Detection of mutant free circulating tumor DNA in the plasma of patients with gastrointestinal stromal tumor harboring activating mutations of CKIT or PDGFRA.

PURPOSE: In gastrointestinal stromal tumor (GIST), there is no biomarker available that indicates success or failure of therapy. We hypothesized that tumor-specific v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (CKIT)- or platelet-derived growth factor receptor-α (PDGFRA)-mutant DNA fragments can be detected and quantified in plasma samples of patients with GIST. EXPERIMENTAL DESIGN: We prospectively collected 291 plasma samples from 38 subjects with GIST harboring activating mutations of CKIT or PDGFRA detected in tumor tissue, irrespective of current disease status or treatment. We used allele-specific ligation PCR to detect mutant free circulating DNA (fcDNA). RESULTS: We were able to detect fcDNA harboring the tumor mutation in 15 of 38 patients. Patients with active disease displayed significantly higher amounts of mutant fcDNA compared with patients in complete remission (CR). The amount of mutant fcDNA correlated with disease course. We observed repeated positive test results or an increase of mutant fcDNA in five patients with progressive disease or relapse. A decline of tumor fcDNA or conversion from positive to negative was seen in five patients responding to treatment. A negative to positive conversion was seen in two patients with relapse and one patient with progression. In two cases, we aimed to identify additional mutations and found four additional exchanges, including mutations not known from sequentially conducted tumor biopsies. CONCLUSIONS: Our results indicate that fcDNA harboring tumor-specific mutations in the plasma of patients with GIST can be used as tumor-specific biomarker. The detection of resistance mutations in plasma samples might allow earlier treatment changes and obviates the need for repeated tumor biopsies.

Hepatic angiosarcoma: cross-sectional imaging findings in seven patients with emphasis on dynamic contrast-enhanced and diffusion-weighted MRI.

OBJECTIVE: Primary hepatic angiosarcoma is a very rare and aggressive malignancy of vascular origin. We describe cross-sectional imaging findings of this entity with emphasis on dynamic contrast-enhanced (DCE) and diffusion-weighted (DWI) MR imaging. METHODS: Seven cases of pathologically confirmed hepatic angiosarcoma were retrospectively reviewed (CT and MRI examinations were available in seven and six patients, respectively). Two radiologists evaluated lesion growth patterns, attenuation, signal intensity characteristics, contrast enhancement patterns, and apparent diffusion coefficients (ADCs). RESULTS: Multifocal hepatic disease was present in six patients by means of a mixed pattern of large dominant masses and multiple small nodules; one patient had a solitary large mass. Unenhanced images depicted hemorrhagic areas and a markedly heterogeneous internal architecture within large tumors. Contrast-enhanced early phase images showed variable patterns including patchy peripheral or bizarre shaped intralesional foci of enhancement, peripheral rim enhancement, and small lesions without enhancement. On DCE images, the majority of lesions presented with varying degrees of progressive enhancement. Small nodules frequently displayed homogeneous enhancement on delayed phase images due to complete fill-in. DWI revealed a high interlesional variability of ADC values (range 0.57-2.41 × 10(-3 )mm(2)/s, mean 1.37 × 10(-3 )mm(2)/s). CONCLUSION: Cross-sectional imaging findings of hepatic angiosarcoma reflect the varied histopathological composition of the tumors. Multifocal disease, hemorrhage within large lesions, as well as progressive enhancement on DCE images are typical features of hepatic angiosarcoma. The mean ADC of lesions was found to be slightly elevated in comparison with other hepatic malignancies.

Intra- and inter-observer variability in measurement of target lesions: implication on response evaluation according to RECIST 1.1.

