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Abstract: This 65-year-old man suffering from hypercalcemia in a context of hyperparathyroidism treated by calcimimetics was referred to our institution to perform an 18 F-fluorocholine PET/CT in order to localize the pathological parathyroid gland(s). We incidentally discovered a brain metastatic pulmonary large cell neuroendocrine carcinoma in addition to a parathyroid adenoma. This case illustrates the value of FCH PET/CT in hyperparathyroidism workup event under calcimimetic treatment, as well as the potential of FCH PET/CT to reveal occult malignancies., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the early radiological features and survival of Large Cell Carcinoma (LCC) cases diagnosed in low-dose computed tomography (LDCT) screening trials., Methods: Two radiologists jointly reviewed the radiological features of screen-detected LCCs observed in NLST, ITALUNG, and LUSI trials between 2002 and 2016, comprising a total of 29,744 subjects who underwent 3-5 annual screening LDCT examinations. Survival or causes of death were established according to the mortality registries extending more than 12 years since randomization., Results: LCC was diagnosed in 30 (4 %) of 750 subjects with screen-detected lung cancer (LC), including 15 prevalent and 15 incident cases. Three additional LCCs occurred as interval cancers during the screening period. LDCT images were available for 29 cases of screen-detected LCCs, and 28 showed a single, peripheral, and well-defined solid nodule or mass with regularly smooth (39 %), lobulated (43 %), or spiculated (18 %) margins. One case presented as hilar mass. In 9 incident LCCs, smaller solid nodules were identified in prior LDCT examinations, allowing us to calculate a mean Volume Doubling Time (VDT) of 98.7 ± 47.8 days. The overall five-year survival rate was 50 %, with a significant (p = 0.0001) difference between stages I-II (75 % alive) and stages III-IV (10 % alive)., Conclusions: LCC is a fast-growing neoplasm that can escape detection by annual LDCT screening. LCC typically presents as a single solid peripheral nodule or mass, often with lobulated margins, and exhibits a short VDT. The 5-year survival reflects the stage at diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anterior mediastinal large cell neuroendocrine carcinomas (LCNECs) are extremely rare, extremely aggressive malignancies that carry a dismal prognosis. We discuss a woman aged 60 years who presented with a 2-month history of recurrent severe constant epigastric pain. Abdominal examination revealed massive hepatomegaly and a CT scan of the liver confirmed coarse liver lesions. Histology from a liver biopsy was consistent with a large cell (non-small cell) neuroendocrine carcinoma. A CT scan of the chest showed a large anterior mediastinal mass unrelated to the lung, suggesting that the anterior mediastinum was the primary origin of the tumour. The patient was planned to receive platinum/etoposide chemotherapy for a metastatic mediastinal large cell neuroendocrine carcinoma. Unfortunately, her health deteriorated, and she was unfit to undergo any further treatment. She was treated palliatively and died 2 months after the diagnosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Radiological characteristics and radiomics signatures can aid in differentiation between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). We investigated whether molecular subtypes of large cell neuroendocrine carcinoma (LCNEC), i.e. SCLC-like (with pRb loss) vs. NSCLC-like (with pRb expression), can be distinguished by imaging based on (1) imaging interpretation, (2) semantic features, and/or (3) a radiomics signature, designed to differentiate between SCLC and NSCLC., Materials and Methods: Pulmonary oncologists and chest radiologists assessed chest CT-scans of 44 LCNEC patients for 'small cell-like' or 'non-small cell-like' appearance. The radiologists also scored semantic features of 50 LCNEC scans. Finally, a radiomics signature was trained on a dataset containing 48 SCLC and 76 NSCLC scans and validated on an external set of 58 SCLC and 40 NSCLC scans. This signature was applied on scans of 28 SCLC-like and 8 NSCLC-like LCNEC patients., Results: Pulmonary oncologists and radiologists were unable to differentiate between molecular subtypes of LCNEC and no significant differences in semantic features were found. The area under the receiver operating characteristics curve of the radiomics signature in the validation set (SCLC vs. NSCLC) was 0.84 (95% confidence interval (CI) 0.77-0.92) and 0.58 (95% CI 0.29-0.86) in the LCNEC dataset (SCLC-like vs. NSCLC-like)., Conclusion: LCNEC appears to have radiological characteristics of both SCLC and NSCLC, irrespective of pRb loss, compatible with the SCLC-like subtype. Imaging interpretation, semantic features and our radiomics signature designed to differentiate between SCLC and NSCLC were unable to separate molecular LCNEC subtypes, which underscores that LCNEC is a unique disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is an uncommon malignant bladder tumor, and the overall prognosis is poor. Contrast-enhanced ultrasound (CEUS) provides a new effective modality for tumor detection and diagnosis., Case Presentation: A 30-year-old man complained of repeated painless gross haematuria for half a month. Conventional ultrasound demonstrated a hypoechoic solitary lesion with hyperechoic margins measuring 3.4 × 3.1 cm in the anterior wall of the bladder. Superb microvascular imaging (SMI) showed a strong flow signal in the mass. CEUS revealed that the lesion was characterized by hyper-enhancement in the early phase and hypo-enhancement in the late phase. The entire bladder wall was disrupted by homogeneous hyper-enhanced tumor tissue on CEUS. Time-intensity curves (TICs) showed a rapid wash-in with a high maximum signal intensity (SI) and quick wash-out. Finally, partial cystectomy was performed and the pathological examination confirmed the diagnosis of LCNEC with invasion into the whole layer of the bladder wall., Conclusion: This case suggested that CEUS was a valuable imaging method to detect and diagnose LCNEC in the bladder, and that CEUS can provide information related to the depth of wall invasion and the microvasculature.

Background: The aim of this study was to compare adaptive intensity modulated proton therapy (IMPT) robustness and organ sparing capabilities with that of adaptive volumetric arc photon therapy (VMAT). Material and methods: Eighteen lung cancer patients underwent a planning 4DCT (p4DCT) and 5 weekly repeated 4DCT (r4DCT) scans. Target volumes and organs at risk were manually delineated on the three-dimensional (3D) average scans of the p4DCT (av&#95;p4DCT) and of the r4DCT scans (av&#95;r4DCT). Planning target volume (PTV)-based VMAT plans and internal clinical target volume (ICTV)-based robust IMPT plans were optimized in 3D on the av&#95;p4DCT and re-calculated on the av&#95;r4DCTs. Re-planning on av&#95;r4DCTs was performed when indicated and accumulated doses were evaluated on the av&#95;p4DCT. Results: Adaptive VMAT and IMPT resulted in adequate ICTV coverage on av&#95;r4DCT in all patients and adequate accumulated-dose ICTV coverage on av&#95;p4DCT in 17/18 patients (due to a shrinking target in one patient). More frequent re-planning was needed for IMPT than for VMAT. The average mean heart dose reduction with IMPT compared with VMAT was 4.6 Gy ( p  = .001) and it was >5 Gy for five patients (6, 7, 8, 15, and 22 Gy). The average mean lung dose reduction was 3.2 Gy ( p  < .001). Significant reductions in heart and lung V5 Gy were observed with IMPT. Conclusion: Robust-planned IMPT required re-planning more often than VMAT but resulted in similar accumulated ICTV coverage. With IMPT, heart and lung mean dose values and low dose regions were significantly reduced. Substantial cardiac sparing was obtained in a subgroup of five patients (28%).

