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Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Background: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC 50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test., Methods: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides., Results: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response., Conclusions: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform., (© 2023. The Author(s).)

In radiomics research, the issue of different instruments being used is significant. In this study, we compared three correction methods to reduce the batch effects in radiogenomic data from fluorodeoxyglucose (FDG) PET/CT images of lung cancer patients. Texture features of the FDG PET/CT images and genomic data were retrospectively obtained. The features were corrected with different methods: phantom correction, ComBat method, and Limma method. Batch effects were estimated using three analytic tools: principal component analysis (PCA), the k-nearest neighbor batch effect test (kBET), and the silhouette score. Finally, the associations of features and gene mutations were compared between each correction method. Although the kBET rejection rate and silhouette score were lower in the phantom-corrected data than in the uncorrected data, a PCA plot showed a similar variance. ComBat and Limma methods provided correction with low batch effects, and there was no significant difference in the results of the two methods. In ComBat- and Limma-corrected data, more texture features exhibited a significant association with the TP53 mutation than in those in the phantom-corrected data. This study suggests that correction with ComBat or Limma methods can be more effective or equally as effective as the phantom method in reducing batch effects., (© 2023. Springer Nature Limited.)

Pulmonary lymphangitic carcinomatosis (PLC) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to determine prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC with radiologically diagnosed PLC. We retrospectively reviewed 50 NSCLC patients with radiologically diagnosed PLC. Among eight clinical variables and five imaging parameters, metabolic PLC burden, which represents the overall tumor burden of PLC, and cPLC, which represents the location and extent of PLC in a three-grade system, were used. In multivariate analyses for progression-free survival, metabolic PLC burden (P = 0.0181), cPLC (P = 0.0401), and clinical stage (P = 0.0284) were identified as independent prognostic factors. High metabolic PLC burden had a worse prognosis, and the prognosis of cPLC3 was significantly worse than that of cPLC1 or cPLC2. In univariate analyses for overall survival, only age (P = 0.0073) was identified a prognostic factor. In conclusion, FDG PET/CT parameters were identified as independent prognostic factors in NSCLC with radiologically diagnosed PLC. Furthermore, a combination of anatomical and metabolic information about PLC obtained using FDG PET/CT provides insight into the overall tumor burden of PLC and is useful in predicting prognosis., (© 2023. The Author(s).)

Purpose: We aimed to evaluate the performance of a deep learning system for differential diagnosis of lung cancer with conventional CT and FDG PET/CT using transfer learning (TL) and metadata., Methods: A total of 359 patients with a lung mass or nodule who underwent noncontrast chest CT and FDG PET/CT prior to treatment were enrolled retrospectively. All pulmonary lesions were classified by pathology (257 malignant, 102 benign). Deep learning classification models based on ResNet-18 were developed using the pretrained weights obtained from ImageNet data set. We propose a deep TL model for differential diagnosis of lung cancer using CT imaging data and metadata with SUVmax and lesion size derived from PET/CT. The area under the receiver operating characteristic curve (AUC) of the deep learning model was measured as a performance metric and verified by 5-fold cross-validation., Results: The performance metrics of the conventional CT model were generally better than those of the CT of PET/CT model. Introducing metadata with SUVmax and lesion size derived from PET/CT into baseline CT models improved the diagnostic performance of the CT of PET/CT model (AUC = 0.837 vs 0.762) and the conventional CT model (AUC = 0.877 vs 0.817)., Conclusions: Deep TL models with CT imaging data provide good diagnostic performance for lung cancer, and the conventional CT model showed overall better performance than the CT of PET/CT model. Metadata information derived from PET/CT can improve the performance of deep learning systems., Competing Interests: Conflicts of interest and sources of funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2017R1D1A1B03028735) and the Soonchunhyang University Cheonan Hospital Research Fund. None declared to all authors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We aimed to find the best machine learning (ML) model using 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for evaluating metastatic mediastinal lymph nodes (MedLNs) in non-small cell lung cancer, and compare the diagnostic results with those of nuclear medicine physicians., Methods: A total of 1329 MedLNs were reviewed. Boosted decision tree, logistic regression, support vector machine, neural network, and decision forest models were compared. The diagnostic performance of the best ML model was compared with that of physicians. The ML method was divided into ML with quantitative variables only (MLq) and adding clinical information (MLc). We performed an analysis based on the 18 F-FDG-avidity of the MedLNs., Results: The boosted decision tree model obtained higher sensitivity and negative predictive values but lower specificity and positive predictive values than the physicians. There was no significant difference between the accuracy of the physicians and MLq (79.8% vs. 76.8%, p = 0.067). The accuracy of MLc was significantly higher than that of the physicians (81.0% vs. 76.8%, p = 0.009). In MedLNs with low 18 F-FDG-avidity, ML had significantly higher accuracy than the physicians (70.0% vs. 63.3%, p = 0.018)., Conclusion: Although there was no significant difference in accuracy between the MLq and physicians, the diagnostic performance of MLc was better than that of MLq or of the physicians. The ML method appeared to be useful for evaluating low metabolic MedLNs. Therefore, adding clinical information to the quantitative variables from 18 F-FDG PET/CT can improve the diagnostic results of ML., Key Points: • Machine learning using two-class boosted decision tree model revealed the highest value of area under curve, and it showed higher sensitivity and negative predictive values but lower specificity and positive predictive values than nuclear medicine physicians. • The diagnostic results from machine learning method after adding clinical information to the quantitative variables improved accuracy significantly than nuclear medicine physicians. • Machine learning could improve the diagnostic significance of metastatic mediastinal lymph nodes, especially in mediastinal lymph nodes with low 18F-FDG-avidity.

Objective: The aim of the study was to evaluate computed tomography (CT) findings of pulmonary NUT midline carcinoma., Methods: We assessed clinical and CT features of pulmonary NUT carcinoma in 10 consecutive patients (M:F, 7:3; mean, 39 years)., Results: The primary tumors (size range, 15-65 mm) manifested as either a peripheral tumor (5/10) or a central tumor (5/10). All tumors showed relatively low-attenuation at contrast-enhanced CT (mean net enhancement, 26 HU). Associated CT findings were metastatic hilar or mediastinal lymphadenopathy (8/10), ipsilateral pleural seeding with malignant pleural effusion (2/10), and distant metastasis (2/10). Five patients with low tumor-node-metastasis stages after optimal treatment showed no evidence of disease (50%) for 6 to 35 months., Conclusions: Pulmonary NUT carcinoma presented as a peripheral or a central lung mass showing mild degree of contrast enhancement, frequent metastatic regional lymphadenopathy, affecting relatively young adults. Although known to be highly aggressive, an early diagnosis in low TNM stages can lead to a favorable prognosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This study investigated the associations between image features extracted from tumor 18 F-fluorodeoxyglucose (FDG) uptake and genetic alterations in patients with lung cancer. A total of 137 patients (age, 62.7 ± 10.2 years) who underwent FDG positron emission tomography/computed tomography (PET/CT) and targeted deep sequencing analysis for a tumor lesion, comprising 61 adenocarcinoma (ADC), 31 squamous cell carcinoma (SQCC), and 45 small cell lung cancer (SCLC) patients, were enrolled in this study. From the tumor lesions, 86 image features were extracted, and 381 genes were assessed. PET features were associated with genetic mutations: 41 genes with 24 features in ADC; 35 genes with 22 features in SQCC; and 43 genes with 25 features in SCLC (FDR < 0.05). Clusters based on PET features showed an association with alterations in oncogenic signaling pathways: Cell cycle and WNT signaling pathways in ADC (p = 0.023, p = 0.035, respectively); Cell cycle, p53, and WNT in SQCC (p = 0.045, 0.009, and 0.029, respectively); and TGFβ in SCLC (p = 0.030). In addition, SUV peak and SUV max were associated with a mutation of the TGFβ signaling pathway in ADC (FDR = 0.001, < 0.001). In this study, PET image features had significant associations with alterations in genes and oncogenic signaling pathways in patients with lung cancer.

