Lung Cancers Manifesting as Part-Solid Nodules in the National Lung Screening Trial.

OBJECTIVE: The objective of our study was to determine how often death occurred from lung cancers that manifested as part-solid nodules in the National Lung Screening Trial (NLST). MATERIALS AND METHODS: NLST radiologists classified nodules as solid, ground-glass, or mixed. All lung cancers classified as mixed nodules by NLST radiologists were reviewed by four experienced radiologists and reclassified as solid, nonsolid, or part-solid nodules. When possible, volume doubling times (VDTs) were calculated separately for the entire nodule and for the solid component of the nodule. RESULTS: Of 88 screening-diagnosed lung cancer cases identified by the NLST radiologists as mixed nodules, study radiologists confirmed that 19 were part-solid nodules. All the part-solid nodules were present at baseline (time 0), and none of the patients with a part-solid nodule had lymph node enlargement at CT before diagnosis or metastases at resection. Multilobar stage IV (T4N0M1) bronchioloalveolar carcinoma was diagnosed in one patient 25.0 months after study randomization, and the patient died 67.9 months after randomization. All 18 patients with a solitary or dominant part-solid nodule underwent surgery, and none died of lung cancer. From randomization, the average time to diagnosis was 18.6 months and the average time of follow-up was 79.2 months. On the last CT examination performed before diagnosis, the average size of the solid component of the part-solid nodules was 9.2 mm (SD, 4.9); the solid component was larger than 10 mm in five patients. The median VDT based on the entire nodule was 476 days, and the median VDT based on the solid component alone was 240 days. CONCLUSION: None of the patients with lung cancer manifesting as a solitary or dominant part-solid nodule had lymph node enlargement or metastases at pathology, and none died of lung cancer within the follow-up time of the NLST.

Low-Dose CT Screening for Lung Cancer: Computer-aided Detection of Missed Lung Cancers.

Purpose To update information regarding the usefulness of computer-aided detection (CAD) systems with a focus on the most critical category, that of missed cancers at earlier imaging, for cancers that manifest as a solid nodule. Materials and Methods By using a HIPAA-compliant institutional review board-approved protocol where informed consent was obtained, 50 lung cancers that manifested as a solid nodule on computed tomographic (CT) scans in annual rounds of screening (time 1) were retrospectively identified that could, in retrospect, be identified on the previous CT scans (time 0). Four CAD systems were compared, which were referred to as CAD 1, CAD 2, CAD 3, and CAD 4. The total number of accepted CAD-system-detected nodules at time 0 was determined by consensus of two radiologists and the number of CAD-system-detected nodules that were rejected by the radiologists was also documented. Results At time 0 when all the cancers had been missed, CAD system detection rates for the cancers were 56%, 70%, 68%, and 60% (κ = 0.45) for CAD systems 1, 2, 3, and 4, respectively. At time 1, the rates were 74%, 82%, 82%, and 78% (κ = 0.32), respectively. The average diameter of the 50 cancers at time 0 and time 1 was 4.8 mm and 11.4 mm, respectively. The number of CAD-system-detected nodules that were rejected per CT scan for CAD systems 1-4 at time 0 was 7.4, 1.7, 0.6, and 4.5 respectively. Conclusion CAD systems detected up to 70% of lung cancers that were not detected by the radiologist but failed to detect about 20% of the lung cancers when they were identified by the radiologist, which suggests that CAD may be useful in the role of second reader. (©) RSNA, 2016.

Lung Cancer Deaths in the National Lung Screening Trial Attributed to Nonsolid Nodules.

