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In the evolution of breast cancer, the appearance of metastases represents a decisive moment. Scientists have been trying for a long time to decipher how the metastases appear. The aim of this study is to highlight and compare the immunohistochemical characteristics of the cells from breast cancer metastases found in the uterus and ovaries. A 62-year-old patient diagnosed four years before with poorly differentiated breast ductal carcinoma arrived at the "Sf. Ioan" Emergency Clinical Hospital from Bucharest because a control computed tomography detected abnormal tumoral changes at the level of the internal genital organs. After reassessment, a hysterectomy with bilateral adnexectomy was performed. The histopathological and immunohistochemical examination of tumors found in the uterus and ovaries, which aimed to identify their nature, established that they were metastases of the ductal breast carcinoma. This situation allowed us to study comparatively their characteristics. We found significant differences: the PGR expression declined from 65-70% of cells in the primary tumor to 40% in the ovarian metastases and to 3% of cells in uterine metastases, and Ki67 expression increased from 2-4% of cells in the primary tumor to 10-15% in the ovarian metastases and up to 30% of cells in uterine metastases. These significant differences in the expression of immunohistochemical markers suggest that newly formed cell lines gain new characteristics that create advantages for them, so that they are favored in terms of dissemination, grafting and growth in a specific host organ. [ABSTRACT FROM AUTHOR]

Aim: To evaluate preliminary experience with 18F-fluorocholine PET/CT (FCh PET/CT) restaging imaging in prostate cancer patients with biochemical failure and stress the problems with prostate cancer recurrence detection in patients with low prostate specific antigen (PSA) levels. Methods: FCh PET/CT was performed for prostate cancer recurrence detection in 24 patients during 16 months. Of them, 14 patients with known clinical outcome were further retrospectively evaluated. We evaluated FCh PET/CT diagnostic performance in relation to PSA levels and PSA kinetics, Gleason score and initial staging. Results: Median of their PSA levels was 1.76 ng/ml, range: 0.44--2.88. Prostate cancer recurrence was detected in only 6 patients out of 14 using FCh PET/CT, sensitivity reached 43%. FCh PET/CT positive patients had clearly shorter PSA doubling time (median 4.15 versus 10.2 in FCh PET/CT negative ones) and slightly higher Gleason score. Conclusions: Although we achieved low FCh PET/CT sensitivity in patients with biochemical failure with low PSA levels, our data suggest that FCh PET/CT could be useful in those with still low PSA levels, but short PSA doubling time. PSA doubling time seems to be helpful in selecting (still) low level PSA patients for FCh PET/CT. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether radiographic and metabolic changes on midchemoradiation therapy (CRT) fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) for cervical cancer predict outcome.Methods and Materials: Women with International Federation of Gynecology and Obstetrics stage IB1-IVB cervical cancer treated with concurrent cisplatin-based CRT and brachytherapy were enrolled on a single-institution prospective clinical trial; FDG-PET/CT was obtained before CRT and at 30 to 36 Gy. Max and mean standard uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) for the primary tumor and clinically involved lymph nodes from the pre-CRT and intra-CRT FDG-PET/CT were recorded. Clinical endpoints analyzed include overall survival (OS), disease-free survival (DFS), and rates of cervical recurrence (CR), nodal recurrence (NR), and distant metastasis (DM). FDG-PET/CT variables and other prognostic factors associated with clinical endpoints were identified via univariate Cox proportional hazards modeling and competing risk analysis.Results: Thirty women were enrolled from 2012 to 2016. After a median follow-up of 24 months, 2-year rates of OS, DFS, DM, NR, and CR were 68% (95% confidence interval [CI], 51%-85%), 44% (95% CI, 26%-63%), 42% (95% CI, 23%-59%), 14% (95% CI, 4%-30%), and 10% (95% CI, 2%-24%), respectively. Intra-PET metrics and TLG across all PET scans were most consistently associated with OS, DFS, DM, and NR on univariate analysis. Intra-CRT TLG was associated with OS (hazard ratio [HR] 1.35; 95% CI, 1.15-1.55; P = .001), DFS (HR 1.19; 95% CI, 1.04-1.34; P = .018), and NR (HR 1.25; 95% CI, 1.10-1.40; P = .002). No absolute or relative changes between parameters of baseline and mid-CRT FDG-PET/CT were associated with disease outcomes on univariate analysis, with the exception of relative change in mean standard uptake values and CR (P = .004).Conclusions: In this group of patients with high-risk cervical cancer treated with CRT and brachytherapy, TLG and metabolic tumor volume on intra-CRT FDG-PET/CT was associated with OS. These metrics may provide an early signal for selective treatment intensification with either dose escalation or adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most diagnosable forms of cancer worldwide. The early diagnoses of pulmonary nodules in computed tomography (CT) chest scans are crucial for potential patients. Recent researches have showed that the methods based on deep learning have made a significant progress for the medical diagnoses. However, the achievements on identification of pulmonary nodules are not yet satisfactory enough to be adopted in clinical practice. It is largely caused by either the existence of many false positives or the heavy time of processing. With the development of fully convolutional networks (FCNs), in this study, we proposed a new method of identifying the pulmonary nodules. The method segments the suspected nodules from their environments and then removes the false positives. Especially, it optimizes the network architecture for the identification of nodules rapidly and accurately. In order to remove the false positives, the suspected nodules are reduced using the 2D models. Furthermore, according to the significant differences between nodules and non-nodules in 3D shapes, the false positives are eliminated by integrating into the 3D models and classified via 3D CNNs. The experiments on 1000 patients indicate that our proposed method achieved 97.78% sensitivity rate for segmentation and 90.1% accuracy rate for detection. The maximum response time was less than 30 s and the average time was about 15 s. Graphical Abstract This paper has proposed a new method of identifying the pulmonary nodules. The method segments the suspected nodules from CT images and removes the false positives. As shown in the above, the proposed approach consists of three stages. In stage I, raw data are filtered and normalized. The clean normalized data are then segmented in stage II to extract the suspected nodular lesions through 2D FCNs. Stage III is to remove some false positives generated at stage II via 3D CNNs and outputs the final results. The experiments on 1000 patients indicate that our proposed method has achieved 97.78% sensitivity rate for segmentation and 90.1% accuracy rate for detection. The maximum response time was less than 30 s and the average time was about 15 s. [ABSTRACT FROM AUTHOR]

TMEM16A (also known as anoctamin 1, ANO1) is the molecular basis of the calcium‐activated chloride channels, with ten transmembrane segments. Recently, atomic structures of the transmembrane domains of mouse TMEM16A (mTMEM16A) were determined by single‐particle electron cryomicroscopy. This gives us a solid ground to discuss the electrophysiological properties and functions of TMEM16A. TMEM16A is reported to be dually regulated by Ca2+ and voltage. In addition, the dysfunction of TMEM16A has been found to be involved in many diseases including cystic fibrosis, various cancers, hypertension, and gastrointestinal motility disorders. TMEM16A is overexpressed in many cancers, including gastrointestinal stromal tumors, gastric cancer, head and neck squamous cell carcinoma (HNSCC), colon cancer, pancreatic ductal adenocarcinoma, and esophageal cancer. Furthermore, overexpression of TMEM16A is related to the occurrence, proliferation, and migration of tumor cells. To date, several studies have shown that many natural compounds and synthetic compounds have regulatory effects on TMEM16A. These small molecule compounds might be novel drugs for the treatment of diseases caused by TMEM16A dysfunction in the future. In addition, recent studies have shown that TMEM16A plays different roles in different diseases through different signal transduction pathways. This review discusses the topology, electrophysiological properties, modulators and functions of TMEM16A in mediates nociception, gastrointestinal dysfunction, hypertension, and cancer and focuses on multiple regulatory mechanisms regarding TMEM16A. This review discusses the topology, electrophysiological properties, modulators and functions of TMEM16A in mediates nociception, gastrointestinal dysfunction, hypertension, and cancer and focuses on multiple regulatory mechanisms regarding TMEM16A. [ABSTRACT FROM AUTHOR]

Objective: To determine the correlation of displacement of the mediastinal metastatic lymph nodes with adjacent organs in non‐small cell lung cancer using four‐dimensional computed tomography. Methods: The displacements of 51 mediastinal metastatic lymph nodes located in the left–right, anterior–posterior, and superior–inferior directions were measured using four‐dimensional computed tomography. Correlation analyses were carried out to determine the association between the displacement of lymph nodes and volumetric change of the lungs and heart. Results: A significant correlation of displacement of the left group lymph nodes in left–right and the right group in anterior–posterior directions with volumetric change of the ipsilateral lung was observed. There were significant correlations between displacement of the left group lymph nodes and volumetric change of the heart. Conclusion: Displacement of the mediastinal metastatic lymph nodes was relevant to the adjacent organs. [ABSTRACT FROM AUTHOR]