Introduction: The maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may be of prognostic significance for patients with malignant pleural mesothelioma (MPM). This retrospective study aimed to investigate the prognostic value of the SUVmax in patients with MPM., Materials and Methods: Medical records were retrospectively reviewed for the patients who were diagnosed with histopathologically proven MPM between 2009 and 2018 at Samsung Medical Center. For each patient, SUVmax was calculated for the primary lesion on PET/CT. To determine optimal cutoff values for predicting mortality, receiver operating characteristic curves were used., Results: Among the 54 study patients, 34 (63.0%) had epithelioid subtype, 13 (24.1%) had sarcomatoid or biphasic subtype, and 7 (13.0%) had mesothelioma, not otherwise specified (NOS). The median overall survival (OS) was 8.7 months, and the median SUVmax was 9.9. The median values of SUVmax were 5.5 in patients with epithelioid subtype, 11.7 in those with sarcomatoid/biphasic subtype, and 13.3 in those with NOS subtype (P = 0.003). The optimal cutoff values of SUVmax to predict mortality were 10.1 in all patients, and 8.5 in patients with epithelioid subtype. In multivariate analysis, SUVmax was significantly associated with overall survival in all patients (P = 0.003) and in patients with epithelioid subtype (P = 0.012), but not in those with non-epithelioid subtype., Conclusions: SUVmax in PET/CT is an independent prognostic factor in patients with MPM, especially those with epithelioid subtype. The histologic subtype of MPM should be considered when evaluating the prognostic significance of SUVmax., Competing Interests: The authors have declared that no competing interests exist.

Objective: Little is known about prognostic factors for lung squamous cell carcinoma (SCC). We aimed to explore radiologic and clinical factors affecting prognosis and to compare the prognosis of both central and peripheral lung SCCs., Materials and Methods: Radiologic, clinical, and pathologic profiles of surgically confirmed SCCs from 382 patients were retrospectively reviewed. Tumor location, enhancement, necrosis, the presence of obstructive pneumonitis/atelectasis and underlying lung disease were evaluated on chest CT examination. Age, pulmonary function, tumor marker, and cancer stage were also assessed. Univariate and multivariate Cox regression analyses were performed to identify any correlation to overall survival (OS) and disease-free survival (DFS). Hazard rate estimation and competing risk analysis were done to evaluate recurrence pattern., Results: The median follow-up period was 56.2 months. Tumors were located centrally in 230 patients (60.2%) and peripherally in 152 patients (39.8%). Age (p = 0.002, hazard ratio [HR] 1.03, 95% confidence interval [CI] = [1.01, 1.06]) and interstitial lung abnormalities (ILAs) (p<0.001, HR 5.41, 95% CI = [3.08, 9.52]) were associated with poor OS on multivariate analysis. ILAs also had a strong association to DFS (p<0.001, HR 4.25, 95% CI = [3.08, 9.52]). Central cancers had two peaks of local recurrence development at 15 and 60 months after surgery, and peripheral tumors showed rising curves for metastasis development at 60 months., Conclusions: CT-determined ILAs are a strong biomarker predicting poor outcome. Prognosis may not vary according to tumor location, but the two groups exhibited different recurrence patterns., Competing Interests: The authors have declared that no competing interests exist.

Introduction: We hypothesized that, in non-small cell lung cancer (NSCLC) with N1 metastasis, N1 nodal 18 F-fluorodeoxyglucose (FDG) status offers independent and incremental prognostic value., Methods: We enrolled 106 NSCLC patients with pathology-confirmed N1 metastasis. N1 node FDG positivity, primary tumor maximum standard uptake value (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Kaplan-Meier method and Cox regression analyses were performed for cancer-specific survival (CSS) and disease-free survival (DFS)., Results: Subjects were 67 males and 39 females (61.9 ± 9.4 years). Eighty-one (76.4%) and 25 (23.6%) had pathologic stage IIB and IIIA NSCLC, respectively. All underwent complete tumor resection. FDG-positive N1 nodes were larger and had higher primary tumor SUV max . During a follow-up of 42 months, there were 56 recurrences and 31 cancer deaths. Significant univariate predictors were stage, no adjuvant therapy, and FDG-positive nodes for DFS, and stage, no adjuvant therapy, node size, tumor MTV, TLG, and SUV max , and FDG-positive nodes for CSS. Independent predictors on multivariate analyses were FDG-positive nodes (HR = 3.071, p = 0.003), greater tumor TLG (HR = 3.224, p = 0.002), and no adjuvant therapy (HR = 3.631, p < 0.001) for poor CSS, and FDG-positive nodes (HR = 1.771, p = 0.040) and no adjuvant therapy (HR = 2.666, p = 0.002) for poor DFS. Harrell's concordance and net reclassification improvement tests showed that CSS prediction was significantly improved by the addition of N1 FDG status to a model containing tumor TLG., Conclusion: N1 node FDG status can be useful for predicting the outcome of NSCLC patients with N1 metastasis beyond that provided by other prognostic variables., Key Points: • In NSCLC with N1 disease, N1 node FDG status is useful as a prognostic predictor. • FDG-positive N1 nodes provide additional prognostic value beyond TLG of primary tumor. • Combining TLG of primary tumor and N1 node uptake can stratify the survival of patients.

We investigated the relationship between tumor 18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans and thymidylate synthase (TS) expression. In addition, we evaluated the value of FDG uptake in predicting treatment response and prognosis when combined with TS expression in patients with advanced non-small cell lung cancer (NSCLC). We measured the maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of tumor lesions on pretreatment scan in 234 patients (age: 60.1 ± 9.4 years; males: 56.4%) with stage IV non-squamous NSCLC who were enrolled in the prospective phase II clinical trial. We investigated the correlation of the parameters with TS expression and the predictive values of the parameters compared with other clinical factors. Among these parameters, TLG was the most relevant parameter that had a significant correlation with TS expression (ρ = 0.192, P = 0.008). A multivariable Cox proportional-hazards model revealed that high TLG was a significant independent predictor for treatment response (hazard ratio [HR]: 2.05; P = 0.027), progression-free survival (HR: 1.39; P = 0.043), and overall survival (HR: 1.65; P = 0.035) with other factors. In patients with advanced non-squamous NSCLC, tumor TLG on pretreatment PET/CT scan has predictive and prognostic value.

We evaluated the relationships among functional imaging modality such as PET-CT and DW-MRI and lung adenocarcinoma pathologic heterogeneity, extent of invasion depth, and tumor cellularity as a marker of tumor microenvironment.In total, 74 lung adenocarcinomas were prospectively included. All patients underwent 18F-fluorodeoxyglucose (FDG) PET-CT and MRI before curative surgery. Pathology revealed 68 stage I tumors, 3 stage II tumors, and 3 stage IIIA tumors. Comprehensive histologic subtyping was performed for all surgically resected tumors. Maximum standardized uptake value (SUVmax) and ADC values were correlated with pathologic grade, extent of invasion, solid tumor size, and tumor cellularity.Mean solid tumor size (low: 1.7 ± 3.0 mm, indeterminate: 13.9 ± 14.2 mm, and high grade: 30.3 ± 13.5 mm) and SUVmax (low: 1.5 ± 0.2, indeterminate: 3.5 ± 2.5, and high grade: 15.3 ± 0) had a significant relationship with pathologic grade based on 95% confidence intervals (P = .01 and P < .01, respectively). SUVmax showed a strong correlation with tumor cellularity (R = 0.713, P < .001), but was not correlated with extent of invasion (R = 0.387, P = .148). A significant and strong positive correlation was observed among SUVmax values and higher cellularity and pathologic grade. ADC did not exhibit a significant relationship with tumor cellularity.Intratumor heterogeneity quantification using a multimodal-multiparametric approach might be effective when tumor volume consists of a real tumor component as well as a non-tumorous stromal component.

Objectives: We investigated the capacity of fluorodeoxyglucose (FDG) PET/CT features for stratifying probability of metastasis for single-bone FDG lesions in non-small-cell lung cancer (NSCLC)., Methods: Subjects were 118 newly diagnosed NSCLC patients with a solitary bone FDG lesion and no evidence of other distant metastasis based on PET/CT, brain MRI, and contrast-enhanced chest CT. Bone lesion SUV max and CT findings, primary tumor SUV max , clinical T stage, and N stage were analyzed., Results: The bone lesions were determined by biopsy, characteristic MRI findings and clinical follow-up to be metastatic in 33 (28.0%) and benign in 85 cases (72.0%). A cutoff bone SUV max of 4.3 showed good diagnostic performance (81.8% sensitivity, 84.7% specificity, and 83.9% accuracy), but there was considerable overlap. Bone lesion PET/CT features of SUV max  ≤ 2, osteosclerotic rim or fracture correctly diagnosed 20/20 benign, while SUV max  > 10, soft-tissue mass or bone destruction correctly diagnosed 18/18 metastatic cases. In the remaining 80 cases, bone features of SUV max  > 4.3 and osteolytic change, and lung tumor features of SUV max  > 6.4, ≥ T2 stage (n = 70), and ≥ N1 stage (n = 43) favored metastasis. The presence of one or less of these features correctly diagnosed 38/38 benign, while the presence of four or more features correctly diagnosed 5/5 metastatic cases. The 37 cases with two or three features had either benign (n = 27) or metastatic bone disease (n = 10)., Conclusion: Combining bone lesion and lung tumor PET/CT features can help stratify risk of bone metastasis in these patients., Key Points: • In NSCLC with a single-bone FDG lesion, lesion SUV max is useful for differential diagnosis. • CT features of the single-bone FDG lesions provide additional diagnostic value. • High NSCLC SUV max , greater T stage, and FDG positive nodes also favor metastasis.

