Imaging of pediatric calvarial and skull base tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper.

A standardized imaging protocol for pediatric oncology patients is essential for accurate and efficient imaging, while simultaneously promoting collaborative understanding of pathologies and radiologic assessment of treatment response. The objective of this article is to provide standardized pediatric imaging guidelines and parameters for evaluation of tumors of the pediatric orbit, calvarium, skull base, and temporal bone. This article was drafted based on current scientific literature as well as consensus opinions of imaging experts in collaboration with the Children's Oncology Group Diagnostic Imaging Committee, Society of Pediatric Radiology Oncology Committee, and American Society of Pediatric Neuroradiology.

Imaging in Chiari I Malformation.

Chiari I Malformation represents a hindbrain anomaly best demonstrated radiographically with MRI. Brain and spine MRI provide optimal anatomic detail of cerebellar tonsillar descent below the foramen magnum and may reveal additional imaging features including ventriculomegaly (potentially leading to the diagnosis of hydrocephalus), characteristics of intracranial hypertension or hypotension, spinal cord syrinx, scoliosis, and/or tethered spinal cord. Specialized imaging sequences provide enhanced visualization of ventral and dorsal cervicomedullary cisterns and cerebrospinal fluid flow. Although these studies contribute critical information for evaluation, their impact on surgical decision-making remains uncertain. Additional radiographic measures (pBC2 and clival-axial angle) may impact surgical planning and risk assessment.

A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study.

BACKGROUND: Pediatric low-grade gliomas (pLGGs) are the most common childhood brain tumor. Progression-free survival (PFS) is much lower than overall survival, emphasizing the need for alternative treatments. Sporadic (without neurofibromatosis type 1) optic pathway and hypothalamic gliomas (OPHGs) are often multiply recurrent and cause significant visual deficits. Recently, there has been a prioritization of functional outcomes. METHODS: We present results from children with recurrent/progressive OPHGs treated on a PBTC (Pediatric Brain Tumor Consortium) phase II trial evaluating efficacy of selumetinib (AZD6244, ARRY-142886) a MEK-1/2 inhibitor. Stratum 4 of PBTC-029 included patients with sporadic recurrent/progressive OPHGs treated with selumetinib at the recommended phase II dose (25mg/m2/dose BID) for a maximum of 26 courses. RESULTS: Twenty-five eligible and evaluable patients were enrolled with a median of 4 (1-11) previous therapies. Six of 25 (24%) had partial response, 14/25 (56%) had stable disease, and 5 (20%) had progressive disease while on treatment. The median treatment courses were 26 (2-26); 14/25 patients completed all 26 courses. Two-year PFS was 78 ± 8.5%. Nineteen of 25 patients were evaluable for visual acuity which improved in 4/19 patients (21%), was stable in 13/19 (68%), and worsened in 2/19 (11%). Five of 19 patients (26%) had improved visual fields and 14/19 (74%) were stable. The most common toxicities were grade 1/2 CPK elevation, anemia, diarrhea, headache, nausea/emesis, fatigue, AST and ALT increase, hypoalbuminemia, and rash. CONCLUSIONS: Selumetinib was tolerable and led to responses and prolonged disease stability in children with recurrent/progressive OPHGs based upon radiographic response, PFS, and visual outcomes.

Pediatric Functional Neuroimaging: Practical Tips and Pearls.

OBJECTIVE. Functional MRI (fMRI) is clinically used for localization of eloquent cortex before surgical intervention, most commonly motor and language function in patients with tumors or epilepsy. In the pediatric population, special considerations for fMRI relate to limited examination tolerance, small head size, developing anatomy and physiology, and diverse potential abnormalities. In this article, we will highlight pearls and pitfalls of clinical pediatric fMRI including blood oxygenation level-dependent imaging principles, patient preparation, study acquisition, data postprocessing, and examination interpretation. CONCLUSION. Clinical fMRI is indicated for presurgical localization of eloquent cortex in patients with tumors, epilepsy, or other neurologic conditions and requires a solid understanding of technical considerations and data processing. In children, special approaches are needed for patient preparation as well as study design, acquisition, and interpretation. Radiologists should be cognizant of developmental neuroanatomy, causes of neuropathology, and capacity for neuroplasticity in the pediatric population.

Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial.

BACKGROUND: Paediatric low-grade glioma is the most common CNS tumour of childhood. Although overall survival is good, disease often recurs. No single universally accepted treatment exists for these patients; however, standard cytotoxic chemotherapies are generally used. We aimed to assess the activity of selumetinib, a MEK1/2 inhibitor, in these patients. METHODS: The Pediatric Brain Tumor Consortium performed a multicentre, phase 2 study in patients with paediatric low-grade glioma in 11 hospitals in the USA. Patients aged 3-21 years with a Lansky or Karnofsky performance score greater than 60 and the presence of recurrent, refractory, or progressive paediatric low-grade glioma after at least one standard therapy were eligible for inclusion. Patients were assigned to six unique strata according to histology, tumour location, NF1 status, and BRAF aberration status; herein, we report the results of strata 1 and 3. Stratum 1 comprised patients with WHO grade I pilocytic astrocytoma harbouring either one of the two most common BRAF aberrations (KIAA1549-BRAF fusion or the BRAFV600E [Val600Glu] mutation). Stratum 3 comprised patients with any neurofibromatosis type 1 (NF1)-associated paediatric low-grade glioma (WHO grades I and II). Selumetinib was provided as capsules given orally at the recommended phase 2 dose of 25 mg/m2 twice daily in 28-day courses for up to 26 courses. The primary endpoint was the proportion of patients with a stratum-specific objective response (partial response or complete response), as assessed by the local site and sustained for at least 8 weeks. All responses were reviewed centrally. All eligible patients who initiated treatment were evaluable for the activity and toxicity analyses. Although the trial is ongoing in other strata, enrolment and planned follow-up is complete for strata 1 and 3. This trial is registered with ClinicalTrials.gov, number NCT01089101. FINDINGS: Between July 25, 2013, and June 12, 2015, 25 eligible and evaluable patients were accrued to stratum 1, and between Aug 28, 2013, and June 25, 2015, 25 eligible and evaluable patients were accrued to stratum 3. In stratum 1, nine (36% [95% CI 18-57]) of 25 patients achieved a sustained partial response. The median follow-up for the 11 patients who had not had a progression event by Aug 9, 2018, was 36·40 months (IQR 21·72-45·59). In stratum 3, ten (40% [21-61]) of 25 patients achieved a sustained partial response; median follow-up was 48·60 months (IQR 39·14-51·31) for the 17 patients without a progression event by Aug 9, 2018. The most frequent grade 3 or worse adverse events were elevated creatine phosphokinase (five [10%]) and maculopapular rash (five [10%]). No treatment-realted deaths were reported. INTERPRETATION: Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma. These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1. FUNDING: National Cancer Institute Cancer Therapy Evaluation Program, the American Lebanese Syrian Associated Charities, and AstraZeneca.

ACR Appropriateness Criteria® Scoliosis-Child.

Scoliosis is frequently encountered in childhood, with prevalence of 2%. The majority is idiopathic, without vertebral segmentation anomaly, dysraphism, neuromuscular abnormality, skeletal dysplasia, tumor, or infection. As a complement to clinical assessment, radiography is the primary imaging modality used to classify scoliosis and subsequently monitor its progression and response to treatment. MRI is utilized selectively to assess for neural axis abnormalities in those at higher risk, including those with congenital scoliosis, early onset idiopathic scoliosis, and adolescent idiopathic scoliosis with certain risk factors. CT, although not routinely employed in the initial evaluation of scoliosis, may have a select role in characterizing the bone anomalies of congenital scoliosis and in perioperative planning. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Suspected Spine Trauma-Child.

Choosing the appropriate imaging in children with accidental traumatic spine injuries can be challenging because the recommendations based on scientific evidence at this time differ from those applied in adults. This differentiation is due in part to differences in anatomy and physiology of the developing spine. This publication uses scientific evidence and a panel of pediatric experts to summarize best current imaging practices for children with accidental spine trauma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

3D T1-weighted contrast-enhanced brain MRI in children using a fat-suppressed golden angle radial acquisition: an alternative to Cartesian inversion-recovery imaging.

