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About 5% of children with retinoblastoma from germline mutation of the RB1 gene are at risk of developing trilateral retinoblastoma—intraocular retinoblastoma combined with a histologically similar brain tumour, most commonly in the pineal gland. We aimed to provide a systematic overview of published data for trilateral retinoblastoma, and to analyse how survival has changed. We searched Medline and Embase for scientific literature published between Jan 1, 1966, and April 14, 2014, that assessed trilateral retinoblastoma cases. We undertook a meta-analysis of survival with the Kaplan-Meier method and Cox proportional hazards regression, stratified on the basis of the original study, to account for between-study heterogeneity. We included 90 studies, with 174 patients with trilateral retinoblastoma. 5-year survival after pineal trilateral retinoblastoma increased from 6% (95% CI 2–15) in patients diagnosed before 1995, to 44% (26–61; p<0·0001) in those diagnosed from 1995 onwards. Before 1995, no patients with non-pineal trilateral retinoblastoma survived, but from 1995 onwards, 5-year survival was 57% (30–77; p=0·035). Hazard ratios (HR) adjusted for the presence of leptomeningeal metastases and trilateral retinoblastoma location, suggested that both conventional (HR 0·059, 95% CI 0·016–0·226; p<0·0001) and high-dose chemotherapy with stem-cell rescue (0·013, 0·002–0·064; p<0·0001) most strongly contributed to this improvement. Absence of leptomeningeal metastases (HR 2·13, 95% CI 0·98–4·60; p=0·055) were associated with improved survival. Non-pineal trilateral retinoblastomas were larger than pineal tumours (median 30 mm [range 6–100] vs 22 mm [7–60]; p=0·012), but both had similar outcomes since 1995. Our results suggest that improvements in overall survival are attributable to improved chemotherapy regimens and early detection of pineal trilateral retinoblastoma. As such, successful treatment of trilateral retinoblastoma should include screening at least at the time of retinoblastoma diagnosis and chemotherapy, which would preferably be a high-dose regimen with autologous stem-cell rescue. None.

In retinoblastoma, accurate segmentation of ocular structure and tumor tissue is important when working towards personalized treatment. This retrospective study serves to evaluate the performance of multi-view convolutional neural networks (MV-CNNs) for automated eye and tumor segmentation on MRI in retinoblastoma patients. Forty retinoblastoma and 20 healthy-eyes from 30 patients were included in a train/test (N = 29 retinoblastoma-, 17 healthy-eyes) and independent validation (N = 11 retinoblastoma-, 3 healthy-eyes) set. Imaging was done using 3.0 T Fast Imaging Employing Steady-state Acquisition (FIESTA), T2-weighted and contrast-enhanced T1-weighted sequences. Sclera, vitreous humour, lens, retinal detachment and tumor were manually delineated on FIESTA images to serve as a reference standard. Volumetric and spatial performance were assessed by calculating intra-class correlation (ICC) and dice similarity coefficient (DSC). Additionally, the effects of multi-scale, sequences and data augmentation were explored. Optimal performance was obtained by using a three-level pyramid MV-CNN with FIESTA, T2 and T1c sequences and data augmentation. Eye and tumor volumetric ICC were 0.997 and 0.996, respectively. Median [Interquartile range] DSC for eye, sclera, vitreous, lens, retinal detachment and tumor were 0.965 [0.950–0.975], 0.847 [0.782–0.893], 0.975 [0.930–0.986], 0.909 [0.847–0.951], 0.828 [0.458–0.962] and 0.914 [0.852–0.958], respectively. MV-CNN can be used to obtain accurate ocular structure and tumor segmentations in retinoblastoma.

