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Background MYCN-amplified RB1 wild-type (MYCNARB1+/+) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of MYCNARB1+/+ retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with MYCNARB1+/+ retinoblastoma and age-matched children with RB1-/- subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing (RB1/MYCN status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected P values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with MYCNARB1+/+ retinoblastoma and 88 control children with RB1-/- retinoblastoma. Children in the MYCNARB1+/+ group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the RB1-/- group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). MYCNARB1+/+ retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; P < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; P = .011) with irregular margins (in 16 of 22 children; specificity, 70%; P = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; P < .001). MYCNARB1+/+ retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; P < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; P = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; P = .008). Conclusion MYCNARB1+/+ retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue.

Simple Summary Immunotherapy may induce early treatment response in head and neck squamous cell carcinoma (HNSCC) for some patients. Routine imaging parameters fail to diagnose these responses; however, magnetic resonance (MR) diffusion-weighted imaging (DWI) may be able to do so. This study sought to correlate DWI parameters with treatment response early after immunotherapy treatment in HNSCC. We analyzed 24 patients with advanced HNSCC with imaging before and after the immunotherapy. We found that rounder tumors that were smaller in diameter before treatment were more likely to respond. A decrease in skewness of the tumor after treatment compared to before treatment, as well as an overall low skewness post-treatment, were linked to better treatment response. Though this study was explorative in nature, these results are promising for the predictive use of MR-DWI in HNSCC treated with immunotherapy. Background: Neoadjuvant immune checkpoint blockade (ICB) prior to surgery may induce early pathological responses in head and neck squamous cell carcinoma (HNSCC) patients. Routine imaging parameters fail to diagnose these responses early on. Magnetic resonance (MR) diffusion-weighted imaging (DWI) has proven to be useful for detecting HNSCC tumor mass after (chemo)radiation therapy. METHODS: 32 patients with stage II-IV, resectable HNSCC, treated at a phase Ib/IIa IMCISION trial (NCT03003637), were retrospectively analyzed using MR-imaging before and after two doses of single agent nivolumab (anti-PD-1) (n = 6) or nivolumab with ipilimumab (anti-CTLA-4) ICB (n = 26). The primary tumors were delineated pre- and post-treatment. A total of 32 features were derived from the delineation and correlated with the tumor regression percentage in the surgical specimen. Results: MR-DWI data was available for 24 of 32 patients. Smaller baseline tumor diameter (p = 0.01-0.04) and higher sphericity (p = 0.03) were predictive of having a good pathological response to ICB. Post-treatment skewness and the change in skewness between MRIs were negatively correlated with the tumor's regression (p = 0.04, p = 0.02). Conclusion: Pre-treatment DWI tumor diameter and sphericity may be quantitative biomarkers for the prediction of an early pathological response to ICB. Furthermore, our data indicate that ADC skewness could be a marker for individual response evaluation.

Objectives To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. Methods Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses. Results In total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p GTV (HR = 1.252), Ktrans (HR = 1.223), and Ve (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADCGTV (HR = 1.102), ADCmean (HR = 1.137), D* (HR = 0.862), Ktrans (HR = 1.106), Ve (HR = 1.195), SUVmax (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046). Conclusions Functional imaging parameters, performing DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (Ktrans), and high extravascular extracellular space (Ve) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival. Key Points • Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics. • Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (Ktrans), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence. • In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.

BACKGROUND AND PURPOSE: New imaging techniques such as hybrid imaging of ultrasound and FDG-PET/CT are available but not yet investigated for node staging. The aim of the study was to evaluate the feasibility and added diagnostic value of real-time image-fused ultrasound-guided fine-needle aspiration with FDG-PET/CT data for node staging. MATERIALS AND METHODS: Ninety-six patients who were referred for cervical lymph node staging with FDG-PET/CT before ultrasound were prospectively included. After routine ultrasound-guided fine-needle aspiration, all FDG-PET-positive nodes were marked on FDG-PET/CT, and real-time image fusing of ultrasound and FDG-PET/CT was performed using the electromagnetic navigation system PercuNav. Already-punctured nodes were confirmed to be PET-positive, and additional fused-ultrasound-guided fine-needle aspiration was performed in previously missed PET-positive nodes. RESULTS: Of 96 patients, 87 (91%) patients had suspicious nodes requiring fine-needle aspiration cytology. Ultrasound-guided fine-needle aspiration was performed in 175 nodes. Cytology was inconclusive in 9/175 (5%) nodes, and 85/166 (51%) nodes were malignant. Target planning was performed in 201 PET-positive nodes; 195/201 (97%) of those nodes were fused successfully. Twenty of 175 ultrasound-guided fine-needle aspiration nodes turned out to be FDG-PET-negative, and 149/175 (85%) of the fused ultrasound-guided fine-needle aspiration nodes were confirmed to be FDG-PET-positive. Of 201 PET-positive nodes, 46 (23%) were additionally identified, and fused ultrasound-guided fine-needle aspiration was performed. Cytology was inconclusive in 4/46 nodes (9%), and 13/42 (31%) nodes were malignant. CONCLUSIONS: Real-time ultrasound image fusion with FDG-PET-positive nodes is feasible in cervical lymph nodes, and fused ultrasound-guided fine-needle aspiration increases the number of malignant nodes detected.

Purpose: The intravoxel incoherent motion (IVIM) model for DWI might provide useful biomarkers for disease management in head and neck cancer. This study compared the repeatability of three IVIM fitting methods to the conventional nonlinear least-squares regression: Bayesian probability estimation, a recently introduced neural network approach, IVIM-NET, and a version of the neural network modified to increase consistency, IVIM-NET mod. Methods: Ten healthy volunteers underwent two imaging sessions of the neck, two weeks apart, with two DWI acquisitions per session. Model parameters (ADC, diffusion coefficient (Formula presented.), perfusion fraction (Formula presented.), and pseudo-diffusion coefficient (Formula presented.)) from each fit method were determined in the tonsils and in the pterygoid muscles. Within-subject coefficients of variation (wCV) were calculated to assess repeatability. Training of the neural network was repeated 100 times with random initialization to investigate consistency, quantified by the coefficient of variance. Results: The Bayesian and neural network approaches outperformed nonlinear regression in terms of wCV. Intersession wCV of (Formula presented.) in the tonsils was 23.4% for nonlinear regression, 9.7% for Bayesian estimation, 9.4% for IVIM-NET, and 11.2% for IVIM-NET mod. However, results from repeated training of the neural network on the same data set showed differences in parameter estimates: The coefficient of variances over the 100 repetitions for IVIM-NET were 15% for both (Formula presented.) and (Formula presented.), and 94% for (Formula presented.); for IVIM-NET mod, these values improved to 5%, 9%, and 62%, respectively. Conclusion: Repeatabilities from the Bayesian and neural network approaches are superior to that of nonlinear regression for estimating IVIM parameters in the head and neck.

BACKGROUND AND PURPOSE: Manual delineation of head and neck tumor contours for radiomics analyses is tedious and time consuming. This study investigates if fast or readily available tumor contours can substitute full tumor contours by an experienced observer for an MR-based radiomics model to predict locoregional control (LRC) in oropharyngeal squamous cell carcinoma (OPSCC) tumors.MATERIALS AND METHODS: Radiomic features were extracted from postcontrast T1-weighted MRIs of 177 OPSCC primary tumors using six different manual delineation strategies. LRC prediction models based on recursive feature elimination combined with logistic regression were built. Models were trained and tested on data from each separate delineation. Additionally, the model derived from segmentations from the experienced reader was tested by each of the alternative delineations. Complementary, this was repeated with removal of size and shape features. Model performance was evaluated using area under the curve (AUC).RESULTS: Prediction performance of the experienced radiologist tumor delineation (AUC: 0.74) was superior compared to all other delineations when trained and tested (AUCs: 0.41-0.56) or trained on experienced delineations and tested (AUC: 0.56-0.67) on alternative segmentations. Removal of size and shape features considerably decreases prediction performance (AUC: 0.54). Applying the model based on expert delineations to spherical or single slice delineations makes prediction worthless since these models predict one class.CONCLUSION: Fast or readily available contours cannot substitute full expert tumor delineations in radiomics models predictive of LRC in OPSCC.