BACKGROUND: T1-weighted post-contrast MRI is essential in brain protocols. We demonstrate the feasibility and utility of a 3D non-Cartesian radial acquisition in children. PURPOSE: To compare bulk motion artifacts, image quality, and lesion conspicuity in 3D T1-weighted post-contrast brain MRI between a new fat-suppressed radial gradient-echo and a traditional non-fat-suppressed inversion-recovery Cartesian gradient-echo sequence. MATERIAL AND METHODS: Images from 53 patients acquired at 3 Tesla were compared. Three radiologists rated the images in three categories, including the presence of bulk motion and whether it impacted diagnosis, whether one sequence was preferred over the other in overall image quality and conspicuity of vascular structures and lesions, and whether diagnosis was possible if only the new fat-suppressed radial acquisition was obtained. RESULTS: The Fleiss' kappa for inter-rater agreement was 0.67 for bulk motion and 0.54 for sequence preference. Of the 53 cases, 56% were identified to have significant motion on conventional imaging, while only 13% had motion artifacts on the radial acquisition (p < 0.05). There were no cases where motion was seen on the radial acquisition but not on conventional imaging. Both sequences were equally preferred in 87% of the cases. All radiologists agreed that the radial approach had lower gray-white matter contrast than the conventional inversion-recovery method, but preferred the former for making diagnosis in uncooperative patients. CONCLUSION: We demonstrate the potential utility of a fat-suppressed 3D T1-weighted post-contrast brain gradient-echo sequence in children. The technique is useful in non-sedate pediatric imaging due to its reduced sensitivity to bulk motion.

Increased risk of pseudoprogression among pediatric low-grade glioma patients treated with proton versus photon radiotherapy.

BACKGROUND: Pseudoprogression (PsP) is a recognized phenomenon after radiotherapy (RT) for high-grade glioma but is poorly characterized for low-grade glioma (LGG). We sought to characterize PsP for pediatric LGG patients treated with RT, with particular focus on the role of RT modality using photon-based intensity-modulated RT (IMRT) or proton beam therapy (PBT). METHODS: Serial MRI scans from 83 pediatric LGG patients managed at 2 institutions between 1998 and 2017 were evaluated. PsP was scored when a progressive lesion subsequently decreased or stabilized for at least a year without therapy. RESULTS: Thirty-two patients (39%) were treated with IMRT, and 51 (61%) were treated with PBT. Median RT dose for the cohort was 50.4 Gy(RBE) (range, 45-59.4 Gy[RBE]). PsP was identified in 31 patients (37%), including 8/32 IMRT patients (25%) and 23/51 PBT patients (45%). PBT patients were significantly more likely to have post-RT enlargement (hazard ratio [HR] 2.15, 95% CI: 1.06-4.38, P = 0.048). RT dose >50.4 Gy(RBE) similarly predicted higher rates of PsP (HR 2.61, 95% CI: 1.20-5.68, P = 0.016). Multivariable analysis confirmed the independent effects of RT modality (P = 0.03) and RT dose (P = 0.01) on PsP incidence. Local progression occurred in 10 patients: 7 IMRT patients (22%) and 3 PBT patients (6%), with a trend toward improved local control for PBT patients (HR 0.34, 95% CI: 0.10-1.18, P = 0.099). CONCLUSIONS: These data highlight substantial rates of PsP among pediatric LGG patients, particularly those treated with PBT. PsP should be considered when assessing response to RT in LGG patients within the first year after RT.

Post-contrast T1-weighted spine 3T MRI in children using a golden-angle radial acquisition.

