Comparative postoperative outcomes of GGN-dominant vs single lesion lung adenocarcinomas.

BACKGROUND: Multiple synchronous ground glass nodules (GGNs) are known to be malignant, however, they tend to progress slowly. Multiple synchronous lesions in the same patient which show different characteristics must be treated individually. METHODS: This was a retrospective review of 34 lung adenocarcinoma patients with multiple synchronous GGNs in an Asian population. One hundred twenty-seven single lung adenocarcinoma patients were included for comparison purposes. The follow-up period was 5 years for all patients. RESULTS: The 5-year overall survival (OS) patients with multiple lesions did not differ from that of the patients with single lesions to a statistically significant extent (Single: 81.8% vs. Multiple: 88.2%, P = 0.3602). Dominant tumors (DTs) with a ground glass component and consolidation were divided into three categories based on the consolidation-to-tumor ratio on radiological imaging. No significant differences were observed among the three DT categories. Twenty-four patients had unresected GGNs, while a progression of the unresected GGN occurred in 10 of these cases. The OS and disease-free survival (DFS) curves of patients with and without GGN progression did not differ to a statistically significant extent (OS: 80% vs. 92.9%, P = 0.3870; DFS: 80% vs. 100%, P = 0.0977). CONCLUSIONS: The outcomes were best predicted by the stage of the DT. After surgery patients require a careful follow-up because unresected GGNs may show progression. At the same time, the increase in residual lesions and the appearance of new GGNs were not related to OS. The management of such patients should be determined according to the DT with the worst prognosis.

Multidisciplinary selection of pulmonary nodules for surgical resection: Diagnostic results and long-term outcomes.

OBJECTIVE: Pulmonary nodules found incidentally or by lung cancer screening differ in prevalence, risk profile, and diagnostic intervention. The results of surgical intervention for incidental versus screening lung nodules during multidisciplinary Pulmonary Nodule and Lung Cancer Screening Clinic (PNLCSC) follow-up have not been reported. METHODS: All patients evaluated at a PNLCSC from 2012 to 2018 following referral by primary care physicians, specialist physicians, or self-referral after computed tomography (CT) identified nodules on routine diagnostic CT (incidental group) or lung cancer screening CT (screening group) were included. Follow-up interval, invasive intervention, histology, postoperative events, survival, and recurrence were compared. RESULTS: Of 747 patients evaluated in the PNLCSC, 129 (17.2%) underwent surgical intervention. The surgical cohort consisted of 104 (80.6%) incidental and 25 (19.3%) screening patients followed over a mean of 122 and 70 days, respectively. More benign lesions were excised in the incidental group (20.2%, 21/104)-representing 3.3% (21/632) of all incidental nodules evaluated-than in the screening group (4%, 1/25) (P = .038). Operative mortality was zero. Among 99 patients with primary lung cancer, 87% (screening) and 86.8% (incidental) were pathologic stage Ia. Complete follow-up was available in 725 of 747 (97%), and no patient developed progressive disease. Disease-free survival at 5 years was 74.9% (incidental) and 89.3% (screening) (P = .48). CONCLUSIONS: A unique multidisciplinary PNLCSC for incidental and lung cancer screening-detected nodules with individualized risk assessment reliably identifies primary and metastatic tumors while exposing few patients to diagnostic excision for benign disease. Longer-term outcomes, strategies to limit radiation exposure, and cost control need further study.

Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group.

PURPOSE: To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. RESULTS: In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). CONCLUSION: Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis.

Survival and metastasis in muscle-invasive bladder cancer patients who present with indeterminate pulmonary nodules before treatment.