Topic To determine the age up to which children are at risk of trilateral retinoblastoma (TRb) developing, whether its onset is linked to the age at which intraocular retinoblastomas develop, and the lead time from a detectable pineal TRb to symptoms. Clinical relevance Approximately 45% of patients with retinoblastoma—those with a germline RB1 pathogenic variant—are at risk of pineal TRb developing. Early detection and treatment are essential for survival. Current evidence is unclear regarding the usefulness of screening for pineal TRb and, if useful, the age up to which screening should be continued. Methods We conducted a study according to the Meta-analysis of Observational Studies in Epidemiology guidelines for reporting meta-analyses of observational studies. We searched PubMed and Embase between January 1, 1966, and February 27, 2019, for published literature. We considered articles reporting patients with TRb with survival and follow-up data. Inclusion of articles was performed separately and independently by 2 authors, and 2 authors also independently extracted the relevant data. They resolved discrepancies by consensus. Results One hundred thirty-eight patients with pineal TRb were included. Of 22 asymptomatic patients, 21 (95%) were diagnosed before the age of 40 months (median, 16 months; interquartile range, 9–29 months). Age at diagnosis of pineal TRb in patients diagnosed with retinoblastoma at 6 months or younger versus older than 6 months were comparable (P = 0.44), suggesting independence between the ages at diagnosis of intraocular retinoblastoma and pineal TRb. The laterality of intraocular retinoblastoma and its treatment were not associated with the age at which pineal TRb was diagnosed. The lead time from asymptomatic to symptomatic pineal TRb was approximately 1 year. By performing a screening magnetic resonance imaging scan every 6 months after the diagnosis of heritable retinoblastoma (median age, 6 months) until 36 months of age, at least 311 and 776 scans would be required to detect 1 case of asymptomatic pineal TRb and to save a single life, respectively. Conclusions Patients with retinoblastoma are at risk of pineal TRb developing for a shorter period than previously assumed, and the age at diagnosis of pineal TRb is independent of the age at diagnosis of retinoblastoma. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) level of evidence for these conclusions remains low.

We present a 6-year-old boy with unilateral retinoblastoma of the left eye. MRI showed an intraocular tumor that extended into the optic nerve beyond the lamina cribrosa. The affected eye was enucleated and the optic nerve resection margin proved to be free. Following protocol, this patient received six courses of adjuvant systemic chemotherapy. Unfortunately, after 5 months this patient returned with the leptomeningeal spread of the tumor and died quickly thereafter.Histopathologic analysis of the enucleated eye and distal optic nerve revealed that the postlaminar tumor cells occupied the entire width of the optic nerve, extending all the way up to the pia mater, whereas, more often the tumor invasion is restricted to the center of the optic nerve. This was also visible on the MR images where contrast enhancement occupied the entire nerve width. A resection margin with tumor cells is recognized as a risk factor for metastasis, but perhaps the proximity of tumor cells to the leptomeninges should also be judged with caution as a potential increased risk for metastatic spread.

OBJECTIVES: To externally validate a pre-treatment MR-based radiomics model predictive of locoregional control in oropharyngeal squamous cell carcinoma (OPSCC) and to assess the impact of differences between datasets on the predictive performance.METHODS: Radiomic features, as defined in our previously published radiomics model, were extracted from the primary tumor volumes of 157 OPSCC patients in a different institute. The developed radiomics model was validated using this cohort. Additionally, parameters influencing performance, such as patient subgroups, MRI acquisition, and post-processing steps on prediction performance will be investigated. For this analysis, matched subgroups (based on human papillomavirus (HPV) status of the tumor, T-stage, and tumor subsite) and a subgroup with only patients with 4-mm slice thickness were studied. Also the influence of harmonization techniques (ComBat harmonization, quantile normalization) and the impact of feature stability across observers and centers were studied. Model performances were assessed by area under the curve (AUC), sensitivity, and specificity.RESULTS: Performance of the published model (AUC/sensitivity/specificity: 0.74/0.75/0.60) drops when applied on the validation cohort (AUC/sensitivity/specificity: 0.64/0.68/0.60). The performance of the full validation cohort improves slightly when the model is validated using a patient group with comparable HPV status of the tumor (AUC/sensitivity/specificity: 0.68/0.74/0.60), using patients acquired with a slice thickness of 4 mm (AUC/sensitivity/specificity: 0.67/0.73/0.57), or when quantile harmonization was performed (AUC/sensitivity/specificity: 0.66/0.69/0.60).CONCLUSION: The previously published model shows its generalizability and can be applied on data acquired from different vendors and protocols. Harmonization techniques and subgroup definition influence performance of predictive radiomics models.KEY POINTS: • Radiomics, a noninvasive quantitative image analysis technique, can support the radiologist by enhancing diagnostic accuracy and/or treatment decision-making. • A previously published model shows its generalizability and could be applied on data acquired from different vendors and protocols.

Background: Patients with locally-advanced head and neck squamous cell carcinoma (HNSCC) have variable responses to (chemo)radiotherapy. A reliable prediction of outcomes allows for enhancing treatment efficacy and follow-up monitoring. Methods: Fifty-seven histopathologically-proven HNSCC patients with curative (chemo)radiotherapy were prospectively included. All patients had an MRI (DW,-IVIM, DCE-MRI) and 18F-FDG-PET/CT before and 10 days after start-treatment (intratreatment). Primary tumor functional imaging parameters were extracted. Univariate and multivariate analysis were performed to construct prognostic models and risk stratification for 2 year locoregional recurrence-free survival (LRFFS), distant metastasis-free survival (DMFS) and overall survival (OS). Model performance was measured by the cross-validated area under the receiver operating characteristic curve (AUC). Results: The best LRFFS model contained the pretreatment imaging parameters ADC_kurtosis, Kep and SUV_peak, and intratreatment imaging parameters change (Δ) Δ-ADC_skewness, Δ-f, Δ-SUV_peak and Δ-total lesion glycolysis (TLG) (AUC = 0.81). Clinical parameters did not enhance LRFFS prediction. The best DMFS model contained pretreatment ADC_kurtosis and SUV_peak (AUC = 0.88). The best OS model contained gender, HPV-status, N-stage, pretreatment ADC_skewness, D, f, metabolic-active tumor volume (MATV), SUV_mean and SUV_peak (AUC = 0.82). Risk stratification in high/medium/low risk was significantly prognostic for LRFFS (p = 0.002), DMFS (p < 0.001) and OS (p = 0.003). Conclusions: Intratreatment functional imaging parameters capture early tumoral changes that only provide prognostic information regarding LRFFS. The best LRFFS model consisted of pretreatment, intratreatment and Δ functional imaging parameters; the DMFS model consisted of only pretreatment functional imaging parameters, and the OS model consisted ofHPV-status, gender and only pretreatment functional imaging parameters. Accurate clinically applicable risk stratification calculators can enable personalized treatment (adaptation) management, early on during treatment, improve counseling and enhance patient-specific post-therapy monitoring.

Purpose: To investigate the prevalence and magnetic resonance imaging (MRI) phenotype of retinoblastoma-associated orbital cellulitis. Additionally, this study aimed to identify postlaminar optic nerve enhancement (PLONE) patterns differentiating between inflammation and tumor invasion. Design: A monocenter cohort study assessed the prevalence of orbital cellulitis features on MRI in retinoblastoma patients. A multicenter case–control study compared MRI features of the retinoblastoma-associated orbital cellulitis cases with retinoblastoma controls. Participants: A consecutive retinoblastoma patient cohort of 236 patients (311 eyes) was retrospectively investigated. Subsequently, 30 retinoblastoma cases with orbital cellulitis were compared with 30 matched retinoblastoma controls without cellulitis. Methods: In the cohort study, retinoblastoma MRI scans were scored on presence of inflammatory features. In the case–control study, MRI scans were scored on intraocular features and PLONE patterns. Postlaminar enhancement patterns were compared with histopathologic assessment of postlaminar tumor invasion. Interreader agreement was assessed, and exact tests with Bonferroni correction were adopted for statistical comparisons. Main Outcome Measures: Prevalence of retinoblastoma-associated orbital cellulitis on MRI was calculated. Frequency of intraocular MRI features was compared between cases and controls. Sensitivity and specificity of postlaminar optic nerve patterns for detection of postlaminar tumor invasion were assessed. Results: The MRI prevalence of retinoblastoma-associated orbital cellulitis was 6.8% (16/236). Retinoblastoma with orbital cellulitis showed significantly more tumor necrosis, uveal abnormalities (inflammation, hemorrhage, and necrosis), lens luxation (all P < 0.001), and a larger eye size (P = 0.012). The inflammatory pattern of optic nerve enhancement (strong enhancement similar to adjacent choroid) was solely found in orbital cellulitis cases, of which none (0/16) showed tumor invasion on histopathology. Invasive pattern enhancement was found in both cases and controls, of which 50% (5/10) showed tumor invasion on histopathology. Considering these different enhancement patterns suggestive for either inflammation or tumor invasion increased specificity for detection of postlaminar tumor invasion in orbital cellulitis cases from 32% (95% confidence interval [CI], 16–52) to 89% (95% CI, 72–98). Conclusions: Retinoblastoma cases presenting with orbital cellulitis show MRI findings of a larger eye size, extensive tumor necrosis, uveal abnormalities, and lens luxation. Magnetic resonance imaging contrast-enhancement patterns within the postlaminar optic nerve can differentiate between tumor invasion and inflammatory changes.