Background: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy., Methods: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell)., Results: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively., Conclusions: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening., Competing Interests: Conflict of interest: S.G. Spiro has nothing to disclose. Conflict of interest: P.L. Shah has nothing to disclose. Conflict of interest: R.C. Rintoul has nothing to disclose. Conflict of interest: J. George has nothing to disclose. Conflict of interest: S. Janes reports personal fees for advisory board work from BARD1, Achilles Therapeutics and AstraZeneca, personal fees for conference travel from AstraZeneca, outside the submitted work. Conflict of interest: M. Callister has nothing to disclose. Conflict of interest: M. Novelli has nothing to disclose. Conflict of interest: P. Shaw has nothing to disclose. Conflict of interest: G. Kocjan has nothing to disclose. Conflict of interest: C. Griffiths has nothing to disclose. Conflict of interest: M. Falzon has nothing to disclose. Conflict of interest: R. Booton has nothing to disclose. Conflict of interest: N. Magee has nothing to disclose. Conflict of interest: M. Peake reports personal fees for lectures from Roche Products Ltd, grants and personal fees for lectures from MSD Ltd, personal fees for advisory board work from BMS and Pfizer Ltd, outside the submitted work. Conflict of interest: P. Dhillon has nothing to disclose. Conflict of interest: K. Sridharan has nothing to disclose. Conflict of interest: A.G. Nicholson has nothing to disclose. Conflict of interest: S. Padley has nothing to disclose. Conflict of interest: M.N. Taylor has nothing to disclose. Conflict of interest: A. Ahmed has nothing to disclose. Conflict of interest: J. Allen has nothing to disclose. Conflict of interest: Y. Ngai has nothing to disclose. Conflict of interest: N. Chinyanganya has nothing to disclose. Conflict of interest: V. Ashford-Turner has nothing to disclose. Conflict of interest: S. Lewis has nothing to disclose. Conflict of interest: D. Oukrif has nothing to disclose. Conflict of interest: P. Rabbits has nothing to disclose. Conflict of interest: N. Counsell has nothing to disclose. Conflict of interest: A. Hackshaw has nothing to disclose., (Copyright ©ERS 2019.)

Neuroendocrine tumors (NET) are a heterogeneous group of malignancies with a broad spectrum of histomorphologies, tissue origins, and clinical outcomes, which arise from neural crest cells with neuroendocrine differentiation. Salivary gland tumors account for 3-6% of all head and neck neoplasms, while large cell neuroendocrine carcinomas (LCNEC) of the salivary gland are extremely rare, with few cases reported in literature, and only 5 cases involving submandibular gland. The rarity of these tumors in salivary glands is probably related to the scarcity of neuroendocrine cells in this tissue, whose presence is still a matter of debate. Regardless of their low frequency, it is imperative to differentiate these tumors from the much more common squamous cell carcinomas and metastatic NETs, due to different therapeutic approach and prognosis. In this paper, we report the case of a 21-year-old man, with a LCNEC involving a submandibular gland followed by several recurrences over the years. In addition, we include a comprehensive review of the available literature on this topic., (Copyright © 2019 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Introduction: The incidence of lung cancer among never-smokers has been increasing rapidly. The U. S. National Lung Screening Trial and the NELSON trial showed that screening using low-dose computerized tomography (LDCT) effectively reduced lung cancer mortality among heavy smokers. However, its effectiveness in never-smokers has not been well investigated. This study investigated the role of LDCT in lung cancer screening among never-smokers., Methods: The study was designed as a single-center, retrospective cohort study. We analyzed the data on patients who underwent LDCT screening between May 2003 and June 2016. Nodules detected by computerized tomography were classified according to the Lung Imaging Reporting and Data System criteria. The detection rate and lung cancer outcomes (type of cancer, staging of lung cancer, and mortality) according to smoking history were determined., Results: Of the 28,807 enrolled patients, 12,176 were never-smokers; of these patients, 7744 (63.6%) were women and 1218 (10.0%) were found to have lung nodules. Overall, lung cancer was diagnosed in 55 never-smokers (0.45%). In contrast, lung cancer was diagnosed in 143 (0.86%) of the 16,631 ever-smokers. Of the never-smokers with lung cancer, 51 (92.7%) presented with stage I disease, and all patients had adenocarcinomas., Conclusions: In the never-smoker population, LDCT screening helped to detect a significant number of lung cancers. Most of these lung cancers were detected at a very early stage. The positive results of the National Lung Screening Trial in the United States and the NELSON trial may have established the value of LDCT screening for heavy smokers, but future research should consider the value of using LDCT screening in the never-smoker population., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

We report a case of large cell neuroendocrine carcinoma of the uterine cervix. A 33-year-old woman presented with a 4-month history of irregular vaginal bleeding and suspicious cervix. Transvaginal ultrasound showed a 3×3.8 cm cervical mass with a marked increase in the blood flow. MRI pelvis showed an exophytic tumour with left external iliac lymph node metastasis. Immunohistochemistry of the tumour cells showed strong positivity for the neuroendocrine markers synaptophysin and a very high Ki67 proliferation index. A diagnosis of high-grade large cell neuroendocrine carcinoma of the uterine cervix was made with FIGO stage IIA2. She was treated with chemotherapy and palliative radiotherapy but died 21 months after presenting. Neuroendocrine tumour of the uterine cervix is an extremely aggressive cancer with the late presentation-the need for a more rigorous treatment protocol as well as potential screening methods could improve outcomes for these patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer, and 40% of patients are in stage IV at initial diagnosis. It has an extremely poor prognosis with a 1-year survival rate of 27%. Patients with LCNEC are predominantly male, older, and heavy smokers. There has been no clinical trial conducted to determine the best treatment for advanced LCNEC. Temozolomide (TMZ) has been successfully used to treat a variety of malignancies, such as glioblastoma multiforme, astrocytoma, non-small-cell lung carcinoma. However, its efficacy in advanced stage pulmonary LCNEC has rarely been studied., Patient Concerns: We present the rare case of a 69-year-old woman with advanced pulmonary LCNEC. She complained of recurrent dry cough for more than 1 month., Diagnoses: After chest computed tomography (CT) and biopsies of supraclavicular lymph nodes, the diagnosis of stage IIIB LCNEC of the lung was made., Interventions: Four cycles of chemotherapy with etoposide and cisplatin was administered as the first-line regimen. As the disease progressed, we administered icotinib and liposomal paclitaxel. Finally, we administrated TMZ as the third-line regimen., Outcomes: The patient showed partial response after 5 months. She has survived for 19 months from the time of diagnosis with a good performance status., Lessons: TMZ appears to be an efficacious option to treat elderly patients with advanced LCNEC.

