Importance of Central Imaging Review in a Pediatric Hodgkin Lymphoma Trial Using Positron Emission Tomography Response Adapted Radiation Therapy.

PURPOSE: We investigated the effects of central review of the interim fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan response (iPET) assessment on treatment allocation in the risk-based, response-adapted, Children's Oncology Group study AHOD1331 (ClinicalTrials.gov identifier: NCT02166463) for pediatric patients with high-risk Hodgkin lymphoma. METHODS AND MATERIALS: Per protocol, after 2 cycles of systemic therapy, patients underwent iPET, with visual response assessment by 5-point Deauville score (DS) at their treating institution and a real-time central review, with the latter considered the reference standard. An area of disease with a DS of 1 to 3 was considered a rapid-responding lesion, whereas a DS of 4 to 5 was considered a slow-responding lesion (SRL). Patients with 1 or more SRLs were considered iPET positive, whereas patients with only rapid-responding lesions were considered iPET negative. We conducted a predefined exploratory evaluation of concordance in iPET response assessment between institutional and central reviews of 573 patients. The concordance rate was evaluated using the Cohen κ statistic (κ > 0.80 was considered very good agreement and κ > 0.60-0.80, good agreement). RESULTS: The concordance rate (514 of 573 [89.7%]) had a κ of 0.685 (95% CI, 0.610-0.759), consistent with good agreement. In terms of the direction of discordance, among the 126 patients who were considered iPET positive by institutional review, 38 (30.2%) were categorized as iPET negative by central review, preventing overtreatment with radiation therapy. Conversely, among the 447 patients who were considered iPET negative by institutional review, 21 patients (4.7%) were categorized as iPET positive by the central review and would have been undertreated without radiation therapy. CONCLUSIONS: Central review is integral to PET response-adapted clinical trials for children with Hodgkin lymphoma. Continued support of central imaging review and education about DS are needed.

Randomized Phase III Trial of Ganitumab With Interval-Compressed Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma: A Report From the Children's Oncology Group.

PURPOSE: Monoclonal antibodies directed against insulin-like growth factor-1 receptor (IGF-1R) have shown activity in patients with relapsed Ewing sarcoma. The primary objective of Children's Oncology Group trial AEWS1221 was to determine if the addition of the IGF-1R monoclonal antibody ganitumab to interval-compressed chemotherapy improves event-free survival (EFS) in patients with newly diagnosed metastatic Ewing sarcoma. METHODS: Patients were randomly assigned 1:1 at enrollment to standard arm (interval-compressed vincristine/doxorubicin/cyclophosphamide alternating once every 2 weeks with ifosfamide/etoposide = VDC/IE) or to experimental arm (VDC/IE with ganitumab at cycle starts and as monotherapy once every 3 weeks for 6 months after conventional therapy). A planned sample size of 300 patients was projected to provide 81% power to detect an EFS hazard ratio of 0.67 or smaller for the experimental arm compared with the standard arm with a one-sided α of .025. RESULTS: Two hundred ninety-eight eligible patients enrolled (148 in standard arm; 150 in experimental arm). The 3-year EFS estimates were 37.4% (95% CI, 29.3 to 45.5) for the standard arm and 39.1% (95% CI, 31.3 to 46.7) for the experimental arm (stratified EFS-event hazard ratio for experimental arm 1.00; 95% CI, 0.76 to 1.33; 1-sided, P = .50). The 3-year overall survival estimates were 59.5% (95% CI, 50.8 to 67.3) for the standard arm and 56.7% (95% CI, 48.3 to 64.2) for the experimental arm. More cases of pneumonitis after radiation involving thoracic fields and nominally higher rates of febrile neutropenia and ALT elevation were reported on the experimental arm. CONCLUSION: Ganitumab added to interval-compressed chemotherapy did not significantly reduce the risk of EFS event in patients with newly diagnosed metastatic Ewing sarcoma, with outcomes similar to prior trials without IGF-1R inhibition or interval compression. The addition of ganitumab may be associated with increased toxicity.

Bedside Ultrasound for the Evaluation of Epidural Hematoma After Infant Lumbar Puncture.

BACKGROUND: Unsuccessful lumbar puncture (LP) attempts may lead to epidural hematoma (EH) formation within the spinal canal at the site of needle insertion, which can affect subsequent attempts. We aimed to determine the rate of EH formation after infant LP using bedside ultrasound (US). Furthermore, we aimed to correlate both perceived trauma during LP and cerebral spinal fluid (CSF) red blood cell (RBC) counts with EH formation. METHODS: We enrolled infants younger than 6 months who underwent LP in the emergency department. The primary investigator performed a bedside US of the lumbar spine, which was reviewed and interpreted by a pediatric radiologist. Treating clinicians performed the procedure and were asked to classify each attempt as "traumatic" or "atraumatic." Cerebral spinal fluid RBC counts were recorded. RESULTS: Thirty-one percent of patients had evidence of post-LP EH, 17% of which completely effaced the thecal sac. Forty percent of patients with at least 1 traumatic attempt had evidence of EH, whereas 25% without reported trauma showed EH (P = 0.17). Patients with EH had a median CSF RBC cell count of 186 cells/mm (range, 0-239,525) compared with 5 cells/mm (range, 0-3429) in patients without evidence of EH (P = 0.008). CONCLUSIONS: Epidural hematomas are frequent after LP. Perceived trauma during LP and CSF RBC counts are not adequate predictors of EH formation. Point-of-care US may be a valuable adjunct to help guide subsequent needle insertions sites for repeat attempts after an unsuccessful LP.

