Prevalence of preexisting articular bone pathology in patients with osteoarthritis screened for fasinumab clinical trials identified by X-ray or magnetic resonance imaging.

OBJECTIVE: To examine the prevalence of preexisting articular bone pathology in patients with hip or knee pain due to osteoarthritis (OA) screened for fasinumab clinical trials. METHOD: This post-hoc analysis included patients with OA screened for three phase 3 fasinumab studies (NCT02683239, NCT03161093, NCT03304379). During screening, participants who met other clinical inclusion/exclusion criteria underwent radiography of knees, hips, and shoulders. Those with Kellgren-Lawrence grade (KLG) ≥ 2 for index joint and without an exclusionary finding proceeded to magnetic resonance imaging (MRI) of index, contralateral, and KLG ≥ 3 joints. Exclusionary findings included bone fragmentation/collapse, bone loss/resorption, osteonecrosis, and fracture, by either X-ray or MRI. Participants with extensive subchondral cysts were also excluded. Prevalence of abnormalities on radiographs and MRIs are reported. RESULTS: Of 27,633 participants screened, 21,997 proceeded to imaging. Of these, 1203 (5.5%) were excluded due to the presence of ≥ 1 joint with severe articular bone pathology (X-ray or MRI): bone fragmentation/collapse (2.60%), subchondral insufficiency fracture (SIF; 1.67%), osteonecrosis (1.11%), and significant bone loss (0.32%). Additionally, 3.13% screen-failed due to extensive subchondral cysts. More than half of the exclusions due to bone fragmentation/collapse (386/572), osteonecrosis (141/245) and significant bone loss (59/71), and approximately one third of SIF (133/367) and extensive subchondral cysts (229/689) were evident on X-rays. CONCLUSIONS: Approximately one in 20 participants with OA who met the clinical screening criteria for fasinumab phase 3 trials were later excluded due to preexisting severe articular bone pathology findings by X-ray or MRI.

Comparison of central and local serial CT assessments of metastatic renal cell carcinoma patients in a clinical phase IIB study.

Background Clinical oncological studies attempt to improve precision of data by central radiological assessments. However, it is unclear, to which extent local and central assessments diverge. Purpose To quantify inter-reader variability and the deviation of local from central radiological assessments of computed tomography (CT) scans. Material and Methods This was a sub-study of a randomized clinical phase IIb trial in metastatic renal cell carcinoma (RCC), comparing first-line sorafenib with interferon-alpha-2a (IFN-α-2a). It analyzed agreements of local with central RECIST CT assessments by Cohen's kappa (κ), symmetry tests, deviations in waterfall plots, Bland-Altman plots, and parametric survival analyses. Results The concordance between local and central radiologic review was quantified by κ = 0.53. While local assessment yielded progressive disease (PD) in 18.6%, central assessment classified 22.5% of patient time points as PD exhibiting only a partial overlap with the 18.6% The tumor shrinkage rates in waterfall plots were 68.1% in local and 55.8% in central review (57.8% and 59% by Reader 1 and Reader 2). Bland-Altman plots identified a systematic shift of tumor change rates by -7.5% in local compared to central assessments, that may reflect a systematic tendency of more favorable results in local assessments. The discordance between local and central review was reflected by a time to progression (TTP) hazard ratio (HR) of 1.73 ( P = 0.0003). Conclusion These data suggest that central radiologic review may reduce technical measurement variability in clinical trials, which should be scrutinized in future studies compared to a volumetric reference.

Comparison of volumetric and linear serial CT assessments of lung metastases in renal cell carcinoma patients in a clinical phase IIB study.

RATIONALE AND OBJECTIVES: Accuracy of radiologic assessment may have a crucial impact on clinical studies and therapeutic decisions. We compared the variability of a central radiologic assessment (RECIST) and computer-aided volume-based assessment of lung lesions in patients with metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: The investigation was prospectively planned as a substudy of a clinical randomized phase IIB therapeutic trial in patients with RCC. Starting with the manual study diameter (SDM) of the central readers using RECIST in the clinical study, we performed computer-aided volume measurements. We compared SDM to an automated RECIST diameter (aRDM) and the diameter of a volume-equivalent sphere (effective diameter [EDM]), both for the individual size measurements and for the change rate (CR) between consecutive time points. One hundred thirty diameter pairs of 30 lung lesions from 14 patients were evaluable, forming 55 change pairs over two consecutive time points each. RESULTS: The SDMs of two different readers showed a correlation of 95.6%, whereas the EDMs exhibited an excellent correlation of 99.4%. Evaluation of CRs showed an SDM-CR correlation of 63.9%, which is substantially weaker than the EDM-CR correlation of 87.6%. The variability of SDM-CR is characterized by a median absolute difference of 11.4% points versus the significantly lower 1.8% points EDM-CRs variability (aRDM: 3.2% points). The limits of agreement between readers suggest that an EDM change of 10% or 1 mm can already be significant. CONCLUSIONS: Computer-aided volume-based assessments result in markedly reduced variability of parameters describing size and change, which may offer an advantage of earlier response evaluations and treatment decisions for patients.