Purpose To validate the recommendation of performing annual follow-up of nonsolid nodules (NSNs) identified by computed tomographic (CT) screening for lung cancer, all cases of lung cancer manifesting as NSN in the National Lung Screening Trial (NLST) were reviewed. Materials and Methods Institutional review board and informed consent were waived for this study. The NLST database was searched to identify all participants with at least one NSN on CT scan with lung cancer as the cause of death (COD) documented by the NLST endpoint verification process. Among the 26 722 participants, 2534 (9.4%) had one or more NSNs, and lung cancer as the COD occurred for 48 participants. On review, 21 of the 48 patients had no NSN in the cancerous lobe, which left 27 patients whose CT scans were reviewed by four radiologists: Group A (n = 12) were cases of lung cancer as the COD because of adenocarcinoma, and group B (n = 15) were cases of lung cancer as the COD because of other cell types. Frequency of lung cancer as the COD because of NSN and the time from randomization to diagnosis within these groups was determined. Results Six of the 12 patients in group A had no NSN in the cancerous lobe whereas the remaining six patients had a dominant solid or part-solid nodule in the lobe that rapidly grew in four patients, was multifocal in one patient, and had a growing NSN in one patient in whom diagnosis was delayed for over 3 years. Five of the 15 patients in group B had no NSN, and for the remaining 10 patients, lung cancer as the COD was not because of NSN. Conclusion It seems unlikely that patients with lung cancer as the COD occurred with solitary or dominant NSN as long as annual follow-up was performed. This lends further support that lung cancers that manifest as NSNs have an indolent course and can be managed with annual follow-up. © RSNA, 2016.

CT Screening for Lung Cancer: Part-Solid Nodules in Baseline and Annual Repeat Rounds.

OBJECTIVE: The purpose of this study was to assess the frequencies of identifying participants with part-solid nodules, of diagnostic pursuit, of diagnoses of lung cancer, and long-term lung cancer survival in baseline and annual repeat rounds of CT screening in the International Early Lung Cancer Action Project. MATERIALS AND METHODS: Screenings were performed under a common protocol. Participants with solid, nonsolid, and part-solid nodules and the diagnoses of lung cancer were documented. RESULTS: Part-solid nodules were identified in 2892 of 57,496 (5.0%) baseline screening studies; 567 (19.6%) of these nodules resolved or decreased in size. Diagnostic pursuit led to the diagnosis of adenocarcinoma in 79 cases, all clinical stage I. At resection, one nodule (12-mm solid component) had a single N2 metastasis. A new part-solid nodule was identified in 541 of 64,677 (0.8%) annual repeat screenings; 377 (69.7%) of these nodules resolved or decreased in size. In eight cases among the 541, the diagnosis of adenocarcinoma manifesting as a part solid nodule was made; on retrospective review the nodule originally had been a nonsolid nodule. In another 20 cases, the cancer originally had manifested as a nonsolid nodule but had progressed to become part-solid at annual repeat screening before any diagnosis was pursued. These 28 annual repeat cases of lung cancer were all pathologic stage IA. Of the 107 cases of lung cancer (79 baseline cases and 28 annual repeat cases), 106 were surgically resected, and one baseline case was followed up with imaging for 4 years. The lung cancer survival rate was 100% with a median follow-up period from diagnosis of 89 months (interquartile range, 52-134 months). CONCLUSION: Lung cancers manifesting as part-solid nodules at repeat screening studies all started as nonsolid nodules. Among 107 cases of adenocarcinoma manifesting as a part-solid nodule, a single lymph node metastasis was found in a single case (solid component, 12 mm).

CT Screening for Lung Cancer: Nonsolid Nodules in Baseline and Annual Repeat Rounds.