PURPOSE: MRI methods that have reduced sensitivity to motion are attractive in pediatric applications. In spine imaging, physiologic motion such as respiration and cerebrospinal fluid pulsation can hamper diagnostic image quality. We compare a 3D T1-weighted non-Cartesian radial acquisition with a conventional Cartesian 2D turbo-spin-echo (TSE) acquisition in axial post-contrast spine imaging at 3T. METHODS: Thirty-two patients (mean age 12.2 ± 5.3 years) scheduled for routine clinical spine exams with contrast were enrolled. Three pediatric neuroradiologists compared the two sequences and assessed the presence of motion, the conspicuity of nerve roots, and whether one of the sequences was preferred in visualizing pathology using Likert scales. RESULTS: The Fleiss' kappa statistic for inter-rater agreement was 0.29 (95% confidence interval, 0.15-0.43) for the presence of motion, 0.30 (0.21-0.38) for conspicuity, and 0.37 (0.19-0.55) for sequence preference. Radial images were less sensitive to motion than TSE (p < 0.01). Motion and consequent artifacts were present in all TSE cases, while it was absent in 51% of the radial cases. In depicting nerve roots, radial images were superior in the cervical (p < 0.05), thoracic (p < 0.01), and lumbar spines (p < 0.01). Lastly, in 28 of the 32 patients who demonstrated contrast-enhancing pathology, radial images were preferred in 51% of the cases, while both sequences were equally preferred in 41% of the cases. CONCLUSION: We demonstrate the potential utility of radial MRI in post-contrast spine imaging. The free-breathing method is robust in generating diagnostic image quality and is superior in visualizing nerve roots and extramedullary metastases than traditional Cartesian TSE acquisitions.

ACR Appropriateness Criteria® Sinusitis-Child.

Sinusitis is common in children that usually resolves spontaneously. Imaging is not part of the standard of care for initial diagnosis, however may be necessary in cases with persistent or chronic sinusitis to guide surgical intervention, or to rule out intracranial and vascular complications of sinusitis. Computed tomography (CT) and magnetic resonance imaging (MRI) are the leading imaging modalities. In this article, appropriateness in use of imaging modalities are discussed under common/clinically relevant scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Headache-Child.

Headaches in children are not uncommon and have various causes. Proper neuroimaging of these children is very specific to the headache type. Care must be taken to choose and perform the most appropriate initial imaging examination in order to maximize the ability to properly determine the cause with minimum risk to the child. This evidence-based report discusses the different headache types in children and provides appropriate guidelines for imaging these children. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Five-Year-Old Boy With Behavioral Changes and Papilledema.

A 5-year-old boy had initial symptoms of behavioral changes, nausea, vomiting, headache, weight loss, and progressive vision failure. Brain MRI revealed abnormal signal intensity in both optic nerves, the optic chiasm, the right medial temporal lobe, and tissues surrounding the right supraclinoid internal carotid artery with associated leptomeningeal and spinal cord enhancement. After nondiagnostic dural and spinal arachnoid biopsies, a temporal lobe biopsy was diagnostic for a rare malignant peripheral nerve sheath tumor.

ACR Appropriateness Criteria® Back Pain-Child.

It is now generally accepted that nontraumatic back pain in the pediatric population is common. The presence of isolated back pain in a child has previously been an indication for imaging; however, recently a more conservative approach has been suggested using clinical criteria. The presence of constant pain, night pain, and radicular pain, alone or in combination, lasting for 4 weeks or more, constitute clinical red flags that should prompt further imaging. Without these clinical red flags, imaging is likely not indicated. Exceptions include an abnormal neurologic examination or clinical and laboratory findings suggesting an infectious or neoplastic etiology, and when present should prompt immediate imaging. Initial imaging should consist of spine radiographs limited to area of interest, with spine MRI without contrast to evaluate further if needed. CT of the spine, limited to area of interest, and Tc-99m bone scan whole body with single-photon emission computed tomography may be useful in some patients. The addition of intravenous contrast is also recommended for evaluation of a potential neoplastic or infectious process. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Comparison of the diagnostic accuracy of PET/MRI to PET/CT-acquired FDG brain exams for seizure focus detection: a prospective study.