We previously compared time-domain diffuse optical spectroscopy (TD-DOS) with magnetic resonance imaging (MRI) using various water/lipid phantoms. However, it is difficult to conduct similar comparisons in the breast, because of measurement differences due to modality-dependent differences in posture. Dual-energy computed tomography (DECT) examination is performed in the same supine position as a TD-DOS measurement. Therefore, we first verified the accuracy of the measured fat fraction of fibroglandular tissue in the normal breast on DECT by comparing it with MRI in breast cancer patients (n = 28). Then, we compared lipid and water signals obtained in TD-DOS and DECT from normal and tumor-tissue regions (n = 16). The TD-DOS breast measurements were carried out using reflectance geometry with a source–detector separation of 3 cm. A semicircular region of interest (ROI), with a transverse diameter of 3 cm and a depth of 2 cm that included the breast surface, was set on the DECT image. Although the measurement area differed between the modalities, the correlation coefficients of lipid and water signals between TD-DOS and DECT were rs = 0.58 (p < 0.01) and rs = 0.90 (p < 0.01), respectively. These results indicate that TD-DOS captures the characteristics of the lipid and water contents of the breast. [ABSTRACT FROM AUTHOR]

Highlights • Daily imaging and frequent treatment adaptation are critically important for proton therapy. • A mobile helical CT scanner has been integrated into a compact proton treatment unit. • The present study demonstrates the feasibility of image guided adaptive proton therapy using a mobile helical CT scanner with superior imaging quality and a large field-of-view. Abstract Purpose To evaluate the feasibility of image-guided adaptive proton therapy (IGAPT) with a mobile helical-CT without rails. Method CT images were acquired with a 32-slice mobile CT (mCT) scanning through a 6 degree-of-freedom robotic couch rotated isocentrically 90 degrees from an initial setup position. The relationship between the treatment isocenter and the mCT imaging isocenter was established by a stereotactic reference frame attached to the treatment couch. Imaging quality, geometric integrity and localization accuracy were evaluated according to AAPM TG-66. Accuracy of relative stopping power ratio (RSPR) was evaluated by comparing water equivalent distance (WED) and dose calculations on anthropomorphic phantoms to that of planning CT (pCT). Feasibility of image-guided adaptive proton therapy was demonstrated on fractional images acquired with the mCT scanner. Results mCT images showed slightly lower spatial resolution and a higher contrast-to-noise ratio compared to pCT images from the standard helical CT scanner. The geometric accuracy of the mCT was <1 mm. Localization accuracy was <0.4 mm and <0.3° with respect to 2D kV/kV matching. WED differences between mCT and pCT images were negligible, with discrepancies of 0.8 ± 0.6 mm and 1.3 ± 0.9 mm for brain and lung phantoms respectively. 3D gamma analysis (3% and 3 mm) passing rate was >95% on dose computed on mCT, with respect to dose calculation on pCT. Conclusion Our study has demonstrated that the geometric integrity, image quality and RSPR accuracy of the mCT are sufficient for IGAPT. [ABSTRACT FROM AUTHOR]

Highlights • Target respiratory-motion over the entire course of treatment can be captured by MRI. • The study compares the accuracy of 4DCT to 30s MR for pretreatment motion estimation. • Both techniques are reliable for lesions moving with amplitudes below 0.7 cm. Abstract Introduction Aim of this study was to investigate the ability of pre-treatment four dimensional computed tomography (4DCT) to capture respiratory-motion observed in thoracic and abdominal lesions during treatment. Treatment motion was acquired using full-treatment cine-MR acquisitions. Results of this analysis were compared to the ability of 30 seconds (s) cine Magnetic Resonance (MR) to estimate the same parameters. Methods A 4DCT and 30 s cine-MR (ViewRay, USA) were acquired on the simulation day for 7 thoracic and 13 abdominal lesions. Mean amplitude, intra- and inter-fraction amplitude variability, and baseline drift were extracted from the full treatment data acquired by 2D cine-MR, and correlated to the motion on pre-treatment 30 s cine-MR and 4DCT. Using the full treatment data, safety margins on the ITV, necessary to account for all motion variability from 4DCT observed during treatment, were calculated. Mean treatment amplitudes were 2 ± 1 mm and 5 ± 3 mm in the anteroposterior (AP) and craniocaudal (CC) direction, respectively. Differences between mean amplitude during treatment and amplitude on 4DCT or during 30 s cine-MR were not significant, but 30 s cine-MR was more accurate than 4DCT. Intra-fraction amplitude variability was positively correlated with both 30 s cine-MR and 4DCT amplitude. Inter-fraction amplitude variability was minimal. Results Mean baseline drift over all fractions and patients equalled 1 ± 1 mm in both CC and AP direction, but drifts per fraction up to 16 mm (CC) and 12 mm (AP) were observed. Margins necessary on the ITV ranged from 0 to 8 mm in CC and 0 to 5 mm in AP direction. Neither amplitude on 4DCT nor during 30 s cine MR is correlated to the magnitude of drift or the necessary margins in both directions. Conclusion Lesions moving with small amplitude show limited amplitude variability throughout treatment, making passive motion management strategies seem adequate. However, other variations such as baseline drifts and shifts still cause significant geometrical uncertainty, favouring real-time monitoring and an active approach for all lesions influenced by respiratory motion. [ABSTRACT FROM AUTHOR]

Objective: To examine the imaging characteristics of intramuscular myxomas (IM) and myxoid liposarcomas (MLS) on 18F-FDG PET/CT and MRI.Materials and Methods: With IRB approval, our institutional imaging database was searched for pathologically proven IM and MLS evaluated by 18F-FDG PET/CT and MRI. PET/CT and MRI imaging characteristics were recorded and correlated with pathologic diagnosis.Results: We found eight patients (2 M, 6 F) with IM (mean age 65.6 ± 10.4 years) and 16 patients (7 F, 9 M) with MLS (mean age 42.8 ± 16.3 years). MRI was available in 7/8 IM and 15/16 MLS patients. There was no significant difference between the two groups in SUVmax (IM 2.7 ± 0.8, MLS 3.0 ± 1.0; p = 0.35), SUVmean (1.7 ± 0.4, 1.5 ± 0.5; p = 0.40), total lesion glycolysis (101.8 ± 127.3, 2420.2 ± 4003.3 cm3*g/ml; p = 0.12), metabolic tumor volume (62.3 ± 71.1, 1742.9 ± 3308.0 cm3; p = 0.17) or CT attenuation (p = 0.70). MLS occurred in younger patients (p = 0.0015), were larger (16.4 ± 8.2 vs. 5.6 ± 2.5 cm; p = 0.0015), more often T1 hyperintense (p = 0.03), with nodular enhancement (p = 0.006), and macroscopic fat on CT (p = 0.0013) and MRI (p = < 0.001) compared to myxomas.Conclusions: IM and MLS most commonly demonstrate low-grade FDG activity and overlapping metabolic measures on PET/CT. MRI is useful in differentiation, but MLS can present without macroscopic fat on MRI, underscoring the importance of radiologic-pathologic correlation for accurate diagnosis. [ABSTRACT FROM AUTHOR]

Computed tomography (CT) is the standard imaging test used for the screening and assessment of suspected lung cancer, but distinguishing malignant from benign nodules by CT is an ongoing challenge. Consequently, a large number of avoidable invasive procedures are performed on patients with benign nodules in order to exclude malignancy. Improving cancer discrimination by non-invasive imaging could reduce the need for invasive diagnostics. In this work we focus on developing a gold nanoparticle contrast agent that targets the epidermal growth factor receptor (EGFR), which is expressed on the cell surface of most lung adenocarcinomas. Three different contrast agents were compared for their tumor targeting effectiveness: non-targeted nanoparticles, nanoparticles conjugated with full-sized anti-EGFR antibodies (cetuximab), and nanoparticles conjugated with a single-domain llama-derived anti-EGFR antibody, which is smaller than the cetuximab, but has a lower binding affinity. Nanoparticle targeting effectiveness was evaluated in vitro by EGFR-binding assays and in cell culture with A431 cells, which highly express EGFR. In vivo CT imaging performance was evaluated in both C57BL/6 mice and in nude mice with A431 subcutaneous tumors. The cetuximab nanoparticles had a significantly shorter blood residence time than either the non-targeted or the single-domain antibody nanoparticles. All of the nanoparticle contrast agents demonstrated tumor accumulation; however, the cetuximab-targeted group had significantly higher tumor gold accumulation than the other two groups, which were statistically indistinguishable from one another. In this study we found that the relative binding affinity of the targeting ligands had more of an effect on tumor accumulation than the circulation half life of the nanoparticles. This study provides useful insight into targeted nanoparticle design and demonstrates that nanoparticle contrast agents can be used to detect tumor receptor overexpression. Combining receptor status data with traditional imaging characteristics has the potential for better differentiation of malignant lung tumors from benign lesions. [ABSTRACT FROM AUTHOR]