BACKGROUND: Indeterminate pulmonary nodules (IPNs) are common during initial evaluation of bladder cancer patients. Their significance is still unknown. OBJECTIVE: Determine the significance of indeterminate pulmonary nodules, including their size and number, in muscle-invasive bladder cancer patients before definitive local therapy by surgery or chemo-radiotherapy. DESIGN: Retrospective review, single-center descriptive study. SETTINGS: A tertiary cancer center. PATIENTS AND METHODS: We performed a retrospective review of patients who underwent definitive local therapy of bladder cancer by either radical cystectomy and lymph node dissection or with chemo-radiotherapy between January 1997 and December 2015. We identified patients with baseline CT scans done during staging work-up prior to definitive treatment. Patients with proven clinical metastasis at pre.sentation were excluded, while patients who had IPNs without features suggesting metastasis were included. MAIN OUTCOME MEASURES: Disease-free survival and overall survival. SAMPLE SIZE: 168 patients. RESULTS: The median age of patients at diagnosis was 66 years; 92% were males and 56% were smokers. IPNs (3 cm or less) were present in 74 patients (44.0%). Median follow-up was 24 months. IPNs were associated with decreased disease-free survival while IPNs did not affect the overall survival (HR=1.9; 95% CI: 1.1-3.4); P=.01 and HR=1.5; 95% CI: 1.0-2.5); P=.07, respectively. In addition, nodules greater than 1 cm had reduced disease-free survival (HR=2.5; 95% CI: 1.1-5.9); P=.04. In the surgery group (n=126), the median number of lymph nodes excised was 14, with no association between lymph nodes status and the presence of IPNs (P=.08). CONCLUSION: The presence of IPNs, especially nodules greater than 1 cm had a negative effect on disease-free survival. Tailored postoperative follow-up of these patients may impact disease outcomes. LIMITATIONS: The retrospective nature, the lack of standardized preoperative imaging protocols, the lack of a central radiology review and the small number of patients. CONFLICT OF INTEREST: None.

CT-guided Microcoil Pulmonary Nodule Localization prior to Video-assisted Thoracoscopic Surgery: Diagnostic Utility and Recurrence-Free Survival.

Background CT-guided microcoil localization has been shown to reduce the need for thoracotomy or video-assisted thoracoscopic surgery (VATS) anatomic resection. However, only short-term follow-up after CT-guided microcoil localization and lung resection has been previously reported. Purpose To assess the diagnostic utility and recurrence-free survival over a minimum of 2 years following CT-guided microcoil localization and VATS. Materials and Methods Among 1950 VATS procedures performed in a single tertiary institution from October 2008 through April 2016, 124 consecutive patients with CT-guided microcoil localization were retrospectively evaluated. Patient demographics, nodule characteristics, and histopathologic findings were recorded. The primary end point was recurrence-free survival after 2 or more years of CT surveillance. Statistical analysis included Kaplan-Meier survival curves and Cox regression. Results In 124 patients (men, 35%; mean age, 65 years ± 12) with a nodule found at CT, microcoil localization and VATS resection were performed for a total of 126 nodules (mean size, 13 mm ± 6; mean distance to pleura, 20 mm ± 9). On presurgical CT evaluation, 42% (53 of 126) of nodules were solid, 33% (41 of 126) were ground glass, and 24% (30 of 126) were subsolid. VATS excisional biopsy altered cytopathologic diagnosis in 21% (five of 24) of patients with prior diagnostic premicrocoil CT-guided biopsy. At histopathologic examination, 17% (21 of 126) of the nodules were adenocarcinoma in situ, 17% (22 of 126) were minimally invasive adenocarcinoma, 30% (38 of 126) were invasive lung primary tumors, and 22% (28 of 126) were metastases. Among the 72 patients with malignancy at histopathologic examination and at least 2 years of CT surveillance, local recurrence occurred in 7% (five of 72), intrathoracic recurrence in 22% (16 of 72), and extrathoracic recurrence in 18% (13 of 72) after 2 or more years of CT surveillance. There was no recurrence for adenocarcinoma in situ, minimally invasive adenocarcinoma, or invasive lung tumors measuring less than 1 cm. After multivariable adjustment, nodule location at a distance greater than 10 mm from the pleura was an independent predictor of time to recurrence (hazard ratio, 2.9 [95% confidence interval: 1.1, 7.4]; P = .03). Conclusion CT-guided microcoil localization and video-assisted thoracoscopic surgical resection alter clinical management and were associated with excellent recurrence-free survival for superficial premalignant, minimally invasive, and small invasive lung tumors. © RSNA, 2019 Online supplemental material is available for this article.

Long-Term Active Surveillance of Screening Detected Subsolid Nodules is a Safe Strategy to Reduce Overtreatment.