Multimodality imaging measurements of treatment response are critical for clinical practice, oncology trials, and the evaluation of new treatment modalities. The current standard for determining treatment response in non-small cell lung cancer (NSCLC) is based on tumor size using the RECIST criteria. Molecular targeted agents and immunotherapies often cause morphological change without reduction of tumor size. Therefore, it is difficult to evaluate therapeutic response by conventional methods. Radiomics is the study of cancer imaging features that are extracted using machine learning and other semantic features. This method can provide comprehensive information on tumor phenotypes and can be used to assess therapeutic response in this new age of immunotherapy. Delta radiomics, which evaluates the longitudinal changes in radiomics features, shows potential in gauging treatment response in NSCLC. It is well known that quantitative measurement methods may be subject to substantial variability due to differences in technical factors and require standardization. In this review, we describe measurement variability in the evaluation of NSCLC and the emerging role of radiomics.

Purpose: This study investigated the prognostic role of tumor F-FDG uptake on pretreatment scans as an independent indicator and whether its addition improves risk prediction from Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)., Methods: We measured the SUVmax of the most F-FDG-avid tumor lesions on pretreatment scans from 222 patients (age, 60.5 ± 9.5 years; males, 55.2%) with advanced nonsquamous non-small-cell lung cancer who were enrolled in a prospective phase II clinical trial. We then examined the prognostic value of SUVmax compared with other clinical factors, including chemotherapy response according to RECIST 1.1 criteria., Results: A multivariable Cox proportional hazards model revealed that an SUVmax greater than 16.3 was an independent predictor of poor progression-free survival (hazards ratio, 3.50; 95% confidence interval, 1.89-6.51; P < 0.000) and overall survival (hazards ratio, 6.87; 95% confidence interval, 2.51-18.76; P < 0.000), whereas RECIST 1.1 did not show a significant association with any survival outcome. Furthermore, improvement was achieved by adding SUVmax to RECIST 1.1, which increased the net reclassification index (27.4%; P = 0.046) and integrated discrimination improvement (integrated discrimination improvement, 10.6%; P = 0.026). Similarly, adding RECIST 1.1 to SUVmax also improved net reclassification index (68.9%, P = 0.006) and integrated discrimination improvement (25.4%, P = 0.006) for prognosis prediction., Conclusions: High tumor F-FDG uptake on a pretreatment scan is an independent prognostic indicator that can significantly improve risk stratification when added to RECIST 1.1 for patients with advanced nonsquamous non-small-cell lung cancer.

Purpose: This study investigated the correlations between parameters of 18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan and indices of genetic properties, heterogeneity index (HI), and tumor mutation burden (TMB), in patients with lung cancer., Methods: We produced 106 PET indices for each tumor site that underwent genomic analysis in a total of 176 study subjects (age, 62.0 ± 10.0 y; males, 68.2%), comprising 101 adenocarcinoma (ADC), 29 squamous cell carcinoma (SQCC), and 46 small cell lung cancer (SCLC) patients. We then examined the correlations of the PET parameters with genetic properties of HI and TMB, according to pathology and tumor site., Results: Comparisons between PET parameters and the genetic properties with false discovery rate (FDR) correction revealed that the surface standard uptake value (SUV) entropy of SUV statistics had a significant correlation with HI only in patients with SCLC who underwent a genetic test in lymph nodes (r = 0.592, p = 0.028), whereas PET parameters did not show a significant correlation with HI or TMB in patients with SCLC who underwent a genetic test in lung tissue. In patients with ADC and SQCC, there was no significant correlation between PET parameters and the genetic properties. Although SUV max showed raw p values less than 0.05 in correlation with HI (r = 0.315, raw p = 0.048) and TMB (r = 0.206, raw p = 0.043) in ADC, and SUV peak had a raw p value less than 0.05 in correlation with HI (r = 0.394, raw p = 0.046) in SQCC, these parameters were not significant when corrected by FDR., Conclusions: In this study, surface SUV entropy had a significant correlation with HI in SCLC. Regarding other PET parameters and tumors, no significant correlation with genetic parameters existed.

Objective: We aimed to assess CT and 18 F-FDG PET/CT findings of colloid adenocarcinoma of the lung in seven patients., Materials and Methods: From 2010 to 2017, seven patients with surgically proven colloid adenocarcinoma of the lung were identified. CT (both enhanced and unenhanced) and PET/CT findings were analyzed, and the imaging features were compared with histopathologic reports. Clinical and demographic features were also analyzed., Results: In all cases except one, tumors showed low attenuation on unenhanced CT scans, ranging in attenuation from -16.5 to 20.7 HU (median, 9.2 HU). After contrast medium injection, enhancement was scant, so net enhancement ranged from 0.4 to 29.0 HU (median, 4.1 HU). All tumors had a lobulated contour. Stippled calcifications within the tumor were seen in one patient. The maximum standardized uptake value of tumors on PET/CT ranged from 1.5 to 4.5 (median, 3.5). In six of seven patients, FDG accumulation was seen in the tumor walls (n = 3, curvilinear uptake) or in both the tumor walls and tumor septa (n = 3, crisscross uptake). Six patients were alive without recurrence after a median follow-up period of 2.3 years (range, 2 months to 5 years). In one patient, who was alive at follow-up 4 years after imaging and had received adjuvant concurrent chemoradiation therapy after lobectomy, recurrent disease was detected 6 months after completion of the therapy., Conclusion: On CT, pulmonary colloid adenocarcinomas present as lobulated homogeneously low-attenuation tumors. At PET, curvilinear or crisscross FDG uptake is seen within the tumor where tumor cells are lining the walls or septal structures.

Purpose: To evaluate conditional survival among patients with surgically resected stage I-IIIa lung adenocarcinoma and identify changes in prognostic contributions for various prognostic factors over time., Patients and Methods: We performed conditional survival analysis at each t0 (=0, 1, 2, 3, 4, 5 years) for 723 consecutive patients who underwent surgical resection for lung adenocarcinoma, stratified by various clinico-demographic features, as well as pathologic and imaging (tumor-shadow disappearance ratio [TDR] on CT and maximum standardized uptake value [SUVmax] on PET) characteristics. Uni- and multivariableCox regression analyses were performed to evaluate relationships between those variables and conditional survival., Results: Three-year conditional overall survival (OS) and disease-free survival (DFS) were 92.12% and 75.51% at baseline, but improved steadily up to 98.33% and 95.95% at 5 years after surgery. In contrast to demographic factors, pathologic (stage, subtype, pathologic grade and differentiation) and radiologic factors (TDR and SUVmax) maintained a statistically significant association with subseqeunt 3-year OS until 3 years after surgery. According to the multivariableanalysis, high SUVmax and low TDR value were independent predictors of subsequent 3-year OS and DFS at baseline, 1 and 2 years after surgery, respectively., Conclusion: Our findings based on CS provide theoretical background for clinicians to plan longer period of surveillance following lung adenocarcinoma resection in survivors with preoperatively high SUVmax and low TDR on PET-CT and chest CT, respectively.

Purpose: To evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment., Results: Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i-uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514-1), 0.8610 (95% CI: 0.7547-0.9672), and 0.8394 (95% CI: 0.7045-0.9743), respectively., Materials and Methods: A total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades., Conclusions: Quantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma.