Objectives: When initially discovered in 1963, techniques did not allow definitive diagnosis of the basketball‐sized mandibular tumour discovered in a woman from the Buffalo site dated to 17th century West Virginia. Her subsequent medical examiners stated that they "can only speculate as to the true nature of the tumor." An interdisciplinary approach was pursued to assess ability of currently available techniques to resolve this conundrum. Materials and methods: Macroscopic examination, X‐ray, computed tomography (CT), micro‐CT (7‐μ resolution), and epi‐illumination microscopy (100‐μ resolution) were utilized to identify diagnostic criteria that would allow discrimination among the possible etiologies. Results: Macroscopic examination revealed a 24 by 23 by 19‐cm tumour attached to the right mandible. X‐ray examination revealed intact trabeculae of reduced size but of uniform thickness. CT examination revealed intact trabeculae of decreased size but uniform thickness. Epi‐illumination microscopy confirmed the CT findings. Trabeculae appeared to be intact, uniform in thickness, and with intact connectivity. Micro‐CT revealed significant variation in trabecular thickness with frequent areas of resorption and loss of interconnections. Discussion: Osteosarcoma was considered macroscopically, on the basis of tumour size. However, the small, uniformly sized, intact trabeculae recognized on X‐ray, CT, and with epi‐illumination microscopy presented the pattern anticipated with an osteoblastoma. Micro‐CT, however, falsified that diagnosis, in favour of an osteosarcoma diagnosis. The final consideration is of an osteoblastic osteosarcoma, apparently the first recognized in the archaeologic record. The misleading nature of routine X‐ray, CT, and even microscopy (at 100‐μ resolution) in this case stands as a caveat. [ABSTRACT FROM AUTHOR]

Purpose: Understanding complex abdominal organ motion is essential for motion management in radiation therapy (RT) of abdominal tumors. This study investigates abdominal motion induced by respiration and peristalsis, during various time durations relevant to RT, using various CT and MRI techniques acquired under free breathing (FB) and breath hold (BH). Methods: A series of CT and MRI images acquired with various techniques under free breathing and/or breath hold from 37 randomly-selected pancreatic or liver cancer patients were analyzed to assess the motion in various time frames. These data include FB 4DCT from 15 patients (for motion in time duration of 5 sec), FB 2D cine-MRI from 4 patients (time duration of 1.7 min, 1 second acquisition time per slice), FB cine-MRI acquired using MR-Linac from 6 patients in various fractions (acquisition time is less than 0.6 seconds per slice), FB 4DMRI from 2 patients (time duration of 2 min), respiration-gated T2 with gating at the end expiration (time duration of 3–5 min), and BH T1 with multiphase dynamic contrast in acquisition times of 17 seconds for each of five phases (pre-contrast, arterial, venous, portal venous and delayed post-contrast) from 10 patients. Motions of various organs including gallbladder (GB) and liver were measured based on these MRI data. The GB motion includes both respiration and peristalsis, while liver motion is primarily respiration. By subtracting liver motion (respiration) from GB motion (respiration and peristalsis), the peristaltic motion, along with small residual motion, was obtained. Results: From cine-MRI, the residual motion beyond the respiratory motion was found to be up to 0.6 cm in superior-inferior (SI) and 0.55 cm in anterior-posterior (AP) directions. From 2D cine-MRI acquired by the MR-Linac, different peristaltic motions were found from different fractions for each patient. The peristaltic motion was found to vary between 0.3–1 cm. From BH T1 phase images, the average motions that were primarily due to peristalsis movements were found to be 1.2 cm in SI, 0.7 cm in AP, and 0.9 cm in left-right (LR) directions. The average motions assessed from 4DCT were 1.0 cm in SI and 0.3 cm in AP directions, which were generally smaller than the motions assessed from cine-MRI, i.e., 1.8 cm in SI and 0.6 cm in AP directions, for the same patients. However, average motions from 4DMRI, which are coming from respiratory were measured to be 1.5, 0.5, and 0.4 cm in SI, AP, and LR directions, respectively. Conclusion: The abdominal motion due to peristalsis can be similar in magnitude to respiratory motion as assessed. These motions can be irregular and persistent throughout the imaging and RT delivery procedures, and should be considered together with respiratory motion during RT for abdominal tumors. [ABSTRACT FROM AUTHOR]

Background: Activation of Ras oncogene in human tumors is associated with radiation-associated metastatic potential. Although ionizing radiation is one important method of cancer treatments, it has been shown to enhance matrix metalloproteinases (MMPs) activity and facilitates a more aggressive cancer phenotype. Our previous studies showed that andrographolide with lower dose rates of radiation could inhibit RAS-transformed cancer metastasis in vivo; however, the molecular mechanisms are not yet clear. In this study, we aimed to explore the anti-metastatic effect of andrographolide combined with radiation on Ras-transformed cells. Methods: RAS-transformed cells were treated with andrographolide in the presence or absence of irradiation (2–4 Gy) or angiotensin II to examine cell invasion. In vivo tumorigenesis assays were also performed. The MMP-2 activity was detected by using Gelatin zymography. Signal transduction of NF-κB subunit, p65 and phosphor-ERK 1/2, were examined by using Western blotting analysis. Results: Treatment with andrographolide inhibited migration of Ras-transformed cells. Andrographolide treatment with radiation significantly inhibited cancer metastasis in vivo. We found that andrographolide exhibited anti-migration and anti-invasive ability against cancer metastasis via inhibition of MMP2 activity rather than affected MMP-9 and EMT. In addition, combined andrographolide with radiation appeared to be more effective in reducing MMP-2 expression, and this effect was accompanied by suppression of ERK activation that inhibits cancer cell migration and invasion. Conclusions: These findings suggest that andrographolide enhances the anti-metastatic effect of radiation in Ras-transformed cells via suppression of ERK–mediated MMP-2 activity. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and compare the diagnostic accuracy of high versus low attenuation thresholds for determining the solid component of ground-glass opacity nodules (GGNs) for the differential diagnosis of adenocarcinoma in situ (AIS) from minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA). Methods: Eighty-six pathologically confirmed GGNs < 3 cm observed in 86 patients (27 male, 59 female; mean age, 59.3 ± 11.0 years) between January 2013 and December 2015 were retrospectively included. The solid component of each GGN was defined using two different attenuation thresholds: high (-160 Hounsfield units [HU]) and low (-400 HU). According to the presence or absence of solid portions, each GGN was categorized as a pure GGN or part-solid GGN. Solid components were regarded as indicators of invasive foci, suggesting MIA or IA. Results: Among the 86 GGNs, there were 57 cases of IA, 19 of MIA, and 10 of AIS. Using the high attenuation threshold, 44 were categorized as pure GGNs and 42 as part-solid GGNs. Using the low attenuation threshold, 13 were categorized as pure GGNs and 73 as part-solid GGNs. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the invasive focus were 55.2%, 100%, 100%, 22.7%, and 60.4%, respectively, for the high attenuation threshold, and 93.4%, 80%, 97.2%, 61.5%, and 91.8%, respectively, for the low attenuation threshold. Conclusion: The low attenuation threshold was better than the conventional high attenuation threshold for determining the solid components of GGNs, which indicate invasive foci. [ABSTRACT FROM AUTHOR]

18F fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) is a standard imaging tool in staging as well as response evaluation for lymphoma. Here, we present a young male with extensive extranodal lymphoma with cardiac involvement which presented as diffuse myocardial lesion mimicking hypertrophic obstructive cardiomyopathy. 18F-FDG PET/CT helped in the staging by revealing multiple systemic involvements. Interim PET after three cycles of chemotherapy showed a complete metabolic response to therapy in all the extranodal sites including the cardiac involvement, thus retrospectively confirming the lymphomatous involvement. Previous literature also conforms to the superior role of 18F-FDG PET/CT in the clinical management of extensive extranodal lymphoma. [ABSTRACT FROM AUTHOR]