In this study, the effectiveness of transthoracic ultrasound elastography in the benign and malign distinction of subpleural/pleural solid lesions was investigated.Between July 2015 and December 2016, 33 consecutive patients with subpleural solid lesions detected via computed tomography (CT) of the thorax were identified and prospectively included in this study. The average for each lesion's shear wave velocity (SWV) value was detected, and benign and malignant lesions' SWV values are statistically compared. The CT and pathology results were used as a reference to compare these values. A receiver operating characteristic analysis was used to determine the cutoff value for benign/malignant neoplasms.The 33 patients (10 female, 23 male) included in the study had a mean age of 56.2 ± 15.40 years (range, 17-84 years), and the mean SWV value of the lesions in 13 (39%) cases evaluated benign after a CT scan, histopathological examination, or both 2.18 ± 0.49 m/s. The mean SWV value of the lesions which were histopathologically diagnosed as malign in 23 (61%) cases was 3.50 ± 0.69 m/s. (P < 0.001). When the cutoff value was set as 2.47 m/s for the SVW value, sensitivity and specificity were determined to be 97.7%.The present study has shown that transthoracic ultrasound shear wave elastography can be an effective radiological examination method in the benign and malign differentiation of subpleural lesions and has the potential for use in the routine clinical application of transthoracic ultrasound elastography, a noninvasive method for evaluating the malignancy potentials of such lesions.

Background: Emerging data support aggressive local treatment of oligometastatic non-small-cell lung cancer (NSCLC) patients. We sought to determine whether the metabolic burden of disease found by fluorodeoxyglucose positron emission tomography at the time of high-dose radiotherapy (RT) for oligometastatic NSCLC can serve as a prognostic biomarker., Materials and Methods: We conducted a retrospective cohort study of 67 RT treatment courses in 55 patients with oligometastatic NSCLC who had undergone high-dose RT to all sites of active disease at our institution. The metabolic tumor volume, total lesion glycolysis (TLG), and maximum standardized uptake value of all lesions were measured on the pretreatment fluorodeoxyglucose positron emission tomography scans. Cox regression analysis was used to assess the influence of imaging and clinical factors on overall survival (OS)., Results: On univariate analysis, a greater metabolic tumor volume and TLG were predictive of shorter OS (hazard ratio of death, 2.42 and 2.14, respectively; P = .009 and P = .004, respectively). The effects remained significant on multivariate analysis. Neither the maximum standardized uptake value nor the number of lesions was significantly associated with OS. Patients within the highest quartile of TLG values (> 86.8 units) had a shorter median OS than those within the lower 3 quartiles (12.4 vs. 30.1 months; log-rank P = .014)., Conclusion: The metabolic tumor burden was prognostic of OS and might help to better select oligometastatic NSCLC patients for locally ablative therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a relatively rare subtype of lung malignancy. According to revised 2015 World Health Organization (WHO) criteria for the pathological diagnosis of LCNEC, neuroendocrine markers must be examined by immunohistochemistry. In this study, we reevaluated endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples of patients previously diagnosed with LCNEC using the revised WHO criteria., Methods: Clinical tissue samples that had been obtained by EBUS-TBNA between January 2004 and December 2011, and that had been pathologically diagnosed as LCNEC according to the previous criteria, were reevaluated according to the revised WHO criteria., Results: The records of 471 lung cancer patients with mediastinal or hilar lymph node metastasis diagnosed by EBUS-TBNA were analyzed. Thirteen patients were diagnosed with LCNEC; one of which was diagnosed based on cytology alone because the histological material was insufficient for a histological examination. Among the 12 cases in which a histological examination was performed, nine were diagnosed with possible LCNEC based on neuroendocrine marker positivity, while three were diagnosed with suspected LCNEC because they did not meet the immunostaining criteria. The patient who was cytologically diagnosed was found to have non-small cell carcinoma with neuroendocrine morphology., Conclusion: LCNEC could be pathologically diagnosed based on 2015 WHO criteria using EBUS-TBNA samples., (© 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

In the absence of screening, most patients with lung cancer are not diagnosed until later stages, when the prognosis is poor. The most common symptoms are cough and dyspnea, but the most specific symptom is hemoptysis. Digital clubbing, though rare, is highly predictive of lung cancer. Symptoms can be caused by the local tumor, intrathoracic spread, distant metastases, or paraneoplastic syndromes. Clinicians should suspect lung cancer in symptomatic patients with risk factors. The initial study should be chest x-ray, but if results are negative and suspicion remains, the clinician should obtain a computed tomography scan with contrast. The diagnostic evaluation for suspected lung cancer includes tissue diagnosis, staging, and determination of functional capacity, which are completed simultaneously. Tissue samples should be obtained using the least invasive method possible. Management is based on the individual tumor histology, molecular testing results, staging, and performance status. The management plan is determined by a multidisciplinary team consisting of a pulmonology subspecialist, medical oncology subspecialist, radiation oncology subspecialist, and thoracic surgeon. The family physician should remain involved with the patient to ensure that patient priorities are supported and, if necessary, to arrange for end-of-life care., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) with regard to PD-L1 protein expression. PD-L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative 18 F-FDG PET/CT. The cut-off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD-L1 protein expression compared with those without PD-L1 protein expression (P < 0.0001). However, there was no correlation between SUVmax and PD-L1 protein expression in patients with neuroendocrine tumors (P = 0.6545). Multivariate analysis revealed that smoking, the presence of pleural invasion, and high SUVmax were independent predictors of PD-L1 positivity. PD-L1-expressing NSCLC had a high glucose metabolism. The SUVmax in preoperative 18 F-FDG PET/CT was a predictor of PD-L1 protein expression in patients with NSCLC., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Cone-beam CT (CBCT) scans are typically acquired daily for positioning verification of non-small cell lung cancer (NSCLC) patients. Quantitative information, derived using radiomics, can potentially contribute to (early) treatment adaptation. The aims of this study were to (1) describe and investigate a methodology for feature selection of a longitudinal radiomics approach (2) investigate which time-point during treatment is potentially useful for early treatment response assessment., Material and Methods: For 90 NSCLC patients CBCT scans of the first two fractions of treatment (considered as 'test-retest' scans) were analyzed, as well as weekly CBCT images. One hundred and sixteen radiomic features were extracted from the GTV of all scans and subsequently absolute and relative differences were calculated between weekly CBCT images and the CBCT of the first fraction. Test-retest scans were used to determine the smallest detectable change (C = 1.96 * SD) allowing for feature selection by choosing a minimum number of patients for which a feature should change more than 'C' to be considered as relevant. Analysis of which features change at which moment during treatment was used to investigate which time-point is potentially relevant to extract longitudinal radiomics information for early treatment response assessment., Results: A total of six absolute delta features changed for at least ten patients at week 2 of treatment and increased to 61 at week 3, 79 at week 4 and 85 at week 5. There was 93% overlap between features selected at week 3 and the other weeks., Conclusions: This study describes a feature selection methodology for longitudinal radiomics that is able to select reproducible delta radiomics features that are informative due to their change during treatment, which can potentially be used for treatment decisions concerning adaptive radiotherapy. Nonetheless, the prognostic value of the selected delta radiomic features should be investigated in future studies.