Simple Summary Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for N-staging in head and neck squamous cell carcinoma (HNSCC). The specificity of USgFNAC is always in the order of 100% as false positive cytology is rare. The difference in sensitivity is mainly attributable to selection of the lymph nodes to aspirate and aspiration technique. The aim of this study was to improve the selection criteria of lymph nodes to aspirate. Ultrasound features of nodes such as a short axis diameter, S/L ratio, loss of a fatty hilum sign, resistive index, and peripheral or mixed hilar and peripheral vascularization, obtained by Micro-flow imaging (MFI), which is a new technique to obtain micro-vascularization, were evaluated. To calculate the sensitivity and PPV of each feature, data of sonographic findings and cytological results of all aspirated nodes were statistically analyzed. We found that next to size, peripheral vascularisation obtained by MFI and absent hilum sign have a high predictive value for malignancy and should be added as selection criteria for fine needle aspiration in lymph nodes. Abstract Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for nodal staging in head and neck squamous cell cancer (HNSCC). Peripheral vascularity is a described feature for node metastasis. Micro-flow imaging (MFI) is a new sensitive technique to evaluate micro-vascularization. Our goal is to assess the additional value of MFI to detect malignancy in lymph nodes. A total of 102 patients with HNSCC were included prospectively. USgFNAC was performed with the Philips eL18–4 transducer. Cytological results served as a reference standard to evaluate the prediction of cytological malignancy depending on ultrasound features such as resistive index (RI), absence of fatty hilum sign, and peripheral vascularization. Results were obtained for all US examinations and for the subgroup of clinically node-negative neck (cN0). USgFNAC was performed in 211 nodes. Peripheral vascularization had a positive predictive value (PPV) of 83% (cN0: 50%) and the absence of a fatty hilum had a PPV of 82% (cN0 50%) The combination of peripheral vascularization and absent fatty hilum had a PPV of 94% (cN0: 72%). RI (threshold: 0.705) had a PPV of 61% (cN0: RI-threshold 0.615, PPV 20%), whereas the PPV of short axis diameter (threshold of 6.5mm) was 59% for all patients and 19% in cN0 necks (threshold of 4 mm). Peripheral vascularization assessed by MFI and absent hilum has a high predictive value for cytological malignancy in neck metastases. Next to size, both features should be used as additional selection criteria for USgFNAC.

OBJECTIVES: New markers are required to predict chemoradiation response in oropharyngeal squamous cell carcinoma (OPSCC) patients. This study evaluated the ability of magnetic resonance (MR) radiomics to predict locoregional control (LRC) and overall survival (OS) after chemoradiation and aimed to determine whether this has added value to traditional clinical outcome predictors.METHODS: 177 OPSCC patients were eligible for this study. Radiomic features were extracted from the primary tumor region in T1-weighted postcontrast MRI acquired before chemoradiation. Logistic regression models were created using either clinical variables (clinical model), radiomic features (radiomic model) or clinical and radiomic features combined (combined model) to predict LRC and OS 2-years posttreatment. Model performance was evaluated using area under the curve (AUC), 95 % confidence intervals were calculated using 500 iterations of bootstrap. All analyses were performed for the total population and the Human papillomavirus (HPV) negative tumor subgroup.RESULTS: A combined model predicted treatment outcome with a higher AUC (LRC: 0.745 [0.734-0.757], OS: 0.744 [0.735-0.753]) than the clinical model (LRC: 0.607 [0.594-0.620], OS: 0.708 [0.697-0.719]). Performance of the radiomic model was comparable to the combined model for LRC (AUC: 0.740 [0.729-0.750]), but not for OS prediction (AUC: 0.654 [0.646-0.662]). In HPV negative patients, the performance of all models was not sufficient with AUCs ranging from 0.587 to 0.660 for LRC and 0.559 to 0.600 for OS prediction.CONCLUSION: Predictive models that include clinical variables and radiomic tumor features derived from MR images of OPSCC better predict LRC after chemoradiation than models based on only clinical variables. Predictive models that include clinical variables perform better than models based on only radiomic features for the prediction of OS.

Background and purpose: In head and neck squamous cell carcinoma (HNSCC) (chemo)radiotherapy is increasingly used to preserve organ functionality. The purpose of this study was to identify predictive pretreatment DWI- and 18F-FDG-PET/CT-parameters for treatment failure (TF), locoregional recurrence (LR) and death in HNSCC patients treated by (chemo)radiotherapy. Materials and methods: We retrospectively included 134 histologically proven HNSCC patients treated with (chemo)radiotherapy between 2012-2017. In 58 patients pre-treatment DWI and 18F-FDG-PET/CT were performed, in 31 patients DWI only and in 45 patients 18F-FDG-PET/CT only. Primary tumor (PT) and largest lymph node (LN) metastasis were quantitatively assessed for TF, LR and death. Multivariate analysis was performed for 18F-FDG-PET/CT and DWI separately and thereafter combined. In patients with both imaging modalities, positive and negative predictive value in TF and differences in LR and death, were assessed. Results: Mean follow-up was 25.6 months (interquartile-range; 14.0–37.1 months). Predictors of treatment failure, corrected for TNM-stage and HPV-status, were SUVmax-PT, ADCmax-PT, total lesion glycolysis (TLG-LN), ADCp20-LN (P = 0.049, P = 0.024, P = 0.031, P = 0.047, respectively). TLG-PT was predictive for LR (P = 0.003). Metabolic active tumor volume (MATV-PT) (P = 0.003), ADCGTV-PT (P < 0.001), ADCSD (P = 0.048) were significant predictors for death. In patients with both imaging modalities SUVmax-PT remained predictive for treatment failure (P = 0.049), TLG-LN for LR (P = 0.003) and ADCGTV-PT for death (P < 0.001). Higher predictive value for treatment failure was found for the combination of SUVmax-PT and ADCmax-PT, compared to either one separately. Conclusion: Both DWI- and 18F-FDG-PET/CT-parameters appear to have predictive value for treatment failure, locoregional recurrence and death. Combining SUVmax-PT and ADCmax-PT resulted in better prediction of treatment failure compared to single parameter assessment.

Retinoblastoma mimickers, or pseudoretinoblastoma, are conditions that show similarities with the pediatric cancer retinoblastoma. However, false-positive retinoblastoma diagnosis can cause mistreatment, while false-negative diagnosis can cause life-threatening treatment delay. The purpose of this study is to identify the MR imaging features that best differentiate between retinoblastoma and the most common pseudoretinoblastoma diagnoses: Coats&rsquo, disease and persistent fetal vasculature (PFV). Here, six expert radiologists performed retrospective assessments (blinded for diagnosis) of MR images of patients with a final diagnosis based on histopathology or clinical follow-up. Associations between 20 predefined imaging features and diagnosis were assessed with exact tests corrected for multiple hypothesis testing. Sixty-six patients were included, of which 33 (50%) were retinoblastoma and 33 (50%) pseudoretinoblastoma patients. A larger eye size, vitreous seeding, and sharp-V-shaped retinal detachment were almost exclusively found in retinoblastoma (p &lt, 0.001&ndash, 0.022, specificity 93&ndash, 97%). Features that were almost exclusively found in pseudoretinoblastoma included smaller eye size, ciliary/lens deformations, optic nerve atrophy, a central stalk between optic disc and lens, Y-shaped retinal detachment, and absence of calcifications (p &lt, 0.022, specificity 91&ndash, 100%). Additionally, three newly identified imaging features were exclusively present in pseudoretinoblastoma: intraretinal macrocysts (p &lt, 0.001, 38% [9/24] in Coats&rsquo, disease and 20% [2/10] in PFV), contrast enhancement outside the solid lesion (p &lt, 0.001, 30% [7/23] in Coats&rsquo, disease and 57% [4/7] in PFV), and enhancing subfoveal nodules (38% [9/24] in Coats&rsquo, disease). An assessment strategy was proposed for MR imaging differentiation between retinoblastoma and pseudoretinoblastoma, including three newly identified differentiating MR imaging features.

Abstract Background Radiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy. Methods Between 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent 18F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order 18F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with 18F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients’ outcome. Results Based on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764). Conclusions Combining HPV-status, first-order 18F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care. Trial registration Trial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946

To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or 18F-FDG-PET and the combination of modalities for the detection of unknown primary tumor (UPT) in patients presenting with cervical lymph node metastasis from squamous cell carcinoma (SCC). Between 2014&ndash, 2019, patients with histologically proven cervical lymph node metastasis of UPT SCC were prospectively included and underwent DWI, ultrafast-DCE, and 18F-FDG-PET/CT. Qualitative assessment was performed by two observers per modality. Interobserver agreement was calculated using the proportion specific agreement. Diagnostic accuracy of combined use of DWI, ultrafast-DCE and 18F-FDG-PET/CT was assessed. Twenty-nine patients were included (20 males. [68%], median age 60 years). Nine (31%) primary tumors remained occult. Ultrafast-DCE added reader confidence for suspicious locations (one additional true positive (5%), 2 decisive true malignant (10%). The per-location analysis showed highest specific positive agreement for ultrafast-DCE (77.6%). The per-location rating showed highest sensitivity (95%, 95%CI = 75.1&ndash, 99.9, YI = 0.814) when either one of all modalities was scored positive, and 97.4% (95%CI = 93.5&ndash, 99.3, YI = 0.774) specificity when co-detected on all. The per-patient analysis showed highest sensitivity (100%) for 18F-FDG-PET/CT (YI = 0.222) and either DWI or PET (YI = 0.111). Despite highest trends, no significant differences were found. The per-patient analysis showed highest specific positive agreement when co-detected on all modalities (55.6%, 95%CI = 21.2&ndash, 86.3, YI = 0.456). Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity.