Introduction: In the 2015 World Health Organization classification, invasive mucinous adenocarcinoma (IMA) is categorized as one of various subtypes of lung invasive adenocarcinoma (ADC). However, no comprehensive analysis regarding the clinicoradiologic and prognostic features of IMA has been reported. We aimed to report prognostic factors in IMA and to compare the prognosis of IMAs with that of nonmucinous ADCs., Methods: We included 81 patients with a solitary IMA of the lung and analyzed them from the standpoint of clinicoradiologic presentation. Survival rates were assessed and compared with those of 646 resected solitary invasive nonmucinous ADCs., Results: Patients with IMA showed longer disease-free survival (DFS) than did those with nonmucinous ADCs, whereas overall survival (OS) did not differ significantly (p = 0.023 and p = 0.824, respectively). The DFS of patients with IMA was between that of patients with lepidic predominant (low-grade) and acinar/papillary predominant (intermediate-grade) ADC. In terms of OS, the survival curve of IMA was similar to that of acinar/papillary predominant ADC. Multivariate analysis revealed that tumor size (hazard ratio [HR] = 1.370, 95% confidence interval [CI]: 1.141-1.645, p = 0.001) and maximum standardized uptake value (HR = 1.338, 95% CI: 1.160-1.544, p < 0.001) were independent poor prognostic predictors for DFS. Regarding OS, tumor size (HR = 1.309, 95% CI: 1.092-1.570; p = 0.004) was the only predictor of poor prognosis., Conclusion: Patients with IMA demonstrate a DFS between that of patients with low-grade nonmucinous ADC and that of patients with intermediate-grade nonmucinous ADC and an OS similar to that of patients with intermediate-grade nonmucinous ADC. In IMA, tumor size and maximum standardized uptake value are the factors related to mitigating DFS and tumor size is the only predictor for reduced OS., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: Lung adenocarcinoma frequently manifests as subsolid nodules, and the solid portion and ground-glass-opacity (GGO) portion on CT have different prognostic significance. Therefore, current T descriptor, defined as the whole tumour diameter without discrimination between solid and GGO, is insufficient. We aimed to determine the prognostic significance of solid tumour size and attempt to include prognostic factors such as tumour disappearance rate (TDR) on CT and SUVmax on PET/CT., Methods: Five hundred and ninety-five patients with completely resected lung adenocarcinoma were analyzed. We developed a nomogram using whole tumour size, TDR, and SUVmax. External validation was performed in another 102 patients., Results: In patients with tumours measuring ≤2 cm and >2 to 3 cm, disease free survival (DFS) was significantly associated with solid tumour size (P < 0.001), but not with whole tumour size (P = 0.052). Developed nomogram was significantly superior to the conventional T stage (area under the curve of survival ROC; P = 0.013 by net reclassification improvement) in stratification of patient survival. In the external validation group, significant difference was noted in DFS according to proposed T stage (P = 0.009)., Conclusions: Nomogram-based T descriptors provide better prediction of survival and assessment of individual risks than conventional T descriptors., Key Points: • Current measurement of whole tumour diameter including ground-glass opacity is insufficient • TDR enables differentiation between invasive solid portion and non-invasive GGO portion • SUVmax demonstrates the biological aggressiveness of the tumour • We developed a nomogram using whole tumour size, TDR, and SUVmax • Nomogram-based clinical T descriptors provide better prediction of survival.

Background: The impact of host energy balance status on outcome of lung cancer has not been fully explored. It is also unknown if there is a potential modifying effect of body mass index (BMI) on tumor cell behavior in patients with early-stage non-small cell lung cancer (NSCLC). We therefore investigated the interactive effects of tumor [18F]-fluorodeoxyglucose (FDG) avidity and BMI., Methods: We investigated 1,197 patients with stage I NSCLC who underwent preoperative FDG positron emission tomography followed by curative resection. The primary outcome measure was disease-free survival (DFS). A multivariable Cox proportional hazards model was used to assess the potential independent effects of the prognostic variables. A stratified Cox regression analysis was also performed to assess the potential modifying effects of BMI on the relationship between tumor FDG uptake and patient survival., Results: There were 145 tumor recurrences and 19 deaths during a median follow-up of 30 months. Tumor-related variables, including tumor size, maximum standardized uptake value (SUVmax), histologic cell type, differentiation, lymphovascular invasion, and visceral pleural invasion, did not differ significantly according to BMI status. In multivariable Cox regression analysis, overweight or obesity [hazard ratio (HR), 0.59; 95% CI, 0.43-0.81; P = 0.001] and tumor SUVmax (HR, 1.72; 95% CI, 1.43-2.07; P < 0.001) were significantly associated with DFS. There was a significant modifying effect of BMI (P for interaction < 0.001 in multivariable analysis). High tumor SUVmax was more strongly associated with worse DFS in normal weight patients (HR, 4.72; 95% CI, 2.77-8.06; P < 0.001) than in overweight or obese patients (HR, 2.61; 95% CI, 1.58-4.31; P < 0.001)., Conclusions: Tumor FDG avidity is an independent predictor of DFS in patients with early-stage NSCLC and this prognostic value was strengthened in normal weight patients than in overweight or obese patients. These results suggest that the host-tumor interaction between host energy balance status and tumor glucose metabolism plays an important role in the outcome of early-stage NSCLC.

Introduction: Recently, a new lung adenocarcinoma classification scheme was published. The prognostic value of this new classification has not been elaborated together with the value of imaging biomarkers including computed tomography (CT) and positron emission tomography (PET)., Methods: We reviewed pathologic specimens and imaging characteristics of primary tumors from 723 consecutive patients who underwent surgical resection for lung adenocarcinoma. On pathology, the predominant histologic subtype and pattern group were quantified. Tumor-shadow disappearance ratio (TDR) on CT and maximum standardized uptake value (SUVmax) on PET were assessed. The relationships between those variables and survival (overall survival [OS] and disease-free survival) were analyzed by using Kaplan-Meier curves and Cox regression analyses., Results: The median follow-up period was 3.8 years. There were 137 patients (19%) with recurrence and 167 patients (23%) with metastasis after surgical resection. Among 723 patients, 35 patients (4.8%) had adenocarcinoma in situ, 34 patients (4.7%) had minimally invasive adenocarcinoma, 125 patients (17.3%) had lepidic predominant, 314 patients (43.4%) had acinar predominant, 65 patients (9.0%) had papillary predominant, 23 patients (3.2%) had micropapillary predominant, 113 patients (15.6%) had solid predominant, and 14 patients (1.9%) had variant adenocarcinomas. OS and disease-free survival rates were significantly different according to TDR on CT and SUVmax on PET, predominant subtypes, and pattern groups. On multivariate analysis, the SUVmax (p < 0.001), TDR (p = 0.038), and pattern group (p = 0.015) were independent predictors of OS., Conclusions: TDR on CT, SUVmax on PET, and the new histologic classification schemes appear to be promising parameters for the prognostic stratification of patients with lung adenocarcinomas, allowing for the triage of patients who necessitate further staging workup and adjuvant therapy.

18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is an evolving tool in the field of oncology. 18F-fluorodeoxyglucose, however, is not a specific tool for malignant tumor that it may also accumulate in benign processes. To avoid false-positive interpretation of 18F-FDG-PET/computed tomography (CT), having knowledge of the potential pitfalls is important.The authors present a case of a patient with a lung mass who underwent fluoroscopy-guided transthoracic lung biopsy followed by 18F-FDG-PET/CT scan with a 4-hour interval between biopsy and scanning. Abnormally increased FDG uptake in the mass and pleural effusion was detected. Pathologic examination of the specimen, however, revealed only fibrous tissues with chronic inflammatory cells. On performing CT imaging, 1 month later, the mass and effusion had spontaneously resolved without treatment.Our findings suggest that PET/CT performed immediately following invasive procedures can result in false-positive results and thus mislead diagnosis. Therefore, the interval and order, in which PET/CT and invasive procedures are performed, should be carefully considered in oncologic work-up.

