rate of the nodule provides for one of the most accurate noninvasive methods of determining malignancy. In this paper, we present methods for measuring the change in nodule size from two computed tomography image scans recorded at different times; from this size change the growth rate may be established. The impact of partial voxels for small nodules is evaluated and isotropic resampling is shown to improve measurement accuracy. Methods for nodule location and sizing, pleural segmentation, adaptive thresholding, image registration, and knowledge-based shape matching are presented. The latter three techniques provide for a significant improvement in volume change measurement accuracy by considering both image scans simultaneously. Improvements in segmentation are evaluated by measuring volume changes in benign or slow growing nodules. In the analysis of 50 nodules, the variance in percent volume change was reduced from 11.54% to 9.35% (p = 0.03) through the use of registration, adaptive thresholding, and knowledge-based shape matching.

Algorithms↗
PubMed2006

CT screening for lung cancer: the value of short-term CT follow-up.

BACKGROUND: Although CT screening for lung cancer results in a diagnosis of stage I > 80% of the time, benign noncalcified nodules are also found. We recognized that some nodules appeared to represent infectious bronchopneumonia or other inflammatory processes, as they resolved on follow-up CT, sometimes after antibiotic therapy. To determine the extent to which short-term CT radiographic follow-up might shorten the workup of nodules, we reviewed our experience with baseline and annual repeat CT screenings performed subsequent to the original Early Lung Cancer Action Project series. METHODS: The initial CT of 1,968 consecutive baseline and 2,343 annual repeat screenings performed from 1999 to 2002 was reviewed. We identified all those recommended for antibiotics on the initial CT who had a follow-up CT within 2 months and determined whether the nodule(s) resolved, decreased in size, remained unchanged, or grew. We then determined whether further follow-up resulted in a diagnosis of cancer. RESULTS: At baseline, among the 41 individuals who had follow-up CT within 2 months of the initial CT, 12 patients (29%) had complete or partial resolution; none of them subsequently received a diagnosis of lung cancer. On annual repeat screening, among the 39 individuals who had follow-up CT within 2 months of the initial CT, 29 patients (74%) had complete or partial resolution; none of them subsequently received a diagnosis of lung cancer. Among the 29 patients with nodules at baseline that were unchanged or grew, a total of 15 cancers were subsequently diagnosed; among the 10 patients on annual repeat scanning, there were 2 cancers. CONCLUSIONS: In asymptomatic individuals undergoing CT screening for lung cancer, short-term follow-up CT within 2 months with or without antibiotics may circumvent the need for further evaluation in some individuals, particularly on annual repeat screening.

Anti-Bacterial Agents↗
PubMed2006

Computed tomography screening for lung cancer: prospects of surviving competing causes of death.

PURPOSE: The primary objective of this study was to shed light on the frequency of death from a "competing" cause among persons who enter into computed tomography (CT) screening for lung cancer and to determine the 5- and 10-year rates of death from causes other than lung cancer in a cohort of older smokers and former smokers with the initiation of CT screening for lung cancer. PATIENTS AND METHODS: We followed a cohort of 2141 men and women aged 60-75 years with a history of 30-100 pack-years of cigarette smoking who enrolled for CT screening for lung cancer in 1993-2004. The National Death Index retrieval program was used to identify all deaths and causes of death. Follow-up time from the date of the initial CT to death, loss to follow-up, or December 31, 2004, whichever came first, was calculated for each subject. Median duration of follow-up was 50 months (range, 1-133 months). Kaplan-Meier analysis was used to derive the 5- and 10-year survival rates with the exclusion of deaths from lung cancer. RESULTS: The 5- and 10-year survival rates, conditional on not dying from lung cancer, were 96% and 90.7%, respectively. The corresponding 95% confidence intervals were 95%-97% and 88.2%-95.2%, respectively. CONCLUSION: Older smokers and former smokers seeking and receiving CT screening for lung cancer have a low 10-year risk of dying from causes other than lung cancer, and early treatment of screen-diagnosed cancer can be life-saving.

Aged↗
PubMed2005

Bronchioloalveolar carcinoma in small pulmonary nodules: clinical relevance.

Increased use of chest computed tomography (CT) as well as improvements in CT resolution has led to increased detection of subcentimeter pulmonary nodules. Although the majority of these nodules are benign in etiology, a subset will harbor bronchioloalveolar carcinoma. The diagnosis of malignancy in this setting can be challenging to radiologists, surgeons, and occasionally pathologists as well. The challenge is compounded by a lack of knowledge about the natural course of these lesions--specifically, whether they represent life-threatening aggressive malignancies or indolent lesions of little or no consequence. Given the relative infrequency of these abnormalities, it will be essential to establish a sufficiently large database, to organize multi-institutional registries, and to collaborate on correlative studies. Only in this way will we be able to determine the clinical and molecular characteristics of these lesions and thus hopefully gain insight into their clinical relevance.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2005

CT screening for lung cancer: past and ongoing studies.