Objectives Head and neck squamous cell carcinoma (HNSCC) shows a remarkable heterogeneity between tumors, which may be captured by a variety of quantitative features extracted from diagnostic images, termed radiomics. The aim of this study was to develop and validate MRI-based radiomic prognostic models in oral and oropharyngeal cancer. Materials and Methods Native T1-weighted images of four independent, retrospective (2005–2013), patient cohorts (n = 102, n = 76, n = 89, and n = 56) were used to delineate primary tumors, and to extract 545 quantitative features from. Subsequently, redundancy filtering and factor analysis were performed to handle collinearity in the data. Next, radiomic prognostic models were trained and validated to predict overall survival (OS) and relapse-free survival (RFS). Radiomic features were compared to and combined with prognostic models based on standard clinical parameters. Performance was assessed by integrated area under the curve (iAUC). Results In oral cancer, the radiomic model showed an iAUC of 0.69 (OS) and 0.70 (RFS) in the validation cohort, whereas the iAUC in the oropharyngeal cancer validation cohort was 0.71 (OS) and 0.74 (RFS). By integration of radiomic and clinical variables, the most accurate models were defined (iAUC oral cavity, 0.72 (OS) and 0.74 (RFS); iAUC oropharynx, 0.81 (OS) and 0.78 (RFS)), and these combined models outperformed prognostic models based on standard clinical variables only (p < 0.001). Conclusions MRI radiomics is feasible in HNSCC despite the known variability in MRI vendors and acquisition protocols, and radiomic features added information to prognostic models based on clinical parameters. Key Points • MRI radiomics can predict overall survival and relapse-free survival in oral and HPV-negative oropharyngeal cancer. • MRI radiomics provides additional prognostic information to known clinical variables, with the best performance of the combined models. • Variation in MRI vendors and acquisition protocols did not influence performance of radiomic prognostic models.

Objectives To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. Methods Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses. Results In total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p

PURPOSE: The emerge of improved personalized treatment adaptations and outcome prediction is accompanied with increasing non-invasive assessments in early treatment phase, leading to increased patient burden. This study assessed the adherence of patients with head and neck squamous cell carcinoma (HNSCC) to undergo pretreatment and research-related intratreatment imaging, and assessed which factors caused drop-out.METHOD: Between 2013 and 2019, advanced-staged HNSCC patients were prospectively included, underwent (chemo) radiotherapy with curative intent and planned for both pre-treatment and intratreatment sequential 18F-FDG-PET/CT, 18F-FDG-PET/MRI and thereafter MRI (including DWI/DCE). Drop-out-factors were described as healthcare-related (logistics and imaging-system defects) and patient-related (psychological, physical, not-specified). Common Toxicity Criteria (CTC) were routinely scored by radiation/medical oncologists throughout the first 3 weeks, and compared between patient drop-outs and who complete imaging.RESULTS: Ninety-seven patients (mean age 61 ± 6.8 years) were included; 95 patients (97.9%) underwent pretreatment imaging and 63 (64.9%) intratreatment imaging. For 18F-FDG-PET/CT, 18F-FDG-PET/MRI and MRI pretreatment drop-outs were 2, 10 and 3 patients and for intratreatment drop-outs were 34, 39 and 35 patients, respectively. Patient-related drop-out-factors were physical (n = 16, e.g. dysphagia), psychological (n = 6, e.g. claustrophobia) and non-specified (n = 12). Healthcare-related drop-out-factors were logistics (n = 6) and 18F-FDG-PET/CT-/MRI-system defects (n = 2). The CTC mucosal toxicity was significantly higher (p = 0.023) at week 2 of (chemo)radiotherapy in patient drop-outs than with complete imaging.CONCLUSIONS: The drop-out frequency of advanced-staged HNSCC patients for imaging during (chemo)radiotherapy in a research-setting was high and mainly patient-related. Treatment of patient-related inconveniences, communication of rationale and healthcare-related imaging protocol efficiency improvements may contribute to improved adherence.

Introduction: For the detection of local recurrences of head and neck squamous cell carcinomas (HNSCC) after (chemo)radiation, diagnostic imaging is generally performed. Diffusion weighted magnetic resonance imaging (DW-MRI) has been proven to be able to adequately diagnose the presence of cancer. However evaluation of DW-MR images for recurrences is difficult and could be subject to individual interpretation.Aim: To determine the interobserver agreement, intraobserver agreement and influence of experience of radiologists in the assessment of DW-MRI in patients clinically suspected of local recurrent HNSCC after (chemo) radiation.Methods: Ten experienced head and neck radiologists assessed follow-up MRI including DW-MRI series of 10 patients for the existence of local recurrence on a two point decision scale (local recurrence or local control). Patients were clinically suspected for a recurrence of laryngeal (n = 3), hypopharyngeal (n = 3) or oropharyngeal (n = 4) cancer after (chemo)radiation with curative intent. Fleiss' and Cohen's Kappa were used to determine interobserver agreement and intraobserver agreement, respectively.Results: Interobserver agreement was kappa = 0.55. Intraobserver agreement was kappa = 0.80. Prior experience within the field of radiology and with DW-MRI had no significant influence on the scoring.Conclusion: For the assessment of HNSCC recurrence after (chemo)radiation by DW-MRI, moderate interobserver agreement and substantial intraobserver agreement was found.

With targeted treatments playing an increasing role in oncology, the need arises for fast non-invasive genotyping in clinical practice. Radiogenomics is a rapidly evolving field of research aimed at identifying imaging biomarkers useful for non-invasive genotyping. Radiogenomic genotyping has the advantage that it can capture tumor heterogeneity, can be performed repeatedly for treatment monitoring, and can be performed in malignancies for which biopsy is not available. In this systematic review of 187 included articles, we compiled a database of radiogenomic associations and unraveled networks of imaging groups and gene pathways oncology-wide. Results indicated that ill-defined tumor margins and tumor heterogeneity can potentially be used as imaging biomarkers for 1p/19q codeletion in glioma, relevant for prognosis and disease profiling. In non-small cell lung cancer, FDG-PET uptake and CT-ground-glass-opacity features were associated with treatment-informing traits including EGFR-mutations and ALK-rearrangements. Oncology-wide gene pathway analysis revealed an association between contrast enhancement (imaging) and the targetable VEGF-signalling pathway. Although the need of independent validation remains a concern, radiogenomic biomarkers showed potential for prognosis prediction and targeted treatment selection. Quantitative imaging enhanced the potential of multiparametric radiogenomic models. A wealth of data has been compiled for guiding future research towards robust non-invasive genomic profiling.

Objectives The detection of distant metastases is of major importance in management of head and neck squamous cell carcinoma patients. Design All patients underwent 18 FDG PET/CT for the detection of distant metastases. Setting Retrospective single-centre study. Participants Head and neck squamous cell carcinoma patients with high-risk factors for distant metastases. Main outcome measures Accuracy of 18 FDG PET/CT for the detection of distant metastases using clinical development of distant metastases and a minimal follow-up of twelve months as reference standard. Comparison of overall survival between patients diagnosed with distant metastases during initial screening and patients diagnosed with distant metastases during follow-up. Results In 23 (12%) of the 190 patients, 18 FDG PET/CT detected distant metastases at screening. Sensitivity and negative predictive value were 46.2% (95% CI 32.6-59.7) and 82.6% (95% CI 76.8-88.5). No difference in median overall survival from the time of distant metastases detection was found between patients diagnosed with DM during work-up or during follow-up. Conclusions In head and neck squamous cell carcinoma patients with high-risk factors, 18 FDG PET/CT has a high negative predictive value for the detection of distant metastases and should be used in daily clinical practice, although the sensitivity is limited when long-term follow-up is used as reference standard.

Aims: Our purpose was to assess the diagnostic accuracy and prognostic value of diffusion-weighted imaging (DWI) and 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) carried out 3–6 months after (chemo)radiotherapy in head and neck squamous cell carcinoma. Materials and methods: For this retrospective cohort study we included 82 patients with advanced-stage head and neck squamous cell carcinoma treated between 2012 and 2015. Primary tumours and lymph nodes were assessed separately. DWI was analysed qualitatively and quantitatively. 18F-FDG-PET/CT was evaluated using the Hopkins criteria. Dichotomous qualitative analysis was carried out for both modalities. Cox regression analysis was used for univariate analysis of recurrence-free survival (RFS). Significant univariate parameters were included in multivariate analysis. Results: In 12 patients, locoregional recurrence occurred. With all imaging strategies, either single-modality or multi-modality, a high negative predictive value (NPV) was achieved (94.3–100%). In response evaluation of the primary site, the preferred strategy is 18F-FDG-PET/CT only, which resulted in a sensitivity of 85.7%, specificity of 86.5%, positive predictive value (PPV) of 37.5% and NPV of 98.5%. For response evaluation of the neck, the best results were obtained with a sequential approach only including the second modality in positive reads of the first modality. It did not matter which modality was assessed first. This strategy for lymph node assessment resulted in a sensitivity, specificity, PPV and NPV of 83.3%, 95.6%, 62.5%, and 98.5%, respectively. After correction for received treatment and human papillomavirus status, primary tumour (P = 0.009) or lymph node (P < 0.001) Hopkins score ≥4 on 18F-FDG-PET/CT remained significant predictors of RFS. Conclusion: For response evaluation of the primary tumour 18F-FDG-PET/CT only is the preferred strategy, whereas for the neck a sequential approach including both DWI and 18F-FDG-PET/CT resulted in the best diagnostic accuracy for follow-up after (chemo)radiotherapy. Qualitative analysis of 18F-FDG-PET/CT is a stronger predictor of RFS than DWI analysis.