Objective: We evaluated the prognostic impact of volume-based assessment by pretreatment (18)F-FDG PET/CT in patients who had clinical stage IIIA-N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection., Materials and Methods: We reviewed 161 consecutive patients who had stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery. In all cases, N2 disease was pathologically confirmed by mediastinoscopic biopsy, endobronchial ultrasound-guided transbronchial needle aspiration, or video-assisted thoracoscopic surgery. We measured the total metabolic tumor volume (total MTV) and the maximum standardized uptake value (SUVmax), including a primary tumor and metastatic nodes on the pretreatment scan. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. The association of PET parameters with OS and DFS was determined by univariable and multivariable analyses performed using the Cox regression model., Results: A higher total MTV was significantly associated with poor DFS (hazard ratio [HR], 1.82; p = 0.036) and OS (HR = 2.97; p = 0.012) in the multivariable analysis. In contrast, a higher SUVmax was not significantly associated with poor DFS and OS. Patients with a high total MTV (> 22 cm(3)) had a median survival time that was significantly shorter than that of patients with a low total MTV (median DFS, 11.3 vs 42.0 months, respectively [p < 0.001]; median OS, 38.3 months vs not reached [p < 0.001]). Kaplan-Meier curves showed significant differences on the basis of total MTV in patients with or without mediastinal downstaging after CCRT. Patients with a high total MTV had significantly worse DFS when they had post-neoadjuvant pathologic (yp) stage 0-II disease (p = 0.020) or yp stage III disease (p = 0.036). Higher total MTV was also associated with worse OS in patients with yp stage 0-II disease (p = 0.013) or yp stage III disease (p = 0.007)., Conclusion: A higher pretreatment total MTV is associated with worse outcome, independent of yp stage, in patients with stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery.

Objective: The utility of (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning and brain magnetic resonance imaging (MRI) as a staging workup for lung adenocarcinoma manifesting as pure ground glass opacity (GGO) is unknown. The purpose of this study was to determine the utility of these 2 tests for preoperative staging of pure GGO nodular lung adenocarcinoma., Methods: The study included 164 patients (male:female, 73:91; mean age, 62 years) with pure GGO nodular lung adenocarcinoma who underwent PET/CT (in 136 patients) and/or brain MRI (in 109 patients) before surgery. Pathologic N staging and dedicated standard imaging or follow-up imaging findings for M staging were used as reference standards. The median follow-up time was 47.9 months., Results: On PET/CT scan, abnormal FDG uptake of lymph nodes was found in 2 of 136 patients (1.5%); both were negative on final pathology. Abnormal FDG uptake of the liver was detected in 1 patient, which was also confirmed to be negative by dedicated abdominal CT. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT in detecting metastases were not applicable, 98% (95% confidence interval [CI], 94%-100%), 0% (95% CI, 0%-71%), 100% (95% CI, 97%-100%), and 98% (95% CI, 94%-100%), respectively. No brain metastasis was found in preoperative brain MRI of 109 patients. Of 109 patients, 1 (0.9%) developed brain metastasis 30 months after surgical resection., Conclusions: PET/CT and brain MRI is not necessary in the staging of pure GGO nodular lung adenocarcinoma., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

We report a rare case of primary pulmonary low-grade angiosarcoma on dynamic contrast-enhanced CT and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. A 38-year-old, asymptomatic woman was hospitalized because of an abnormality on chest radiography. A dynamic contrast-enhanced chest CT showed a 1.2 cm-sized irregular-margined nodule with strong and persistent enhancement in the right lower lobe. The lesion had low metabolic activity on an (18)F-FDG PET/CT scan. The patient underwent a wedge resection for the lesion, and pathology revealed a primary pulmonary low-grade angiosarcoma.

Objective: The maximum standardized uptake value (SUVmax) of pulmonary mucoepidermoid carcinoma (PMEC) in fluorine-18fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was evaluated as a preoperative predictor of pathologic grade and survival rate., Materials and Methods: Twenty-three patients who underwent preoperative PET/CT and complete resection for PMEC were enrolled. The optimal cut-off SUVmax for tumor grade was calculated as 6.5 by receiver operating characteristic curve. The patients were divided into a high SUV group (n = 7) and a low SUV group (n = 16). Clinicopathologic features were compared between the groups by χ(2) test and overall survival was determined by Kaplan-Meier analysis., Results: The mean SUVmax was 15.4 ± 11.5 in the high SUV group and 3.9 ± 1.3 in the low SUV group. All patients except one from the low SUV group had low grade tumors and all had no nodal metastasis. The sensitivity and specificity of SUVmax from PET/CT for predicting tumor grade was 85.7% and 93.8%, respectively. During the follow-up period (mean, 48.6 ± 38.7 months), four patients from the high SUV group experienced cancer recurrence, and one died of cancer. In contrast, none of the low SUV group had recurrence or mortality. Five-year overall survival rate was significantly higher in the low SUV group (100% vs. 71.4%, p = 0.031)., Conclusion: Pulmonary mucoepidermoid carcinoma patients with high SUVmax in PET/CT had higher tumor grade, more frequent lymph node metastasis and worse long-term outcome. Therefore, PMEC patients with high uptake on PET/CT imaging might require aggressive mediastinal lymph node dissection and adjuvant therapies.

Introduction: Correct mediastinal staging is critical for determination of the most appropriate management strategy in patients with non-small-cell lung cancer (NSCLC). The purpose of this study was to compare the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with that of mediastinoscopy in patients with NSCLC., Methods: A prospective trial was conducted in a tertiary referral center in Korea. Patients with histologically proven NSCLC and suspicion for N1, N2, or N3 metastasis were enrolled. Each patient underwent EBUS-TBNA followed by mediastinoscopy. Surgical resection and complete lymph node dissection were conducted in patients for whom no evidence of mediastinal metastasis was apparent after mediastinoscopy., Results: In total, 138 patients underwent EBUS-TBNA and 127 completed both EBUS-TBNA and mediastinoscopy. N2/N3 disease was confirmed in 59.1% of the patients. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) of EBUS-TBNA on a per-person analysis were 88.0%, 100%, 92.9%, 100%, and 85.2%, respectively. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and NPV of mediastinoscopy on a per-person analysis were 81.3%, 100%, 89.0%, 100%, and 78.8%, respectively. Significant differences in the sensitivity, accuracy, and NPV were evident between EBUS-TBNA and mediastinoscopy (p < 0.005)., Conclusions: EBUS-TBNA was superior to mediastinoscopy in terms of its diagnostic performance for mediastinal staging of cN1-3 NSCLC. Because EBUS-TBNA is both less invasive and affords superior diagnostic sensitivity, it should be the first-line procedure performed in patients with NSCLC.

Objectives: For the ultimately efficient screening of anaplastic lymphoma kinase gene (ALK)-positive cases, combination of radiometabolic characteristics with clinicopathologic features may be more useful. Therefore, we determined radiologic characteristics and metabolic characteristics in patients with adenocarcinoma harboring ALK mutations., Patients and Methods: We retrospectively reviewed clinicopathologic CT and PET/CT data from patients with advanced lung adenocarcinoma screened for identifying ALK rearrangement. Lesion size, solidity, location, margins, CT attenuation, and SUVmax were assessed. Pathologic features such as differentiation, the presence of signet ring cell, EGFR/KRAS mutation status, and TTF-1 expression were also reviewed., Results: Of the screened 221 patients, 41 patients (19%) demonstrated ALK rearrangements, and these individuals were younger than the ALK-negative patients (P < 0.001) and showed significant association with no exposure to tobacco (P = 0.028). ALK-positive lung adenocarcinomas were significantly less differentiated than those without rearrangements (P = 0.005). ALK-positive tumors showed significantly higher SUVmax than ALK-negative tumors (P = 0.016). Multivariate logistic regression modeling for predicting the ALK-positive lung adenocarcinoma disclosed that lower CT attenuation and higher SUVmax were significant independent factors of ALK rearrangements (odds ratio, 0.87 and 1.06; P = 0.03 and 0.01, respectively). Receiver operating characteristic analysis showed that the area under the receiver operating characteristic curve for SUVmax/CT attenuation ratio was 0.788, and the optimal cutoff value of SUVmax/CT attenuation ratio for identifying ALK-positive lung adenocarcinoma was greater than or equal to 0.208 (sensitivity, 74.2%; specificity, 81.0%)., Conclusions: This study shows that ALK-rearranged lung adenocarcinoma represents younger age, no history of smoking, the absence of spiculation on CT, and higher SUVmax/CT attenuation greater than or equal to 0.208 compared with those without ALK mutation.

A 51-year-old woman with dyspnea on exertion, fever, pleural effusion, and pericardial thickening underwent F-FDG PET/CT, which revealed focal hypermetabolic lesions in the right lung and left breast. The histopathology of the lesions was compatible with infiltration of inflammatory cells. Blood eosinophil counts were elevated, and enzyme-linked immunoassays were positive for antibodies to several parasites. After antiparasite medication, blood eosinophil counts were normalized, and PET/CT demonstrated complete disappearance of abnormal FDG accumulation in the lung and breast.