INTRODUCTION: Lung cancer presenting as subsolid nodule (SSN) can show slow growth, hence treating SSN is controversial. Our aim was to determine the long-term outcome of subjects with unresected SSNs in lung cancer screening. METHODS: Since 2005, the Multicenter Italian Lung Detection (MILD) screening trial implemented active surveillance for persistent SSN, as opposed to early resection. Presence of SSNs was related to diagnosis of cancer at the site of SSN, elsewhere in the lung, or in the body. The risk of overall mortality and lung cancer mortality was tested by Cox proportional hazards model. RESULTS: SSNs were found in 16.9% (389 of 2303) of screenees. During 9.3 ± 1.2 years of follow-up, the hazard ratio of lung cancer diagnosis in subjects with SSN was 6.77 (95% confidence interval: 3.39-13.54), with 73% (22 of 30) of cancers not arising from SSN (median time to diagnosis 52 months from SSN). Lung cancer-specific mortality in subjects with SSN was significantly increased (hazard ratio = 3.80; 95% confidence interval: 1.24-11.65) compared to subjects without lung nodules. Lung cancer arising from SSN did not lead to death within the follow-up period. CONCLUSIONS: Subjects with SSN in the MILD cohort showed a high risk of developing lung cancer elsewhere in the lung, with only a minority of cases arising from SSN, and never representing the cause of death. These results show the safety of active surveillance for conservative management of SSN until signs of solid component growth and the need for prolonged follow-up because of high risk of other cancers.

Identification of preoperative prediction factors of tumor subtypes for patients with solitary ground-glass opacity pulmonary nodules.

BACKGROUND: Recent wide spread use of low-dose helical computed tomography for the screening of lung cancer have led to an increase in the detection rate of very faint and smaller lesions known as ground-glass opacity nodules. The purpose of this study was to investigate the clinical factors of lung cancer patients with solitary ground-glass opacity pulmonary nodules on computed tomography. METHODS: A total of 423 resected solitary ground-glass opacity nodules were retrospectively evaluated. We analyzed the clinical, imaging and pathological data and investigated the clinical differences in patient with adenocarcinoma in situ / minimally invasive adenocarcinoma and those with invasive adenocarcinoma. RESULTS: Three hundred and ninety-three adenocarcinomas (92.9%) and 30 benign nodules were diagnosed. Age, the history of family cancer, serum carcinoembryonic antigen level, tumor size, ground-glass opacity types, and bubble-like sign in chest CT differed significantly between adenocarcinoma in situ / minimally invasive adenocarcinoma and invasive adenocarcinoma (p:0.008, 0.046, 0.000, 0.000, 0.000 and 0.001). Receiver operating characteristic curves and univariate analysis revealed that patients with more than 58.5 years, a serum carcinoembryonic antigen level > 1.970 µg/L, a tumor size> 13.50 mm, mixed ground-glass opacity nodules and a bubble-like sign were more likely to be diagnosed as invasive adenocarcinoma. The combination of five factors above had an area under the curve of 0.91, with a sensitivity of 82% and a specificity of 87%. CONCLUSION: The five-factor combination helps us to distinguish adenocarcinoma in situ / minimally invasive adenocarcinoma from invasive adenocarcinoma and to perform appropriate surgery for solitory ground-glass opacity nodules.

Baseline and annual repeat rounds of screening: implications for optimal regimens of screening.

OBJECTIVES: Differences in results of baseline and subsequent annual repeat rounds provide important information for optimising the regimen of screening. METHODS: A prospective cohort study of 65,374 was reviewed to examine the frequency/percentages of the largest noncalcified nodule (NCN), lung cancer cell types and Kaplan-Meier (K-M) survival rates, separately for baseline and annual rounds. RESULTS: Of 65,374 baseline screenings, NCNs were identified in 28,279 (43.3%); lung cancer in 737 (1.1%). Of 74,482 annual repeat screenings, new NCNs were identified in 4959 (7%); lung cancer in 179 (0.24%). Only adenocarcinoma was diagnosed in subsolid NCNs. Percentages of lung cancers by cell type were significantly different (p < 0.0001) in the baseline round compared with annual rounds, reflecting length bias, as were the ratios, reflecting lead times. Long-term K-M survival rate was 100% for typical carcinoids and for adenocarcinomas manifesting as subsolid NCNs; 85% (95% CI 81-89%) for adenocarcinoma, 74% (95% CI 63-85%) for squamous cell, 48% (95% CI 34-62%) for small cell. The rank ordering by lead time was the same as the rank ordering by survival rates. CONCLUSIONS: The significant differences in the frequency of NCNs and frequency and aggressiveness of diagnosed cancers in baseline and annual repeat need to be recognised for an optimal regimen of screening. KEY POINTS: • Lung cancer aggressiveness varies considerably by cell type and nodule consistency. • Kaplan-Meier survival rates varied by cell type between 100% and 48%. • The percentages of lung cancers by cell type in screening rounds reflect screening biases. • Rank ordering by cell type survival is consistent with that by lead times. • Empirical evidence provides critical information for the regimen of screening.