Background Retinoblastoma is the most common intraocular tumor in childhood with a good prognosis in terms of mortality, but detailed information about tumor morphology and disease extent in retinoblastoma is important for treatment decision making. Purpose To demonstrate ultrahigh-field MRI tumor morphology and tumor extent in retinoblastoma correlating with in and ex vivo images with histopathology. Study type Prospective case series. Population Six retinoblastoma patients (median age 5.5 months, range 2-14) were prospectively included in this study. Median time between diagnosis and enucleation was 8 days (range 7-19). Field strength/sequence In vivo pre-enucleation at 1.5T MRI with a circular surface coil. Ex vivo imaging (FLASH T1 -weighted and RARE T2 -weighted) was performed at field strengths of 9.4T and 17.6T. Assessment After ex vivo imaging, the eyes were histopathologically analyzed and morphologically matched with MRI findings by three authors (two with respectively 14 and 4 years of experience in ocular MRI and one with 16 years of experience in ophthalmopathology). Results Small submillimeter morphological aspects of intraocular retinoblastoma were successfully depicted with higher-resolution MRI and matched with histopathology images. With ex vivo MRI a small subretinal tumor seed (300 μm) adjacent to the choroid was morphologically matched with histopathology. Also, a characteristic geographical pattern of vital tumor tissue (400 μm) surrounding a central vessel interspersed with necrotic areas correlated with histopathology images. Tumor invasion into the optic nerve showed a higher signal intensity on T1 -weighted higher-resolution MRI. Data conclusion Higher-resolution MRI allows for small morphological aspects of intraocular retinoblastoma and extraocular disease extent not visible on currently used clinical in vivo MRI to be depicted. Level of evidence 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1487-1497.

The presence of distant metastases at initial evaluation influences treatment selection, since no effective systemic treatment for disseminated head and neck squamous cell carcinoma (HNSCC) is currently available. The reported sensitivity for the detection of distant metastases by contrast-enhanced (ce)CT and FDG-PET(/CT) differs substantially between studies. We hypothesized that these sensitivity values are highly dependent on the reference standard use, e.g., follow-up term. Therefore, we analyze our results of FDG-PET/CT (including chest ceCT) with long-term follow-up and compare these findings with data from the literature, with particular interest in the different reference standards. Forty-six HNSCC patients with high-risk factors underwent pretreatment screening for distant metastases by FDG-PET/CT (including chest ceCT). In 16 (35%) patients, distant metastases were detected during screening (6 patients) or during a mean follow-up of 39.4 months after screening (10 patients). The sensitivity and negative predictive value were 83.3 and 97.2% when 6 months, 60.0 and 89.9% when 12 months, and 37.5 and 72.2% when 30 months follow-up were used as reference standard, respectively. This is comparable with reported studies with similar reference standards. This critical appraisal on the reference standards used in our and reported studies shows room for improvement for the detection of distant metastases to refrain more patients from unnecessary extensive locoregional treatment for occult metastatic HNSCC.

BACKGROUND AND PURPOSE: Head and neck squamous cell carcinoma (HNSCC) may present with cervical metastases without an apparent primary tumor. Detecting the primary tumor results in more targeted treatment. Acquisition of DWI is improving with less artifacts and image distortion. We assessed the diagnostic value of DWI and 18F-FDG-PET/CT for detecting primary tumors in patients presenting with nodal metastasis of an unknown primary HNSCC.MATERIALS AND METHODS: For this retrospective study we included 31 patients (male/female ratio = 23/8, median age = 66 years, age range = 40-80 years) who presented with a pathologically proven cervical nodal metastasis from HNSCC without overt primary tumor location between January 2013 and November 2016 and underwent both DWI and 18F-FDG-PET/CT. Both modalities were assessed qualitatively and quantitatively. With ROC analysis we determined the optimal cut-off for imaging parameters in separating occult malignancy from benign tissue.RESULTS: Qualitative analysis of MRI including DWI resulted in a sensitivity of 81.3% (95%CI) = 53.7-95.0) and specificity of 73.3% (95%CI = 44.8-91.1). With qualitative scoring of 18F-FDG-PET/CT a sensitivity and specificity of 93.8% (95%CI = 67.8-99.7) and 73.3% (95%CI = 44.8-91.1) were found. With quantitative analysis sensitivity and specificity of SUVmax were 81.3% (95%CI = 53.6-95.0) and 93.3% (95%CI = 66.0-99.7), respectively. Combining DWI and 18F-FDG-PET/CT resulted in a sensitivity of 93.8% (95%CI = 67.7-99.7%) and specificity of 60.0% (95%CI = 32.9-82.5%).CONCLUSION: In this study on HNSCC patients presenting with clinically UP lesions the diagnostic accuracy of qualitative analysis with DWI and 18F-FDG-PET/CT and quantitative analysis of 18F-FDG-PET/CT using SUVmax were high. Adding DWI did not improve the accuracy of 18F-FDG-PET/CT.

Head and neck squamous cell carcinoma (HNSCC) may present with cervical metastases without an apparent primary tumor. Detecting the primary tumor results in more targeted treatment. Acquisition of DWI is improving with less artifacts and image distortion. We assessed the diagnostic value of DWI andFor this retrospective study we included 31 patients (male/female ratio = 23/8, median age = 66 years, age range = 40-80 years) who presented with a pathologically proven cervical nodal metastasis from HNSCC without overt primary tumor location between January 2013 and November 2016 and underwent both DWI andQualitative analysis of MRI including DWI resulted in a sensitivity of 81.3% (95%CI) = 53.7-95.0) and specificity of 73.3% (95%CI = 44.8-91.1). With qualitative scoring ofIn this study on HNSCC patients presenting with clinically UP lesions the diagnostic accuracy of qualitative analysis with DWI and

Purpose To identify associations between magnetic resonance (MR) imaging features and gene expression in retinoblastoma. Materials and Methods A retinoblastoma MR imaging atlas was validated by using anonymized MR images from referral centers in Essen, Germany, and Paris, France. Images were from 39 patients with retinoblastoma (16 male and 18 female patients [the sex in five patients was unknown]; age range, 5-90 months; inclusion criterion: pretreatment MR imaging). This atlas was used to compare MR imaging features with genome-wide messenger RNA (mRNA) expression data from 60 consecutive patients obtained from 1995 to 2012 (35 male patients [58%]; age range, 2-69 months; inclusion criteria: pretreatment MR imaging, genome-wide mRNA expression data available). Imaging pathway associations were analyzed by means of gene enrichment. In addition, imaging features were compared with a predefined gene expression signature of photoreceptorness. Statistical analysis was performed with generalized linear modeling of radiology traits on normalized log2-transformed expression values. P values were corrected for multiple hypothesis testing. Results Radiogenomic analysis revealed 1336 differentially expressed genes for qualitative imaging features (threshold P = .05 after multiple hypothesis correction). Loss of photoreceptorness gene expression correlated with advanced stage imaging features, including multiple lesions (P = .03) and greater eye size (P < .001). The number of lesions on MR images was associated with expression of MYCN (P = .04). A newly defined radiophenotype of diffuse-growing, plaque-shaped, multifocal tumors displayed overexpression of SERTAD3 (P = .003, P = .049, and P = .06, respectively), a protein that stimulates cell growth by activating the E2F network. Conclusion Radiogenomic biomarkers can potentially help predict molecular features, such as photoreceptorness loss, that indicate tumor progression. Results imply a possible role for radiogenomics in future staging and treatment decision making in retinoblastoma.