Background: We evaluated the prognostic value of volume-based metabolic positron emission tomography (PET) parameters in patients with small cell lung cancer (SCLC) compared with other factors., Methods: The subjects were 202 patients with pathologically proven SCLC who underwent pretreatment 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT). Volumetric metabolic parameters of intrathoracic malignant hypermetabolic lesions, including maximum and average standardized uptake value, sum of metabolic tumor volume (MTV), and sum of total lesion glycolysis (TLG) were measured., Results: 164 patients had died during follow-up (median 17.4 months) and median overall survival was 14 months. On univariate survival analysis, age, stage, treatment modality, sum of MTV (cutoff = 100 cm3), and sum of TLG (cutoff = 555) were significant predictors of survival. There was a very high correlation between the sum of MTV and the sum of TLG (r = 0.963, P < 0.001). On multivariate survival analysis, age (HR = 1.04, P < 0.001), stage (HR = 2.442, P < 0.001), and sum of MTV (HR = 1.662, P = 0.002) were independent prognostic factors. On subgroup analysis based on limited disease (LD) and extensive disease (ED), sum of MTV and sum of TLG were significant prognostic factors only in LD., Conclusion: Both sum of MTV and sum of TLG of intrathoracic malignant hypermetabolic lesions are important independent prognostic factors for survival in patients with SCLC, in addition to age and clinical stage. However, it may be more useful in limited disease rather than in extensive disease.

Purpose: We evaluated the prognostic impact of volume-based assessment by (18)F-FDG PET/CT in patients with stage III non-small-cell lung cancer (NSCLC)., Methods: We reviewed 194 consecutive patients with stage IIIA NSCLC treated with surgical resection (surgical group) and 115 patients treated with nonsurgical therapy (nonsurgical group: 50 stage IIIA, 65 stage IIIB). Metabolic tumour volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) of primary tumours were measured using pretreatment (18)F-FDG PET/CT. Overall survival was assessed using the Kaplan-Meier method. The prognostic significance of PET parameters and other clinical variables was assessed using Cox proportional hazards regression analyses. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used., Results: In the Cox proportional hazards models, MTV (HR=1.27 for a doubling of MTV, P=0.008) and TLG (HR=1.22 for a doubling of TLG, P=0.035) were significantly associated with an increased risk of death after adjusting for age, gender, histological cell type, T stage, N stage, and treatment variables in the surgical group. SUVmax was not a significant prognostic factor in either the surgical or nonsurgical group. In the time-dependent ROC curve analysis, volume-based PET parameters predicted survival better than SUVmax., Conclusion: The volume-based PET parameters (MTV and TLG) are significant prognostic factors for survival independent of tumour stage and better prognostic imaging biomarkers than SUVmax in patients with stage IIIA NSCLC after surgical resection.

Purpose: Among patients with advanced non-small cell lung cancer (NSCLC), identification of a subgroup of patients for immediate maintenance treatment after first-line chemotherapy has great importance in improving survival. The purpose of this study was to investigate whether the metabolic responses evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be a potential screening tool for identifying patients with early disease progression who may benefit from immediate maintenance treatment., Methods: A total of 52 patients with advanced NSCLC (36 men and 16 women, mean age 57.2 ± 10.6 years) who underwent baseline and follow-up (18)F-FDG PET/CT after four cycles of first-line chemotherapy were enrolled. Maximum standardized uptake value (SUV(max)), SUV(peak), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the tumour lesions were measured and percentage decrease of the parameters was calculated. The prognostic significance of percentage decrease of these parameters and other clinical variables related to progression-free survival (PFS) and overall survival (OS) were assessed by Cox proportional hazards regression analysis. Receiver-operating characteristic (ROC) curve analysis was used to define the optimal cut-off value of percentage decrease of the parameters that could distinguish between early (PFS < 6 months) and late (PFS ≥ 6 months) disease progression groups., Results: Multivariate analysis showed that percentage decrease of TLG [hazard ratio per 10% decrease = 1.030, 95% confidence interval (CI) = 1.012-1.048, p = 0.001) was a significant predictor of PFS and OS. ROC curves identified a 50.0% decrease in TLG as the optimal cut-off value to distinguish disease progression groups. Positive and negative predictive values of the optimal TLG value for selecting patients with late disease progression were 36.4 and 100.0%, respectively., Conclusion: The percentage decrease in TLG of measurable tumour lesions may be a potential parameter to appropriately identify a subgroup of patients for immediate maintenance treatment after first-line chemotherapy in patients with advanced NSCLC.

The two-stage system of limited and extensive disease has been widely employed for small cell lung cancer (SCLC). However, the International Association for the Study of Lung Cancer has proposed that the TNM classification should be incorporated into clinical practice. The purpose of this study was to evaluate the applicability of the Union for International Cancer Control (UICC) 7th TNM staging system to SCLC. We retrospectively reviewed the medical records of consecutive patients with newly diagnosed histologically proven SCLC between March 2005 and January 2010. Patients who had other concurrent malignancies or had combined-type SCLC were excluded. We assessed overall survival (OS) according to the T descriptor, N descriptor, M descriptor, and TNM stage grouping. In total, 320 SCLC patients were included. Median age was 65 years and 286 patients (89.4%) were male. Median OS was 12.7 months. There were no significant differences in OS according to the T descriptor (P = 0.880). However, there were significant differences in OS according to the N (P < 0.001) and M (P < 0.001) descriptors and TNM stage grouping (P < 0.001). Hazard ratios for OS, adjusted for known prognostic factors, differed significantly according to the N and M descriptor, and TNM stage grouping, but not according to the T descriptors. The UICC 7th TNM staging system may contribute to a more precise prognosis in SCLC patients. Further studies are required to evaluate the applicability of the TNM staging system to SCLC., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging-positron emission tomography (MRI-PET) would increase the number of correctly upstaged patients compared with WB PET-computed tomography (PET-CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC)., Methods: From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI-PET or WB PET-CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging., Results: Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI-PET group and in 26 of 120 patients (21.7%) in the PET-CT plus brain MRI group (4.2% difference; 95% confidence interval, -6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI-PET group and in 7 of 120 patients (5.8%) in the PET-CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%-20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (-10.7% difference; 95% confidence interval, -20.1% to -1.4%; P = .022)., Conclusions: Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI-PET did not appear to help identify significantly more correctly upstaged patients than PET-CT plus brain MRI in patients with NSCLC., (Copyright © 2013 American Cancer Society.)

A pulmonary mucinous cystadenocarcinoma is an extremely rare tumor that is considered to be a cystic variant of mucin-producing lung adenocarcinoma. We present a case of pulmonary mucinous cystadenocarcinoma in a 54-year-old woman. Chest CT scans showed a 4.3-cm-sized, lobulated, well-defined, and homogeneous mass in the right middle lobe with peripheral stippled calcifications that demonstrated low-attenuation with no enhancement after contrast administration; (18)F-fluorodeoxyglucose (FDG) PET/CT demonstrated mild heterogeneous FDG uptake. The mass was diagnosed as adenocarcinoma with mucin production by transbronchial lung biopsy. Right middle lobectomy was performed, and the pathologic examination disclosed a pulmonary mucinous cystadenocarcinoma.

Objective: To evaluate the prognostic significance and predictive performance of volume-based parameters of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in early-stage non-small cell lung cancer (NSCLC)., Background: Although surgical resection remains the optimal treatment for early-stage NSCLC, approximately 40% of patients with stage I and 60% of patients with stage II NSCLC relapse and die within 5 years after curative resection. Therefore, identification of additional prognostic biomarkers is needed to develop risk-adapted treatment strategies., Methods: We retrospectively reviewed 529 consecutive patients with pathologically proven early-stage NSCLC who underwent preoperative F-FDG PET/CT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumors were measured. Overall survival (OS) and disease-free survival (DFS) were assessed by the Kaplan-Meier method. The prognostic significance of PET parameters and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used., Results: In the multivariate analyses, volume-based parameters of PET (MTV and TLG) that were analyzed as continuous variables were significantly associated with an increased risk of recurrence (P = 0.001 for MTV, P < 0.001 for TLG) and death (P = 0.009 for MTV, P = 0.007 for TLG), after adjusting for age, sex, histology, tumor stage, and type of surgery. SUVmax analyzed as a continuous variable was not a significant prognostic factor for both DFS (P = 0.056) and OS (P = 0.525). In the time-dependent ROC curve analysis, the volume-based parameter of PET showed better predictive performance than SUVmax (P < 0.001)., Conclusions: The volume-based parameter of PET is an independent prognostic factor for survival in addition to pathological tumor-node-metastasis stage and a promising tool for better prediction of outcome in patients with early-stage NSCLC.