Background: Most solid tumors contain inadequately oxygenated (i.e., hypoxic) regions, which tend to be more aggressive and treatment resistant. Hypoxia PET allows visualization of hypoxia and may enable treatment adaptation. However, hypoxia PET imaging is expensive, time-consuming and not widely available. We aimed to predict hypoxia levels in non-small cell lung cancer (NSCLC) using more easily available imaging modalities: FDG-PET/CT and dynamic contrast-enhanced CT (DCE-CT)., Material and Methods: For 34 NSCLC patients, included in two clinical trials, hypoxia HX4-PET/CT, planning FDG-PET/CT and DCE-CT scans were acquired before radiotherapy. Scans were non-rigidly registered to the planning CT. Tumor blood flow (BF) and blood volume (BV) were calculated by kinetic analysis of DCE-CT images. Within the gross tumor volume, independent clusters, i.e., supervoxels, were created based on FDG-PET/CT. For each supervoxel, tumor-to-background ratios (TBR) were calculated (median SUV/aorta SUV mean ) for HX4-PET/CT and supervoxel features (median, SD, entropy) for the other modalities. Two random forest models (cross-validated: 10 folds, five repeats) were trained to predict the hypoxia TBR; one based on CT, FDG, BF and BV, and one with only CT and FDG features. Patients were split in a training (trial NCT01024829) and independent test set (trial NCT01210378). For each patient, predicted, and observed hypoxic volumes (HV) (TBR > 1.2) were compared., Results: Fifteen patients (3291 supervoxels) were used for training and 19 patients (1502 supervoxels) for testing. The model with all features (RMSE training: 0.19 ± 0.01, test: 0.27) outperformed the model with only CT and FDG-PET features (RMSE training: 0.20 ± 0.01, test: 0.29). All tumors of the test set were correctly classified as normoxic or hypoxic (HV > 1 cm 3 ) by the best performing model., Conclusions: We created a data-driven methodology to predict hypoxia levels and hypoxia spatial patterns using CT, FDG-PET and DCE-CT features in NSCLC. The model correctly classifies all tumors, and could therefore, aid tumor hypoxia classification and patient stratification.

Introduction: Noninvasive biomarkers that capture the total tumor burden could provide important complementary information for precision medicine to aid clinical decision making. We investigated the value of radiomic data extracted from pretreatment computed tomography images of the primary tumor and lymph nodes in predicting pathological response after neoadjuvant chemoradiation before surgery., Methods: A total of 85 patients with resectable locally advanced (stage II-III) NSCLC (median age 60.3 years, 65% female) treated from 2003 to 2013 were included in this institutional review board-approved study. Radiomics analysis was performed on 85 primary tumors and 178 lymph nodes to discriminate between pathological complete response (pCR) and gross residual disease (GRD). Twenty nonredundant and stable features (10 from each site) were evaluated by using the area under the curve (AUC) (all p values were corrected for multiple hypothesis testing). Classification performance of each feature set was evaluated by random forest and nested cross validation., Results: Three radiomic features (describing primary tumor sphericity and lymph node homogeneity) were significantly predictive of pCR with similar performances (all AUC = 0.67, p < 0.05). Two features (quantifying lymph node homogeneity) were predictive of GRD (AUC range 0.72-0.75, p < 0.05) and performed significantly better than the primary features (AUC = 0.62). Multivariate analysis showed that for pCR, the radiomic features set alone had the best-performing classification (median AUC = 0.68). Furthermore, for GRD classification, the combination of radiomic and clinical data significantly outperformed all other feature sets (median AUC = 0.73)., Conclusion: Lymph node phenotypic information was significantly predictive for pathological response and showed higher classification performance than radiomic features obtained from the primary tumor., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Lung cancer screening using low-dose CT scanning reduces lung-cancer-specific and overall mortality in high-risk patients. A significant limitation of lung cancer screening is the false-positive rate. The American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) was designed to standardize reporting of low-dose lung cancer screening results and to decrease the false-positive rate without significantly compromising sensitivity. Implementing Lung-RADS can also improve cost-effectiveness. However, Lung-RADS has never been studied in a prospective fashion. It also does not have a specific reporting category for patients with isolated hilar and mediastinal adenopathy or pleural effusion in the absence of lung nodules. We report four such cases from our lung cancer screening program. We believe that this is a significant limitation of Lung-RADS and should be revised in its new version., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Lung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and noncurable stage. Computed tomography (CT) screening on high-risk individuals has shown that early detection could reduce the mortality rate. However, the still high false-positive rate of CT screening may harm healthy individuals because of unnecessary follow-up scans and invasive follow-up procedures. Alternatively, false-negative and indeterminate results may harm patients due to the delayed diagnosis and treatment of lung cancer. Noninvasive biomarkers, complementary to CT screening, could lower the false-positive and false-negative rate of CT screening at baseline and thereby reduce the number of patients that need follow-up and diagnose patients at an earlier stage of lung cancer. Lung cancer tissue generates lung cancer-associated proteins to which the immune system might produce high-affinity autoantibodies. This autoantibody response to tumor-associated antigens starts during early stage lung cancer and may endure over years. Identification of tumor-associated antigens or the corresponding autoantibodies in body fluids as potential noninvasive biomarkers could thus be an effective approach for early detection and monitoring of lung cancer. We provide an overview of differentially expressed protein, antigen, and autoantibody biomarkers that combined with CT imaging might be of clinical use for early detection of lung cancer.

Background: The anti-programmed death-1 antibody nivolumab is an important treatment option for non-small-cell lung carcinoma.However, its effectiveness for large-cell neuroendocrine carcinomas(LCNEC)is still controversial.Here, we report 2 cases of LCNECs that responded to nivolumab.Case 1: A 62-year-old man received chemotherapy and radiotherapy for stage III A lung adenocarcinoma.One year later, another lung lesion was observed and diagnosed as LCNEC using surgical lung biopsy.Although he subsequently received some chemotherapy regimens, the patient developed new brain metastasis, expanded mediastinal lesion, and increased levels of the tumor marker pro-gastrin releasing peptide(ProGRP).We started nivolumab as the sixth-line treatment.In response, ProGRP levels significantly decreased and the mediastinal lesion became smaller.Case 2: A 55-year-old man was diagnosed with stage III A LCNEC and received chemotherapy and radiotherapy.The primary lesion was controlled; however, lung metastases developed and chemotherapy was unable to control them.We provided treatment with nivolumab as the third-line therapy.The tumor marker ProGRP decreased and the lung metastases became smaller., Conclusion: Nivolumab can be a valuable treatment option for LCNEC.

Purpose: There is broad consensus regarding evaluating response to chemotherapy (CHT) by means of computerized tomography (CT) in patients with localized or locally advanced non-small cell lung carcinoma (NSCLC). We present a study comparing the usefulness of CT versus chest X-ray (XR) and clinical findings when indicating radiotherapy (RT) following CHT., Methods: Ninety-eight of 150 subjects with unresectable locally advanced NSCLC were blindly and independently evaluated by XR and CT, with pairs of chest XR and CT (before and after CHT). A null hypothesis (H0) was established of the conditioned probability of detecting progression by CT and not by XR of 10 % or more, with a statistical power of 80 %., Results: Sensitivity, specificity, positive and negative predictive value of XR versus CT were 98, 89, 99, and 80 % respectively. A 4 % (p = 0.0451) probability of improvement of CT versus XR was calculated, enabling the H0 to be ruled out., Conclusion: The CT failed to prove to be significantly superior to the chest XR + clinical picture in indicating a change in treatment approach in patients with unresectable locally advanced NSCLC after CHT.