Background Different clinical high-risk factors for the development of distant metastases have been identified but not tested in the same cohort of patients with head and neck squamous cell carcinoma (HNSCC). Methods In 145 patients with previously identified clinical high risk factors, the presence of extranodal spread (ENS) and matted node on pretreatment CT (n = 96) and/or MRI (n = 111) were determined. Results Of 145 patients, ENS was detected in 87 patients (60.0%) and matted nodes in 53 patients (36.6%). Kaplan–Meier curves for presence or absence of ENS (on CT and/or MRI) and matted nodes (on CT) differ significantly. In a Cox regression analysis, only ENS was a significant risk factor (hazard ratio [HR] = 3.3; 95% confidence interval [CI] = 2.0–5.5; p < .001). Conclusion In patients with high-risk HNSCC with clinically (palpably or radiologically) ENS and matted nodes, both determined radiologically, are high risk factors for development of distant metastases. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

ObjectivesEvaluation of accuracy and interobserver variation of diffusion-weighted magnetic resonance imaging (DW-MRI) and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDGPET-CT) to detect residual lymph node metastases after chemoradiotherapy (CRT) in advanced staged head and neck squamous cell carcinoma (HNSCC).Materials and methodsRetrospectively, routinely performed DW-MRI (n = 73) and 18F-FDG-PET-CT (n = 58) 3 months after CRT in HNSCC-patients with advanced nodal disease (N2-N3) were assessed by two radiologists and two nuclear medicine physicians (individually and in consensus). Imaging was scored dichotomously and on a five-point Likert scale. We also explored different scenarios for the potential added value of DW-MRI to PET-CT using the consensus Likert scale. Histopathology and a follow-up of 9 months after CRT served as reference standard.ResultsFive patients (7%) had residual regional disease. DW-MRI showed a sensitivity of 60% and a specificity of 93%, vs. 100% and 84% for PET-CT, respectively. DW-MRI and PET-CT observers had ‘moderate’ and ‘substantial’ interobserver agreement (κ = 0.58 and κ = 0.64, respectively) with the dichotomous system. The combination of PET-CT and DW-MRI showed a sensitivity of 100% and a specificity of 95%.ConclusionThe high sensitivity of PET-CT authorizes a neck dissection in all patients with a positive test result and the high specificity of DW-MRI justifies avoidance of invasive neck dissections if the test is negative. Interobserver agreement varied as a function of test positivity criteria. Adding DW-MRI to PET-CT seemed to increase the specificity of PET-CT alone, thereby ensuring that less patients are exposed to unnecessary neck dissections.

BACKGROUND AND PURPOSE: DWI is typically performed with EPI sequences in single-center studies. The purpose of this study was to determine the reproducibility of ADC values in the head and neck region in healthy subjects. In addition, the reproducibility of ADC values in different tissues was assessed to identify the most suitable reference tissue. MATERIALS AND METHODS: We prospectively studied 7 healthy subjects, with EPI and TSE sequences, on 5 MR imaging systems at 3 time points in 2 institutions. ADC maps of EPI (with 2 b-values and 6 b-values) and TSE sequences were compared. Mean ADC values for different tissues (submandibular gland, sternocleidomastoid muscle, spinal cord, subdigastric lymph node, and tonsil) were used to evaluate intra- and intersubject, intersystem, and intersequence variability by using a linear mixed model. RESULTS: On 97% of images, a region of interest could be placed on the spinal cord, compared with 87% in the tonsil. ADC values derived from EPI-DWI with 2 b-values and calculated EPI-DWI with 2 b-values extracted from EPI-DWI with 6 b-values did not differ significantly. The standard error of ADC measurement was the smallest for the tonsil and spinal cord (standard error of measurement = 151.2 × 10(−6) mm/s(2) and 190.1 × 10(−6) mm/s(2), respectively). The intersystem difference for mean ADC values and the influence of the MR imaging system on ADC values among the subjects were statistically significant (P < .001). The mean difference among examinations was negligible (ie

ObjectivesTo assess disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy ([C]RT).MethodsPretreatment MR-images of 78 patients were retrospectively studied. Apparent diffusion coefficients (ADC) were calculated with two sets of two b-values: 0–750s/mm2 (ADC750) and 0–1000s/mm2 (ADC1000). One observer assessed tumor volume on T1-WI. Two independent observers assessed ADC-values of primary tumor and largest lymph node in two sessions (i.e. without and with including CE-T1WI in image analysis). Interobserver and intersession agreement were assessed with intraclass correlation coefficients (ICC) separately for ADC750 and ADC1000. Lesion volumes and ADC-values were related to DFS using Cox regression analysis.ResultsMedian follow-up was 18 months. Interobserver ICC was better without than with CE-T1WI (primary tumor: 0.92 and 0.75–0.83, respectively; lymph node: 0.81–0.83 and 0.61–0.64, respectively). Intersession ICC ranged from 0.84 to 0.89. With CE-T1WI, mean ADC-values of primary tumor and lymph node were higher at both b-values than without CE-T1WI (P

Objective Diagnosing residual malignancy after (chemo)radiotherapy presents a diagnostic challenge because of overlapping symptoms and imaging characteristics. We assessed the added diagnostic value of diffusion-weighted imaging (DWI) to positron emission tomography combined with computed tomography (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) with residual fluorodeoxyglucose (18F-FDG) uptake at the primary tumor site 3 months after (chemo)radiotherapy. Study Design For this retrospective study from January 2010 to June 2012, 22 cases (median patient age of 61 years; range 41-77 years) were included for analysis. Both PET-CT and magnetic resonance imaging (MRI), including DWI, were performed as part of the institutional protocol and were qualitatively assessed for the presence of residual malignancy at the primary tumor site. Results The sensitivity and specificity of PET-CT were 100% and 47%, respectively. For DWI, sensitivity and specificity were 80% and 82%, respectively. When DWI was added to PET-CT with residual 18F-FDG uptake, and only a positive read on both PET-CT and DWI was considered to be overall positive, sensitivity remained 80% (95% confidence interval [CI] 28%-99%), and specificity was 88% (95% CI 64%-99%). Conclusions In this pilot study of the selected patients with residual 18F-FDG uptake at the primary tumor site 3 months after (chemo)radiotherapy, we demonstrated that the addition of DWI to PET-CT has the potential to increase the specificity of the response evaluation with limited decrease in sensitivity.

Background: Retinoblastoma is the most common intraocular tumor in childhood with a good prognosis in terms of mortality, but detailed information about tumor morphology and disease extent in retinoblastoma is important for treatment decision making. Purpose: To demonstrate ultrahigh-field MRI tumor morphology and tumor extent in retinoblastoma correlating with in and ex vivo images with histopathology. Study Type: Prospective case series. Population: Six retinoblastoma patients (median age 5.5 months, range 2–14) were prospectively included in this study. Median time between diagnosis and enucleation was 8 days (range 7–19). Field Strength/Sequence: In vivo pre-enucleation at 1.5T MRI with a circular surface coil. Ex vivo imaging (FLASH T1-weighted and RARE T2-weighted) was performed at field strengths of 9.4T and 17.6T. Assessment: After ex vivo imaging, the eyes were histopathologically analyzed and morphologically matched with MRI findings by three authors (two with respectively 14 and 4 years of experience in ocular MRI and one with 16 years of experience in ophthalmopathology). Results: Small submillimeter morphological aspects of intraocular retinoblastoma were successfully depicted with higher-resolution MRI and matched with histopathology images. With ex vivo MRI a small subretinal tumor seed (300 μm) adjacent to the choroid was morphologically matched with histopathology. Also, a characteristic geographical pattern of vital tumor tissue (400 μm) surrounding a central vessel interspersed with necrotic areas correlated with histopathology images. Tumor invasion into the optic nerve showed a higher signal intensity on T1-weighted higher-resolution MRI. Data Conclusion: Higher-resolution MRI allows for small morphological aspects of intraocular retinoblastoma and extraocular disease extent not visible on currently used clinical in vivo MRI to be depicted. Level of Evidence: 4. Technical Efficacy: Stage 2. J. Magn. Reson. Imaging 2018;47:1487–1497.

Intravoxel incoherent motion (IVIM) imaging is increasingly applied in the assessment of head and neck cancer (HNC). Our purpose was to determine the diagnostic and prognostic performance of IVIM in HNC by performing a critical review of the literature. Pubmed and EMBASE were searched until May 2016. Study and patients characteristics, imaging protocol and diagnostic or prognostic outcomes were extracted by 2 independent reviewers. The studied IVIM parameters were diffusion coefficient (D), pseudodiffusion coefficient (D∗), and perfusion fraction (f). We included 10 diagnostic studies, 5 prognostic studies and 2 studies assessing both. Studies were very heterogeneous in terms of applied b-values, imaging protocols, outcome measurements and reference standards; therefore we did not perform a meta-analysis. The most commonly used sequence was “spin-echo planar imaging”. A median of 10.5 b-values (range, 3–17) were used. All but three studies included at least 4 b-values below b = 200 s/mm2. By combining IVIM-parameters squamous cell carcinomas, lymphomas, malignant salivary gland tumors, Warthin's tumors and pleomorphic adenomas could be differentiated with a sensitivity of 85–87% and specificity of 80–100%. Low pre-treatment D or f and an increase in D during treatment were associated with a favorable response to treatment. D∗ appeared to be the parameter with the lowest prognostic value. Future research should focus on finding the optimal IVIM protocol, using uniformly accepted study methods and larger patient populations.