Objectives: To determine the positive reading criteria for malignant nodes when interpreting combined MRI and PET/CT images for preoperative nodal staging in non-small-cell lung cancer (NSCLC)., Methods: Forty-nine patients with biopsy-proven NSCLC underwent both PET/CT and thoracic MRI [diffusion weighted imaging (DWI)]. Each nodal station was evaluated for the presence of metastasis by applying either inclusive (positive if either one read positive) or exclusive (positive if both read positive) criteria in the combined interpretation of PET/CT and MRI. Nodal stage was confirmed pathologically. The combined diagnostic accuracy of PET/CT and MRI was determined on per-nodal station and per-patient bases and compared with that of PET/CT alone., Results: In 49 patients, 39 (19%) of 206 nodal stations harboured malignant cells. Out of 206 nodal stations, 186 (90%) had concordant readings, while the rest (10%) had discordant readings. Inclusive criteria of combined PET/CT and MRI helped increase sensitivity for detecting nodal metastasis (69%) compared with PET/CT alone (46%; P = 0.003), while specificity was not significantly decreased., Conclusion: Inclusive criteria in combined MRI and PET/CT readings help improve significantly the sensitivity for detecting nodal metastasis compared with PET/CT alone and may decrease unnecessary open thoracotomy. Key Points • Combined interpretation of MRI and PET/CT enhances the detection of nodal metastasis. • Inclusive criteria of combined MRI/PET/CT improved the sensitivity for detecting nodal metastasis. • Combined interpretation of MRI and PET/CT may reduce unnecessary open thoracotomies.

The purpose of this article is to review the imaging features of thoracic epithelioid hemangioendotheliomas with pathologic correlation. The thoracic manifestation of epithelioid hemangioendotheliomas is one of three different CT patterns: multiple pulmonary nodules, multiple pulmonary reticulonodular opacities, or diffuse infiltrative pleural thickening. Without any evidence of histological malignancy, malignant features (multiplicity of pulmonary nodules, hepatic or bone involvement, lymphangitic tumor spread, and infiltrative pleural masses) are characteristic of these infrequent tumors.

Introduction: The intensity of 18F-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography could be of prognostic significance for patients with non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic value of the FDG uptake in patients with resected pathologic stage I NSCLC according to histologic types of the tumors., Methods: For each patient, a maximum standardized uptake value (SUVmax) and a partial volume corrected (PVC) SUVmax were calculated for the primary lesion on positron emission tomography. To find optimal cutoff values for cancer recurrences, receiver operating characteristic curves were used., Results: Among 145 study patients, the mean values of SUVmax were 7.7 in those with adenocarcinoma (n = 70) and 16.0 in those with other histologies (n = 75; p < 0.001). Furthermore, the optimal cutoff values of SUVmax to predict cancer recurrences were identified as 5.2 in patients with adenocarcinoma and 13.8 in those with other histologies. In whole patients with pathologic stage I NSCLC, SUVmax (p = 0.025), PVC SUVmax (p = 0.014), tumor size (p = 0.048), and weight loss (p = 0.041) were significantly associated with disease-free survival (DFS). Moreover, PVC SUVmax (p = 0.034) and SUVmax (p = 0.012) were significantly associated with DFS in the multivariate analyses., Conclusions: The intensity of FDG uptake for the primary tumor was an independent prognostic factor for DFS in whole patients with pathologic stage I NSCLC. However, caution is needed for the interpretation of optimal cutoff values of SUVmax according to tumor histologies.

Purpose: To compare prospectively the diagnostic efficacies of integrated positron emission tomography (PET)/computed tomography (CT) and 3.0-T whole-body magnetic resonance (MR) imaging for determining TNM stages in non-small cell lung cancer (NSCLC)., Materials and Methods: Institutional review board approval and informed consent were obtained. The study included 165 patients (125 men, 40 women; mean age, 61 years) with NSCLC proved at pathologic examination who underwent both unenhanced PET/CT and whole-body MR imaging. Pathologic findings for T (n = 123) and N (n = 150) staging and pathologic or follow-up imaging findings (n = 154) for M staging were reference standards. The efficacies of PET/CT and whole-body MR imaging for lung cancer staging were compared by using the McNemar test., Results: Primary tumors (n = 123 patients) were correctly staged in 101 (82%) patients at PET/CT and in 106 (86%) patients at whole-body MR imaging (P = .263). N stages (n = 150 patients) were correctly determined in 105 (70%) patients at PET/CT and in 102 (68%) patients at whole-body MR imaging (P = .880). Thirty-one (20%) of 154 patients had metastatic lesions. Accuracy for detecting metastases was 86% (133 of 154 patients) at PET/CT, and that at whole-body MR imaging was 86% (132 of 154 patients) (P > .99). Although the differences were not statistically significant, whole-body MR imaging was more useful for detecting brain and hepatic metastases, whereas PET/CT was more useful for detecting lymph node and soft-tissue metastases., Conclusion: Both PET/CT and 3.0-T whole-body MR imaging appear to provide acceptable accuracy and comparable efficacy for NSCLC staging, but for M-stage determination, each modality has its own advantages.

Objective: The aim of this study was to assess the diagnostic efficacy of integrated PET/CT using fluorodeoxyglucose (FDG) for the differentiation of benign and metastatic adrenal gland lesions in patients with lung cancer and to compare the diagnostic efficacy with the use of PET alone., Materials and Methods: Sixty-one adrenal lesions (size range, 5-104 mm; mean size, 16 mm) were evaluated retrospectively in 42 lung cancer patients. Both PET images alone and integrated PET/CT images were assessed, respectively, at two-month intervals. PET findings were interpreted as positive if the FDG uptake of adrenal lesions was greater than or equal to that of the liver, and the PET/CT findings were interpreted as positive if an adrenal lesion show attenuation > 10 HU and showed increased FDG uptake. Final diagnoses of adrenal gland lesions were made at clinical follow-up (n = 52) or by a biopsy (n = 9) when available. The diagnostic accuracies of PET and PET/CT for the characterization of adrenal lesions were compared using the McNemar test., Results: Thirty-five (57%) of the 61 adrenal lesions were metastatic and the remaining 26 lesions were benign. For the depiction of adrenal gland metastasis, the sensitivity, specificity, and accuracy of PET were 74%, 73%, and 74%, respectively, whereas those of integrated PET/CT were 80%, 89%, and 84%, respectively (p values; 0.5, 0.125, and 0.031, respectively)., Conclusion: The use of integrated PET/CT is more accurate than the use of PET alone for differentiating benign and metastatic adrenal gland lesions in lung cancer patients.

Objective: Our purpose was to evaluate the usefulness of integrated 18F-FDG PET/CT in the detection and characterization of nonpalpable supraclavicular lymph node metastasis in patients with the initial diagnosis of lung cancer., Subjects and Methods: This study was conducted from May 2005 to May 2006 and included 32 consecutively registered lung cancer patients in whom supraclavicular lymph nodes were not palpable but were identified on contrast-enhanced CT or exhibited increased FDG uptake on integrated PET/CT. Three patients had bilateral nodes, for a total of 35 nodes in the 32 patients. Results of cytologic analysis of a specimen obtained with sonographically guided fine-needle aspiration (n = 27), normal initial and follow-up sonographic findings (n = 3), and no change in the size of supraclavicular lymph nodes on follow-up sonography (n = 2) were the reference standards. The presence of supraclavicular lymph node metastasis was determined with integrated PET/CT (uptake greater than that of surrounding tissue) and contrast-enhanced CT (node short-axis diameter of 5 mm or more). The diagnostic efficacies of these methods in the detection of supraclavicular lymph node metastasis were compared., Results: Supraclavicular lymph node metastasis was diagnosed cytologically in 12 (34%) of 35 lesions. The diagnostic accuracies of integrated PET/CT and contrast-enhanced CT in the detection of supraclavicular lymph node metastasis were 71% and 66%, respectively; the difference was not statistically significant. Although the difference was not statistically significant, the sensitivity (92%) and negative predictive value (93%) of integrated PET/CT were higher than those of contrast-enhanced CT., Conclusion: Because of its high sensitivity and negative predictive value, integrated PET/CT is useful in the detection and characterization of nonpalpable supraclavicular lymph nodes in lung cancer patients.