Introduction: The treatment for differentiated thyroid cancers (DTCs) has always been radioactive iodine 131I therapy after definitive surgical management. Clinicians are faced with therapeutic challenges when dealing with patients having thyroglobulin-elevated negative iodine scintigraphy (TENIS) syndrome (elevated serum thyroglobulin [Tg] levels but negative whole-body scans [WBSs]). Objective: The aim of the study was to determine the prevalence of TENIS syndrome in our local setting and to evaluate the use of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) in the management. Methodology: The data from DTC patients treated in the Department of Nuclear Medicine, Hospital Pulau Pinang from December 1, 2010, to November 30, 2016, with negative WBS and elevated Tg were reviewed. These patients should have undergone 18F-FDG PET-CT to be included in the study. Results: Only forty (10.4%) out of a total of 386 patients treated in Hospital Pulau Pinang during the study fulfilled the inclusion criteria. There were 28 women (70%) with median age of 59 years old. Thirty-four patients (85%) had papillary thyroid cancer (PTC) and six patients had follicular thyroid cancer. The use of 18F-FDG PET-CT revealed 23 patients (57.5%) with 18F-FDG avid metastases suggesting dedifferentiation of thyroid cancers. Based on this study, the probability of detecting FDG-avid disease is higher (P = 0.03) if 18F-FDG PET-CT was performed when Tg =15 ng/mL. Conclusion: TENIS syndrome constitutes a significant number of cases in our setting. Our data suggest a cutoff Tg =15 ng/mL for performing 18F-FDG PET-CT for these patients would be more beneficial than the currently American Thyroid Association recommended cutoff of 10 ng/mL. [ABSTRACT FROM AUTHOR]

A failure in any of the hardware components can lead to degradation in image quality and accuracy of quantification. Few artifacts may bring serious impacts on the image quality and finally lead to the wrong diagnosis. We encountered a sudden appearance of the cold area, being more prominently visible on Positron Emission Tomography image in comparison to the fused image. A daily quality assurance scan was performed to evaluate the status of the machine after giving a restart to the system. It was discovered that the module number 9-11 showed dark black color in the graph due to scarcity of counts indicating a failure/malfunctioning of the detector or electronic board-Cassette Electronic Module board (CEM board) supporting the module 9-11. Further evaluation of the system helped us diagnose that one of the electronic board (CEM Board) had become nonfunctional. A new functional electronic board (CEM board) was ordered and placed and the error rectified. [ABSTRACT FROM AUTHOR]

68Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography imaging (PET/CT) is a rapidly evolving imaging modality for prostate cancer. Many studies have proved its superiority in staging, restaging, and detecting the recurrent prostate cancer. However, case reports describing the incidental tracer uptake in benign and nonprostatic malignancies are also reported in the literature, thus questioning the specificity of the tracer. This pictorial assay illustrates the nonspecific tracer uptake encountered during PSMA PET/CT imaging, knowledge of which can increase the confidence of interpreting physicians and may also open a new path for peptide receptor radionuclide therapy in nonprostatic malignancies. [ABSTRACT FROM AUTHOR]

Objective: The aim of the report is to present time efficient whole-body positron emission tomography/magnetic resonance imaging (PET/MRI) protocol evolved and tested for comprehensive evaluation of cancer patients. Materials and Methods: Whole body as well as regional simultaneous PET and MRI was performed on Biograph mMR (Siemens, Erlangen, Germany) Simultaneous PET/MRI system in 4500 clinical cases of various cancers from 2013 to 2017 with an in-house designed imaging protocol to assess its utility. Results: Using this protocol, the whole body is covered with optimized sequences (T1, T2, short tau inversion recovery, diffusion, and 3D volumetric interpolated breath-held) with PET which has been found adequate for complete metastatic workup in 30-45 min. With region-specific studies, it provides a comprehensive staging workup in an additional 10-15 min. The workflow offered additive advantages of effectively addressing incidentalomas besides being useful in terms of diagnostic utility. Conclusion: The proposed whole-body PET MRI imaging protocol used in a clinical setting is found acceptable and reasonably time efficient to optimally exploit the potentials of the technique in oncology. [ABSTRACT FROM AUTHOR]

Purpose: 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is now recognized as a staging investigation for locally advanced breast cancer. This retrospective review of data was performed to correlate the maximum standardized uptake value (SUVmax;) of the primary tumor with the molecular subtype of breast cancer. Materials and Methods: Patients with biopsy-proven, treatment naïve, Stage III breast cancer, for whom 18F-FDG PET/CT data and immunohistochemistry 4 was available were included in the study. Correlations were deduced between the SUVmax; of primary tumor to the molecular subtypes. Results: Three hundred and two patients were included in the study. Fifty-two (17.2%) tumors were Luminal A (LA), 131 (43.4%) Luminal B (LB), 42 (13.9%) human epidermal growth factor receptor-2 enriched (HE), and 77 (25.5%) basal-like (BL). SUVmax; of the primary tumor differed significantly between LA and other subtypes (SUVmax;: LA Median 7.4, LB 11.65, HE 13.5, BL 15.35, P < 0.001). Estrogen receptor (ER) and progesterone receptor (PR) positivity were inversely correlated to the SUVmax; of the primary (SUVmax;: ER + Median 10.4, ER - 14.2, P < 0.001, PR + 9.65, PR - 13.9, P < 0.001). There was a strong positive correlation observed between Ki67 and SUVmax; (Pearson Coefficient 0.408, P < 0.001). A SUVmax; value of 9.65 was determined as a cutoff on receiver operating characteristic curve to differentiate between LA and other subtypes with a sensitivity of 92.3% and specificity of 70.6%. Conclusions: SUVmax; of primary showed a statistically significant difference between LA subtypes when compared to other subtypes. However, there was overlap of values in each subgroup and thus 18F-FDG PET/CT cannot be used to accurately assess the molecular characteristics of the tumor. [ABSTRACT FROM AUTHOR]

Early lung cancer detection is extremely challenging as symptoms are not exposed till advanced stage. This study is aimed at developing a computer aided diagnosis (CAD) system with image processing techniques and support vector machine (SVM) in lung cancer classification from positron emission tomography/computed tomography (PET/CT) images. The developed CAD system utilized fuzzy enhancement for contrast improvement. Texture and fractal features were used for training the SVM. This study utilized 82 PET/CT images and 10-fold cross validation to analyze the performance of the classifiers. Experimental study showed that SVM classifier with radial basis function (RBF) kernel of width, s = 1 outperformed the other SVM models. It produced maximum accuracy of 98.13% using texture and fractal features from PET/CT images. The RBF kernel is effective in handling sparse, non-linear, multi-dimensional data to transform it into linearly separable. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated whether the metabolic avidity of primary tumors and/ or metastatic lymph nodes (LNs) measured by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was related to survival after surgery in patients with advanced gastric cancer (AGC). Materials and Methods: One hundred sixty-eight patients with AGC who underwent preoperative 18F-FDG PET/CT and curative resection were included. The 18F-FDG avidity of the primary gastric tumor and LNs was determined quantitatively and qualitatively. The diagnostic performance of 18F-FDG PET/CT was calculated, and the prognostic significance of 18F-FDG avidity for recurrence-free survival (RFS) and overall survival (OS) was assessed. Results: In all, 51 (30.4%) patients experienced recurrence, and 32 (19.0%) died during follow-up (median follow-up duration, 35 months; range, 3-81 months); 119 (70.8%) and 33 (19.6%) patients showed 18F-FDG-avid primary tumors and LNs, respectively. 18F-FDG PET/ CT showed high sensitivity (73.8%) for the detection of advanced pathologic T (pT ≥3) stage and high specificity (92.2%) for the detection of advanced pN (≥2) stage. 18F-FDG avidity of LNs was significantly associated with RFS (P=0.012), whereas that of primary tumors did not show significance (P=0.532). Univariate and multivariate analyses revealed that 18F-FDG avidity of LNs was an independent prognostic factor for RFS (hazard ratio=2.068; P=0.029). Conclusions: 18F-FDG avidity of LNs is an independent prognostic factor for predicting RFS. Preoperative 18F-FDG PET/CT can be used to determine the risk and prognosis of patients with AGC after curative resection. [ABSTRACT FROM AUTHOR]