Contains fulltext : 174260.pdf (Publisher’s version ) (Open Access) BACKGROUND: Considerable variation exists in diagnostic tests used for local response evaluation after chemoradiation in patients with advanced oropharyngeal cancer. The yield of invasive examination under general anesthesia (EUA) with biopsies in all patients is low and it may induce substantial morbidity. We explored four response evaluation strategies to detect local residual disease in terms of diagnostic accuracy and cost-effectiveness. METHODS: We built a decision-analytic model using trial data of forty-six patients and scientific literature. We estimated for four strategies the proportion of correct diagnoses, costs concerning diagnostic instruments and the proportion of unnecessary EUA indications. Besides a reference strategy, i.e. EUA for all patients, we considered three imaging strategies consisting of 18FDG-PET-CT, diffusion-weighted MRI (DW-MRI), or both 18FDG-PET-CT and DW-MRI followed by EUA after a positive test. The impact of uncertainty was assessed in sensitivity analyses. RESULTS: The EUA strategy led to 96% correct diagnoses. Expected costs were euro468 per patient whereas 89% of EUA indications were unnecessary. The DW-MRI strategy was the least costly strategy, but also led to the lowest proportion of correct diagnoses, i.e. 93%. The PET-CT strategy and combined imaging strategy were dominated by the EUA strategy due to respectively a smaller or equal proportion of correct diagnoses, at higher costs. However, the combination of PET-CT and DW-MRI had the highest sensitivity. All imaging strategies considerably reduced (unnecessary) EUA indications and its associated burden compared to the EUA strategy. CONCLUSIONS: Because the combined PET-CT and DW-MRI strategy costs only an additional euro927 per patient, it is preferred over immediate EUA since it reaches the same diagnostic accuracy in detecting local residual disease while leading to substantially less unnecessary EUA indications. However, if healthcare resources are limited, DW-MRI is the strategy of choice because of lower costs while still providing a large reduction in unnecessary EUA indications.

Contains fulltext : 153872.pdf (Publisher’s version ) (Closed access) Following failure of chemoradiotherapy (CRT) for advanced staged oropharyngeal squamous cell carcinomas (OPSCC), residual tumor can often be treated successfully with salvage surgery, if detected early. Current clinical practice in the VU University Medical Center is to perform routine response evaluation, i.e., examination under general anesthesia (EUA), 12 weeks after treatment. However, in the Netherlands there is no consensus on response evaluation in patients with advanced oropharyngeal cancer. Questionnaire on current clinical practice concerning response evaluation after CRT for advanced OPSCC in all eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group. The response rate was 100 %. Response evaluation was routinely performed with various methods in five institutions (62.5 %) and in one institute (12.5 %) only if clinical evaluation was difficult. Two centers (25 %) did not perform response evaluation. In case of suspicion of residual disease during follow-up, six centers (75 %) performed imaging prior to EUA and two centers (25 %) only if clinical evaluation was difficult. Diagnostic techniques used prior to EUA were MRI (87.5 %), diffusion-weighted MRI (37.5 %), 18F-FDG-PET-CT (75-87.5 %) and CT (37.5 %). This survey shows a substantial variation in the diagnostic policy concerning response evaluation after CRT for advanced OPSCC in the Netherlands. There is a need for guidelines for response evaluation in patients with advanced oropharyngeal cancer.

Regional metastasis is a prominent feature of head and neck squamous cell carcinoma (HNSCC) and is an important prognostic factor. The currently available imaging techniques for assessment of the neck have limitations in accuracy; thus, elective neck dissection has remained the usual choice of management of the clinically N0 neck (cN0) for tumors with significant (≥20%) incidence of occult regional metastasis. As a consequence, the majority of patients without regional metastasis will undergo unnecessary treatment. The purpose of this review was to discuss new developments in techniques that potentially improve the accuracy of the assessment of the neck in patients with HNSCC. Although imaging has improved in the last decades, a limitation common to all imaging techniques is a lack of sensitivity for small tumor deposits. Therefore, complementary to improvements in imaging techniques, developments in more invasive diagnostic procedures, such as sentinel node biopsy (SNB) will add to the accuracy of diagnostic algorithms for the staging of the neck.

Purpose To determine and compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) for the diagnosis of tumor extent in advanced retinoblastoma, using histopathologic analysis as the reference standard. Design Systematic review and meta-analysis. Participants Patients with advanced retinoblastoma who underwent MRI, CT, or both for the detection of tumor extent from published diagnostic accuracy studies. Methods Medline and Embase were searched for literature published through April 2013 assessing the diagnostic performance of MRI, CT, or both in detecting intraorbital and extraorbital tumor extension of retinoblastoma. Diagnostic accuracy data were extracted from included studies. Summary estimates were based on a random effects model. Intrastudy and interstudy heterogeneity were analyzed. Main Outcome Measures Sensitivity and specificity of MRI and CT in detecting tumor extent. Results Data of the following tumor-extent parameters were extracted: anterior eye segment involvement and ciliary body, optic nerve, choroidal, and (extra)scleral invasion. Articles on MRI reported results of 591 eyes from 14 studies, and articles on CT yielded 257 eyes from 4 studies. The summary estimates with their 95% confidence intervals (CIs) of the diagnostic accuracy of conventional MRI at detecting postlaminar optic nerve, choroidal, and scleral invasion showed sensitivities of 59% (95% CI, 37%–78%), 74% (95% CI, 52%–88%), and 88% (95% CI, 20%–100%), respectively, and specificities of 94% (95% CI, 84%–98%), 72% (95% CI, 31%–94%), and 99% (95% CI, 86%–100%), respectively. Magnetic resonance imaging with a high (versus a low) image quality showed higher diagnostic accuracies for detection of prelaminar optic nerve and choroidal invasion, but these differences were not statistically significant. Studies reporting the diagnostic accuracy of CT did not provide enough data to perform any meta-analyses. Conclusions Magnetic resonance imaging is an important diagnostic tool for the detection of local tumor extent in advanced retinoblastoma, although its diagnostic accuracy shows room for improvement, especially with regard to sensitivity. With only a few—mostly old—studies, there is very little evidence on the diagnostic accuracy of CT, and generally these studies show low diagnostic accuracy. Future studies assessing the role of MRI in clinical decision making in terms of prognostic value for advanced retinoblastoma are needed.

Recently, a new MRI technique was developed at 3 Tesla (T), called fluid attenuated inversion recovery* (FLAIR*). In this study, we implemented FLAIR* in an existing MS cohort at 7 T, to investigate whether we could corroborate results of previous 7 T studies that introduced specific MS lesion characteristics. Furthermore, we aimed to investigate the meaning of these lesion characteristics by relating them to clinical characteristics of the MS patient. Three-dimensional FLAIR and T2*-weighted images of 33 MS patients and 7 healthy controls were fused into FLAIR* images. Lesion type, signal intensity and morphology were analysed on FLAIR*, side-by-side with the original FLAIR and T2*, and correlated with clinical characteristics using Spearman’s rho. Three morphological features of MS lesions were visualised: (1) central vessel (CV) within lesions, present in 78 % of total MS lesions; (2) hypointense rims around MS lesions, present in eight patients; (3) FLAIR* lesions that were hypointense at T2*, present in 13 patients. The presence of hypointense (rims around) lesions was not related to clinical characteristics. The simultaneous presence of rimlike lesions and hypointense lesions within MS patients was significantly correlated (ρ = 0.52, P

Diagnosing residual malignancy after (chemo)radiotherapy presents a diagnostic challenge because of overlapping symptoms and imaging characteristics. We assessed the added diagnostic value of diffusion-weighted imaging (DWI) to positron emission tomography combined with computed tomography (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) with residual fluorodeoxyglucose (For this retrospective study from January 2010 to June 2012, 22 cases (median patient age of 61 years; range 41-77 years) were included for analysis. Both PET-CT and magnetic resonance imaging (MRI), including DWI, were performed as part of the institutional protocol and were qualitatively assessed for the presence of residual malignancy at the primary tumor site.The sensitivity and specificity of PET-CT were 100% and 47%, respectively. For DWI, sensitivity and specificity were 80% and 82%, respectively. When DWI was added to PET-CT with residualIn this pilot study of the selected patients with residual

This systematic review gives an extensive overview of the current state of functional imaging during (chemo)radiotherapy to predict locoregional control (LRC) and overall survival (OS) for head and neck squamous cell carcinoma. MEDLINE and EMBASE were searched for literature until April 2018 assessing the predictive performance of functional imaging (computed tomography perfusion (CTp), MRI and positron-emission tomography (PET)) within 4 weeks after (chemo)radiotherapy initiation. Fifty-two studies (CTp: n = 4, MRI: n = 19, PET: n = 26, MRI/PET: n = 3) were included involving 1623 patients. Prognostic information was extracted according the PRISMA protocol. Pooled estimation and subgroup analyses were performed for comparable parameters and outcome. However, the heterogeneity of included studies limited the possibility for comparison. Early tumoral changes from (chemo)radiotherapy can be captured by functional MRI and 18F-FDG-PET and could allow for personalized treatment adaptation. Lesions showed potentially prognostic intratreatment changes in perfusion, diffusion and metabolic activity. Intratreatment ADCmean increase (decrease of diffusion restriction) and low SUVmax (persistent low or decrease of 18F-FDG uptake) were most predictive of LRC. Intratreatment persistent high or increase of perfusion on CT/MRI (i.e. blood flow, volume, permeability) also predicted LRC. Low SUVmax and total lesion glycolysis (TLG) predicted favorable OS. The optimal timing to perform functional imaging to predict LRC or OS was 2–3 weeks after treatment initiation.