Case 1: A 66-year-old man who had undergone upper right lobe resection for large cell lung carcinoma 2 months earlier presented with abdominal pain and vomiting. Computed tomography showed intussusception of the small intestine. Partial resection of the small intestine was performed. The tumor was pathologically diagnosed as lung cancer metastasis to the small intestine. The patient died 30 days after surgery. Case 2: A 57-year-old man was admitted to hospital due to appetite loss. Computed tomography showed a large intestinal tumor and a small lung tumor, as well as multiple liver metastases and lymph node metastases. We diagnosed perforation of the small intestine tumor, and partial resection of small intestine was performed. Pathological examination and immunohistochemical staining revealed that the tumor was a metastatic adenocarcinoma, and the patient was diagnosed with small intestine metastasis of lung cancer. He died 75 days after surgery. Although small intestine metastasis of lung cancer is rare, the incidence is increasing. The prognosis of lung cancer metastasis of the small intestine is poor, and therefore, we must urgently decide the appropriate treatment.

This study aimed to identify the computed tomography characteristics of treatment-naïve patients with lung adenocarcinoma and known driver mutations in EGFR, KRAS, or ALK. Patients with advanced lung adenocarcinoma (stage IIIB-IV) and known mutations in EGFR, KRAS, or ALK were assessed. The radiological findings for the main tumor and intra-thoracic status were retrospectively analyzed in each group, and the groups' characteristics were compared. We identified 265 treatment-naïve patients with non-small-cell carcinoma, who had EGFR mutations (n = 159), KRAS mutations (n = 55), or ALK rearrangements (n = 51). Among the three groups, we evaluated only patients with stage IIIB-IV lung adenocarcinoma who had EGFR mutations (n = 126), KRAS mutations (n = 35), or ALK rearrangements (n = 47). We found that ground-glass opacity at the main tumor was significantly more common among EGFR-positive patients, compared to ALK-positive patients (p = 0.009). Lymphadenopathy was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.003). Extranodal invasion was significantly more common among ALK-positive patients, compared to EGFR-positive patients and KRAS-positive patients (p = 0.001 and p = 0.049, respectively). Lymphangitis was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.049). Pleural effusion was significantly less common among KRAS-positive patients, compared to EGFR-positive patients and ALK-positive patients (p = 0.046 and p = 0.026, respectively). Lung metastases were significantly more common among EGFR-positive patients, compared to KRAS-positive patients and ALK-positive patients (p = 0.007 and p = 0.04, respectively). In conclusion, EGFR mutations were associated with ground-glass opacity, KRAS-positive tumors were generally solid and less likely to metastasize to the lung and pleura, and ALK-positive tumors tended to present with lymphadenopathy, extranodal invasion, and lymphangitis. These mutation-specific imaging characteristics may be related to the biological differences between these cancers.

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration is of diagnostic value in hilar/mediastinal (N1/N2) lymph node staging. We assessed the utility of endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients with N1/N2 lymph nodes detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography., Methods: Fifty lung cancer patients with N1/N2 disease on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography underwent endobronchial ultrasound-guided transbronchial needle aspiration for pathological lymph nodes between November 2012 and April 2015. The diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration, lymph node site and size, number of needle passes and complications were evaluated retrospectively from patients' medical records. Malignancy was defined as a maximum standardized uptake value (SUVmax) >2.5., Results: The median longest diameter of the 61 lymph nodes (29 subcarinal, 21 right lower paratracheal, 6 left lower paratracheal, 4 right hilar and 1 upper paratracheal) was 23.4 mm (range: 10.4-45.7); the median number of needle passes was 2 (range: 1-5). There were no severe complications. A definitive diagnosis was made by endobronchial ultrasound-guided transbronchial needle aspiration in 39 patients (31 adenocarcinomas, 3 small-cell carcinomas, 2 squamous-cell carcinomas, 3 large-cell neuroendocrine carcinomas). In the remaining 11 patients, the diagnosis was indefinite: insufficient endobronchial ultrasound-guided transbronchial needle aspiration material was collected in two patients and non-specific lymphadenopathy was confirmed by endobronchial ultrasound-guided transbronchial needle aspiration or thoracotomy in the other nine patients. The mean lymph node SUVmax was 7.09 (range: 2.90-26.9) and was significantly higher in true-positive than in false-positive nodes (P < 0.05, t-test). Non-specific lymphadenopathy was diagnosed by expert visual interpretation of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography images in five of the nine patients., Conclusion: Endobronchial ultrasound-guided transbronchial needle aspiration accurately diagnoses N1/N2 disease detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography., (© The Author 2016. Published by Oxford University Press.)

Background: Endobronchial ultrasonography (EBUS) facilitates a lung cancer diagnosis. However, qualitative tissue characterization of lung tumors is difficult using EBUS. Integrated backscatter (IBS) is an ultrasound technique that calculates the power of the ultrasound signal to characterize tissue components in coronary arteries. We hypothesized that qualitative diagnosis of lung tumors is possible using the IBS technique. The aim of the present study was to elucidate whether the IBS technique can be used in lung tissue diagnoses., Methods: Thirty-five consecutive patients who underwent surgery for lung cancer were prospectively enrolled. Surgical specimens of the lung and the tumor tissue were obtained, and the IBS values were measured within 48 h after surgery. Histologic images of lung and tumor tissues were compared with IBS values, and the relative interstitial area according to results of Masson's trichrome staining were determined by using an imaging processor., Results: The IBS values in tumor tissue were significantly lower than those in normal lung tissue (-50.9 ± 2.6 dB and -47.6 ± 2.6 dB, respectively; P < .001). The IBS values of adenocarcinomas associated with a good 5-year survival rate were higher than those of non-adenocarcinomas (-48.1 ± 1.6 dB and -52.6 ± 1.4 dB; P < .001). There were significant correlations between the IBS values and the relative interstitial area or micro air area in tumor (r = 0.53 and r = 0.67; P < .01). After combining normal lung tissue and adenocarcinomas with a good prognosis, the sensitivity and specificity for establishing the presence of lung tumors were 84% and 85%., Conclusions: Qualitative diagnosis of lung tumors was possible, with a sensitivity of 84% and a specificity of 85%, using the ultrasound IBS technique., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Tracheal bronchus is a rarely seen congenital anomaly generally originating from the right lateral wall of the trachea and approximately 2 cm above the carina. It was firstly defined by Sandifort in 1785 and its frequency of incidence in normal population changes between 0.1% and 2%. There are two types called ''Supernumerary'' and ''Displaced''. It is a rarely seen kind of tracheal anomaly although fairly well defined. The cases accompanied by lung cancer are seen more rarely. Nine cases of this association were reported in literature and tracheal bronchus-lung cancer association whose pathological result is undifferentiated large-cell carcinoma has not been stated so far. We present a 75 years old male patient as possibly the first case having tracheal bronchus and large-cell carcinoma association in literature.

Primary large-cell neuroendocrine carcinoma of the endometrium is extremely rare and has a poor prognosis. This report describes a case of combined large-cell neuroendocrine carcinoma and endometrioid adenocarcinoma of the endometrium diagnosed as stage IIIA. The patient underwent surgery and chemotherapy and has been well with no evidence of disease for 20 months. The optimal treatment for this rare tumor has not been established. Considering its rarity and variability, it is difficult to establish an evidence-based therapeutic regimen., (© 2016 Japan Society of Obstetrics and Gynecology.)