Purpose: In patients with Hodgkin (HL) and non-Hodgkin lymphoma (NHL), primary staging, as well as intermediate and late response assessment, is often performed by integrated 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/X-ray computed tomography (PET/CT). The purpose of this analysis was to evaluate if findings in patients with histopathologically proven HL or NHL might correlate with semi-automated density measurements of target lesions (TLs) in the CT component of the integrated PET/CT examination.Procedures: After approval by the institutional review board, 176 lymph nodes (LN) in 90 PET/CT examinations of 90 patients were retrospectively analyzed (HL, 108 TLs out of 55 patients; NHL, 68 TLs out of 35 patients). PET/CT was performed for reasons of primary staging, response evaluation as interim PET, or as final examination after therapy, according to the clinical schedule. Analyses of TLs were performed on the basis of tracer uptake (SUV) 60 min after tracer injection and volumetric CT histogram analysis in non-contrast-enhanced CT.Results: All patients were diagnosed with HL or NHL in a pretreatment biopsy. Prior to therapy induction, staging of all patients was performed using contrast-enhanced CT of the neck to the pelvis, or by [18F]FDG PET/CT. Of the 176 TLs, 119 were classified as malignant, and 57 were benign. Malignant TLs had significantly higher CT density values compared to benign (p < 0.01).Conclusion: Density measurements of TLs in patients with HL and NHL correlate with the dignity of TLs and might therefore serve as a complementary surrogate parameter for the differentiation between malignant and benign TLs. A possible density threshold in clinical routine might be a 20-Hounsfield units (HU) cutoff value to rule out benignancy in TLs that are above the 20-HU threshold. [ABSTRACT FROM AUTHOR]

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Purpose: Four-dimensional (4D) adaptive radiation therapy (ART) treatment planning is an alternative to the conventional margin-based treatment planning approach. In 4D ART, interfraction patient geometric variations, gathered from computed tomography (CT) or cone beam CT (CBCT) images acquired during the patient treatment course, are directly incorporated into the adaptive plan optimization using a probabilistic treatment planning method. The goal of the present planning study was to evaluate the dosimetric differences between 4D ART and conventional margin-based adaptive planning strategies for head and neck cancers. In addition, we examined whether the dose differences achieved with 4D ART would translate into clinically relevant toxicity reductions using the existing normal tissue complication probability (NTCP) models.Methods and Materials: For 18 head and neck cancer patients, the treatment plans were retrospectively generated for 4 different treatment strategies, including a solely image guided radiation therapy (IGRT) strategy (IGRT-only), 2 conventional adaptive treatment planning strategies using 3- and 0-mm planning target volume (PTV) margins, and the 4D ART strategy. In the IGRT-only strategy, a conventional 3-mm PTV margin treatment plan was applied for the entire treatment course. In the 2 conventional adaptive strategies, 2 new treatment plans were generated during the treatment course using diagnostic planning CT scans acquired after the 10th and 22nd fractions. The 4D ART followed the same adaptive schedule, except that the 4D adaptive plan was generated using 5 CBCT images acquired during the 5 most recent treatment fractions. For each strategy, the actual delivered dose for the entire treatment course was constructed by calculating the daily doses on 35 CBCT scans, deforming back to the pretreatment planning CT scan, and accumulating over all 35 fractions. The target coverage was evaluated using the percentage of target volume receiving ≥100% of the prescription dose (V100%) and the minimum dose to 99% of the target volume (D99). It was considered adequate if the V100% was ≥95% and the dose deficit in D99 was ≤2 Gy (with respect to the prescription dose). For each strategy, the dose received by the organs at risk (OARs) was also evaluated, and the corresponding NTCP values were subsequently calculated using 3 NTCP models.Results: Adequate target coverage was achieved for the primary clinical target volume (CTV1) and elective nodal CTV (CTV2) with a 3-mm PTV margin, regardless of adaptation. The 3-mm ART plan reduced the OAR mean dose by 1 to 2 Gy compared with the IGRT-only plan. The 0-mm ART plan further reduced the OAR dose by another 2 to 3 Gy at the expense of target coverage: 3 and 1 patient had V100% <95%, and 6 and 5 patients had a >2 Gy dose deficit in D99 for the CTV1 and CTV2, respectively. Use of 4D ART improved target coverage and attained OAR sparing similar to that with 0-mm ART. The number of patients with V100% <95% and >2 Gy D99 deficit decreased to 0 and 0 for CTV1 and 0 and 2 for CTV2, respectively. The NTCP calculations suggested that 4D ART could benefit a substantial portion of patients compared with IGRT-only because 17 and 12 patients had ≥5% and ≥10% NTCP reductions for parotid toxicity and 18 and 3 patients had ≥5% and ≥10% NTCP reductions for swallowing toxicity, respectively.Conclusions: Compared with margin-based adaptive planning strategies, 4D ART provides a better balance between target coverage and OAR sparing. NTCP estimation predicted for theoretical clinical benefits that warrant further clinical validation. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of single time-point half-body (skull base to thighs) fluorine-18 choline positron emission tomography-computed tomography (PET-CT) compared to a triple-phase acquisition protocol in the detection of prostate carcinoma recurrence.Materials and Methods: Consecutive choline PET-CT studies performed at a single tertiary referral centre in patients with biochemical recurrence of prostate carcinoma between September 2012 and March 2017 were reviewed retrospectively. The indication for the study, imaging protocol used, imaging findings, whether management was influenced by the PET-CT, and subsequent patient outcome were recorded.Results: Ninety-one examinations were performed during the study period; 42 were carried out using a triple-phase protocol (dynamic pelvic imaging for 20 minutes after tracer injection, half-body acquisition at 60 minutes and delayed pelvic scan at 90 minutes) between 2012 and August 2015. Subsequently following interim review of diagnostic performance, a streamlined protocol and appropriate-use criteria were introduced. Forty-nine examinations were carried out using the single-phase protocol between 2015 and 2017. Twenty-nine (69%) of the triple-phase studies were positive for recurrence compared to 38 (78%) of the single-phase studies. Only one patient who had a single-phase study would have benefited from a dynamic acquisition, they have required no further treatment or imaging and are currently under prostate-specific antigen (PSA) surveillance.Conclusion: Choline PET-CT remains a useful tool for the detection of prostate recurrence when used in combination with appropriate-use criteria. Removal of dynamic and delayed acquisition phases reduces study time without adversely affecting accuracy. Benefits include shorter imaging time which improves patient comfort, reduced cost, and improved scanner efficiency. [ABSTRACT FROM AUTHOR]

Introduction: Use of SPECT/CT data is the most accurate method for patient-specific internal dosimetry when isotopes emit single gamma rays. The manual or semi-automatic segmentation of organs is a major obstacle that slows down and limits the patient-specific dosimetry. Using digital phantoms that mimic patient's anatomy can bypass the segmentation step and facilitate the dosimetry process. In this study, the results of a patient-specific dosimetry based on CT data and XCAT phantom, a flexible phantom with predefined organs, are compared. Methods: The dosimetry results (S-value and SAF) were calculated for a patient with breast cancer who received Samarium-153 ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid (153Sm-EDTMP). Biodistribution of activity was obtained from the SPECT scan. The anatomical data and attenuation map were extracted from CT as well as the XCAT phantom with different BMIs. GATE Monte-Carlo simulator was used to calculate the dose to different organs based on the activity distribution and segmented anatomy. Results: The whole body dosimetry results are the same for both calculations based on the CT and XCAT with different BMIs; however for target organs, the differences between SAFs and S-values are high. In the spine, the clinically important target organ for Samarium therapy, the dosimetry results obtained from phantoms with unmatched BMIs between XCAT phantom and CT are substantially different. Conclusion: We showed that atlas-based dosimetry using XCAT phantom even with matched BMI may lead to considerable errors as compared to calculations based on patient's own CT. For accurate dosimetry results, calculations should be done using CT data. [ABSTRACT FROM AUTHOR]

Background and Aim: Pain is a prevalent and serious problem in patients with cancer. This study aimed to investigate the clinical value of the implantation of radioactive particle 125I in treating cancer and its pain.Materials and Methods: From February 2014 to February 2015, 38 patients with malignant tumor received computed tomography (CT)-guided 125I radioactive particle implantation to treat cancer pain in this hospital. Before surgery, the lesions were calculated by brachytherapy treatment planning system (TPS) to get the local number of particles that are required for implantation. For a period after implantation, TPS was used again to assess the effect of treatment. The 38 patients received 6-month follow-up, and the CT scan was used to evaluate the local tumor. The visual analogue scale (VAS) was used to assess the pain.Results: The curative effect was evaluated at postoperative 2, 4, and 6 months, and the curative effect was 34.2%, 73.68%, and 89.47%, respectively. The preoperative VAS score of the 38 patients was 5.48 ± 2.50 (13 cases of mild pain, 19 cases of moderate pain, and 6 cases of severe pain), and their pain was improved in different degrees after operation.Conclusions: CT-guided 125I radioactive particle implantation is a safe and effective treatment for cancer and its pain. [ABSTRACT FROM AUTHOR]

