Indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcoma: A study of the European paediatric Soft Tissue Sarcoma Study Group.

BACKGROUND: The aim of this study was to assess the clinical impact of indeterminate pulmonary nodules (no more than four pulmonary nodules of less than 5 mm or one nodule measuring between 5 and less than 10 mm by computed tomography [CT]) in children and adolescents with adult-type non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) at diagnosis. METHODS: Patients with NRSTS treated in 11 centers as part of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) were retrospectively assessed. Local radiologists, blinded to clinical information except for patients' age and tumor histotype, reviewed the chest CT at diagnosis and filled out a case report form. Because patients with or without indeterminate nodules in the EpSSG NRSTS 2005 study received the same type of treatment, event-free survival (EFS) and overall survival (OS) between groups by log-rank test were compared. RESULTS: Overall, 206 patients were examined: 109 (52.9%) were without any nodules, 78 (38%) had at least one indeterminate nodule, and 19 (9.2%) had nodules meeting the definition of metastases, which were then considered to be misclassified and were excluded from further analyses. Five-year EFS was 78.5% (95% CI, 69.4%-85.1%) for patients without nodules and 69.6% (95% CI, 57.9%-78.7%) for patients with indeterminate nodules (p = .135); 5-year OS was 87.4% (95% CI, 79.3%-92.5%) and 79.0% (95% CI, 67.5%-86.8%), respectively (p = .086). CONCLUSIONS: This study suggests that survival does not differ in otherwise nonmetastatic patients with indeterminate pulmonary nodules compared to nonmetastatic patients without pulmonary nodules. PLAIN LANGUAGE SUMMARY: Radiologists should be aware of the classification of indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcomas and use it in their reports. More than a third of patients with non-rhabdomyosarcoma soft tissue sarcoma can be affected by indeterminate pulmonary nodules. Indeterminate pulmonary nodules do not significantly affect the overall survival of pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma.

Use of Pretreatment Perfusion MRI-based Intratumoral Heterogeneity to Predict Pathologic Response of Triple-Negative Breast Cancer to Neoadjuvant Chemoimmunotherapy.

Background Neoadjuvant chemoimmunotherapy (NACI) has significantly increased the rate of pathologic complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC), although predictors of response to this regimen have not been identified. Purpose To investigate pretreatment perfusion MRI-based radiomics as a predictive marker for pCR in patients with TNBC undergoing NACI. Materials and Methods This prospective study enrolled women with early-stage TNBC who underwent NACI at two different centers from August 2021 to July 2023. Pretreatment dynamic contrast-enhanced MRI scans obtained using scanners from multiple vendors were analyzed using the Tofts model to segment tumors and analyze pharmacokinetic parameters. Radiomics features were extracted from the rate constant for contrast agent plasma-to-interstitial transfer (or Ktrans), volume fraction of extravascular and extracellular space (Ve), and maximum contrast agent uptake rate (Slopemax) maps and analyzed using unsupervised correlation and least absolute shrinkage and selector operator, or LASSO, to develop a radiomics score. Score effectiveness was assessed using the area under the receiver operating characteristic curve (AUC), and multivariable logistic regression was used to develop a multimodal nomogram for enhanced prediction. The discrimination, calibration, and clinical utility of the nomogram were evaluated in an external test set. Results The training set included 112 female participants from center 1 (mean age, 52 years ± 11 [SD]), and the external test set included 83 female participants from center 2 (mean age, 47 years ± 11). The radiomics score demonstrated an AUC of 0.80 (95% CI: 0.70, 0.89) for predicting pCR. A nomogram incorporating the radiomics score, grade, and Ki-67 yielded an AUC of 0.86 (95% CI: 0.78, 0.94) in the test set. Associations were found between higher radiomics score (>0.25) and tumor size (P < .001), washout enhancement (P = .01), androgen receptor expression (P = .009), and programmed death ligand 1 expression (P = .01), demonstrating a correlation with tumor immune environment in participants with TNBC. Conclusion A radiomics score derived from pharmacokinetic parameters at pretreatment dynamic contrast-enhanced MRI exhibited good performance for predicting pCR in participants with TNBC undergoing NACI, and could potentially be used to enhance clinical decision making. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Rauch in this issue.

Correlation of gene expression with magnetic resonance imaging features of retinoblastoma: a multi-center radiogenomics validation study.