While RB1 loss initiates retinoblastoma development, additional somatic copy number alterations (SCNAs) can drive tumor progression. Although SCNAs have been identified with good concordance between studies at a cytoband resolution, accurate identification of single genes for all recurrent SCNAs is still challenging. This study presents a comprehensive meta-analysis of genome-wide SCNAs integrated with gene expression profiling data, narrowing down the list of plausible retinoblastoma driver genes. We performed SCNA profiling of 45 primary retinoblastoma samples and eight retinoblastoma cell lines by high-resolution microarrays. We combined our data with genomic, clinical and histopathological data of ten published genome-wide SCNA studies, which strongly enhanced the power of our analyses (N = 310). Comprehensive recurrence analysis of SCNAs in all studies integrated with gene expression data allowed us to reduce candidate gene lists for 1q, 2p, 6p, 7q and 13q to a limited gene set. Besides the well-established driver genes RB1 (13q-loss) and MYCN (2p-gain) we identified CRB1 and NEK7 (1q-gain), SOX4 (6p-gain) and NUP205 (7q-gain) as novel retinoblastoma driver candidates. Depending on the sample subset and algorithms used, alternative candidates were identified including MIR181 (1q-gain) and DEK (6p gain). Remarkably, our study showed that copy number gains rarely exceeded change of one copy, even in pure tumor samples with 100% homozygosity at the RB1 locus (N = 34), which is indicative for intra-tumor heterogeneity. In addition, profound between-tumor variability was observed that was associated with age at diagnosis and differentiation grades. Since focal alterations at commonly altered chromosome regions were rare except for 2p24.3 (MYCN), further functional validation of the oncogenic potential of the described candidate genes is now required. For further investigations, our study provides a refined and revised set of candidate retinoblastoma driver genes.

Objectives To investigate whether a new magnetic resonance image (MRI) technique called T2*-weighted fluid attenuation inversion recovery (FLAIR*) can differentiate between multiple sclerosis (MS) and vascular brain lesions, at 7 Tesla (T). Methods We examined 16 MS patients and 16 age-matched patients with (risk factors for) vascular disease. 3D-FLAIR and T2*-weighted images were combined into FLAIR* images. Lesion type and intensity, perivascular orientation and presence of a hypointense rim were analysed. Results In total, 433 cerebral lesions were detected in MS patients versus 86 lesions in vascular patients. Lesions in MS patients were significantly more often orientated in a perivascular manner: 74 % vs. 47 % ( P  < 0.001). Ten MS lesions (2.3 %) were surrounded by a hypointense rim on FLAIR*, and 24 MS lesions (5.5 %) were hypointense on T2*. No lesions in vascular patients showed any rim or hypointensity. Specificity of differentiating MS from vascular lesions on 7-T FLAIR* increased when the presence of a central vessel was taken into account (from 63 % to 88 %), most obviously for deep white matter lesions (from 69 % to 94 %). High sensitivity remained (81 %). Conclusion 7-T FLAIR* improves differentiation between MS and vascular lesions based on lesion location, perivascular orientation and presence of hypointense (rims around) lesions. Key Points • A new MRI technique T2*-weighted fluid attenuation inversion recovery (FLAIR*) was investigated. • FLAIR* at 7-T MRI combines FLAIR and T2* images into a single image. • FLAIR* at 7 T does not require enhancement with contrast agents. •High-resolution 7-T FLAIR* improves differentiation between MS and vascular brain lesions. • FLAIR* revealed a central vessel more frequently in MS than vascular lesions.

Objectives To determine and compare the diagnostic performance of stress myocardial perfusion imaging (MPI) for the diagnosis of obstructive coronary artery disease (CAD), using conventional coronary angiography (CCA) as the reference standard. Methods We searched Medline and Embase for literature that evaluated stress MPI for the diagnosis of obstructive CAD using magnetic resonance imaging (MRI), contrast-enhanced echocardiography (ECHO), single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Results All pooled analyses were based on random effects models. Articles on MRI yielded a total of 2,970 patients from 28 studies, articles on ECHO yielded a sample size of 795 from 10 studies, articles on SPECT yielded 1,323 from 13 studies. For CAD defined as either at least 50 %, at least 70 % or at least 75 % lumen diameter reduction on CCA, the natural logarithms of the diagnostic odds ratio (lnDOR) for MRI (3.63; 95 % CI 3.26–4.00) was significantly higher compared to that of SPECT (2.76; 95 % CI 2.28–3.25; P  = 0.006) and that of ECHO (2.83; 95 % CI 2.29–3.37; P  = 0.02). There was no significant difference between the lnDOR of SPECT and ECHO ( P  = 0.52). Conclusion Our results suggest that MRI is superior for the diagnosis of obstructive CAD compared with ECHO and SPECT. ECHO and SPECT demonstrated similar diagnostic performance. Key Points • MRI can assess myocardial perfusion . • MR perfusion diagnoses coronary artery disease better than echocardiography or SPECT . • Echocardiography and SPECT have similar diagnostic performance . • MRI can save coronary artery disease patients from more invasive tests . • MRI and SPECT show evidence of publication bias, implying possible overestimation .