We present a very rare case of de novo large cell neuroendocrine carcinoma (LCNEC) of the prostate in an 84-year-old man on a background of high grade, superficially invasive transitional cell carcinoma of the bladder. Pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate are thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing neuroendocrine differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease and a worse prognosis., (2014 BMJ Publishing Group Ltd.)

Background and Objective: Volume doubling time (VDT) contributes to the evaluation of the indeterminate pulmonary nodule, an increasingly frequent problem given the rising use of computed tomography (CT). We aimed to correlate patient and tumour characteristics with VDT and growth rates of primary non-small cell lung cancers (NSCLC)., Methods: Surgically treated NSCLC, which underwent two or more CT scans separated by 25 or more days were studied. Tumour volume was measured using semi-automated volumetric software. VDT and growth rate (1/VDT) were correlated with patient and tumour characteristics., Results: Thirty-six adenocarcinomas (AC), six squamous cell carcinoma (SCC), two large cell and two carcinoids in 46 patients had 109 eligible scans. Median VDT was 191 days (range -9435 to 2256 days); median growth rate was 0.0038 (range -0.0086 to 0.0186). Median growth rate of AC was significantly slower than SCC (0.0034 vs. 0.0103, P = 0.037). Nine AC had VDT >400 days, three of which developed distant metastases. Median growth rate of AC was faster in smokers compared with never-smokers (0.0052 vs. 0.0014, P = 0.02). Growth rate was not related to symptoms at diagnosis (P = 0.16). Less differentiated tumours tended to grow faster than more differentiated (P = 0.0038). Growth curves of 12 multi-imaged tumours conformed best with the exponential model of growth., Conclusions: NSCLC growth rate appears to be highly variable and related to histological subtype and smoking history, but not the presence of symptoms at diagnosis. Significant growth may be detected in as little as 2 months in NSCLC in smokers. Relatively slow-growing AC can metastasize., (© 2014 Asian Pacific Society of Respirology.)

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows a reliable and accurate diagnosis of neoplasms of the gallbladder and bile ducts. We report the cytopathologic findings of a case of large cell neuroendocrine carcinoma (LCNEC) of the gallbladder and extrahepatic bile ducts in a 67-year-old woman who presented with progressive abdominal pain and jaundice. EUS-FNA of the mass involving the common bile duct and of a porta hepatis lymph node showed abundant cellularity with tumor cells arranged singly and occasionally in tight and loose clusters and rosette-like structures in a background showing extensive necrotic debris. The tumor cells were predominantly plasmacytoid, showed a moderate amount of focally vacuolated cytoplasm and large round to oval hyperchromatic nuclei with prominent nucleoli, numerous mitoses, and apoptotic bodies. The differential diagnosis included poorly differentiated adenocarcinoma, lymphoma, melanoma, and poorly differentiated neuroendocrine carcinoma (NEC), large cell type. The tumor cells were strongly and diffusely positive for cytokeratin AE1/AE3, CD56, synaptophysin, and chromogranin and showed a very high proliferative fraction on Ki67 staining, supporting the diagnosis of a high-grade NEC. Due to the large size of the neoplastic cells, moderate amounts of cytoplasm and prominent nucleoli, a diagnosis of LCNEC was made on the EUS-FNA sample. Despite the prompt institution of chemotherapy, the patient died shortly thereafter and the diagnosis was confirmed at autopsy. This is to our knowledge the first case of LCNEC of the gallbladder and bile ducts diagnosed by EUS-FNA., (Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.)

Despite the advances in video-assisted thoracoscopic surgery (VATS), vascular reconstruction of the pulmonary artery (PA) is still infrequently performed by thoracic surgeons because of the technical difficulties and the increased operative risk during thoracoscopy. The few published reports have been performed by using 3-4 incisions. We present the first report of a pulmonary artery reconstruction procedure performed by a single-incision VATS technique. A 73-year old male patient was operated on by the thoracoscopic approach through a single 4-cm incision with no rib spreading. The postoperative recovery was uneventful.

Objective: To determine whether CT-perfusion (CT-p) can be used to evaluate the effects of chemotherapy and anti-angiogenic treatment in patients with non-small-cell lung carcinoma (NSCLC) and whether CT-p and standard therapeutic response assessment (RECIST) data obtained before and after therapy correlate., Methods: 55 patients with unresectable NSCLC underwent CT-p before the beginning of therapy and 50 of them repeated CT-p 90 days after it. Therapeutic protocol included platinum-based doublets plus bevacizumab for non-squamous carcinoma and platinum-based doublets for squamous carcinoma. RECIST measurements and calculations of blood flow (BF), blood volume (BV), time to peak (TTP) and permeability surface (PS) were performed, and baseline and post-treatment measurements were tested for statistically significant differences. Baseline and follow-up perfusion parameters were also compared based on histopathological subclassification (2004 World Health Organization Classification of Tumours) and therapy response assessed by RECIST., Results: Tumour histology was consistent with large cell carcinoma in 14/50 (28%) cases, adenocarcinoma in 22/50 (44%) cases and squamous cell carcinoma in the remaining 14/50 (28%) cases. BF and PS differences for all tumours between baseline and post-therapy measurements were significant (p=0.001); no significant changes were found for BV (p=0.3) and TTP (p=0.1). The highest increase of BV was demonstrated in adenocarcinoma (5.2±34.1%), whereas the highest increase of TTP was shown in large cell carcinoma (6.9±22.4%), and the highest decrease of PS was shown in squamous cell carcinoma (-21.5±18.5%). A significant difference between the three histological subtypes was demonstrated only for BV (p<0.007). On the basis of RECIST criteria, 8 (16%) patients were classified as partial response (PR), 2 (4%) as progressive disease (PD) and the remaining 40 (80%) as stable disease (SD). Among PR, a decrease of both BF (18±9.6%) and BV (12.6±9.2%) were observed; TTP increased in 3 (37.5%) cases, and PS decreased in 6 (75%) cases. SD patients showed an increase of BF, BV, TTP and PS in 6 (15%), 21 (52.5%), 23 (57.5%) and 2 (5%) cases, respectively. PD patients demonstrated an increase of BF (26±0.2%), BV (2.7±0.1%) and TTP (3.1±0.8%) while only PS decreased (23±0.2%)., Conclusion: CT-p can adequately evaluate therapy-induced alterations in NSCLC, and perfusion parameters correlate with therapy response assessment performed with RECIST criteria., Advances in Knowledge: Evaluating perfusional parameters, CT-p can demonstrate therapy-induced changes in patients with different types of lung cancer and identify response to treatment with excellent agreement to RECIST measurements.