OBJECTIVES: To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma. METHODS: In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort. RESULTS: Thirty-six retinoblastoma patients were included, 15 were female (42%), and mean age was 24 (SD 18) months. Similar to the prior evaluation, this validation study showed that low photoreceptorness gene expression was associated with advanced stage imaging features. Validated imaging features associated with low photoreceptorness were multifocality, a tumor encompassing the entire retina or entire globe, and a diffuse growth pattern (all p < 0.05). There were a number of radiogenomic associations that were also not validated. CONCLUSIONS: A part of the radiogenomic associations could not be validated, underlining the importance of validation studies. Nevertheless, cross-center validation of imaging features associated with photoreceptorness gene expression highlighted the capability radiogenomics to non-invasively inform on molecular subtypes in retinoblastoma. CLINICAL RELEVANCE STATEMENT: Radiogenomics may serve as a surrogate for molecular subtyping based on histopathology material in an era of eye-sparing retinoblastoma treatment strategies. KEY POINTS: • Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. • A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. • Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma.

Image-guided core-needle or surgical biopsy for neuroblastoma diagnosis in children: A systematic review and meta-analysis from the International Society of Pediatric Surgical Oncology (IPSO).

BACKGROUND: Image-guided core-needle biopsy (IGCNB) is a widely used and valuable clinical tool for tissue diagnosis of pediatric neuroblastoma. However, open surgical biopsy remains common practice even if children undergo more invasive and painful procedures. This review aims to determine the diagnostic accuracy and safety of IGCNBs in pediatric patients with neuroblastoma. METHODS: We conducted a systematic review of peer-reviewed original articles published between 1980 and 2023, by searching "pediatric oncology," "biopsy," "interventional radiology," and "neuroblastoma." Exclusion criteria were patients older than 18 years, studies concerning non-neurogenic tumors, case reports, and language other than English. Both the systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of 533 abstracts articles were analyzed. Of these, eight retrospective studies met inclusion criteria (490 infants, 270 surgical biopsies [SB], 220 image-guided biopsies). Tissue adequacy for primary diagnosis (SB: n = 265, 98%; IGCNB: n = 199, 90%; p = .1) and biological characterization (SB: n = 186, 95%; IGCNB: n = 109, 89%; p = .15) was similar with both biopsy techniques, while intraoperative transfusion rate (SB: n = 51, 22%; IGCNB: n = 12, 6%; p = .0002) and complications (%) (SB: n = 58, 21%; IGCNB: n = 14, 6%; p = .005) were higher with surgical biopsy. Length of stay was similar in both groups; however, no additional data about concurrent diagnostic or treatment procedures were available in the analyzed studies. CONCLUSIONS: IGCNB is a safe and effective strategic approach for diagnostic workup of NB and should be considered in preferance to SB wherever possible.

A subset of image-defined risk factors predict completeness of resection in children with high-risk neuroblastoma: An international multicenter study.

BACKGROUND: Image-defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high-risk NB was interrogated to answer this question. DESIGN/METHODS: Patients with high-risk NB (age <20 years) were eligible if cross-sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from operative reports. RESULTS: There were 211 of 229 patients with IDRFs at diagnosis, and 171 patients with IDRFs present pre-surgery. A ≥90% resection was significantly more likely in the absence of tumor invading or encasing the porta hepatis, hepatoduodenal ligament, superior mesenteric artery (SMA), renal pedicles, abdominal aorta/inferior vena cava (IVC), iliac vessels, and/or diaphragm at diagnosis or an overlapping subset of IDRFs (except diaphragm) at pre-surgery. There were no significant differences in event-free survival (EFS) and overall survival (OS) when patients were stratified by the presence versus absence of any IDRF either at diagnosis or pre-surgery. CONCLUSION: Two distinct but overlapping subsets of IDRFs present either at diagnosis or after induction chemotherapy significantly influence the probability of a complete resection in children with high-risk NB. The presence of IDRFs was not associated with significant differences in OS or EFS in this cohort.

MRI Features for Identifying MYCN-amplified RB1 Wild-type Retinoblastoma.

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.

Optic nerve thickening on high-spatial-resolution MRI predicts early-stage postlaminar optic nerve invasion in retinoblastoma.