Purpose: Retinoblastoma (Rb) tumor recurrence in the papillary or macular region is a threat to life and visual prognosis respectively, making early detection indispensable. This study demonstrates the value of optical coherence tomography (OCT) in the early detection of subclinical tumor recurrence. Methods: Since June 2012, hand-held SD-OCT (spectral domain Optical Coherence Tomography) of retro-equatorial foci, the optic head nerve and macula, is systematically performed under anesthesia in children treated and followed for Rb. Results: Between June 2012 and January 2017, 16 subclinical recurrent tumors in 14 children were detected only by OCT in flat pigmented scars (n = 9), in type 2 regression (n = 3), on the optic nerve head (n = 3), and as secondary retinal seeding (n = 1). Conclusion: OCT has become invaluable in the modern management of Rb. It allows not only early detection of a lesion before any tumor extension towards the macula or optic nerve head, but also the monitoring of the therapeutic response. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to identify predictive factors on baseline [18F]NaF positron emission tomography (PET)/computed tomography (CT) of early response to radium-223 dichloride after 3 cycles of treatment in metastatic castration-resistant prostate cancer patients.Procedures: Analysis of 152 metastases was performed in six consecutive patients who underwent [18F]NaF PET/CT at baseline and for early monitoring after 3 cycles of radium-223 dichloride. All metastases depicted on whole-body [18F]NaF PET/CT were contoured and CT (density in Hounsfield units, sclerotic, mixed, or lytic appearance) as well as [18F]NaF [maximum standardized uptake value (SUVmax), SUVmean, and lesion volume (V18F-NaF)] patterns were recorded. Tumor response was defined as percentage change in SUVmax and SUVmean between baseline and post-treatment PET. Bone lesions were defined as stable, responsive, or progressive, according to thresholds derived from a recent multicentre test-retest study in [18F]NaF PET/CT. Total [18F]NaF uptake in metastases, defined as MATV × SUVmean, was correlated to uptake of radium-223 on biodistribution scintigraphy performed 7 days after the first cycle of treatment.Results: Among metastases, 116 involved the axial skeleton and 36 the appendicular skeleton. Lesions were sclerotic in 126 cases and mixed in 26 cases. No lytic lesion was depicted. ROC analysis showed that SUVmax and SUVmean were better predictors of lesion response than V18F-NaF and density on CT (P < 0.0001 and P = 0.001, respectively). SUVmax and SUVmean were predictors of individual tumor response in separate multivariate models (P = 0.01 and P = 0.02, respectively). CT pattern (mixed versus sclerotic) and lesion density were independent predictors only when assessing response with delta SUVmax (P = 0.002 and 0.007, respectively). A good correlation between total [18F]NaF uptake within metastases and their relative radium-223 uptake assessed by two observers 7 days after treatment (r = 0.72 and 0.77, P < 0.0001) was found.Conclusions: SUVmax and SUVmean on baseline [18F]NaF PET/CT are independent predictors of bone lesions' response to 3 cycles of radium-223 dichloride, supporting the use of NaF to select patients more likely to respond to treatment. [ABSTRACT FROM AUTHOR]

There have been only a few reports investigating the clinical efficacy of follow-up endoscopy for detection of recurrent gastric cancer after total gastrectomy (TG). We reviewed the records of 747 patients undergoing TG from 2003 to 2012 and enrolled 267 patients (70 with early gastric cancer (EGC) and 197 with advanced gastric cancer (AGC)), who received one or more follow-up endoscopy and contrast abdominal computed tomography (CT) scan. We found no tumor recurrence in the 70 EGC patients during the mean follow-up periods of 42.1 ± 18 and 43.2 ± 19 months by endoscopy and contrast abdominal CT scan. In 197 AGC patients, 59 patients (29.8%) had confirmed tumor recurrence during mean follow-up periods of 40.5 ± 21 and 45.3 ± 22 months. The most common pattern of tumor recurrence was distant metastasis (n = 35) followed by peritoneal metastasis (n = 11). Among the other 13 cases with loco-regional recurrence, seven cases were regional lymph node metastases, four were anastomosis site recurrences, and two were duodenal stump and jejunal loop site recurrences. Three of the four cases of anastomosis site recurrence were found by both endoscopy and contrast abdominal CT scan; one case was missed by contrast abdominal CT scan. However, the two cases with duodenal stump and jejunal loop recurrences were detected by contrast abdominal CT scan only. An annual follow-up endoscopy for gastric cancer after TG might have a limited role in the detection of tumor recurrence, especially in patients with EGC. Contrast abdominal CT scan may be sufficient as a follow-up method for recurrent gastric cancer after TG. [ABSTRACT FROM AUTHOR]

Introduction: CT imaging is the standard examination for renal cystic lesions and defines the Bosniak category, which dictates further management. Given that Bosniak II/IIF/III renal cystic lesions can potentially harbor renal cell carcinoma (RCC), additional diagnostic modalities may be required in management decision making.Aim: To determine the value of additional magnetic resonance imaging in CT-defined Bosniak IIF-III renal cystic lesions.Materials and methods: This a multicenter retrospective study of 46 consecutive patients, diagnosed with cystic renal lesions between 2009 and 2016. The inclusion criteria were: (1) cystic renal lesion classified as Bosniak IIF-III on CT, (2) a subsequent MRI examination, and (3) documented outcome via surgery for cystic renal mass or follow-up.Results: 46 patients (35 males, 11 females) were included. The mean size of the cystic lesion was 3.92 cm (0.7-10 cm). According to the CT findings, Bosniak IIF and III were found in 12 (26.1%) and 34 (73.9%) cases. Reclassification of Bosniak category was done after MRI examination in 31 cases (67.4%). An upgrade rate of 58.7% (27 cases) to a higher category was made, while the downgrade rate to a lower category was achieved in 4 cases (8.7%). As a result, significant therapeutic management change was made in 12/31 patients (38.7%), of whom 8 underwent subsequent surgery.Conclusion: MRI study may reduce the use of Bosniak IIF category (in comparison with CT), which has a direct impact on therapeutic management (surgery vs. surveillance) in a significant proportion of patients. [ABSTRACT FROM AUTHOR]

Uterine leiomyomas are the most common gynecological tumors in premenopausal women. While the lung is the most common extrauterine organ afflicted, benign metastasizing leiomyomas (BML) of the heart are rarities. We report an incidental finding of a cardiac mass in a 36-year-old woman who presented to the Emergency Department after a motor vehicle accident. CT scan of the chest revealed 2 well-circumscribed pulmonary nodules and a filling defect in the right ventricle. Echocardiogram showed a 4 cm mass attached to the right ventricular (RV) septum. The cardiac tumor was resected and showed benign histologic features. Immunohistochemical staining was positive for smooth muscle α-actin and desmin, as well as estrogen and progesterone receptors, consistent with the diagnosis of uterine leiomyoma. [ABSTRACT FROM AUTHOR]

Retroperitoneal extraskeletal osteosarcoma is a rare tumor. Typical imaging findings include a soft tissue mass accompanied with internal calcifications. The authors encountered a case involving a 44-year-old woman with a large retroperitoneal extraskeletal osteosarcoma, without calcification, that mimicked a pancreatic tumor. The present report highlights computed tomography features of retroperitoneal extraskeletal osteosarcoma, followed by a brief literature review. It is challenging for radiologists to diagnose retroperitoneal masses. However, in patients who present with large retroperitoneal masses, combined with clinical information including the elevation of serum alkaline phosphatase levels, retroperitoneal extraskeletal osteosarcoma should be considered in the differential diagnosis, even if the mass does not exhibit a gross calcification on the imaging. [ABSTRACT FROM AUTHOR]