Low-Dose Computed Tomography Reduces Radiation Exposure by 90% Compared With Traditional Computed Tomography Among Patients Undergoing Hip-Preservation Surgery.

PURPOSE: To compare the delivered radiation dose between a low-dose hip computed tomography (CT) scan protocol and traditional hip CT scan protocols (i.e., "traditional CT"). METHODS: This was a retrospective comparative cohort study. Patients who underwent hip-preservation surgery (including arthroscopy, surgical hip dislocation, or periacetabular osteotomy procedures) at our institution between 2016 and 2017 were identified. Patients were excluded if they had a body mass index (BMI) greater than 35, they underwent previous surgery, or a radiation dose report was absent. The low-dose group included patients who underwent hip CT at our institution using a standardized protocol of 100 kV (peak), 100 milliampere-seconds (mAs), and a limited scanning field. The traditional CT group included patients who had hip CT scans performed at outside institutions. The total effective dose (Ehip), effective dose per millimeter of body length scanned, patients' age, and patients' BMI were compared by univariate analysis. The correlation of Ehip to BMI was assessed. RESULTS: The study included 41 consecutive patients in the low-dose group and 18 consecutive patients in the traditional CT group. Low-dose CT resulted in a 90% reduction in radiation exposure compared with traditional CT (Ehip, 0.97 ± 0.28 mSv vs 9.68 ± 6.67 mSv; P < .0001). Age (28 ± 11 years vs 26 ± 10 years, P = .42), sex (83% female patients vs 76% female patients, P = .74), and BMI (24 ± 3 vs 24 ± 3, P = .75) were not different between the 2 groups. Ehip had a poor but significant correlation to BMI in the low-dose CT group (R2 = 0.14, slope = 0.03, P = .02) and did not correlate to BMI in the traditional CT group (R2 = 0.13, P = .14). CONCLUSIONS: A low-dose hip CT protocol for the purpose of hip-preservation surgical planning resulted in a 90% reduction in radiation exposure compared with traditional CT. LEVEL OF EVIDENCE: Level II, diagnostic study.

Rapid non-contrast magnetic resonance imaging for post appendectomy intra-abdominal abscess in children.

BACKGROUND: Acute appendicitis, especially if perforated at presentation, is often complicated by postoperative abscess formation. The detection of a postoperative abscess relies primarily on imaging. This has traditionally been done with contrast-enhanced computed tomography. Non-contrast magnetic resonance imaging (MRI) has the potential to accurately detect intra-abdominal abscesses, especially with the use of diffusion-weighted imaging (DWI). OBJECTIVE: To evaluate our single-center experience with a rapid non-contrast MRI protocol evaluating post-appendectomy abscesses in children with persistent postsurgical symptoms. MATERIALS AND METHODS: In this retrospective, institutional review board-approved study, all patients underwent a clinically indicated non-contrast 1.5- or 3-Tesla abdomen/pelvis MRI consisting of single-shot fast spin echo, inversion recovery and DWI sequences. All MRI studies were reviewed by two blinded pediatric radiologists to identify the presence of a drainable fluid collection. Each fluid collection was further characterized as accessible or not accessible for percutaneous or transrectal drainage. Imaging findings were compared to clinical outcome. RESULTS: Seven of the 15 patients had a clinically significant fluid collection, and 5 of these patients were treated with percutaneous drain placement or exploratory laparotomy. The other patients had a phlegmon or a clinically insignificant fluid collection and were discharged home within 48 h. CONCLUSION: Rapid non-contrast MRI utilizing fluid-sensitive and DWI sequences can be used to identify drainable fluid collections in post-appendectomy patients. This protocol can be used to triage patients between conservative management vs. abscess drainage without oral/intravenous contrast or exposure to ionizing radiation.

Musculoskeletal MRI findings of juvenile localized scleroderma.

BACKGROUND: Juvenile localized scleroderma comprises a group of autoimmune conditions often characterized clinically by an area of skin hardening. In addition to superficial changes in the skin and subcutaneous tissues, juvenile localized scleroderma may involve the deep soft tissues, bones and joints, possibly resulting in functional impairment and pain in addition to cosmetic changes. OBJECTIVE: There is literature documenting the spectrum of findings for deep involvement of localized scleroderma (fascia, muscles, tendons, bones and joints) in adults, but there is limited literature for the condition in children. We aimed to document the spectrum of musculoskeletal magnetic resonance imaging (MRI) findings of both superficial and deep juvenile localized scleroderma involvement in children and to evaluate the utility of various MRI sequences for detecting those findings. MATERIALS AND METHODS: Two radiologists retrospectively evaluated 20 MRI studies of the extremities in 14 children with juvenile localized scleroderma. Each imaging sequence was also given a subjective score of 0 (not useful), 1 (somewhat useful) or 2 (most useful for detecting the findings). RESULTS: Deep tissue involvement was detected in 65% of the imaged extremities. Fascial thickening and enhancement were seen in 50% of imaged extremities. Axial T1, axial T1 fat-suppressed (FS) contrast-enhanced and axial fluid-sensitive sequences were rated most useful. CONCLUSION: Fascial thickening and enhancement were the most commonly encountered deep tissue findings in extremity MRIs of children with juvenile localized scleroderma. Because abnormalities of the skin, subcutaneous tissues and fascia tend to run longitudinally in an affected limb, axial T1, axial fluid-sensitive and axial T1-FS contrast-enhanced sequences should be included in the imaging protocol.