BACKGROUND: The assessment of cancer treatment in oncological clinical trials is usually based on serial measurements of tumours' size according to the Response Evaluation Criteria in Solid Tumours (RECIST) guidelines. The aim of our study was to evaluate the variability of measurements of target lesions by readers as well as the impact on response evaluation, workflow and reporting. PATIENTS AND METHODS: Twenty oncologic patients were included to the study with CT examinations from thorax to pelvis performed at a 64 slices CT scanner. Four readers defined and measured the size of target lesions independently at baseline and follow-up with PACS (Picture Archiving and Communication System) and LMS (Lesion Management Solutions, Median technologies, Valbonne Sophia Antipolis, France), according to the RECIST 1.1 criteria. Variability in measurements using PACS or LMS software was established with the Bland and Altman approach. The inter- and intra-observer variabilities were calculated for identical lesions and the overall response per case was determined. In addition, time required for evaluation and reporting in each case was recorded. RESULTS: For single lesions, the median intra-observer variability ranged from 4.9-9.6% (mean 5.9%) and the median inter-observer variability from 4.3-11.4% (mean 7.1%), respecting different evaluation time points, image systems and observers. Nevertheless, the variability in change of Δ sum longest diameter (LD), mandatory for classification of the overall response, was 24%. The overall response evaluation assessed by a single respectively different observer was discrepant in 6.3% respectively 12% of the cases compared with the mean results of multiple observers. The mean case evaluation time was 286s vs. 228s at baseline and 267s vs. 196s at follow-up for PACS and LMS, respectively. CONCLUSIONS: Uni-dimensional measurements of target lesions show low intra- and inter-observer variabilities, but the high variability in change of Δ sum LD shows the potential for misclassification of the overall response according to the RECIST 1.1 guidelines. Nevertheless, the reproducibility of RECIST reporting can be improved for the case assessment by a single observer and by mean results of multiple observers. Case-based evaluation time was shortened up to 27% using custom software.

Detection, classification, and characterization of focal liver lesions: Value of diffusion-weighted MR imaging, gadoxetic acid-enhanced MR imaging and the combination of both methods.

AIM: To evaluate diffusion-weighted MR imaging (DWI), gadoxetic acid-enhanced MR imaging and the combination of both methods in the detection, classification, and characterization of focal liver lesions (FLL). METHODS: A total of 119 FLL (28 HCCs, 39 metastases, 15 FNHs, 11 adenomas, 13 hemangiomas, 13 cysts) were retrospectively analyzed in 36 patients. In those patients MR imaging of the liver comprising respiratory-triggered DWI (b values of 50, 300, and 600 s/mm(2)) and gadoxetic acid-enhanced MR imaging including image acquisition in the hepatocyte-selective phase (20 min post injection) had been performed. Three image sets were assigned and compared: DWI only (set A), gadoxetic acid-enhanced MR imaging only (set B), and both modalities in combination (set C). Two readers independently interpreted the images in random order. For each reader and image set, the area under the receiver operating characteristic curve (Az) and sensitivity in the detection of FLL was determined as well as the accuracy in the classification and characterization of FLL. RESULTS: There was no significant difference between the three image sets in the detection of FLL with regards to Az. However, when only lesions with a diameter of 10 mm or less were analyzed, the Az values of set C were significantly higher than those of sets A and B for both readers. For classifying and characterizing FLL both set B and C were significantly superior to set A. CONCLUSION: Adding DWI to gadoxetic acid-enhanced MR imaging significantly increases the accuracy in the detection of small FLL.

Hepatic epithelioid hemangioendothelioma: findings at CT and MRI including preliminary observations at diffusion-weighted echo-planar imaging.

OBJECTIVE: Hepatic epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with low- to intermediate-grade malignant potential. We describe cross-sectional imaging findings of pathologically confirmed EHE including preliminary observations on lesion characteristics and apparent diffusion coefficients (ADCs) at diffusion-weighted MR imaging (DWI). METHODS: CT and MRI examinations in five patients were retrospectively reviewed. Two radiologists evaluated lesion growth patterns, attenuation, signal intensity characteristics, and contrast enhancement patterns. Additionally, DWI features on low and high b-value images as well as ADCs were assessed in three patients. RESULTS: Imaging features of EHE included multifocal hepatic disease (n = 5), predominantly subcapsular location (n = 5), coalescence of nodules (n = 5), capsular retraction (n = 3), and intralesional calcifications (n = 3). Contrast-enhanced CT and MR images showed variable degrees of peripheral rim enhancement. T2-weighted MR images, low b-value DWI and ADC maps frequently depicted a "target-sign" appearance of tumor nodules. A markedly hyperintense central area corresponding to hypocellular stroma was surrounded by a moderately hyperintense outer rim reflecting hypercellular tumor regions. The mean ADC of lesions was 1.86 × 10(-3) mm(2)/s. CONCLUSION: Cross-sectional imaging displayed typical features of EHE. The mean ADC value of lesions was found to be relatively high in comparison with other hepatic malignancies, which may be helpful in suggesting the diagnosis.

Inter- and intraobserver variability of MR arthrography in the detection and classification of superior labral anterior posterior (SLAP) lesions: evaluation in 78 cases with arthroscopic correlation.