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.

Microwave Ablation for Lung Neoplasms: A Retrospective Analysis of Long-Term Results.

PURPOSE: To determine the long-term safety and efficacy of microwave (MW) ablation in the treatment of lung tumors at a single academic medical center. MATERIALS AND METHODS: Retrospective review was performed of 108 patients (42 female; mean age, 72.5 y ± 10.3 [standard deviation]) who underwent computed tomography (CT)-guided percutaneous MW ablation for a single lung malignancy. Eighty-two were primary non-small-cell lung cancers and 24 were metastatic tumors (9 colorectal carcinoma, 2 renal-cell carcinoma, 4 sarcoma, 2 lung, and 7 other). Mean maximum tumor diameter was 29.6 mm ± 17.2. Patient clinical and imaging data were reviewed. Statistical analysis was performed by Kaplan-Meier modeling and logistic regression. RESULTS: Odds of primary technical success were 11.1 times higher for tumors < 3 cm vs those > 3 cm (95% confidence interval [CI], 2.97-41.1; P = .0003). For every millimeter increase in original tumor maximal diameter (OMD), the odds of not attaining success increased by 7% (95% CI, 3%-10%; P = .0002). For every millimeter increase in OMD, the odds of complications increased by 3% (95% CI, 0.1%-5%; P = .04). Median time to tumor recurrence was 62 months (95% CI, 29, upper bound not reached; range, 0.2-96.6 mo). Recurrence rates were estimated at 22%, 36%, and 44% at 1, 2, and 3 years, respectively. Recurrence rates were estimated at 31% at 13 months for tumors > 3 cm and 17% for those < 3 cm. Complications included pneumothorax (32%), unplanned hospital admission (28%), pain (20%), infection (7%), and postablation syndrome (4%). CONCLUSIONS: This study further supports the safe and effective use of MW ablation for the treatment of lung tumors.

Computed Tomography Screening for Lung Cancer: Mediastinal Lymph Node Resection in Stage IA Nonsmall Cell Lung Cancer Manifesting as Subsolid and Solid Nodules.

OBJECTIVE: To compare long-term survival rates of patients with first, primary, clinical stage IA nonsmall cell lung cancer from a large cohort undergoing computed tomography screening with and without mediastinal lymph node resection (MLNR) under an Institutional Review Board-approved common protocol from 1992 to 2014. BACKGROUND: Assessing survival differences of patients with and without MLNR manifesting as solid and subsolid nodules. METHODS: Long-term Kaplan-Meier (K-M) survival rates for those with and without MLNR were compared and Cox regression analyses were used to adjust for demographic, computed tomography, and surgical covariates. RESULTS: The long-term K-M rates for 462 with and 145 without MLNR was 92% versus 96% (P = 0.19), respectively. For 203 patients with a subsolid nodule, 151 with and 52 without MLNR, the rate was 100%. For the 404 patients with a solid nodule, 311 with and 93 without MLNR, the rate was 87% versus 94% (P = 0.24) and Cox regression showed no statistically significant difference (P = 0.28) when adjusted for all covariates. Risk of dying increased significantly with increasing decades of age (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4-3.8), centrally located tumor (HR 2.5, 95% CI 1.2-5.2), tumor size 21 to 30 mm (HR 2.7, 95% CI 1.2-6.0), and invasion beyond the lung stroma (HR 3.0, 95% CI 1.4-6.1). For the 346 patients with MLNR, tumor size was 20 mm or less; K-M rates for the 269 patients with and 169 patients without MLNR were also not significantly different (HR 2.1, P = 0.24). CONCLUSIONS: It is not mandatory to perform MLNR when screen-diagnosed nonsmall cell lung cancer manifests as a subsolid nodule.

[Establishment of A Clinical Prediction Model of Solid Solitary Pulmonary Nodules].