Purpose To retrospectively analyse the safety and efficacy of radiofrequency ablation (RFA) versus microwave ablation (MWA) in the treatment of unresectable colorectal liver metastases (CRLM) in proximity to large vessels and/or major bile ducts. Method and Materials A database search was performed to include patients with unresectable histologically proven and/or 18 F–FDG–PET avid CRLM who were treated with RFA or MWA between January 2001 and September 2014 in a single centre. All lesions that were considered to have a peribiliary and/or perivascular location were included. Univariate logistic regression analysis was performed to assess the distribution of patient, tumour and procedure characteristics. Multivariate logistic regression was used to correct for potential confounders. Results Two hundred and forty-three patients with 774 unresectable CRLM were ablated. One hundred and twenty-two patients (78 males; 44 females) had at least one perivascular or peribiliary lesion ( n  = 199). Primary efficacy rate of RFA was superior to MWA after 3 and 12 months of follow-up ( P  = 0.010 and P  = 0.022); however, after multivariate analysis this difference was non-significant at 12 months ( P  = 0.078) and vanished after repeat ablations ( P  = 0.39). More CTCAE grade III complications occurred after MWA versus RFA (18.8 vs. 7.9 %; P  = 0.094); biliary complications were especially common after peribiliary MWA ( P  = 0.002). Conclusion For perivascular CRLM, RFA and MWA are both safe treatment options that appear equally effective. For peribiliary CRLM, MWA has a higher complication rate than RFA, with similar efficacy. Based on these results, it is advised to use RFA for lesions in the proximity of major bile ducts.

MYCN -amplified RB1 wild-type ( MYCN amp RB1 +/+ ) retinoblastoma is a rare and aggressive subtype, often resistant to standard therapies. Identifying unique MRI features is crucial for diagnosing this subtype, as biopsy is not recommended. This study aimed to differentiate MYCN amp RB1 +/+ from the most prevalent RB1 -/- retinoblastoma using pretreatment MRI and radiomics. Ninety-eight unilateral retinoblastoma patients (19 MYCN cases and 79 matched controls) were included. Tumors on T2-weighted MR images were manually delineated and validated by experienced radiologists. Radiomics analysis extracted 120 features per tumor. Several combinations of feature selection methods, oversampling techniques and machine learning (ML) classifiers were evaluated in a repeated fivefold cross-validation machine learning pipeline to yield the best-performing prediction model for MYCN . The best model used univariate feature selection, data oversampling (duplicating MYCN cases), and logistic regression classifier, achieving a mean AUC of 0.78 (SD 0.12). SHAP analysis highlighted lower sphericity , higher flatness , and greater gray-level heterogeneity as predictive for MYCN amp RB1 +/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCN amp RB1 +/+ and RB1 -/- retinoblastoma subtypes.

PurposeIn percutaneous ablation procedures, periprocedural pain, unrest and respiratory concerns can be detrimental to achieve a safe and efficacious ablation and impair treatment outcome. This study aimed to compare the association between anesthetic technique and local disease control in patients undergoing percutaneous microwave ablation (MWA) of colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC).Materials and MethodsThis IRB-exempted single-center comparative, retrospective analysis of three cohorts analyzed 90 patients treated for hepatic malignancies from January 2013 until September 2018. The local tumor progression-free survival (LTPFS), safety and periprocedural pain perception were assessed using univariate and multivariate Cox proportional hazard regression analyses to correct for potential confounders.ResultsIn 114 procedures (22 general anesthesia; 32 midazolam; 60 propofol), 171 liver tumors (136 CRLM; 35 HCC) were treated with percutaneous MWA. Propofol and general anesthesia were superior to midazolam/fentanyl sedation regarding LTPFS (4/94 [4.3%] vs. 19/42 [45.2%] vs. 2/35 [5.7%]; P < 0.001, respectively). Local tumor progression rate was 14.6% (25/171). Eighteen tumors (72.0%) were retreated by ablation. Of them, 14 (78%) were previously treated with midazolam. Propofol versus midazolam (P < 0.001), general anesthesia versus midazolam (P = 0.016), direct postprocedural visual analog pain score above 5 (P = 0.050) and more than one tumor per procedure (P = 0.045) were predictors for LTPFS. Multivariate analysis revealed that propofol versus midazolam (HR 7.94 [95% CI 0.04–0.39; P < 0.001]) and general anesthesia versus midazolam (HR 6.33 [95% CI 0.04–0.69; P = 0.014]) were associated with LTPFS. Pain during and directly after treatment was significantly worse in patients who received midazolam sedation (P < 0.001).ConclusionsCompared to propofol and general anesthesia, midazolam/fentanyl sedation was associated with an increased periprocedural perception of pain and lower local tumor progression-free survival. To reduce the number of repeat procedures required to eradicate hepatic malignancies, general anesthesia and propofol sedation should be favored over midazolam.