Gastroenteropancreatic neuroendocrine tumors: multimodality imaging features with pathological correlation.

Neuroendocrine tumors of the gastrointestinal tract are rare entities. Functioning neuroendocrine tumors tend to present early because of hormone-induced clinical symptoms, but detection of the primary lesion may be difficult owing to their small size. Neuroendocrine tumors are typically hypervascular and show enhancement after contrast administration on computed tomography (CT) or magnetic resonance imaging (MRI). Large nonfunctioning tumors may be found in asymptomatic patients. In such cases, the synchronous presence of hypervascular hepatic metastases should be explored. This pictorial review illustrates imaging features of functioning and nonfunctioning neuroendocrine tumors arising in the gastrointestinal tract and the pancreas. Modalities included are CT, MRI, ultrasonography, and nuclear medicine. Characteristic histological specimens of these lesions are presented.

MRI features of cystic lesions around the knee.

Cystic lesions around the knee are a diverse group of entities, frequently encountered during routine MRI of the knee. These lesions range from benign cysts to complications of underlying diseases such as infection, arthritis, and malignancy. MRI is the technique of choice in characterizing lesions around the knee: to confirm the cystic nature of the lesion, to evaluate the anatomical relationship to the joint and surrounding tissues, and to identify associated intra-articular disorders. We will discuss the etiology, clinical presentation, MRI findings, and differential diagnosis of various cystic lesions around the knee including meniscal and popliteal (Baker's) cysts, intra-articular and extra-articular ganglia, intra-osseous cysts at the insertion of the cruciate ligaments and meniscotibial attachments, proximal tibiofibular joint cysts, degenerative cystic lesions (subchondral cyst), cystic lesions arising from the bursae (pes anserine, prepatellar, superficial and deep infrapatellar, iliotibial, tibial collateral ligament, and suprapatellar), and lesions that may mimic cysts around the knee including normal anatomical recesses. Clinicians must be aware about the MRI features and the differential diagnosis of cystic lesions around the knee to avoid misdiagnosis.

Multispectral analysis of bone lesions in the hands of patients with rheumatoid arthritis.

Quantitative measures of rheumatoid arthritis (RA) disease progression can provide valuable tools for evaluation of new treatments during clinical trials. In this study, a novel multispectral (MS) MRI analysis method is presented to quantify changes in bone lesion volume (DeltaBLV) in the hands of RA patients. Image registration and MS analysis were employed to identify MS tissue class transitions between two serial MRI exams. DeltaBLV was determined from MS class transitions between two time points. The following three classifiers were investigated: (a) multivariate Gaussian (MVG), (b) k-nearest neighbor (k-NN), and (c) K-means (KM). Unlike supervised classifiers (MVG, k-NN), KM, an unsupervised classifier, does not require labeled training data, resulting in potentially greater clinical utility. All MS estimates of DeltaBLV were linearly correlated (r(p)) with manual estimates. KM and k-NN estimates also exhibited a significant rank-order correlation (r(s)) with manual estimates. For KM, r(p) = 0.94 p < 0.0001, r(s) = 0.76 p = 0.002; for k-NN, r(p) = 0.86 p = 0.0001, r(s) = 0.69 p = 0.009; and for MVG, r(p) = 0.84 p = 0.0003, r(s) = 0.49 p = 0.09. Temporal classification rates were as follows: for KM, 90.1%; for MVG, 89.5%; and for k-NN, 86.7%. KM matched the performance of k-NN, offering strong potential for use in multicenter clinical trials. This study demonstrates that MS tissue class transitions provide a quantitative measure of DeltaBLV.

MR findings in knee osteoarthritis.

Knee osteoarthritis (OA) is a leading cause of disability. Recent advances in drug discovery techniques and improvements in understanding the pathophysiology of osteoarthritic disorders have resulted in an unprecedented number of new therapeutic agents. Of all imaging modalities, radiography has been the most widely used for the diagnosis and management of the progression of knee OA. Magnetic resonance imaging is a relatively recent technique and its applications to osteoarthritis have been limited. Compared with conventional radiography, MR imaging offers unparalleled discrimination among articular soft tissues by directly visualizing all components of the knee joint simultaneously and therefore allowing the knee joint to be evaluated as a whole organ. In this article we present the MR findings in knee OA including cartilage abnormalities, osteophytes, bone edema, subarticular cysts, bone attrition, meniscal tears, ligament abnormalities, synovial thickening, joint effusion, intra-articular loose bodies, and periarticular cysts.