PURPOSE: To address the frequency of identifying nonsolid nodules, diagnosing lung cancer manifesting as such nodules, and the long-term outcome after treatment in a prospective cohort, the International Early Lung Cancer Action Program. MATERIALS AND METHODS: A total of 57,496 participants underwent baseline and subsequent annual repeat computed tomographic (CT) screenings according to an institutional review board, HIPAA-compliant protocol. Informed consent was obtained. The frequency of participants with nonsolid nodules, the course of the nodule at follow-up, and the resulting diagnoses of lung cancer, treatment, and outcome are given separately for baseline and annual repeat rounds of screening. The χ(2) statistic was used to compare percentages. RESULTS: A nonsolid nodule was identified in 2392 (4.2%) of 57,496 baseline screenings, and pathologic pursuit led to the diagnosis of 73 cases of adenocarcinoma. A new nonsolid nodule was identified in 485 (0.7%) of 64,677 annual repeat screenings, and 11 had a diagnosis of stage I adenocarcinoma; none were in nodules 15 mm or larger in diameter. Nonsolid nodules resolved or decreased more frequently in annual repeat than in baseline rounds (322 [66%] of 485 vs 628 [26%] of 2392, P < .0001). Treatment of the cases of lung cancer was with lobectomy in 55, bilobectomy in two, sublobar resection in 26, and radiation therapy in one. Median time to treatment was 19 months (interquartile range [IQR], 6-41 months). A solid component had developed in 22 cases prior to treatment (median transition time from nonsolid to part-solid, 25 months). The lung cancer-survival rate was 100% with median follow-up since diagnosis of 78 months (IQR, 45-122 months). CONCLUSION: Nonsolid nodules of any size can be safely followed with CT at 12-month intervals to assess transition to part-solid. Surgery was 100% curative in all cases, regardless of the time to treatment.

CT screening for lung cancer: value of expert review of initial baseline screenings.

OBJECTIVE. Appropriate radiologic interpretation of screening CT can minimize unnecessary workup and intervention. This is particularly challenging in the baseline round. We report on the quality assurance process we developed for the International Early Lung Cancer Action Program. MATERIALS AND METHODS. After initial training at the coordinating center, radiologists at 10 participating institutions and at the center independently interpreted the first 100 baseline screenings. The radiologist at the institutions had access to the center interpretations before issuing the final reports. After the first 100 screenings, the interpretations were jointly discussed. This report summarizes the results of the initial 100 dual interpretations at the 10 institutions. RESULTS. The final institution interpretations agreed with the center in 895 of the 1000 interpretations. Compared with the center, the frequency of positive results was higher at eight of the 10 institutions. The most frequent reason of discrepant interpretations was not following the protocol (n = 55) and the least frequent was not identifying a nodule (n = 3). CONCLUSION. The quality assurance process helped focus educational programs and provided an excellent vehicle for review of the protocol with participating physicians. It also suggests that the rate of positive results can be reduced by such measures.

Retrospective review of lung cancers diagnosed in annual rounds of CT screening.

OBJECTIVE: The purpose of this study was to review the records of patients with diagnoses of lung cancer in annual repeat rounds of CT screening in the International Early Lung Cancer Action Program to determine whether the cancer could have been identified in the previous round of screening. MATERIALS AND METHODS: Three radiologists reviewed the scans of 104 lung cancer patients and assigned the findings to one of three categories: 1, cancer was not visible at previous CT screening; 2, cancer was visible at previous CT screening but not identified; 3, abnormality was identified at previous CT screening but not classified as malignant. Nodule size, nodule consistency, cell type, and stage at the previous screening and when identified for further workup for each of the three categories were tabulated. RESULTS: Twenty-four (23%) patients had category 1 findings; 56 (54%) category 2; and 24 (23%) category 3. When diagnosed, seven (29%) category 1, 10 (18%) category 2, and four (17%) category three cancers had progressed beyond stage I. All cancers seen in retrospect were in clinical stage I at the previous screening. Category 1 cancers, compared with categories 2 and 3, had faster growth rates, were less frequently adenocarcinomas (29% vs 54% and 67%, p = 0.01), and were more often small cell carcinomas (29% vs 14% and 12%, p = 0.12). CONCLUSION: Lung cancers found on annual repeat screenings were frequently identified in the previous round of screening, suggesting that review of the varied appearance and incorporation of advanced image display may be useful for earlier detection.

Study on chemical constituents of Cyclocarya paliurus.

A new dammarane triterpenoid glycoside named cyclocarioside J (1) and other three known triterpenoid glycosides were isolated from the leaves of Cyclocarya paliurus. Based on ESI-MS, HR-ESI-MS, (1)H NMR, (13)C NMR, and 2D NMR techniques including (1)H-(1)H COSY, HMBC, HMQC, and NOESY correlations, the structure of cyclocarioside J was elucidated as (20S,24R)-epoxydammarane 3ß,12ß,25-trihydroxy-12-O-ß-d-quinovopyranosyl-3-O-α-l-arabinopyranoside.