BACKGROUND: The solitary pulmonary nodule (SPN) is a common and challenging clinical problem, especially solid SPN. The object of this study was to explore the predictive factors of SPN appearing as pure solid with malignance and to establish a clinical prediction model of solid SPNs. METHODS: We had a retrospective review of 317 solid SPNs (group A) having a final diagnosis in the department of thoracic surgery, Shanghai Chest Hospital from January 2015 to December 2015, and analyzed their clinical data and computed tomography (CT) images, including age, gender, smoking history, family history of cancer, previous cancer history, diameter of nodule, nodule location (upper lobe or non-upper lobe, left or right), clear border, smooth margin, lobulation, spiculation, vascular convergence, pleural retraction sign, air bronchogram sign, vocule sign, cavity and calcification. By using univariate and multivariate analysis, we found the independent predictors of malignancy of solid SPNs and subsequently established a clinical prediction model. Then, another 139 solid SPNs with a final diagnosis were chosen in department of Cardiothoracic Surgery, Affiliated Zhoushan Hospital of Wenzhou Medical University as group B, and used to verify the accuracy of the prediction model. Receiver-operating characteristic (ROC) curves were constructed using the prediction model. RESULTS: Multivariate Logistic regression analysis was used to identify eight clinical characteristics (age, family history of cancer, previous cancer history, clear border, lobulation, spiculation, air bronchogram sign, calcification) as independent predictors of malignancy of in solid SPNs. The area under the ROC curve for our model (0.922; 95%CI: 0.865-0.961). In our model, diagnosis accuration rate was 84.89%. Sensitivity was 90.41%, and specificity was 78.79%, and positive predictive value was 80.50%, and negative predictive value was 88.14%. CONCLUSIONS: Our prediction model could accurately identify malignancy in patients with solid SPNs, thereby it can provide help for diagnosis of solid SPNs.

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).

Use of [(18)F]Fluoro-2-deoxy-d-glucose Positron Emission Tomographic Imaging in the National Lung Screening Trial.

BACKGROUND: Positron emission tomography (PET) is a diagnostic tool for lung cancer evaluation. No studies have ascertained practice patterns and determined the appropriateness of PET imaging in a large group of US patients with screen-detected lung nodules. METHODS: We analyzed participants in the National Lung Screening Trial (NLST) with positive screening test results and identified individuals with a PET scan performed prior to lung cancer diagnosis (diagnostic PET). Appropriate scan was defined as one performed in a patient with a nodule ≥ 0.8 cm. Logistic regression was used to assess factors associated with diagnostic PET scan use and appropriateness of PET scan use. RESULTS: Diagnostic PET imaging was performed in 1,556 of 14,195 patients (11%) with positive screen results; 331 of these (21%) were inappropriate. PET scan use by endemic fungal disease area was comparable although patients from the Northeast/Southeast were twice as likely as the West to have a diagnostic PET. Trial arm, older age, sex, nodule size ≥ 0.8 cm, upper lobe location, and spiculated margin were variables positively associated with use. Trial arm, older age, and spiculated margin were positively associated with appropriate use. Only 561 diagnostic PETs (36%) were recommended by a radiologist and 284 PETs performed for nodules < 0.8 cm (86%) were ordered despite no recommendation from a radiologist. CONCLUSIONS: PET imaging was differentially used in the NLST and inappropriately used in many cases against radiologist recommendations. These data suggest PET imaging may be overused in the lung cancer screening population and may contribute to excess health-care costs.

[Three Dimensional Volumetric Analysis of Solid Pulmonary Nodules on Chest CT: 
Cancer Risk Assessment].