Purpose: To assess the computed tomography (CT) findings of primary pulmonary lymphoepithelioma-like carcinoma (LELC)., Materials and Methods: Clinical information and CT findings of 41 patients with pulmonary LELC were reviewed. CT images of 2 or 5mm thickness were obtained with a pre-treatment CT and were jointly evaluated by two radiologists., Results: Thirty central tumors and 11 peripheral tumors with diameters ranging from 1.0 to 8.7cm (mean, 4.1±1.9cm) were identified. Central tumors appeared to be larger than peripheral tumors (P=0.017). Tumors occurred more frequently in right middle lobe (31.7%) and left lower lobe (29.3%). CT findings of patients with early stage were similar to those observed in patients with advanced stage except that lymphadenopathy was significantly more common in patients with advanced stage. CT findings of pulmonary LELC consisted of well defined border (63.4%), lobulation (78.0%), vascular or bronchial encasement (43.9%), obstructive pneumonia (41.5%), pleural effusion (12.2%) and calcification (4.9%). On contrast-enhanced CT scans, inhomogeneously enhanced tumors were significantly larger than homogeneously enhanced tumors (P<0.001). Lymphadenopathy was seen in 28 patients, and lymph nodes with homogeneous enhancement were observed in 24/28 patients. Enlarged lymph nodes were more frequently occurred in peribronchial or hilar nodes (53.7%), subcrinal nodes (39.0%), right lower paratracheal nodes (31.7%) and right upper paratracheal nodes (22.0%)., Conclusion: Pulmonary LELC usually appeared as a large, central, well defined and lobulated tumor with vascular or bronchial encasement and obstructive pneumonia. Calcification was rare in pulmonary LELC. Lymphadenopathy was common, usually with homogeneous enhancement., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Two cases of rheumatoid nodules evaluated by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and video-assisted thoracic surgery (VATS) biopsy are reported. The first case was that of a 44-year-old woman who presented with a cavitated nodule with intense standardized uptake values (SUVs) both in the early (max 3.4) and delayed (max 4.4) phases, suggesting malignancy. However, after VATS biopsy, she was diagnosed as having a rheumatoid nodule with vasculitis. The second case was that of a 74-year-old woman admitted with bilateral lung nodules, two of which showed intense early (max 2.2) and delayed (max 6.0) phase SUVs, and mild early (max 0.6) and delayed (max 0.9) phase SUVs. These two nodules were finally proven to be a lung cancer and rheumatoid nodule without vasculitis, respectively. These cases show that rheumatoid nodules with an enhanced inflammatory process, such as vasculitis, can appear false-positive for malignancy on FDG-PET/CT scan images.

The purpose of this study was to explore the accuracy of (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) in the assessment of mediastinal lymph node in coal workers who had non-small cell lung cancer. We retrospectively reviewed 42 retired coal workers who had lung cancer without distant metastasis, between May 2007 and May 2010. Regarding the mediastinal lymph nodes, when the standard uptake value was greater than 2.5, it was considered "malignancy positive." After histological examination of the mediastinal lymph nodes, anthracotic and metastatic ones were detected. The results of PET/CT were analyzed to determine its accuracy. Of these 42 patients, PET/CT detected 47 positive mediastinal lymph nodes in 24 patients with a mean SUV maximum of 6.2 (2.6-13.8). One hundred and thirty-one mediastinal lymph node foci were dissected. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT in detecting nodal metastases were 84% (16/19), 65% (15/23), 66% (16/24), 83% (15/18), and 74% (31/42) on a per-patient basis, respectively. Mediastinal node staging with FDG-PET/CT in coal workers is insufficient due to the high false-positive rates due to the presence of pneumoconiosis. In these patients, an invasive technique such as mediastinoscopy seems mandatory for confirmation of ipsilateral or contralateral mediastinal lymph node metastasis.

The purpose of this study is to evaluate the effect of Active Breathing Control-moderate deep inspiration breath-hold (ABC-mDIBH) on tumor motion and critical organ doses in non-small cell lung cancer (NSCLC) radiotherapy. 23 patients with locally advanced NSCLC were included in the study. All patients were scanned at free breathing and ABC-mDIBH for radiation treatment planning. 3 separate treatment plans were generated for each patient including one plan with ABC-mDIBH and uniform margins, one plan with free breathing and uniform margins, and one plan with free breathing and 3-dimensional non-uniform margins determined by Cone Beam Computed Tomography (CBCT) and XVI Motion View (X-ray Volume Imaging, Elekta, UK). Critical organ dose-volumes and physical lung parameters were comparatively evaluated on 3 separate dose-volume histograms of each patient acquired from planning software. Individual tumor motion of each patient with and without ABC-mDIBH was documented and compared. Use of ABC-mDIBH resulted in statistically significant improvement in physical lung parameters of V20 (lung volume receiving ≥ 20 Gy) and mean lung dose (MLD) which are predictors of radiation pneumonitis (p<0.001). Reduction in spinal cord dose and tumor motion with ABC-mDIBH was also statistically significant (p<0.001). ABC-mDIBH increases normal lung tissue sparing in definitive NSCLC radiotherapy by improving physical lung parameters along with spinal cord dose reduction through exact tumor immobilization. The incorporation of ABC-mDIBH into NSCLC radiotherapy may have implications for potential margin reduction and dose escalation to improve treatment outcomes.

Objectives: The purpose of this study was to evaluate the geometric accuracy of thoracic anatomic landmarks as target surrogates of intrapulmonary tumors for manual rigid registration during image-guided radiotherapy (IGRT)., Methods: Kilovolt cone-beam computed tomography (CBCT) images acquired during IGRT for 29 lung cancer patients with 33 tumors, including 16 central and 17 peripheral lesions, were analyzed. We selected the "vertebrae", "carina", and "large bronchi" as the candidate surrogates for central targets, and the "vertebrae", "carina", and "ribs" as the candidate surrogates for peripheral lesions. Three to six pairs of small identifiable markers were noted in the tumors for the planning CT and Day 1 CBCT. The accuracy of the candidate surrogates was evaluated by comparing the distances of the corresponding markers after manual rigid matching based on the "tumor" and a particular surrogate. Differences between the surrogates were assessed using 1-way analysis of variance and post hoc least-significant-difference tests., Results: For central targets, the residual errors increased in the following ascending order: "tumor", "bronchi", "carina", and "vertebrae"; there was a significant difference between "tumor" and "vertebrae" (p=0.010). For peripheral diseases, the residual errors increased in the following ascending order: "tumor", "ribs", "vertebrae", and "carina". There was a significant difference between "tumor" and "carina" (p=0.005)., Conclusions: The "bronchi" and "carina" are the optimal surrogates for central lung targets, while "ribs" and "vertebrae" are the optimal surrogates for peripheral lung targets for manual matching of online and planned tumors.

Introduction: The aim of this study was to describe associations between lung tumor location and smoking as well as selected occupational exposures. In the context of lung cancer screening by computed tomography scan, tumor location may have an interest. Computed tomography scan is known to better detect more peripheral tumors., Methods: Lung cancer cases diagnosed in two French University hospitals between 1997 and 2009 were included. Tumors visible on white-light bronchoscopy were defined as central. Occupational exposures were assessed by the same expert. Data were analyzed by case-case comparisons using unconditional logistic regressions., Results: A total of 1701 cases were included, comprising mainly men (86.3%), current smokers (52.8%), or former smokers (42.8%). Main histological subtypes of cancer were adenocarcinomas (33.8%) and squamous cell carcinomas (32.6%). The tumor location was found to be central in 61% of cases, and never smokers and women had more often peripheral tumors. Exposure to asbestos was significantly associated with central location with dose-response relationship (odds ratio [OR] for peripheral tumors = 0.45, 95% confidence interval [CI] 0.29-0.70) for the highest level of exposure. Exposure to silica dust was significantly associated with peripheral tumor (OR for peripheral tumors = 3.28, 95%CI 1.50-7.17) for the highest level of exposure. Exposure to welding fumes was associated with central location (OR for peripheral tumors = 0.51, 95% CI 0.26-0.96) for the first level of exposure)., Conclusions: Smoking characteristics and occupational exposures have to be considered to define more accurately high-risk populations suitable for lung cancer screening or early detection programs.