Objectives: To study the ratio between the CT texture of colorectal liver metastases (CRLM) and the surrounding liver parenchyma and assess the potential of various texture measures and ratios as predictive/prognostic imaging markers.Materials: Seventy patients with colorectal cancer and synchronous CRLM were included. All visible metastases, as well as the whole-volume of the surrounding liver, were separately delineated on the portal venous phase primary staging CT. Texture features entropy (E) and uniformity (U) were extracted and ratios between the texture features (T) of the metastases and background liver (Tmetastases/Tliver) calculated. Texture features were compared with clinical outcome parameters: [1] extent of disease (i.e. number of metastases), [2] response to chemotherapy (in 56/70 patients who underwent chemotherapy and CT for response evaluation), and [3] overall survival.Results: The Emetastases/Eliver ratio was lower in patients with limited disease (P = 0.02) and associated with overall survival, albeit not statistically significant when tested in multivariable analyses (HR 1.90; P = 0.07); Umetastases/Uliver was higher in patients with limited disease (P = 0.02). Emetastases showed a trend towards a higher value in patients that responded well to chemotherapy (P = 0.08).Conclusion: The ratio between the texture of liver metastases and the surrounding liver appears to reflect relevant changes in tissue microarchitecture and may be of value to assess the extent of disease and help predict overall survival. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the disease detection rate, diagnostic performance and interobserver agreement of fluciclovine (18F) PET-CT and multiparametric magnetic resonance imaging (mpMR) in recurrent prostate cancer.Methods: Twenty-four patients with biochemical failure after non-prostatectomy definitive therapy, 16/24 of whom had undergone brachytherapy, underwent fluciclovine PET-CT and mpMR with interpretation by expert readers blinded to patient history, PSA and other imaging results. Reference standard was established via a multidisciplinary truth panel utilizing histology and clinical follow-up (22.9 ± 10.5 months) and emphasizing biochemical control. The truth panel was blinded to investigative imaging results. Diagnostic performance and interobserver agreement (kappa) for the prostate and extraprostatic regions were calculated for each of 2 readers for PET-CT (P1 and P2) and 2 different readers for mpMR (M1 and M2).Results: On a whole body basis, the detection rate for fluciclovine PET-CT was 94.7% (both readers), while it ranged from 31.6-36.8% for mpMR. Kappa for fluciclovine PET-CT was 0.90 in the prostate and 1.0 in the extraprostatic regions. For mpMR, kappa was 0.25 and 0.74, respectively. In the prostate, 22/24 patients met the reference standard with 13 malignant and 9 benign results. Sensitivity, specificity and positive predictive value (PPV) were 100.0%, 11.1% and 61.9%, respectively for both PET readers. For mpMR readers, values ranged from 15.4-38.5% for sensitivity, 55.6-77.8% for specificity and 50.0-55.6% for PPV. For extraprostatic disease determination, 18/24 patients met the reference standard. Sensitivity, specificity and PPV were 87.5%, 90.0% and 87.5%, respectively, for fluciclovine PET-CT, while for mpMR, sensitivity ranged from 50 to 75%, specificity 70-80% and PPV 57-75%.Conclusion: The disease detection rate for fluciclovine PET-CT in non-prostatectomy patients with biochemical failure was 94.7% versus 31.6-36.8% for mpMR. For extraprostatic disease detection, fluciclovine PET-CT had overall better diagnostic performance than mpMR. For the treated prostate, fluciclovine PET-CT had high sensitivity though low specificity for disease detection, while mpMR had higher specificity, though low sensitivity. Interobserver agreement was also higher with fluciclovine PET-CT compared with mpMR. [ABSTRACT FROM AUTHOR]

Purpose To study an original 3D visualization of head and neck squamous cell carcinoma extending to the mandible by using [18F]-NaF PET/CT and [18F]-FDG PET/CT imaging along with a new innovative FDG and NaF image analysis using dedicated software. The main interest of the 3D evaluation is to have a better visualization of bone extension in such cancers and that could also avoid unsatisfying surgical treatment later on. Patients and methods A prospective study was carried out from November 2016 to September 2017. Twenty patients with head and neck squamous cell carcinoma extending to the mandible (stage 4 in the UICC classification) underwent [18F]-NaF and [18F]-FDG PET/CT. We compared the delineation of 3D quantification obtained with [18F]-NaF and [18F]-FDG PET/CT. In order to carry out this comparison, a method of visualisation and quantification of PET images was developed. This new approach was based on a process of quantification of radioactive activity within the mandibular bone that objectively defined the significant limits of this activity on PET images and on a 3D visualization. Furthermore, the spatial limits obtained by analysis of the PET/CT 3D images were compared to those obtained by histopathological examination of mandibular resection which confirmed intraosseous extension to the mandible. Results The [18F]-NaF PET/CT imaging confirmed the mandibular extension in 85% of cases and was not shown in [18F]-FDG PET/CT imaging. The [18F]-NaF PET/CT was significantly more accurate than [18F]-FDG PET/CT in 3D assessment of intraosseous extension of head and neck squamous cell carcinoma. This new 3D information shows the importance in the imaging approach of cancers. All cases of mandibular extension suspected on [18F]-NaF PET/CT imaging were confirmed based on histopathological results as a reference. Conclusions The [18F]-NaF PET/CT 3D visualization should be included in the pre-treatment workups of head and neck cancers. With the use of a dedicated software which enables objective delineation of radioactive activity within the bone, it gives a very encouraging results. The [18F]-FDG PET/CT appears insufficient to confirm mandibular extension. This new 3D simulation management is expected to avoid under treatment of patients with intraosseous mandibular extension of head and neck cancers. However, there is also a need for a further study that will compare the interest of PET/CT and PET/MRI in this indication. [ABSTRACT FROM AUTHOR]

Recurrent breast cancer poses considerable diagnostic and therapeutic challenges for clinic. Clinical suspicion of recurrence must be first confirmed by imaging studies. Then re-biopsy of suspected recurrence and metastasis in patients with breast cancer is recommended in the practice guidelines of the National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) to confirm whether the molecular subtype changes. It may change the individual treatment plan directly. Our research provided an integrated algorithm for locally recurrent or distant metastatic breast cancer, including early relapse detection and subsequently a new practical PET/CT imaging guide biopsy approach for surveilling molecular subtype shifts of the recurrent breast cancer. In our results, 18F-FDG PET/CT appears to be more sensitive and accurate than conventional imaging technologies in early detecting locally recurrent or metastatic breast cancer. PET/CT-guided percutaneous FDG-avid target biopsies offers a new integrated precise re-biopsy algorithm for pathologic confirm and surveillance of molecular subtype shifts of the recurrent breast cancer. The precise algorithm for breast cancer recurrence and metastasis can be established in one stop, opening a window of opportunity for breast cancer patients to improve precise individual therapy and prolong survival. [ABSTRACT FROM AUTHOR]

Purpose: HER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment. PET imaging of HER3 expression may permit a more personalized approach to targeted therapy by allowing for detection of HER3-mediated resistance, in addition to informing clinical trial patient selection for novel therapies targeting HER3.Procedures: Phage display selection targeting the HER3 extracellular domain was performed in order to develop a peptide with optimal blood clearance and highly accurate HER3 quantification.Results: The selection converged to a consensus peptide sequence that was subsequently found to bind HER3 with an affinity of 270 ± 151 nM. The peptide, termed HER3P1, was bound with high selectivity to HER3 over other similar receptor tyrosine kinases such as EGFR and HER2. Furthermore, HER3P1 was able to distinguish between high and low HER3-expressing cells in vitro. The peptide was radiolabeled with Ga-68 and demonstrated to specifically bind HER3 by in vivo PET imaging. Uptake of [68Ga]HER3P1 was highly specific for HER3-positive tumors, with tumor-to-background ratios ranging from 1.59-3.32, compared to those of HER3-negative tumors, ranging from 0.84-0.93. The uptake of [68Ga]HER3P1 also demonstrated high (P < 0.001) correlation with protein expression as quantified by Western blot and confirmed by biodistribution.Conclusions: HER3P1 accurately quantifies expression of HER3 by PET imaging and has potential utility as a clinical imaging agent. [ABSTRACT FROM AUTHOR]

Purpose: We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of tumor models.Procedures: Lysates from n = 15 different tumor models originating from n = 6 institutions were tested for TP and thymidylate synthase (TS) expression using western blots. Results were correlated to [18F]FLT accumulation in the tumors as determined by positron emission tomography (PET) measurements in the different institutions and to previously published thymidine concentrations.Results: Expression of TP correlated positively with [18F]FLT SUVmax (ρ = 0.549, P < 0.05). Furthermore, tumors with high TP levels possessed lower levels of thymidine (ρ = - 0.939, P < 0.001).Conclusions: In a broad range of tumors, [18F]FLT uptake as measured by PET is substantially influenced by TP expression and tumor thymidine concentrations. These data strengthen the role of TP as factor confounding [18F]FLT uptake. [ABSTRACT FROM AUTHOR]