OBJECTIVES: To assess the diagnostic accuracy of nerve thickening on MRI to predict early-stage postlaminar optic nerve invasion (PLONI) in retinoblastoma. Furthermore, this study aimed to incorporate measurements into a multiparametric model for radiological determination of PLONI. METHODS: In this retrospective multicenter case-control study, high-spatial-resolution 3D T2-weighted MR images were used to measure the distal optic nerve. Histopathology was the reference standard for PLONI. Two neuroradiologists independently measured the optic nerve width, height, and surface at 0, 3, and 5 mm from the most distal part of the optic nerve. Subsequently, PLONI was scored on contrast-enhanced T1-weighted and 3D T2-weighted images, blinded for clinical data. Optic nerve measurements with the highest diagnostic accuracy for PLONI were incorporated into a prediction model for radiological determination of PLONI. RESULTS: One hundred twenty-four retinoblastoma patients (median age, 22 months [range, 0-113], 58 female) were included, resulting in 25 retinoblastoma eyes with histopathologically proven PLONI and 206 without PLONI. ROC analysis of axial optic nerve width measured at 0 mm yielded the best area under the curve of 0.88 (95% confidence interval: 0.79, 0.96; p < 0.001). The optimal width cutoff was ≥ 2.215 mm, with a sensitivity of 84% (95% CI: 64, 95%) and specificity of 83% (95% CI: 75, 89%) for detecting PLONI. Combining width measurements with the suspicion of PLONI on MRI sequences resulted in a prediction model with an improved sensitivity and specificity of respectively up to 88% and 92%. CONCLUSION: Postlaminar optic nerve thickening can predict early-stage postlaminar optic nerve invasion in retinoblastoma. CLINICAL RELEVANCE STATEMENT: This study provides an additional tool for clinicians to help determine postlaminar optic nerve invasion, which is a risk factor for developing metastatic disease in retinoblastoma patients. KEY POINTS: • The diagnostic accuracy of contrast-enhanced MRI for detecting postlaminar optic nerve invasion is limited in retinoblastoma patients. • Optic nerve thickening can predict postlaminar optic nerve invasion. • A prediction model combining MRI features has a high sensitivity and specificity for detecting postlaminar optic nerve invasion.

French survey of sedation practices for pediatric magnetic resonance and computed tomography imaging.

BACKGROUND: Pediatric magnetic resonance imaging (MRI) and computed tompgraphy (CT) require patient immobility and therefore often require sedation or general anesthesia of patients. Consensus on these procedures is lacking in France. OBJECTIVE: Thus, the aim of this study was to describe the current sedation practices for pediatric MRI and CT in France. MATERIAL AND METHODS: From January 2019 to December 2019, an online questionnaire was delivered by electronic mail to a representative radiologist in 60 pediatric radiology centers registered by the French-speaking pediatric and prenatal imaging society. Questions included protocols, drugs used, monitoring and side effects. RESULTS: Representatives of 40 of the 60 (67%) radiology centers responded to the survey. Among them, 31 performed sedation including 17 (55%) centers where radiologists performed sedation without anesthesiologists present during the procedure. The premedication drugs were hydroxyzine (n = 8, 80%) and melatonin (n = 2, 20%), Sedation drugs used for children ages 0 to 6 years old were pentobarbital (n = 9, 60%), midazolam (n = 2, 13%), chloral hydrate (n = 2, 13%), diazepam (n = 1, 6.5%) and chlorpromazine (n = 1, 6.5%). A written sedation protocol was available in 10/17 (59%) centers. In 6/17 (35%) centers, no monitoring was used during the procedures. Blood pressure monitoring and capnography were rarely used (< 10%) and post-sedation monitoring was heterogeneous. No life-threatening adverse effect was reported, but 6 centers reported at least one incident per year. CONCLUSION: For half of the responding radiology centers, radiologists performed sedation alone in agreement with the local anesthesiology team. Sedation procedures and monitoring were heterogenous among centers. Adjustment and harmonization of the practices according to the capacity of each center may be useful.

Magnetic Resonance Imaging Can Reliably Differentiate Optic Nerve Inflammation from Tumor Invasion in Retinoblastoma with Orbital Cellulitis.

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.

MRI Characteristics of Pediatric Renal Tumors: A SIOP-RTSG Radiology Panel Delphi Study.

BACKGROUND: The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based treatment initiation, but only for a relatively small percentage of approximately 10% of non-Wilms tumors (non-WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics. PURPOSE: To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors. STUDY TYPE: Consensus process using a Delphi method. POPULATION: Not applicable. FIELD STRENGTH/SEQUENCE: Abdominal MRI including T1- and T2-weighted imaging, contrast-enhanced MRI, and diffusion-weighted imaging at 1.5 or 3 T. ASSESSMENT: Twenty-three radiologists from the SIOP-RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5-point Likert scales, ranking- and multiple choice questions. STATISTICAL TESTS: The cut-off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale. RESULTS: Consensus on specific characteristics mainly concerned the discrimination between WTs and non-WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors. DATA CONCLUSION: Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3.