The International Association for the Study of Lung Cancer proposed changes to the 7th edition of the Tumor, Node, and Metastasis (TNM) staging manual of non-small cell lung cancer (NSCLC) to improve ...the prognostic relevance of its descriptors. These changes include the subdivision of T1 and T2 disease according to size cut points; reassignment of the T and M categories of same-lobe, ipsilateral, and contralateral malignant pulmonary nodules; reassignment of pleural disease to metastatic disease; and introduction of intra- and extrathoracic metastatic disease. Because of movement between T and M descriptors and resultant stage migration, new stage groupings that contain TNM subsets different from those of the previous edition were created. The new staging classification was created on the basis of statistical analysis of a large international database of cases of NSCLC. The new classification has many advantages; however, limitations remain. Problems with routine radiologic staging of NSCLC have not been addressed, the varied survival rates for patients with the different histologic subtypes is not reflected, the new classification is not compatible with the previous system, and application of treatment algorithms on the basis of evidence from the previous edition is less clear.
To investigate the diagnostic value of different whole-body magnetic resonance imaging (WB-MRI) protocols for staging Hodgkin and diffuse-large B-cell lymphomas (HL and DLBCL), twenty-two patients ...(M/F 12/10, median age 32, range 22-87, HL/DLBCL 14/8) underwent baseline WB-MRI and
F-2-fluoro-2-deoxy-D-glucose (
F-FDG) positron emission tomography (PET) fused with computed tomography (CT) scan
F-FDG-PET-CT. The 3.0 T WB-MRI was performed using pre-contrast modified Dixon (mDixon), T2-weighted turbo-spin-echo (TSE), diffusion-weighted-imaging (DWI), dynamic-contrast-enhanced (DCE) liver/spleen, contrast-enhanced (CE) lung MRI and CE whole-body mDixon. WB-MRI scans were divided into: (1) "WB-MRI
": whole-body DWI + in-phase mDixon (2) "WB-MRI
": whole-body T2-TSE (3) "WB-MRI
": whole-body CE mDixon + DCE liver/spleen and CE lung mDixon (4) "WB-MRI All ": the entire protocol. Two radiologists evaluated WB-MRIs at random, independently and then in consensus. Two nuclear-medicine-physicians reviewed
F-FDG PET-CT in consensus. An enhanced-reference-standard (ERS) was derived using all available baseline and follow-up imaging. The sensitivity and specificity of WB-MRI protocols for nodal and extra-nodal staging was derived against the ERS. Agreement between the WB-MRI protocols and the ERS for overall staging was assessed using kappa statistic. For consensus WB-MRI, the sensitivity and specificity for nodal staging were 75%, 98% for WB-MRI
, 76%, 98% for WB-MRI
, 83%, 99% for WB-MRI
and 87%, 100% for WB-MRI
. The sensitivity and specificity for extra-nodal staging were 67% 100% for WB-MRI
, 89%, 100% for WB-MRI
, 89%, 100% for WB-MRI
and 100%, 100% for the WB-MRI
. The consensus WB-MRI
read had perfect agreement with the ERS for overall staging kappa = 1.00 (95% CI: 1.00-1.00). The best diagnostic performance is achieved combining all available WB-MRI sequences.
•Minimal user interaction is needed for a good segmentation of the placenta.•Random forests with high level features improved the segmentation.•Higher accuracy than state-of-the-art interactive ...segmentation methods.•Co-segmentation of multiple volumes outperforms single sparse volume based method.
Segmentation of the placenta from fetal MRI is challenging due to sparse acquisition, inter-slice motion, and the widely varying position and shape of the placenta between pregnant women. We propose a minimally interactive framework that combines multiple volumes acquired in different views to obtain accurate segmentation of the placenta. In the first phase, a minimally interactive slice-by-slice propagation method called Slic-Seg is used to obtain an initial segmentation from a single motion-corrupted sparse volume image. It combines high-level features, online Random Forests and Conditional Random Fields, and only needs user interactions in a single slice. In the second phase, to take advantage of the complementary resolution in multiple volumes acquired in different views, we further propose a probability-based 4D Graph Cuts method to refine the initial segmentations using inter-slice and inter-image consistency. We used our minimally interactive framework to examine the placentas of 16 mid-gestation patients from MRI acquired in axial and sagittal views respectively. The results show the proposed method has 1) a good performance even in cases where sparse scribbles provided by the user lead to poor results with the competitive propagation approaches; 2) a good interactivity with low intra- and inter-operator variability; 3) higher accuracy than state-of-the-art interactive segmentation methods; and 4) an improved accuracy due to the co-segmentation based refinement, which outperforms single volume or intensity-based Graph Cuts.
Objectives
To prospectively investigate concordance between whole-body MRI (WB-MRI) and a composite reference standard for initial staging and interim response evaluation in paediatric and adolescent ...Hodgkin’s lymphoma.
Methods
Fifty patients (32 male, age range 6–19 years) underwent WB-MRI and standard investigations, including
18
F-FDG-PET-CT at diagnosis and following 2–3 chemotherapy cycles. Two radiologists in consensus interpreted WB-MRI using prespecified definitions of disease positivity. A third radiologist reviewed a subset of staging WB-MRIs (
n
= 38) separately to test for interobserver agreement. A multidisciplinary team derived a primary reference standard using all available imaging/clinical investigations. Subsequently, a second multidisciplinary panel rereviewed all imaging with long-term follow-up data to derive an enhanced reference standard. Interobserver agreement for WB-MRI reads was tested using kappa statistics. Concordance for correct classification of all disease sites, true positive rate (TPR), false positive rate (FPR) and kappa for staging/response agreement were calculated for WB-MRI.