BACKGROUND: The management of pulmonary nodules relies on cancer risk assessment, in which the only widely accepted criterion is diameter. The development of volumetric computed tomography (CT) and three-dimensional (3D) software enhances the clarity in displaying the nodules' characteristics. This study evaluated the values of the nodules' volume and 3D morphological characteristics (edge, shape and location) in cancer risk assessment. METHODS: The CT data of 200 pulmonary nodules were retrospectively evaluated using 3D volumetric software. The malignancy or benignity of all the nodules was confirmed by pathology, histology or follow up (>2 years). Logistic regression analysis was performed to calculate the odds ratios (ORs) of the 3D margin (smooth, lobulated or spiculated/irregular), shape (spherical or non-spherical), location (purely intraparenchymal, juxtavascular or pleural-attached), and nodule volume in cancer risk assessment for total and sub-centimeter nodules. The receiver operating characteristic (ROC) curve was employed to determine the optimal threshold for the nodule volume. RESULTS: Out of 200 pulmonary nodules, 78 were malignant, whereas 122 were benign. The Logistic regression analysis showed that the volume (OR=3.3; P<0.001) and the 3D margin (OR=13.4, 9.8; both P=0.001) were independent predictive factors of malignancy, whereas the location and 3D shape exhibited no total predictive value (P>0.05). ROC analysis showed that the optimal threshold for malignancy was 666 mm³. For sub-centimeter nodules, the 3D margin was the only valuable predictive factor of malignancy (OR=60.5, 75.0; P=0.003, 0.007). CONCLUSIONS: The volume and 3D margin are important factors considered to assess the cancer risk of pulmonary nodules. Volumes larger than 666 mm³ can be determined as high risk for pulmonary nodules; by contrast, nodules with lobulated, spiculated, or irregular margin present a high malignancy probability.

Outcome of acute myeloid leukemia patients with pulmonary nodules of uncertain etiology receiving allogeneic hematopoietic progenitor cell transplant.

Pulmonary nodules (PNs) develop frequently in patients with acute myeloid leukemia (AML). They are of infectious or inflammatory origin. They pose potential challenges to successful hematopoietic progenitor cell (HPC) transplant as they may be niches for infection reactivation or sites susceptible to subsequent infections. We retrospectively analyzed the outcome of 20 AML patients with multiple PNs who underwent allogeneic HPC transplants (12 related, 8 unrelated). There were 13 males and seven females (median age 52 yrs). Nine patients were in CR1, seven in CR2, and four with residual disease. The median times from appearance of PNs and from last positive CT scans to transplant were three and two months, respectively. The median time from pretransplant CT scans to transplant was one month. Multiple PNs were still reported in 5/20 of the pretransplant scans. The PNs in all five patients did not worsen after transplant. Four patients (one with positive pretransplant CT scan) died within the first 100 d after transplant, but none from primary pulmonary pathology. The median survival of this group of patients was 350 d. Our results, therefore, suggest that multiple PNs of uncertain etiology in patients with AML do not impact adversely on the outcome of allogeneic HPC transplant.

Lung cancer risk and cancer-specific mortality in subjects undergoing routine imaging test when stratified with and without identified lung nodule on imaging study.

OBJECTIVES: To assess the risk of lung cancer and specific mortality rate in patients with and without solitary pulmonary nodules (SPN) on chest radiograph and CT. METHODS: This prospective study included 16,078 patients ≥35 years old (893 of them had an SPN detected with either chest radiograph or CT) and 15,185 without SPN. Patients were followed up for 18 months or until being diagnosed with lung cancer. Risk and mortality lung cancer were calculated in both groups with Poisson regression. RESULTS: In patients with SPN, incidence of lung cancer was 8.3 % (95 % CI 6.0-11.2) on radiograph and 12.4 % (95 % CI 9.3-15.9) on CT. A chronic obstructive pulmonary disease in patients with radiographs (odds ratio 2.62; 95 % CI 1.03, 6.67) and smoking habit (odds ratio 20.63; 95 % CI 3.84, 110.77) in patients with CT were associated with a higher probability of lung cancer. Large nodule size and spiculated edge were associated with lung cancer on both CT and radiograph. Lung cancer-specific mortality was lower in patients with SPN than in those without SPN (1.73/1000 person-years, 95 % CI 1.08-2.88 vs. 2.15/1000 person-years, 95 % CI 1.25-3.96). CONCLUSIONS: The risk of lung cancer for patients with SPN is higher in clinical populations than in screening studies. Moreover, patients with SPN showed lower mortality than those without SPN. KEY POINTS: • Lung cancer risk is 8 % for SPN detected on routine radiographs. • Lung cancer risk is 12.4 % for SPN detected in routine chest CT. • Smoking, COPD, SPN diameter and edge were predictors of malignancy. • Lung cancer risk of SPN in routine practice seems higher than in screening.

Pulmonary nodules in liver transplant candidates with hepatocellular carcinoma: Imaging characteristics and clinical outcomes.