Objective: Extended cervical mediastinoscopy (ECM) is a method for sampling aortopulmonary window (APW) mediastinal lymph nodes. In this study, the efficacy of integrated positron emission tomography/computed tomography (PET/CT) was compared with ECM for the detection of APW lymph node metastasis., Methods: Fifty-five patients diagnosed of non-small cell lung cancer in whom APW or hilar lymph nodes had been reported to be positive on PET/CT, and/or who had had central tumor and/or in whom ECM had been performed for mediastinal staging due to the presence of APW lymph nodes larger than 1 cm in diameter on the CT between 2005 and 2009, were retrospectively analyzed. All patients underwent PET/CT scanning., Results: Thirty-eight patients were identified as cN0 by standard cervical mediastinoscopy/ECM, and lobectomy, pneumonectomy, and exploratory thoracotomy were performed on 19, 13, and six of these patients, respectively. Mediastinal lymphadenectomy revealed APW lymph node metastases in four patients (ECM false negative). Seventeen patients identified as cN2 by mediastinoscopy, APW lymph node metastasis was present in nine, whereas eight had mediastinal lymph node metastasis that could only be accessed by standard cervical mediastinoscopy but had no APW lymph node metastasis were excluded from the analysis. Sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of ECM/PET/CT were calculated as 0.69/0.53, 1/0.91, 0.89/0.83, 1/0.70, and 0.91/0.80, respectively., Conclusions: ECM, which is an effective technique used in the determination of APW lymph node metastasis, was enough to rule out nodal disease with negative predictive value. PET/CT does not reduce the need for invasive procedures in detecting APW lymph node metastasis.

Background: In computed tomography lung cancer screening programs, up to 30% of all resections are futile., Objective: To investigate whether a preoperative positron emission tomography (PET) after a conclusive or inconclusive nonsurgical workup will reduce the resection rate for benign disease in test-positive participants of a lung cancer screening program., Methods: ¹⁸F-Fluorodeoxyglucose-PET scans were made in 220 test positives. Nodules were classified as positive, indeterminate, or negative based on visual comparison with background activity. Gold standard for a positive PET was the presence of cancer in the resection specimen or the detection of cancer during more than 2 years follow-up. Sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were calculated at participant level and 95% confidence intervals (CIs) constructed., Results: The sensitivity of PET to detect cancer was 84.2% (95% CI: 77.6-90.7%), the specificity 75.2% (95% CI: 67.1-83.3), the positive predictive value 78.9% (95% CI: 71.8-86.0), and the NPV 81.2% (95% CI: 73.6-88.8). The resection rate for benign disease was 23%, but 26% of them had a diagnosis with clinical consequences. A preoperative PET after an inconclusive nonsurgical workup reduced the resection rate for benign lesions by 11 to 15%, at the expense of missing 12 to 18% lung cancer cases. A preoperative PET after a conclusive nonsurgical workup reduced the resection rate by 78% at the expense of missing 3% lung cancer cases., Conclusion: A preoperative PET scan in participants with an inconclusive nonsurgical workup is not recommended because of the very low NPV, but after a conclusive nonsurgical workup, the resection rate for benign disease can be decreased by 72%.

Objective: This study investigated how fluorodeoxyglucose (FDG) uptake on PET in the primary tumor may predict intratumoral vessel invasion (IVI) in it., Methods: A total of 512 patients with lung neoplasms determined by a surgical procedure and histopathological diagnosis had undergone FDG-PET scanning., Results: Among the 440 cases confirmed to be malignant, the maximum standardized uptake value (SUV(max)) was significantly lower in IVI-negative cases than IVI-positive cases (P < 0.001). In the substudy on adenocarcinoma (AC), SUV(max) was significantly lower in IVI-negative cases too (P < 0.001), but SUV(max) in squamous cell carcinoma was without significant difference. In addition, IVI was associated with a significantly higher probability of lymph node metastasis (P < 0.001)., Conclusions: This study indicates that a malignant lung tumor with higher SUV(max) has a significantly higher probability of IVI and lymph node metastasis, particularly if the malignancy is an AC.

Introduction: Patients with non-small cell lung cancer (NSCLC) require careful preoperative staging to define resectability for potential cure. Fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is widely used to stage NSCLC. If the mediastinum is positive on PET-CT examination, some practitioners conclude that the patient is inoperable and refer the patient for nonsurgical treatment., Methods: In this analysis of a previously reported trial comparing PET-CT with conventional imaging in the diagnostic work-up of patients with clinical stage I, II, or IIIA NSCLC, we determined the accuracy of PET-CT in mediastinal staging compared with invasive mediastinal staging either by mediastinoscopy alone or by mediastinoscopy combined with thoracotomy., Results: All 149 patients had mediastinal nodal staging at mediastinoscopy alone (14), thoracotomy alone (64), or both (71). The sensitivity of PET-CT was 70% (95% confidence interval [CI], 48-85%), and specificity was 94% (95% CI, 88-97%). Of 22 patients with a PET-CT interpreted as positive for mediastinal nodes, 8 did not have tumor. The positive predictive value and negative predictive value were 64% (95% CI, 43-80%) and 95% (95% CI, 90-98%), respectively. Based on PET-CT alone, eight patients would have been denied potentially curative surgery if the mediastinal abnormalities detected by PET-CT had not been evaluated with an invasive mediastinal procedure., Conclusions: PET-CT assessment of the mediastinum is associated with a clinically relevant false-positive rate. Our study confirms the need for pathologic confirmation of mediastinal lymph node abnormalities detected by PET-CT.

Introduction: Measurement of tumor response by standard response criteria is challenging in thymic malignancies, especially when the pleura is involved, as it often is in stage IV disease. In this study, we aimed to determine the effectiveness of volumetric response evaluation criteria in solid tumors (volumetrics) for evaluating response in patients with thymic malignancies treated on a phase II study of belinostat., Methods: We evaluated the tumor responses of 25 patients with thymic cancer using computed tomography-based RECIST, World Health Organization (WHO), modified RECIST, and volumetrics. As a control, we assessed 37 patients with non-small cell lung cancer (NSCLC) with RECIST and volumetrics., Results: Agreement analyses in 23 patients with thymic cancer at the time of RECIST-determined progressive disease (PD) compared volumetrics with RECIST, modified RECIST, and WHO criteria. Use of volumetrics was associated with 22% discordance compared with RECIST, 15% versus modified RECIST, and 22% versus WHO criteria. Volumetrics revealed PD 72 days earlier than RECIST (p = 0.016). In another cohort of 35 patients with NSCLC, there was 9% discordance between volumetrics and RECIST at the time of PD. Volumetrics demonstrated PD 32 days earlier than RECIST in NSCLC (p = 0.0078)., Conclusions: Our study suggests that volumetrics might improve detection of PD. Prospective evaluation of this technique in a larger series of patients with thymic malignancies will be required.