PURPOSE: The purpose of this study was to determine inter- and intraobserver variability of MR arthrography of the shoulder in the detection and classification of superior labral anterior posterior (SLAP) lesions. METHODS: MR arthrograms of 78 patients who underwent MR arthrography before arthroscopy were retrospectively analysed by three blinded readers for the presence and type of SLAP lesions. MR arthrograms were reviewed twice by each reader with a time interval of 4 months between the two readings. Inter- and intraobserver agreement for detection and classification of SLAP lesions were calculated using kappa coefficients. RESULTS: Arthroscopy confirmed 48 SLAP lesions: type I (n = 4), type II (n = 37), type III (n = 3), type IV (n = 4). Sensitivity and specificity for detecting SLAP lesions with MR arthrography for each reader were 88.6%/93.3%, 90.9%/80.0% and 86.4%/76.7%. MR arthrographic and arthroscopic grading were concurrent for 72.7%, 68.2% and 70.5% of SLAP lesions for readers 1-3, respectively. Interobserver agreement was excellent (kappa = 0.82) for detection and substantial (kappa = 0.63) for classification of SLAP lesions. For each reader intraobserver agreement was excellent for detection (kappa = 0.93, kappa = 0.97, kappa = 0.97) and classification (kappa = 0.94, kappa = 0.84, kappa = 0.93) of SLAP lesions. CONCLUSION: MR arthrography allows reliable and accurate detection of SLAP lesions. In addition, SLAP lesions can be diagnosed and classified with substantial to excellent inter- and intraobserver agreement.

Characterization of small (≤10 mm) focal liver lesions: value of respiratory-triggered echo-planar diffusion-weighted MR imaging.

PURPOSE: To evaluate respiratory-triggered diffusion-weighted MR imaging (DWI) in the characterization of small (≤10 mm) focal liver lesions (FLL). MATERIALS AND METHODS: A total of 185 FLL (76 metastases, 11 HCCs, 71 cysts, 18 hemangiomas, 6 focal nodular hyperplasias, 3 adenomas) were retrospectively analyzed in 77 patients. DWI was performed at 1.5 T using a respiratory-triggered single-shot echo-planar imaging (SSEPI) sequence (b values: 50, 300, 600 s/mm(2)). Diffusion-weighted images were evaluated by two independent observers and apparent diffusion coefficient (ADC) values were determined. Reference standard of diagnosis was obtained by two other radiologists correlating DWI with histopathologic findings, standard MR sequences and imaging follow-up. Receiver operating characteristic curve analysis was performed to evaluate the utility of ADC values for the diagnosis of malignancy. RESULTS: Accuracy for characterizing FLL was 93.0% for reader 1 and 91.9% for reader 2. Interobserver agreement was excellent between both readers (κ=0.88). Sensitivity and specificity for diagnosing malignancy were 90.8% and 89.9% using a threshold ADC of 1.41×10(-3) mm(2)/s. CONCLUSION: DWI using the respiratory-triggered SSEPI sequence can help to characterize FLL, even when the diameter of lesions is 10mm or less.

Hepatic metastases: use of diffusion-weighted echo-planar imaging.

Diffusion-weighted MR imaging is increasingly applied to detect and characterize focal hepatic lesions. In this update article, technical aspects regarding diffusion-weighted echo-planar imaging (DW-EPI) of the liver will be addressed, and concepts for image interpretation will be provided. The value of DW-EPI for the detection of hepatic metastases is illustrated on the basis of a review of the literature and our personal experience. In this respect, special emphasis is given to the comparison of DW-EPI with well-established MR imaging techniques such as T2-weighted and contrast-enhanced MR imaging, and advantages and limitations of DW-EPI will be described. Based on the review, it is concluded that DW-EPI is more sensitive than T2-weighted MR imaging and at least as accurate as superparamagnetic iron oxide-enhanced or gadolinium-enhanced MR imaging for the detection of hepatic metastases. Although difficulties occasionally arise in further characterizing small lesions detected with DW-EPI, substantial improvements in the preoperative evaluation of liver metastases in candidates for hepatic resection may be expected.

Diagnosis of hepatic metastasis: comparison of respiration-triggered diffusion-weighted echo-planar MRI and five t2-weighted turbo spin-echo sequences.