ObjectivesManagement of the clinically N0 neck in oral cancer patients remains controversial. We describe the outcome of patients with T1-T2 oral cancer and N0 neck based on ultrasound guided fine needle aspiration cytology (USgFNAC) who were treated by transoral excision and followed by a ‘wait and scan’ policy (W&S).Patients and methodsThis retrospective analysis included 285 consecutive patients of whom 234 were followed by W&S and 51 underwent elective neck dissection (END). Survival rates were compared between groups and correction for confounding factors was performed.ResultsOf W&S patients, the 5-year disease-specific (DSS) and overall survival (OS) were 94.2% and 81.6% respectively. During follow-up 72.2% remained free of lymph node metastases and 27.8% developed delayed metastases. W&S patients with delayed metastases had a 5-year DSS and OS of 80.0% and 62.8%, respectively. In patients with positive END these rates were 81.3% and 64.2%, respectively. Between the groups, survival rates were not significantly different. Of the W&S patients with delayed metastases, 90.6% needed adjuvant radiotherapy versus 55.0% of patients with positive END.ConclusionWith regard to survival, in patients with early stage oral cancer and cN0 neck a ‘wait and scan’ policy using strict USgFNAC surveillance is justified as survival is not negatively influenced. Using a ‘wait and scan’ follow-up strategy instead of elective neck treatment, unnecessary neck dissection and its accompanying morbidity can be avoided in 72.2% of patients. However, for the small proportion of patients with delayed metastases, more extensive treatment with adjuvant radiotherapy is needed.

Introduction Hereditary retinoblastoma survivors have an increased risk for cranio-facial second primary tumours (SPT), especially after treatment with external beam radiotherapy (EBRT). This multicentre study evaluates the clinical and imaging characteristics and outcomes of cranio-facial SPTs in irradiated retinoblastoma survivors. Patients and Methods Clinical and radiological data of 42 hereditary retinoblastoma patients with 44 second and third malignancies were reviewed. Radiological data included anatomic location and computed tomography (CT) and magnetic resonance (MR) characteristics. Cox regression and likelihood ratio chi-square test were used to evaluate differences in patients' survival rates. Results Cranio-facial SPTs were diagnosed at a median age of 13years. Histological types included osteosarcomas (43%), rhabdomyosarcomas (20%) (57% embryonal, 43% alveolar) and a variety of other types of SPT (37%). Predilection sites were: temporal fossa (39%), ethmoid sinus (23%), orbit (18%), maxillary sinus (16%) and intracranial dura mater (4%). Most of the osteosarcomas (78%) and rhabdomyosarcomas (80%) occurred in patients treated with EBRT in the first year-of-life. Treatment of SPTs with a microscopically complete surgical resection led to a significantly better 5-year overall survival (OS) ( P =0.017) and event-free survival (EFS) ( P =0.012) compared to patients treated without surgery or incomplete resection (OS: 83% versus 52%; EFS: 80% versus 47%). Conclusions Osteosarcomas and rhabdomyosarcomas are the most common cranio-facial SPTs in irradiated hereditary retinoblastoma survivors, which develop in specific locations and occur predominantly in patients irradiated in their first year-of-life. Microscopically complete surgical resection of SPTs is a major prognostic factor, suggesting the potential benefit of early detection by imaging.

Purpose Orbital tumor recurrence is a rare but serious complication in children with retinoblastoma, leading to a high risk of metastasis and death. Therefore, we assume that these recurrences have to be detected and treated as early as possible. Preliminary studies used magnetic resonance imaging (MRI) to evaluate postsurgical findings in the orbit. In this study, we assessed the diagnostic accuracy of high-resolution MRI to detect orbital tumor recurrence in children with retinoblastoma in a large study cohort. Design Consecutive retrospective study (2007–2013) assessing MRI findings after enucleation. Participants A total of 103 MRI examinations of 55 orbits (50 children, 27 male/23 female, mean age 16.3±12.4 months) with a median time of 8 months (range, 0–93) after enucleation for retinoblastoma. Methods High-resolution MRI using orbital surface coils was performed on 1.5 Tesla MRI systems to assess abnormal orbital findings. Main Outcome Measures Five European experts in retinoblastoma imaging evaluated the MRI examinations regarding the presence of abnormal orbital gadolinium enhancement and judged them as "definitive tumor," "suspicious of tumor," "postsurgical condition/scar formation," or "without pathologic findings." The findings were correlated to histopathology (if available), MRI, and clinical follow-up. Results Abnormal orbital enhancement was a common finding after enucleation (100% in the first 3 months after enucleation, 64.3% >3 years after enucleation). All histopathologically confirmed tumor recurrences (3 of 55 orbits, 5.5%) were correctly judged as "definitive tumor" in MRI. Two orbits from 2 children rated as "suspicious of tumor" received intravenous chemotherapy without histopathologic confirmation; further follow-up (67 and 47 months) revealed no sign of tumor recurrence. In 90.2%, no tumor was suspected on MRI, which was clinically confirmed during follow-up (median follow-up after enucleation, 45 months; range, 8–126). Conclusions High-resolution MRI with orbital surface coils may reliably distinguish between common postsurgical contrast enhancement and orbital tumor recurrence, and therefore may be a useful tool to evaluate orbital tumor recurrence after enucleation in children with retinoblastoma. We recommend high-resolution MRI as a potential screening tool for the orbit in children with retinoblastoma to exclude tumor recurrence, especially in high-risk patients within the critical first 2 years after enucleation.

BACKGROUND AND PURPOSE: Noninvasive evaluation of retinoblastoma treatment response has become more important due to increased use of eye-sparing treatments. We evaluated the relation between DCE-MR imaging and histopathologic parameters to determine the value of DCE-MR imaging in assessing tumor angiogenesis and prognostic features. MATERIALS AND METHODS: Fifteen consecutive patients with retinoblastoma (mean age, 24 months; range, 2–70 months) undergoing enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was evaluated by 2 observers by using curve-pattern analysis, with the first 5 minutes of each curve and the full time-series described as κ 5min and κ 17min , respectively. Assessed histopathologic and immunologic parameters included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and expression of VEGF and Flt-1. RESULTS: The median value of κ 5min was 1.28 (range, 0.87–2.07) and correlated positively with MVD ( P = .008). The median value of κ 17min was 1.33 (range, 0.35–3.08) and correlated negatively with tumor necrosis ( P = .002). Other histopathologic and immunohistopathologic parameters did not correlate with DCE-MR imaging parameters. Interobserver agreement was 0.53 for κ 5min and 0.91 for κ 17min . CONCLUSIONS: In retinoblastoma, the early phase of the DCE time curve positively correlates with MVD, while the presence of late enhancement is correlated with necrosis. Thus, the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and necrosis in retinoblastoma is promising and warrants further investigation.

Patients with hereditary retinoblastoma (Rb) have an increased risk of developing pineoblastoma.1 Unfortunately, most patients with concurrent pineoblastoma do not survive; Kivelä2 has shown that only patients who were diagnosed by screening and had a tumor smaller than 15 mm had a chance of survival. However, not all pineal lesions found with screening at the time of retinoblastoma diagnosis are pineoblastomas. Pineal cysts are a relatively common finding in the general population. In children up to 5 years of age the prevalence of pineal cysts diagnosed with magnetic resonance imaging (MRI) is 2.0%.3 Potentially, about 50% of pineoblastomas can be found at baseline screening and another 25% during the first year after Rb diagnosis.2 Therefore, baseline screening of the brain in newly diagnosed retinoblastoma is currently advised in imaging guidelines.4 In a recent study Rodjan and colleagues5 showed that the majority of pineoblastomas in Rb patients had a cystic appearance. Consequently baseline brain imaging with extended follow-up of pineal cysts might help early detection of pineoblastoma. We present a rare case of unilateral familial retinoblastoma and a suspicious cystic pineal gland on brain MR imaging that progressed into a pineoblastoma.

To investigate changes in hippocampal functional connectivity and structural measures of hippocampal damage in multiple sclerosis (MS) patients with intact spatial memory, a cognitive domain frequently affected in progressive MS.The study protocol was approved by the institutional ethics review board; all subjects gave written informed consent prior to participation. Twenty-five MS patients with intact spatial memory function were compared with 30 age- and sex-matched controls. Hippocampal volume differences, based on manually drawn masks, were evaluated by using the Student t test. Additionally, focal hippocampal lesions and mean diffusivity were obtained as descriptive measures of structural hippocampal damage. Multiple regression analyses of the resting-state functional magnetic resonance (MR) imaging data were performed for each subject by using hippocampal time series. Between-group analyses were conducted with a mixed-effects model, corrected for multiple comparisons by a cluster defining threshold level of z = 2 and a corrected cluster size significance level of P.05.Right hippocampal volume was significantly lower in MS patients as compared with controls (P.01). Left hippocampal volume was also lower in MS patients compared with controls, but not significantly so (P = .09). Resting-state functional connectivity between the hippocampus and its anatomic input or target areas, including the anterior cingulate gyrus, thalamus, and prefrontal cortex, were significantly decreased in MS patients. Decreased hippocampal functional connectivity was more pronounced in a subgroup of MS patients with hippocampal atrophy, although subtle decreases of functional connectivity were also found in patients with normal hippocampal volume.In MS patients, substantial abnormalities of hippocampal functional connectivity are already present before spatial memory function is impaired, especially in those patients with more pronounced hippocampal atrophy. Longitudinal studies should now assess whether these functional connectivity and structural changes may precede memory impairment in MS.