It has been widely recognized that the oft-quoted randomized clinical trials (RCTs) of lung cancer screening by chest radiography--studies that were interpreted as showing no benefit--were seriously flawed. We begin by describing the shortcomings of these trials and presenting an analysis of the problems typically encountered in performing RCTs in this area. Screening for lung cancer using computed tomography (CT) has shown that CT offers great superiority over chest radiography in diagnosing small lung cancers in the three studies that performed both CT and chest radiography on all patients. The Early Lung Cancer Action Project (ELCAP), showed that false-positive results can be kept reasonably low and are much less common on repeat screening, and that CT screening can be managed with no notable excess of percutaneous or surgical biopsies when following a well-defined regimen of screening. This regimen details the parameters of the initial CT, the definition of a positive result, and the subsequent work-up of positive results. Following the updated International (I)-ELCAP protocol, it has been further found that (1) the frequency of positive results is low: 15% for the baseline cycle of screening and 6% for the subsequent cycles. (2) The frequency of screen-diagnoses as compared with all diagnoses is 97% or higher. (3) The relative frequency of presurgical Stage I is well over 80%; the median diameter of the screen-diagnosed cases on repeat screening is 8 mm (versus 15 mm at baseline screening). (4) A high percentage of the screen-diagnosed cases were genuine cancers which led to death if not treated. (5) The estimated 8-year cure rate for resected baseline screen-diagnosed lung cancers without evidence of lymph node metastases is 95% and for resected annual repeat cancers is 98%. (6) CT screening appears to be highly cost-effective. These preliminary results of CT screening suggests that the cure rate of screen-diagnosed lung cancer, using the I-ELCAP regimen of screening, may be over 70% as compared with that of usual care of 10% and that of chest radiographic screening of 20%.

Adenocarcinoma↗
PubMed2005

Thromboembolic disease detection at indirect CT venography versus CT pulmonary angiography.

PURPOSE: To assess the incremental increase in thromboembolic disease detection at indirect computed tomographic (CT) venography versus CT pulmonary angiography and to determine the importance of scan interval for indirect CT venography on the basis of thrombus length. MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was not required. The study included 1590 consecutive patients undergoing CT pulmonary angiography for the suspicion of pulmonary embolism. Two minutes after completion of pulmonary angiography, a contiguous indirect CT venography was performed from the iliac crest to the popliteal fossa. The presence of pulmonary embolism or deep venous thrombosis (DVT) was recorded for all patients. The lengths of all deep venous thrombi found in the first 378 consecutive patients were recorded. RESULTS: Pulmonary embolism was detected in 243 (15%) of 1590 patients at CT pulmonary angiography, and DVT was detected in 148 (9%) patients at indirect CT venography. Among 148 patients with DVT, pulmonary embolism was detected in 100 patients at CT pulmonary angiography. Thus, the addition of indirect CT venography to CT pulmonary angiography resulted in a 20% incremental increase in thromboembolic disease detection compared with that at CT pulmonary angiography alone (99% confidence interval: 17%, 23%). Among the 378 patients, DVT was present in 33 patients at indirect CT venography. Two (6%) of 33 patients had clots measuring 2 cm or less, six (18%) had clots measuring 3-4 cm, and 25 (76%) had clots measuring more than 4 cm in length. CONCLUSION: The addition of indirect CT venography to CT pulmonary angiography incrementally increases the detection rate of thromboembolic disease by 20%. Performance of indirect CT venography by using contiguous section intervals, with a section width of 1 cm, is recommended to accurately detect DVT.

Adolescent↗
PubMed2005

Lung cancer screening: simulations of effects of imperfect detection on temporal dynamics.

PURPOSE: To use a mathematic model to demonstrate effects of imperfect detection on temporal dynamics of radiologic lung cancer screening. MATERIALS AND METHODS: Monte Carlo simulations of lung cancer screening programs were performed in subjects at high risk for developing cancer. The effects of detection probabilities, symptomatic presentation of tumors, tumor volume doubling time, and time between screenings were examined. Computed tomography (CT) and chest radiography models were used. RESULTS: For imperfect detection probabilities, the percentage of subjects with cancers detected with repeated screenings decreased to a steady-state value. The transition period was the period during which screenings were performed and detection rates decreased. At steady-state repeat screening, the proportion of subjects with cancers diagnosed at screening or by means of symptomatic presentation was determined by the annual probability of developing cancer and not by the sensitivity of the screening modality. The sensitivity of the screening technique did affect detected cancer size, number of interval cancers, and total number of cancers observed. CT was used to detect more total cancers over the course of the screening program and cancers with a smaller average size; moreover, fewer interval cancers were observed with CT screening than with chest radiography screening. CONCLUSION: Lung cancer screening with imperfect detection has a transition period between baseline screening and steady-state behavior of annual screenings. Advantages of CT screening include a decrease in the average cancer size at detection, a decrease in the number of observed interval cancers, and an increase in the total number of cancers observed. Steady-state behavior indicates that long-term trials of screening may not be necessary.

Humans↗
PubMed2004

CT screening for lung cancer: suspiciousness of nodules according to size on baseline scans.

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.

Adult↗
PubMed2004

Small pulmonary nodules: reproducibility of three-dimensional volumetric measurement and estimation of time to follow-up CT.

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.

Artifacts↗
PubMed2003

Overdiagnosis in chest radiographic screening for lung carcinoma: frequency.

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.

Adenocarcinoma↗
PubMed2003

Small stage I cancers of the lung: genuineness and curability.

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.

Adult↗