OBJECTIVE: The purpose of this study was to compare the value of respiration-triggered diffusion-weighted (DW) single-shot echo-planar MRI (EPI) and five variants of T2-weighted turbo spin-echo (TSE) sequences in the diagnosis of hepatic metastasis. MATERIALS AND METHODS: Fifty-two patients with extrahepatic primary malignant tumors underwent 1.5-T MRI that included DW EPI and the following variants of T2-weighted TSE techniques: breath-hold fat-suppressed HASTE, breath-hold fat-supressed TSE, respiration-triggered fat-suppressed TSE, breath-hold STIR, and respiration-triggered STIR. Images were reviewed independently by two blinded observers who used a 5-point confidence scale to identify lesions. Results were correlated with surgical and histopathologic findings and follow-up imaging findings. The accuracy of each technique was measured with free-response receiver operating characteristic analysis. RESULTS: A total of 118 hepatic metastatic lesions (mean diameter, 12.8 mm; range, 3-84 mm) were evaluated. Accuracy values were higher (p < 0.001) with DW EPI (0.91-0.92) than with the T2-weighted TSE techniques (0.47-0.67). Imaging with the HASTE sequence (0.47-0.52) was less accurate (p < 0.05) than imaging with the breath-hold TSE, breath-hold STIR, respiration-triggered TSE, and respiration-triggered STIR sequences (0.59-0.67). Sensitivity was higher (p < 0.001) with DW EPI (0.88-0.91) than with T2-weighted TSE techniques (0.45-0.62). For small (< or = 10 mm) metastatic lesions only, the differences in sensitivity between DW EPI (0.85) and T2-weighted TSE techniques (0.26-0.44) were even more pronounced. CONCLUSION: DW EPI was more sensitive and more accurate than imaging with T2-weighted TSE techniques. Because of the black-blood effect on vessels and low susceptibility to motion artifacts, DW EPI was particularly useful for the detection of small (< or = 10 mm) metastatic lesions.

Characterization of focal liver lesions by ADC measurements using a respiratory triggered diffusion-weighted single-shot echo-planar MR imaging technique.

The aim of this study was to determine apparent diffusion coefficients (ADCs) of focal liver lesions on the basis of a respiratory triggered diffusion-weighted single-shot echo-planar MR imaging sequence (DW-SS-EPI) and to evaluate whether ADC measurements can be used to characterize lesions. One hundred and two patients with focal liver lesions [11 hepatocellular carcinomas (HCC), 82 metastases, 4 focal nodular hyperplasias (FNH), 56 hemangiomas and 51 cysts; mean size, 16.6 mm; range 5-92 mm] were examined on a 1.5-T system using respiratory triggered DW-SS-EPI (b-values: 50, 300, 600 s/mm2). Results were correlated with histopathologic data and follow-up imaging. The ADCs of different lesion types were compared, and lesion discrimination using optimal thresholds for ADCs was evaluated. Mean ADCs (x10(-3)mm2/s) were 1.24 and 1.04 for normal and cirrhotic liver parenchyma and 1.05, 1.22, 1.40, 1.92 and 3.02 for HCCs, metastases, FNHs, hemangiomas and cysts, respectively. Mean ADCs differed significantly for all lesion types except for comparison of metastases with HCCs and FNHs. Overall, 88% of lesions were correctly classified as benign or malignant using a threshold value of 1.63 x 10(-3)mm2/s. Measurements of the ADCs of focal liver lesions on the basis of a respiratory triggered DW-SS-EPI sequence may constitute a useful supplementary method for lesion characterization.

MRI of the lung: value of different turbo spin-echo, single-shot turbo spin-echo, and 3D gradient-echo pulse sequences for the detection of pulmonary metastases.

PURPOSE: To compare the value of different MRI sequences of the lung for the detection of pulmonary metastases. MATERIALS AND METHODS: A total of 28 patients with 225 pulmonary metastases confirmed at multidetector-row computed tomography (MDCT) underwent MRI of the lung, including breathhold T2-weighted single-shot turbo spin-echo (half-Fourier single-shot turbo spin-echo [HASTE] and inversion recovery [IR]-HASTE) and conventional turbo spin-echo (TSE and short-tau inversion recovery [STIR]) sequences, a respiratory- and pulse-triggered black-blood STIR sequence (triggered STIR), and breathhold pre- and postcontrast volumetric interpolated 3D gradient-echo (VIBE) sequences. MR images were reviewed by three independent observers and results were correlated with MDCT, which served as standard of reference. Lesion-to-lung contrast-to-noise ratios (CNRs) and image artifacts were also assessed. RESULTS: CNRs were highest on TSE images (P < 0.001). Mean sensitivities for lesion detection with triggered STIR, TSE, and STIR were 72.0%, 69.0%, and 63.4%, respectively. With HASTE, IR-HASTE, and pre- and postcontrast VIBE, significantly lower sensitivities were obtained (P < 0.05), although artifacts due to physiological motion were less distinct with these sequences compared to TSE and STIR (P < 0.05). CONCLUSION: Conventional TSE sequences are more sensitive in depicting pulmonary metastases than single-shot TSE or 3D gradient-echo sequences. Respiratory and pulse triggering can improve lesion detection, but increases acquisition time substantially.