No guidelines exist for the management of pulmonary nodules in patients with hepatocellular carcinoma (HCC) who are being evaluated for liver transplantation. The 172 patients with HCC who were listed for liver transplant at our institution received both pretransplant chest computed tomography (CT) and follow-up CT. Pulmonary nodules on CT were characterized and followed on subsequent scans by a blinded radiologist, with a consensus review with a second radiologist being performed for equivocal cases. Nodule characteristics and outcomes were examined with chi-square tests, and the posttransplant survival of patients with different nodule outcomes was compared. Cumulative probabilities of waiting-list removal for nontransplant patients and cumulative probabilities of undergoing transplantation for all patients were also compared between patients with and without pulmonary nodules. Of all the patients, 76.2% had at least 1 pulmonary nodule on pretransplant CT, with 301 total nodules characterized; 2.7% of nodules represented HCC metastases, 1.0% represented other bronchopulmonary malignancies, and 2.7% represented infections. None of the malignant nodules exhibited a triangular/lentiform shape or calcifications. There were no statistically significant differences in pulmonary nodule outcomes between patients who underwent transplantation and those who did not undergo transplantation. No significant differences in posttransplant survival were found between patients with different nodule outcomes. There was also no significant difference between patients with and without nodules in the cumulative probabilities of waiting-list removal. However, the cumulative probability of undergoing liver transplantation was borderline significantly higher in patients without pulmonary nodules. In conclusion, despite the low prevalence of malignant nodules, all pulmonary nodules besides triangular/lentiform-shaped or calcified nodules should be followed with serial CT while the patient is on the transplant list, with biopsy performed for new and/or enlarged nodules. Both malignancy and active infection must be excluded when one is confronted with enlarged pulmonary nodules. Clinicians should also be aware of the possibility of reactivation of a granulomatous infection after transplantation.

[Lung cancer screening and management of small pulmonary nodules]. / Lungenkrebs-Screening und Management kleinerer pulmonaler Rundherde.

Worldwide lung cancer is the leading cause of death from cancer. Most lung cancers are diagnosed at an advanced stage, so survival after lung cancer is generally poor. Diagnosis of lung cancer at earlier stages may be associated with an increased survival rate. This indicates that the implementation of lung cancer screening programs at the population level by means of low dose computed tomography might helpful to improve the outcome and mortality of lung cancer patients. By means of rapid advances in imaging technologies over the last decades it became possible to detect small lung nodules as small as a couple of millimeters. This recent developments require management algorithms to guide the clinical management of suspicious and indeterminate lung nodules found in computer tomography during lung cancer screening or by incidental finding.This review will focus on both, the recent advances in lung cancer screening and the guidelines for the management of small pulmonary nodules.

Pulmonary adenocarcinomas appearing as part-solid ground-glass nodules: is measuring solid component size a better prognostic indicator?

OBJECTIVE: To assess whether measuring the solid portion of adenocarcinomas appearing as part-solid ground-glass nodules (GGNs) can predict a patient's prognosis accurately and how the prognosis corresponds to that of solid nodules. METHODS: 501 patients (solid nodule group, 304; part-solid GGN group, 197) underwent curative surgery for stage I adenocarcinomas. Maximal diameters of the whole lesion including ground-glass opacities (D whole ) and solid components only (D solid ) were measured on CT. Disease-free survival (DFS) and overall survival (OS) were calculated from the date of surgery. RESULTS: D solid was a significant prognostic factor in the part-solid GGN group, while D whole was not. Part-solid GGNs with D solid ≤2 cm showed significantly better DFS (P = 0.016) and OS (P = 0.004) than solid nodules; however, those with D solid >2 cm did not show a significant difference. Hazard ratio (HR) for increase in D solid was significantly greater in part-solid GGNs than in solid nodules (P = 0.009). For OS, HR for increase in D solid was greater in part-solid GGNs than in solid nodule, which was marginally not significant (P = 0.060). CONCLUSION: D solid was better than D whole for prognosis prediction of adenocarcinomas appearing as part-solid GGNs. In addition, the influence of D solid on prognosis in the part-solid GGN group was greater than in the solid nodule group. KEY POINTS: • Dsolid is a better prognosis indicator than Dsolid in part-solid GGN adenocarcinomas • Part-solid GGN adenocarcinoma show better prognosis than solid adenocarcinomas when Dsolid ≤2 cm • Dsolid has greater prognostic influence in part-solid GGN adenocarcinomas than solid adenocarcinomas.