Objectives To assess specific imaging characteristics after irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) with contrast-enhanced (ce)MRI and ceCT, and to explore the correlation of these characteristics with the development of recurrence. Methods Qualitative and quantitative analyses of imaging data were performed on 25 patients treated with percutaneous IRE for LAPC. Imaging characteristics of the ablation zone on ceCT and ceMRI were assessed over a 6-month follow-up period. Contrast ratio scores between pre- and post-treatment were compared. To detect early imaging markers for treatment failure, attenuation characteristics at 6 weeks were linked to the area of recurrence within 6 months. Results Post-IRE, diffusion-weighted imaging (DWI)-b800 signal intensities decreased in all cases ( p  < 0.05). Both ceMRI and ceCT revealed absent or decreased contrast enhancement, with a hyperintense rim on ceMRI. Ablation zone volume increase was noted on both modalities in the first 6 weeks, followed by a decrease ( p  < 0.05). In the patients developing tumour recurrence (5/25), a focal DWI-b800 hyperintense spot at 6 weeks predated unequivocal recurrence on CT. Conclusion The most remarkable signal alterations after pancreatic IRE were shown by DWI-b800 and ceMRI. These early imaging characteristics may be useful to establish technical success and predict treatment outcome. Key Points • This study describes imaging characteristics after irreversible electroporation (IRE) for pancreatic adenocarcinoma. • Familiarity with typical post-IRE imaging characteristics helps to interpret ablation zones. • Post-IRE, no central and variable rim enhancement are visible on contrast-enhanced imaging. • DWI-b800 may prove useful to predict early tumour recurrence. • Post-IRE examinations reveal an initial volume increase followed by a decrease.

Objectives To assess the accuracy of high-resolution (HR) magnetic resonance imaging (MRI) in diagnosing early-stage optic nerve (ON) invasion in a retinoblastoma cohort. Methods This IRB-approved, prospective multicenter study included 95 patients (55 boys, 40 girls; mean age, 29 months). 1.5-T MRI was performed using surface coils before enucleation, including spin-echo unenhanced and contrast-enhanced (CE) T1-weighted sequences (slice thickness, 2 mm; pixel size <0.3 × 0.3 mm 2 ). Images were read by five neuroradiologists blinded to histopathologic findings. ROC curves were constructed with AUC assessment using a bootstrap method. Results Histopathology identified 41 eyes without ON invasion and 25 with prelaminar, 18 with intralaminar and 12 with postlaminar invasion. All but one were postoperatively classified as stage I by the International Retinoblastoma Staging System. The accuracy of CE-T1 sequences in identifying ON invasion was limited (AUC = 0.64; 95 % CI, 0.55 – 0.72) and not confirmed for postlaminar invasion diagnosis (AUC = 0.64; 95 % CI, 0.47 – 0.82); high specificities (range, 0.64 – 1) and negative predictive values (range, 0.81 – 0.97) were confirmed. Conclusion HR-MRI with surface coils is recommended to appropriately select retinoblastoma patients eligible for primary enucleation without the risk of IRSS stage II but cannot substitute for pathology in differentiating the first degrees of ON invasion. Key Points • HR-MRI excludes advanced optic nerve invasion with high negative predictive value. • HR-MRI accurately selects patients eligible for primary enucleation. • Diagnosis of early stages of optic nerve invasion still relies on pathology. • Several physiological MR patterns may mimic optic nerve invasion.