Multifocal epithelioid hemangioendothelioma of the phalanges of the hand.

Epithelioid hemangioendothelioma (EH) of bone is a rare vascular neoplasm characterized by epithelioid endothelial cells and a variable biologic behaviour. The principal sites of occurrence of this osteolytic tumor are the lower extremity and the axial skeleton. Approximately half of the cases present with multifocal disease. The latter feature can be helpful in suggesting the diagnosis of a vascular tumor; on the other hand, it strengthens the need for a skeletal survey or whole-body MRI/CT. We report on the clinical, histologic and radiologic features-including CT and MRI findings-of EH in a case of multifocal disease of the phalanges of the hand, a very uncommon anatomic site of affliction.

Variants of the superior labrum and labro-bicipital complex: a comparative study of shoulder specimens using MR arthrography, multi-slice CT arthrography and anatomical dissection.

The purpose of the present study was to evaluate the anatomical variability of the superior labrum and to compare the value of MR arthrography and multi-slice CT arthrography in the diagnosis of variants of the labro-bicipital complex. Forty-three human shoulder specimens (age range and mean age at death, 61-89 years and 78.3 years) were examined with the use of MR arthrography and multi-slice CT arthrography prior to joint exploration and macroscopic inspection of the superior labrum and labro-bicipital complex. Two radiologists evaluated MR and CT arthrograms, and the results were compared with macroscopic assessments. Anatomical dissection of all shoulder specimens revealed a sublabral recess in 32/43 (74%) cases. The attachment of the superior labrum was categorised as type 1 in ten (23%) cases, as type 2 in eight (19%), as type 3 in ten (23%), and as type 4 in 14 (33%) cases. One superior labrum showed detachment consistent with a superior labral anteroposterior (SLAP) type 3 lesion. On MR arthrography and CT arthrography the attachment of the superior labrum was categorised in concordance with macroscopic assessments in 79% and 84% of cases, respectively. The anteroposterior extension of sublabral recesses was accurately determined with MR and CT arthrography in 59% and 81% of cases, respectively. The attachment of the superior labrum shows considerable variability. Thus, exact depiction of variants is essential in order to avoid the false positive diagnosis of a superior labral tear (SLAP or Andrews lesion). Both, MR arthrography and multi-slice CT arthrography were effective in the detection and classification of sublabral recesses.

Anterior shoulder instability: accuracy of MR arthrography in the classification of anteroinferior labroligamentous injuries.

PURPOSE: To retrospectively evaluate the accuracy of magnetic resonance (MR) arthrography in the classification of anteroinferior labroligamentous injuries by using arthroscopy as the reference standard. MATERIALS AND METHODS: Ethical committee approval and informed consent were obtained. MR arthrograms obtained in 205 patients, including a study group of 104 patients (74 male and 30 female; mean age, 28.2 years) with arthroscopically proved labroligamentous injuries and a control group of 101 patients (65 male and 36 female; mean age, 31.4 years) with intact labroligamentous complex, were reviewed in random order. MR arthrograms were analyzed for the presence and type (Bankart, anterior labral periosteal sleeve avulsion [ALPSA], Perthes, glenolabral articular disruption [GLAD], or nonclassifiable lesion) of labroligamentous injuries by two radiologists in consensus. Results were compared with arthroscopic findings. Sensitivity, specificity, accuracy, and corresponding 95% confidence intervals for the detection and classification of anteroinferior labroligamentous lesions with MR arthrography were calculated. RESULTS: At arthroscopy, 104 anteroinferior labroligamentous lesions were diagnosed, including 44 Bankart lesions, 22 ALPSA lesions, 12 Perthes lesions, and three GLAD lesions. Twenty-three labral lesions were nonclassifiable at arthroscopy, all of which occurred after a history of chronic instability. Nineteen (83%) of these 23 lesions were also nonclassifiable at MR arthrography. With arthroscopy used as the reference standard, labroligamentous lesions were detected and correctly classified at MR arthrography with sensitivities of 88% and 77%, specificities of 91% and 91%, and accuracies of 89% and 84%, respectively. Bankart, ALPSA, and Perthes lesions were correctly classified in 80%, 77%, and 50% of cases, respectively. The three GLAD lesions were all correctly assessed. CONCLUSION: MR arthrography is accurate in enabling classification of acute and chronic anteroinferior labroligamentous injuries, although correct interpretation of Perthes lesions remains difficult.