Objective: The purpose of this study was to describe retrospectively integrated PET/CT findings on pulmonary neuroendocrine tumors and to correlate the findings with prognosis., Materials and Methods: Between May 2003 and February 2005, 37 consecutively enrolled patients (33 men and four women; mean age, 60 years) with histopathologically proven pulmonary neuroendocrine tumors underwent 18F-FDG PET/CT after enhanced standalone CT. CT was used to analyze the morphologic features of the tumors and PET to measure maximum standardized uptake value (SUV). Maximum SUVs of carcinoid tumors, large-cell neuroendocrine carcinomas (LCNECs), and small-cell lung carcinomas (SCLCs) were compared, and maximum SUV and tumor stage and prognosis were correlated., Results: Four (two typical and two atypical) of the seven carcinoid tumors had no FDG uptake or less than mediastinal uptake. The maximum SUVs of primary tumors, in increasing order, were significantly different for carcinoids (mean, 4.0; median, 3.4), LCNECs (mean, 12.0; median, 10.7), and SCLCs (mean, 11.6; median, 11.7) (p = 0.006, Kruskal-Wallis test). There was no significant correlation between maximum SUV of the primary tumor and the tumor stages of carcinoids, LCNECs, or SCLCs (p = 0.08, Jonckheere-Terpstra test; p = 0.768, Mann-Whitney test). Results of receiver operating characteristics analysis showed a maximum SUV greater than 13.7 suggested a poor survival period in cases of LCNEC and SCLC., Conclusion: The maximum SUVs of neuroendocrine tumors are significantly different for carcinoid tumors, LCNECs, and SCLCs, and a high maximum SUV suggests short survival of patients with LCNEC or SCLC.

Background: Integrated (18)fluorine fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) has shown somewhat variable sensitivity and specificity for mediastinal nodal staging in granulomatous disease endemic areas. The purpose of the study was to prospectively evaluate the efficacy of PET/CT for mediastinal nodal staging in nonsmall cell lung cancer (NSCLC) patients in a tuberculosis-endemic country., Methods: Prospective assessment of the diagnostic efficacy of integrated PET/CT for detecting mediastinal nodal metastasis was performed in 674 patients (M:F ratio = 502:172; mean age, 61 years) with NSCLC. Patients underwent an integrated PET/CT examination and subsequent surgical nodal staging (by mediastinoscopy only in 121 patients and by thoracotomy in 553). Nodes showing greater (18)F-FDG uptake than mediastinum at PET without benign calcification or high attenuation >70 household unit (HU) at unenhanced CT were regarded as being positive for malignancy. The histologic nodal assessment results were used as reference standards., Results: Of 2477 mediastinal nodal stations evaluated in 674 patients, 275 (11%) stations in 180 (27%) patients proved to be malignant. On a per-person basis, the overall sensitivity, specificity, and accuracy of PET/CT for mediastinal nodal staging were 61% (110 of 180), 96% (473 of 494), and 86% (583 of 674), respectively. On a per-nodal station basis, they were 46% (126 of 275), 98% (2154 of 2202), and 92% (2280 of 2477)., Conclusions: Integrated PET/CT provides high specificity and reasonably high accuracy, but somewhat low sensitivity for mediastinal nodal staging of NSCLCs. The high specificity is achieved at the expense of sensitivity by interpreting calcified nodes or nodes with high attenuation at CT, even with high FDG uptake at PET, as benign in a tuberculosis-endemic region.

Purpose: To prospectively evaluate the sensitivity and specificity of integrated fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) (PET/CT) for the preoperative diagnosis of mediastinal nodal metastasis in stage T1 non-small cell lung cancer (NSCLC), with surgical and histologic results as reference standards., Materials and Methods: Institutional review board approval and informed consent were obtained. From June 2003 to February 2005, 150 patients (89 men and 61 women; mean age, 59 years) with stage T1 NSCLC at stand-alone CT underwent integrated PET/CT and surgical staging. Two observers (one radiologist and one nuclear medicine physician) evaluated prospectively and in consensus the mediastinal nodes by analyzing both PET (functional) and CT (anatomic) images. Nodal stages were determined by using the American Joint Committee on Cancer staging system and surgical and histologic findings as the reference standard. Statistical evaluation of malignant lymph nodes was performed on per-nodal-station and per-person bases., Results: A total of 568 mediastinal nodal stations were evaluated. Nodes were positive for malignancy in 34 (23%) of 150 patients and 55 (10%) of 568 nodal stations. For depiction of malignant nodes, the respective sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of integrated PET/CT were 42% (23 of 55), 100% (513 of 513), 100% (23 of 23), 94% (513 of 545), and 94% (536 of 568) on per-nodal-station basis and 47% (16 of 34), 100% (116 of 116), 100% (16 of 16), 87% (116 of 134), and 88% (132 of 150) on a per-patient basis., Conclusion: Integrated FDG PET/CT provides high specificity and positive predictive value of mediastinal nodal staging in stage T1 NSCLC, although the sensitivity is low.

Objective: The aim of this study was to describe retrospectively the CT findings of dry pleural dissemination of peripheral lung adenocarcinoma, and to compare the mutual roles of PET and CT components of integrated PET/CT in the diagnosis of the disease., Methods: The authors analyzed retrospectively the CT findings of pathologically proved dry pleural dissemination in 8 of 172 patients with peripheral adenocarcinoma of the lung. Subsequently, one radiologist and one nuclear medicine physician (unaware of the CT and pathologic results) evaluated together in a random order the integrated PET/CT of 172 adenocarcinoma patients (8 with dry pleural dissemination and 164 without). They recorded the presence of pleural dissemination using PET images only and using both PET and CT images. The diagnostic accuracies with respect to the presence of pleural dissemination were evaluated., Results: The CT findings of dry pleural dissemination were pleural small nodules (n=8, 100%) (>or=6 in number in all patients; 198/204 nodules were <5 mm in diameter and 6/204 were 5-10 mm) and uneven (n=4, 50%) or band-like (n=3, 38%) fissural thickening. By PET only, the sensitivity, specificity, and accuracy of dry pleural dissemination were 25% (2/8), 90% (147/164), and 87% (149/172), respectively; by PET plus CT these were 100% (8/8), 100% (164/164), and 100% (172/172), respectively., Conclusions: The CT findings of dry pleural dissemination are multiple small pleural nodules and uneven pleural thickening. Dry pleural dissemination should be diagnosed using CT findings at integrated PET/CT because lesions causing pleural dissemination without pleural effusion are usually beyond PET resolution.

Purpose: To evaluate prospectively the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) with use of fluorodeoxyglucose (FDG), compared with that of stand-alone CT, for the preoperative staging of non-small cell lung cancer, with surgical and histologic findings used as the reference standard., Materials and Methods: Institutional review board approval and patient informed consent were obtained. From November 2003 to February 2004, 106 patients (78 men, 28 women; mean age, 56 years) with non-small cell lung cancer underwent curative surgical resection (tumor resection and lymph node dissection) after stand-alone CT followed by integrated FDG PET/CT. Tumor stages were determined by using the TNM and American Joint Committee on Cancer staging systems. Histopathologic results served as the reference standard. Statistically significant differences in tumor staging between integrated PET/CT and stand-alone CT were determined with P < .05 obtained by using the McNemar test or with a generalized estimating equation., Results: The primary tumor was correctly staged in 84 patients (79%) at stand-alone CT and in 91 patients (86%) at integrated FDG PET/CT (P = .25). For the depiction of malignant nodes, the sensitivity, specificity, and accuracy of CT were 70% (23 of 33 nodal groups), 69% (248 of 360), and 69% (271 of 393), respectively, whereas those of PET/CT were 85% (28 of 33), 84% (302 of 360), and 84% (330 of 393) (P = .25, P < .001, and P < .001, respectively). There were 112 false-positive interpretations at CT for 54 hilar, 16 subcarinal, 29 paratracheal, 10 subaortic, and two pulmonary ligament nodal groups and one upper paratracheal group, compared with only 58 false-positive interpretations at PET/CT for 32 hilar, seven subcarinal, 13 lower paratracheal, and six subaortic nodal groups. There were 10 false-negative interpretations at CT for four hilar, two lower paratracheal, and two subcarinal nodal groups, one prevascular and retrotracheal group, and one inferior pulmonary group, but only five false-negative interpretations at PET/CT (one each for paratracheal, subaortic, subcarinal, inferior pulmonary, and hilar nodal groups)., Conclusion: Integrated FDG PET/CT is significantly better than stand-alone CT for lung cancer staging and provides enhanced accuracy and specificity in nodal staging.