BACKGROUND: There is great interest in positron emission tomography (PET)/magnetic resonance (MR) as a clinical tool due to its capacity to provide diverse diagnostic information in a single exam. OBJECTIVE: The goal of this exam is to compare the diagnostic accuracy of PET/MR-acquired [F-18]2-fluoro-2-deoxyglucose (FDG) brain exams to that of PET/CT with respect to identifying seizure foci in children with localization-related epilepsy. MATERIALS AND METHODS: Institutional Review Board approval and informed consent were obtained for this Health Insurance Portability and Accountability Act-compliant, prospective study. All patients referred for clinical FDG-PET/CT exams of the brain at our institution for a diagnosis of localization-related epilepsy were prospectively recruited to undergo an additional FDG-PET acquisition on a tandem PET/MR system. Attenuation-corrected FDG images acquired at PET/MR and PET/CT were interpreted independently by five expert readers. Readers were blinded to the scanner used for acquisition and attenuation correction as well as all other clinical and imaging data. A Likert scale scoring system (1-5) was used to assess image quality. The locale of seizure origin determined at multidisciplinary epilepsy surgery work rounds was considered the reference standard. Non-inferiority testing for paired data was used to compare the diagnostic accuracy of PET/MR to that of PET/CT. RESULTS: The final study population comprised 35 patients referred for a diagnosis of localization-related epilepsy (age range: 2-19 years; median: 11 years; 21 males, 14 females). Image quality did not differ significantly between the two modalities. The accuracy of PET/MR was not inferior to that of PET/CT for localization of a seizure focus (P=0.017). CONCLUSION: The diagnostic accuracy of FDG-PET images acquired on a PET/MR scanner and generated using MR-based attenuation correction was not inferior to that of PET images processed by traditional CT-based correction.

Progression-free survival of children with localized ependymoma treated with intensity-modulated radiation therapy or proton-beam radiation therapy.

BACKGROUND: The treatment for childhood intracranial ependymoma includes maximal surgical resection followed by involved-field radiotherapy, commonly in the form of intensity-modulated radiation therapy (IMRT). Proton-beam radiation therapy (PRT) is used at some centers in an effort to decrease long-term toxicity. Although protons have the theoretical advantage of a minimal exit dose to the surrounding uninvolved brain tissue, it is unknown whether they have the same efficacy as photons in preventing local recurrence. METHODS: A retrospective review of medical records from September 2000 to April 2013 was performed. Seventy-nine children with newly diagnosed localized intracranial ependymomas treated with either IMRT (n = 38) or PRT (n = 41) were identified, and progression-free survival (PFS) was analyzed with Kaplan-Meier and Cox multivariate analyses. RESULTS: The median age at diagnosis was 3.7 years for all patients (range, 0.4-18.7 years). There were 54 patients with infratentorial tumors (68% of the total population). Patients treated with PRT were younger (median age, 2.5 vs 5.7 years; P = .001) and had a shorter median follow-up (2.6 vs 4.9 years; P < .0001). Gross total resection (GTR) was achieved in 67 patients (85%) and was more frequent in the PRT group versus the IMRT group (93% vs 76%; P = .043). The 3-year PFS rates were 60% and 82% with IMRT and PRT, respectively (P = .031). CONCLUSIONS: Children with localized ependymomas treated with PRT have a 3-year PFS rate comparable to that of children treated with IMRT. This analysis suggests that local control is not compromised by the use of PRT. The data also support GTR as the only prognostic factor for PFS. Cancer 2017;123:2570-78. © 2017 American Cancer Society.

Performance of computed tomography of the head to evaluate for skull fractures in infants with suspected non-accidental trauma.

BACKGROUND: Young children with suspected abusive head trauma often receive skull radiographs to evaluate for fractures as well as computed tomography (CT) of the head to assess for intracranial injury. Using a CT as the primary modality to evaluate both fracture and intracranial injury could reduce exposure to radiation without sacrificing performance. OBJECTIVE: To evaluate the sensitivity of CT head with (3-D) reconstruction compared to skull radiographs to identify skull fractures in children with suspected abusive head trauma. MATERIALS AND METHODS: This was a retrospective (2013-2014) cross-sectional study of infants evaluated for abusive head trauma via both skull radiographs and CT with 3-D reconstruction. The reference standard was skull radiography. All studies were read by pediatric radiologists and neuroradiologists, with ten percent read by a second radiologist to evaluate for interobserver reliability. RESULTS: One hundred seventy-seven children (47% female; mean/median age: 5 months) were included. Sixty-two (35%) had skull fractures by radiography. CT with 3-D reconstruction was 97% sensitive (95% confidence interval [CI]: 89-100%) and 94% specific (CI: 87-97%) for skull fracture. There was no significant difference between plain radiographs and 3-D CT scan results (P-value = 0.18). Kappa was 1 (P-value <0.001) between radiologist readings of CTs and 0.77 (P = 0.001) for skull radiographs. CONCLUSION: CT with 3-D reconstruction is equivalent to skull radiographs in identifying skull fractures. When a head CT is indicated, skull radiographs add little diagnostic value.