Studies on chemical constituents of Ophiopogon japonicus.

Two new and six known steroidal glucosides were isolated from the tuber of Ophiopogon japonicus. The new steroidal glucosides were established as (20R,25R)-26-O-ß-d-glucopyranosyl-3ß,26-dihydroxycholest-5-en-16,22-dioxo-3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside (1) and 26-O-ß-d-glucopyranosyl-(25R)-furost-5-en-3ß,14α,17α,22α,26-pentaol-3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside (3) on the basis of spectroscopic data as well as chemical evidence.

EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50.

Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As relatively long-lived mammals based on body size, bats display unique telomeric patterns, including the up-regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion. Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro-cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans. In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.

Management of lung nodules detected by volume CT scanning.

BACKGROUND: The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT. METHODS: A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm(3), if it was 50 to 500 mm(3) but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more. RESULTS: In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up. CONCLUSIONS: Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, 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. (Current Controlled Trials number, ISRCTN63545820.)

A new triterpenoid saponin from Gymnema sylvestre.

Besides four known compounds, a new triterpenoid saponin was isolated from the stems of Gymnema sylvestre. The structure of the new triterpenoid saponin was established as 3ß,16ß,22α-trihydroxy-olean-12-ene 3-O-ß-D-xylopyranosyl-(1 → 6)-ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranoside (1) on the basis of 1D and 2D NMR techniques, including COSY, HMBC, HMQC, and NOESY correlations. Four known compounds 2, 3, 4, and 5 were identified on the basis of spectroscopic data.

Molecular convergence and transgenic evidence suggest a single origin of laryngeal echolocation in bats.

The laryngeal echolocation is regarded as one of the conspicuous traits that play major roles in flourishing bats. Whether the laryngeal echolocation in bats originated once, however, is still controversial. We here address this question by performing molecular convergence analyses between ancestral branches of bats and toothed whales. Compared with controls, the molecular convergences were enriched in hearing-related genes for the last common ancestor of bats (LCAB) and extant echolocating bats, but not for the LCA of Old World fruit bats (LCAP). And the convergent hearing gene prestin of the LCAB and the extant echolocating bats functionally converged. More importantly, the high-frequency hearing of the LCAP-prestin knock-in mice decreased with lower cochlear outer hair cell function compared with the LCAB-prestin knock-in mice. Together, our findings provide multiple lines of evidence suggesting a single origin of laryngeal echolocation in the LCAB and the subsequent loss in the LCAP.

Morphological and histological analysis on the in vivo degradation of poly (propylene fumarate)/(calcium sulfate/ß-tricalcium phosphate).

Poly (propylene fumarate)/(Calcium sulfate/ß-tricalcium phosphate) (PPF/(CaSO(4)/ß-TCP)) is a kind of biodegradable composite designed for bone tissue engineering. The in vitro degradation behavior of this composite has been investigated in our previous study. The aim of this study was to investigate the effects of PPF molecular weight and CaSO(4)/ß-TCP molar ratio on the in vivo degradation of PPF/(CaSO(4)/ß-TCP) composite and the bone tissue response to PPF/(CaSO(4)/ß-TCP). Total 36 PPF/(CaSO(4)/ß-TCP) composite samples were implanted into 15.0 mm segmental defects in tibiae of 18 Japanese rabbits, harvested at 2, 4 and 8 weeks after the operation, and analyzed using radiographic and histological analysis to assess the in vivo degradation of the composites as well as tissue response to the implants. The in vivo degradation results show that all the samples maintained their original shape. Tissues penetrated into the pores which formed by the degradation of CaSO(4)/ß-TCP spheres near the surface of the composites. The rate of in vivo degradation and pore forming increased with a decrease in PPF molecular weight and an increase in CaSO(4)/ß-TCP molar ratio. No inflammatory reaction was observed after implantation, and the composites are capable of in situ pore forming. In particular, the pore forming rate can be adjusted by varying the composition of the composites. These results may indicate that PPF/(CaSO(4)/ß-TCP) is a promising osteogenic scaffold for its controllable degradation rate and excellent biocompatibility.