Purpose: The identification and targeting of biomarkers specific to prostate cancer (PCa) could improve its detection. Given the high expression of translocator protein (TSPO) in PCa, we investigated the use of [18F]VUIIS1008 (a novel TSPO-targeting radioligand) coupled with positron emission tomography (PET) to identify PCa in mice and to characterize their TSPO uptake.Procedures: Ptenpc-/-, Trp53pc-/- prostate cancer-bearing mice (n = 9, 4-6 months old) were imaged in a 7T MRI scanner for lesion localization. Within 24 h, the mice were imaged using a microPET scanner for 60 min in dynamic mode following a retro-orbital injection of ~ 18 MBq [18F]VUIIS1008. Following imaging, tumors were harvested and stained with a TSPO antibody. Regions of interest (ROIs) were drawn around the tumor and muscle (hind limb) in the PET images. Time-activity curves (TACs) were recorded over the duration of the scan for each ROI. The mean activity concentrations between 40 and 60 min post radiotracer administration between tumor and muscle were compared.Results: Tumor presence was confirmed by visual inspection of the MR images. The uptake of [18F]VUIIS1008 in the tumors was significantly higher (p < 0.05) than that in the muscle, where the percent injected dose per unit volume for tumor was 7.1 ± 1.6 % ID/ml and that of muscle was < 1 % ID/ml. In addition, positive TSPO expression was observed in tumor tissue analysis.Conclusions: The foregoing preliminary data suggest that TSPO may be a useful biomarker of PCa. Therefore, using TSPO-targeting PET ligands, such as [18F]VUIIS1008, may improve PCa detectability and characterization. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to non-invasively evaluate the anticancer activity of a traditional Chinese medicine-Huaier, combined with paclitaxel (PTX) in breast cancer bearing mice by detecting dynamic metabolic changes with positron emission tomography (PET).Procedures: Balb/c nude mice were randomly divided into one of the four groups: Huaier, PTX, PTX + Huaier, or the control. PET imaging with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was performed to monitor the metabolic changes in BT474 (luminal B) and MDA-MB-231 (triple-negative) breast cancer xenografts. Immunohistochemistry (IHC) study was performed immediately after the final PET scan to assess the expressions of phosphatidylinositol 3-kinase (PI3K), phospho-AKT (p-AKT), caspase-3, and vascular endothelial growth factor (VEGF).Results: Compared to the control group, [18F]FDG accumulation demonstrated a significant decrease in PTX + Huaier (p < 0.01) or Huaier group (p < 0.05), which was consistent to the decreased expression of PI3K (p < 0.05) and p-AKT (p < 0.05) in the breast cancer xenografts.Conclusion: The therapeutic effect of Huaier combined with PTX was superior than the PTX alone in BT474 and MDA-MB-231 breast cancer-bearing mice. [18F]FDG PET imaging could be a potential non-invasive approach to assess the metabolic changes after chemotherapy combined with traditional Chinese medicine in the breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1 h.Procedures: In this prospective clinical trial, 20 children and young adults (11-30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5 mg Fe/kg) and [18F]FDG (2-3 MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n = 5) and after (n = 15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher's exact tests.Results: Tailored workflows significantly reduced scan times from 36 to 24 min for head to mid thigh scans (p < 0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4 mSv) compared to PET/CT with diagnostic CT (mean 13.1 mSv; p = 0.003). Using the iron supplement ferumoxytol "off label" as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5 mm (94 vs. 100 %), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100 %) (p = 0.03). [18F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49 %).Conclusion: Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved. [ABSTRACT FROM AUTHOR]

Purpose: To assess the usefulness of an ultrasound (US)-guided peritoneal biopsy for the solitary peritoneal thickening visualized as only infiltrated fat on a computed tomography (CT) scan. Materials and Methods: This retrospective study included 36 patients (16 males, 20 females; mean age, 51.7 years) who underwent a US-guided biopsy for the solitary peritoneal thickening of unknown cause visualized as only infiltrated fat without an apparent mass formation on a CT scan. The rate of the specific histopathological diagnosis and accuracy for the diagnosis of malignant disease was assessed. Results: The procedure was technically successful with the acquisition of an adequate amount of the specimen for microscopic examination from all patients. A specific histopathological diagnosis was made in 31/36 patients (86.1%): peritoneal carcinomatosis in 15/31 (48.4%), tuberculous peritonitis in 15/31 (48.4%) and panniculitis in 1/31 (3.2%). A non-specific histopathological diagnosis was made in 5/36 (13.9%): chronic inflammation in 4/5 (80%) and mesothelial hyperplasia in 1/5 (20%). The procedure showed sensitivity of 83.3%, with a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 85.7%, and an accuracy rate of 86.1% for the diagnosis of malignant diseases. Conclusion: The US-guided peritoneal biopsy is a fairly accurate diagnostic procedure for the peritoneal thickening visualized as only infiltrated fat on a CT scan, and it can be used before performing laparoscopic or an open biopsy. [ABSTRACT FROM AUTHOR]

Despite recent advances in screening methods, lung cancer remains the leading cause of cancer-related deaths worldwide. By the time lung cancer becomes symptomatic and patients seek treatment, it is often too advanced for curative measures. Low-dose computed tomography (CT) screening has been shown to reduce mortality in patients at high risk of lung cancer. We present a 66-year-old man with a 50-pack-year smoking history who had a right upper lobe (RUL) pulmonary nodule and left lower lobe (LLL) consolidation on a screening CT. He reported a weight loss of 45 pounds over 3 months, had recently been hospitalized for hyponatremia, and was notably cachectic. A CT of the chest showed a stable LLL mass-like consolidation and a 9×21 mm subsolid lesion in the RUL. Navigational bronchoscopy biopsy of the RUL lesion revealed squamous non–small cell lung cancer (NSCLC). Endobronchial ultrasound-guided transbronchial needle aspiration of the LLL lesion revealed small cell lung cancer (SCLC). The final diagnosis was a right-sided Stage I NSCLC (squamous) and a left-sided limited SCLC. The RUL NSCLC was treated with stereotactic radiation; the LLL SCLC was treated with concurrent chemotherapy and radiation. In patients with multiple lung nodules, a diagnosis of synchronous multiple primary lung cancers (MPLCs) is crucial, as inadvertent upstaging of patients with MPLC (to T3 and/or T4 tumors) can lead to erroneous staging, inaccurate prognosis, and improper treatment. Recent advances in the diagnosis of small pulmonary nodules via navigational bronchoscopy and management of these lesions dramatically affect a patient’s overall prognosis. [ABSTRACT FROM AUTHOR]

Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are commonly found in gliomas. AGI-5198, a potent and selective inhibitor of the mutant IDH1 enzyme, was radiolabeled with radioiodine and fluorine-18. These radiotracers were evaluated as potential probes for imaging mutant IDH1 expression in tumors with positron emission tomography (PET). Radioiodination of AGI-5198 was achieved using a tin precursor in 79 ± 6% yield (n = 9), and 18 F-labeling was accomplished by the Ugi reaction in a decay-corrected radiochemical yield of 2.6 ± 1.6% (n = 5). The inhibitory potency of the analogous nonradioactive compounds against mutant IDH1 (IDH1-R132H) was determined in enzymatic assays. Cell uptake studies using radiolabeled AGI-5198 analogues revealed somewhat higher uptake in IDH1-mutated cells than that in wild-type IDH1 cells. The radiolabeled compounds displayed favorable tissue distribution characteristics in vivo, and good initial uptake in IDH1-mutated tumor xenografts; however, tumor uptake decreased with time. Radioiodinated AGI-5198 exhibited higher tumor-to-background ratios compared with 18 F-labeled AGI-5198; unfortunately, similar results were observed in wild-type IDH1 tumor xenografts as well, indicating lack of selectivity for mutant IDH1 for this tracer. These results suggest that AGI-5198 analogues are not a promising platform for radiotracer development. Nonetheless, insights gained from this study may help in design and optimization of novel chemical scaffolds for developing radiotracers for imaging the mutant IDH1 enzyme. [ABSTRACT FROM AUTHOR]

Objectives Appropriate clinical staging of malignant pleural mesothelioma (MPM) is critical for correct treatment decisions. Newly revised TNM staging protocol has been released for MPM. We investigated baseline computed tomography (CT) characteristics of MPM patients, the new staging system and a simple tumor size (TS) assessment in terms of survival. Materials and methods As part of our study that included all MPM patients diagnosed in Finland 2000–2012, we retrospectively reviewed 161 CT scans of MPM patients diagnosed between 2007 and 2012 in the Hospital District of Helsinki and Uusimaa. TS was estimated by using the maximal tumor thickness and grading tumor extension along the chest wall. Cox Regression models were used to identify relationships between survival, clinicopathological factors and CT-findings. Results The median length of follow-up was 9.7 months and the median survival 9.1 months. The right sided tumors tended to be more advanced at baseline and had worse prognosis in the univariate analyses. In the multivariate survival model, TS, pleural effusion along with non-epithelioid histology were predictors of poor survival. Tumor size correlated significantly with a sarcomatoid histopathological finding and several parameters linked to a more advanced TNM stage. Most patients were diagnosed with locally advanced stage, while 12 (7%) had no sign of the tumor in CT. Conclusion In this study, we demonstrate a novel approach for MPM tumor size evaluation that has a strong relationship with mortality, sarcomatoid histology and TNM stage groups. TS could be used for prognostic purposes and it may be a useful method for assessing therapy responses. [ABSTRACT FROM AUTHOR]