Results
There was discordance for full stage in 74% (95% CI 61.9–83.9%) and 44% (32.0–56.6%) of patients against the primary and enhanced reference standards, respectively. Against the enhanced reference standard, the WB-MRI TPR, FPR and kappa were 91%, 1% and 0.93 (0.90–0.96) for nodal disease and 79%, < 1% and 0.86 (0.77–0.95) for extra-nodal disease. WB-MRI response classification was correct in 25/38 evaluable patients (66%), underestimating response in 26% (kappa 0.30, 95% CI 0.04–0.57). There was a good agreement for nodal (kappa 0.78, 95% CI 0.73–0.84) and extra-nodal staging (kappa 0.60, 95% CI 0.41–0.78) between WB-MRI reads
Conclusions
WB-MRI has reasonable accuracy for nodal and extra-nodal staging but is discordant with standard imaging in a substantial minority of patients, and tends to underestimate disease response.
Key Points
• This prospective single-centre study showed discordance for full patient staging of 44% between WB-MRI and a multi-modality reference standard in paediatric and adolescent Hodgkin’s lymphoma
.
• WB-MRI underestimates interim disease response in paediatric and adolescent Hodgkin’s lymphoma
.
• WB-MRI shows promise in paediatric and adolescent Hodgkin’s lymphoma but currently cannot replace conventional staging pathways including
18
F-FDG-PET-CT
.
Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder in which intracellular cystine accumulates. It is caused by mutations in the CTNS gene. Clinical manifestations include ...renal tubular Fanconi syndrome in the first year of life, rickets, hypokalaemia, polyuria, dehydration and acidosis, growth retardation, hypothyroidism, photophobia and renal glomerular deterioration. Late complications include myopathy, pancreatic insufficiency and retinal blindness. Skeletal manifestations described in these patients include failure to thrive, osteomalacia, rickets and short stature. This paper describes progressive bony abnormalities in three unrelated patients with nephropathic cystinosis that have not been reported previously.
To prospectively investigate concordance between whole-body MRI (WB-MRI) and a composite reference standard for initial staging and interim response evaluation in paediatric and adolescent Hodgkin's ...lymphoma.
Fifty patients (32 male, age range 6-19 years) underwent WB-MRI and standard investigations, including
F-FDG-PET-CT at diagnosis and following 2-3 chemotherapy cycles. Two radiologists in consensus interpreted WB-MRI using prespecified definitions of disease positivity. A third radiologist reviewed a subset of staging WB-MRIs (n = 38) separately to test for interobserver agreement. A multidisciplinary team derived a primary reference standard using all available imaging/clinical investigations. Subsequently, a second multidisciplinary panel rereviewed all imaging with long-term follow-up data to derive an enhanced reference standard. Interobserver agreement for WB-MRI reads was tested using kappa statistics. Concordance for correct classification of all disease sites, true positive rate (TPR), false positive rate (FPR) and kappa for staging/response agreement were calculated for WB-MRI.
There was discordance for full stage in 74% (95% CI 61.9-83.9%) and 44% (32.0-56.6%) of patients against the primary and enhanced reference standards, respectively. Against the enhanced reference standard, the WB-MRI TPR, FPR and kappa were 91%, 1% and 0.93 (0.90-0.96) for nodal disease and 79%, < 1% and 0.86 (0.77-0.95) for extra-nodal disease. WB-MRI response classification was correct in 25/38 evaluable patients (66%), underestimating response in 26% (kappa 0.30, 95% CI 0.04-0.57). There was a good agreement for nodal (kappa 0.78, 95% CI 0.73-0.84) and extra-nodal staging (kappa 0.60, 95% CI 0.41-0.78) between WB-MRI reads CONCLUSIONS: WB-MRI has reasonable accuracy for nodal and extra-nodal staging but is discordant with standard imaging in a substantial minority of patients, and tends to underestimate disease response.
• This prospective single-centre study showed discordance for full patient staging of 44% between WB-MRI and a multi-modality reference standard in paediatric and adolescent Hodgkin's lymphoma. • WB-MRI underestimates interim disease response in paediatric and adolescent Hodgkin's lymphoma. • WB-MRI shows promise in paediatric and adolescent Hodgkin's lymphoma but currently cannot replace conventional staging pathways including
F-FDG-PET-CT.
Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder in which intracellular cystine accumulates. It is caused by mutations in the CTNS gene. Clinical manifestations include ...renal tubular Fanconi syndrome in the first year of life, rickets, hypokalaemia, polyuria, dehydration and acidosis, growth retardation, hypothyroidism, photophobia and renal glomerular deterioration. Late complications include myopathy, pancreatic insufficiency and retinal blindness. Skeletal manifestations described in these patients include failure to thrive, osteomalacia, rickets and short stature. This paper describes progressive bony abnormalities in three unrelated patients with nephropathic cystinosis that have not been reported previously.
INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up ...of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt to report was 25.4 days. The highest target priority level was observed in 42 patients (8.1%). Of these, 20 patients received matched targeted treatment with a median progression-free survival of 204 days 95% confidence interval (CI), 99-not applicable, compared with 117 days (95% CI, 106-143;
= 0.011) in all other patients. The respective molecular targets were shown to be predictive for matched treatment response and not prognostic surrogates for improved outcome. Hereditary cancer predisposition syndromes were identified in 7.5% of patients, half of which were newly identified through the study. Integrated molecular analyses resulted in a change or refinement of diagnoses in 8.2% of cases. SIGNIFICANCE: The pediatric precision oncology INFORM registry prospectively tested a target prioritization algorithm in a real-world, multinational setting and identified subgroups of patients benefiting from matched targeted treatment with improved progression-free survival, refinement of diagnosis, and identification of hereditary cancer predisposition syndromes.
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