Phylogenomic relationships and molecular convergences to subterranean life in rodent family Spalacidae.

All extant species in the rodent family Spalacidae are subterranean and have evolved various traits for underground life. However, the phylogenomic relationships among its three subfamilies (Myospalacinae, Spalacinae, and Rhizomyinae) and the molecular basis underlying their adaptations to underground life remain poorly understood. Here, we inferred the phylogenomic relationships among these subfamilies based on de novo sequencing the genome of the hoary bamboo rat ( Rhizomys pruinosus). Analyses showed that ~50% of the identified 11 028 one-to-one orthologous protein-coding genes and the concatenated sequences of these orthologous genes strongly supported a sister relationship between Myospalacinae and Rhizomyinae. The three subfamilies diversified from each other within ~2 million years. Compared with the non-subterranean controls with similar divergence dates, the spalacids shared more convergent genes with the African subterranean mole-rats at the genomic scale due to more rapid protein sequence evolution. Furthermore, these convergent genes were enriched in the functional categories of carboxylic acid transport, vascular morphogenesis, and response to oxidative stress, which are closely associated with adaptations to the hypoxic-hypercapnic underground environment. Our study presents a well-supported phylogenomic relationship among the three subfamilies of Spalacidae and offers new insights into the molecular adaptations of spalacids living underground.

Echolocation in soft-furred tree mice.

Echolocation is the use of reflected sound to sense features of the environment. Here, we show that soft-furred tree mice (Typhlomys) echolocate based on multiple independent lines of evidence. Behavioral experiments show that these mice can locate and avoid obstacles in darkness using hearing and ultrasonic pulses. The proximal portion of their stylohyal bone fuses with the tympanic bone, a form previously only seen in laryngeally echolocating bats. Further, we found convergence of hearing-related genes across the genome and of the echolocation-related gene prestin between soft-furred tree mice and echolocating mammals. Together, our findings suggest that soft-furred tree mice are capable of echolocation, and thus are a new lineage of echolocating mammals.

Cochlear hair cells of echolocating bats are immune to intense noise.

Exposure to intense noise can damage cochlear hair cells, leading to hearing loss in mammals. To avoid this constraint, most mammals have evolved in relatively quiet environments. Echolocating bats, however, are naturally exposed to continuous intense sounds from their own and neighboring sonar emissions for maintaining sonar directionality and range. Here, we propose the presence of intense noise resistance in cochlear hair cells of echolocating bats against noise-induced hearing loss (NIHL). To test this hypothesis, we performed noise exposure experiments for laboratory mice, one nonecholocating bat species, and five echolocating bat species. Contrary to nonecholocating fruit bats and mice, the hearing and the cochlear hair cells of echolocating bats remained unimpaired after continuous intense noise exposure. The comparative analyses of cochleae transcriptomic data showed that several genes protecting cochlear hair cells from intense sounds were overexpressed in echolocating bats. Particularly, the experimental examinations revealed that ISL1 overexpression significantly improved the survival of cochlear hair cells. Our findings support the existence of protective effects in cochlear hair cells of echolocating bats against intense noises, which provides new insight into understanding the relationship between cochlear hair cells and intense noises, and preventing or ameliorating NIHL in mammals.

Two new furostanol saponins from Tribulus terrestris.

Two new furostanol saponins were isolated from the fruits of Tribulus terrestris L. Their structures were established as 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furost-20(22)-en-3beta,26-diol-3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-[beta-D-glucopyranosyl-(1 --> 4)]-beta-D-galactopyranoside (1) and 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furost-20(22)-en-12-one-3beta,26-diol-3-O-beta-D-galactopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 4)-beta-D-galactopyranoside (2) on the basis of spectroscopic data as well as chemical evidence.

[Research on the behavior of fruit and vegetable intake in adolescents with Transtheoretical Model].

OBJECTIVE: To study the current situation and factors influencing the behavior of fruit and vegetable intake in adolescents, and to discuss health education strategy related to the behavior. METHODS: 1677 students were selected from primary school and middle school in urban area of Hangzhou by a multistage sampling method. The behavior of fruit and vegetable intake was surveyed by questionnaires of the patient-centered assessment and counseling for exercise plus nutrition project (PACE+) for adolescent-scale of fruit and vegetable consumption, and analyzed by Transtheoretical Model on the servings of intake, the stage of change, process of change, decisional balance and the current status of self-efficacy. RESULTS: The average intake of fruit and vegetable in adolescents was (3.21 +/- 1.50) servings per day ("one serving" means 100 g cooked vegetable or 100 g fruit). The behavior of consuming fruit and vegetable in most of the adolescents was in the contemplation stage, accounting for 36.91% (619/1677). The process of behavior change, decisional balance (Pros) and self-efficacy existed a positive correlation with the process of stage (r(process) = 0.38, r(decisional balance (Pros)) = 0.26, r(self-efficacy) = 0.33, t values were 16.78, 11.02 and 14.31, P < 0.05). The servings of fruit and vegetable intake existed a positive correlation with stage transition and self-efficacy (beta(stage transition) = 0.665, t = 35.07, P < 0.05; beta(self-efficacy) = 0.050, t = 2.63, P < 0.05), and existed a negative correlation with decisional balance (Cons) (beta(decisional balance (Cons)) = -0.051, t = -2.84, P < 0.05). CONCLUSION: Fruit and vegetable intake of these adolescents are under the recommended dietary intake. Along with behavior stage development and self-efficacy improvement, the intake of fruit and vegetable also increased correspondingly. Intervention strategies should aim at improving the awareness of adolescents on the health benefits of fruit and vegetable intake and promoting their confidence to reach the recommended servings.

Smooth or attached solid indeterminate nodules detected at baseline CT screening in the NELSON study: cancer risk during 1 year of follow-up.

PURPOSE: To retrospectively determine whether baseline nodule characteristics at 3-month and 1-year volume doubling time (VDT) are predictive for lung cancer in solid indeterminate noncalcified nodules (NCNs) detected at baseline computed tomographic (CT) screening. MATERIALS AND METHODS: The study, conducted between April 2004 and May 2006, was institutional review board approved. Patient consent was waived for this retrospective evaluation. NCNs between 5 and 10 mm in diameter (n = 891) were evaluated at 3 months and 1 year to assess growth (VDT < 400 days). Baseline assessments were related to growth at 3 months and 1 year by using chi(2) and Mann-Whitney U tests. Baseline assessments and growth were related to the presence of malignancy by using univariate and multivariate logistic regression analyses. RESULTS: At 3 months and at 1 year, 8% and 1% of NCNs had grown, of which 15% and 50% were malignant, respectively. One-year growth was related to morphology (P < .01), margin (P < .0001), location (P < .001), and size (P < .01). All cancers were nonspherical and purely intraparenchymal, without attachment to vessels, the pleura, or fissures. In nonsmooth unattached nodules, a volume of 130 mm(3) or larger was the only predictor for malignancy (odds ratio, 6.3; 95% confidence interval [CI]: 1.7, 23.0). After the addition of information on the 3-month VDT, large volume (odds ratio, 4.9; 95% CI: 1.2, 20.1) and 3-month VDT (odds ratio, 15.6; 95% CI: 4.5, 53.5) helped predict malignancy. At 1 year, only the 1-year growth remained (odds ratio, 213.3; 95% CI: 18.7, 2430.9) as predictor for malignancy. CONCLUSION: In smooth or attached solid indeterminate NCNs, no malignancies were found at 1-year follow-up. In nonsmooth purely intraparenchymal NCNs, size is the main baseline predictor for malignancy. When follow-up data are available, growth is a strong predictor for malignancy, especially at 1-year follow-up.