Sarcoidosis presenting as granulomatous myositis in a 16-year-old adolescent.

BACKGROUND: Sarcoidosis is a multi-system disease characterized by the presence of non-caseating epithelioid granulomas in affected tissues, including skeletal muscle. These organized collections of immune cells have important pathophysiologic action including cytokine production leading to inflammation as well as enzymatic conversion of cholecalciferol to calcitriol via 1-α hydroxylase. There are limited reports of isolated granulomatous myositis causing hypercalcemia in pediatric patients. Our patient uniquely presented with symptoms from hypercalcemia and renal insufficiency caused by an overwhelming burden of granulomatous myositis in her lower extremities, but was otherwise asymptomatic. CASE PRESENTATION: A 16 year old Caucasian female presented with protracted symptoms of fatigue, nausea and prominent weight loss with laboratory evidence of hypercalcemia and renal insufficiency. She lacked clinical and physical findings of arthritis, weakness, rash, uveitis, fever, lymphadenopathy or respiratory symptoms. After extensive negative investigations, re-examination yielded subtle soft tissue changes in her lower extremities, with striking MRI findings of extensive myositis without correlative weakness or serum enzyme elevation. Biopsy showed the presence of non-caseating epithelioid granulomas and calcium oxalate crystals. The patient responded well to prednisone and methotrexate but relapsed with weaning of steroids. She reachieved remission with addition of adalimumab. CONCLUSIONS: Sarcoidosis should be considered in patients presenting with symptomatic hypercalcemia with no apparent causes and negative routine workup. The absences of decreased muscle strength or elevated muscle enzymes do not preclude the diagnosis of granulomatous myositis.

Fat-containing soft-tissue masses in children.

The diagnosis of soft-tissue masses in children can be difficult because of the frequently nonspecific clinical and imaging characteristics of these lesions. However key findings on imaging can aid in diagnosis. The identification of macroscopic fat within a soft-tissue mass narrows the differential diagnosis considerably and suggests a high likelihood of a benign etiology in children. Fat can be difficult to detect with sonography because of the variable appearance of fat using this modality. Fat is easier to recognize using MRI, particularly with the aid of fat-suppression techniques. Although a large portion of fat-containing masses in children are adipocytic tumors, a variety of other tumors and mass-like conditions that contain fat should be considered by the radiologist confronted with a fat-containing mass in a child. In this article we review the sonographic and MRI findings in the most relevant fat-containing soft-tissue masses in the pediatric age group, including adipocytic tumors (lipoma, angiolipoma, lipomatosis, lipoblastoma, lipomatosis of nerve, and liposarcoma); fibroblastic/myofibroblastic tumors (fibrous hamartoma of infancy and lipofibromatosis); vascular anomalies (involuting hemangioma, intramuscular capillary hemangioma, phosphate and tensin homologue (PTEN) hamartoma of soft tissue, fibro-adipose vascular anomaly), and other miscellaneous entities, such as fat necrosis and epigastric hernia.

Whole-body magnetic resonance imaging in children: technique and clinical applications.

Whole-body MR imaging is being increasingly used in children to evaluate the extent of various oncologic and non-oncologic entities. The lack of exposure to ionizing radiation, excellent soft-tissue contrast (even without the use of contrast agents), and functional imaging capabilities make it especially suitable for screening and surveillance in the pediatric population. Technical developments such as moving table platforms, multi-channel/multi-element surface coils, and parallel imaging allow imaging of the entire body with multiple sequences in a reasonable 30- to 40-min time frame, which has facilitated its acceptance in routine clinical practice. The initial investigations in whole-body MR imaging were primarily focused on oncologic applications such as tumor screening and staging. The exquisite sensitivity of fluid-sensitive MR sequences to many different types of pathology has led to new applications of whole-body MR imaging in evaluation of multifocal rheumatologic conditions. Availability of blood pool contrast agents has allowed whole-body MR angiographic imaging of vascular malformations, vasculitides and vasculopathies. Whole-body MRI is being applied for delineating the extent and distribution of systemic and multifocal diseases, establishing diagnoses, assessing treatment response, and surveillance imaging. This article reviews the technique and clinical applications of whole-body MR imaging in children.

MRI findings of post-traumatic subperiosteal hematoma of the iliac bone with resultant femoral nerve palsy in an adolescent boy.

Post-traumatic subperiosteal hematoma of the iliac bone may present insidiously without external evidence of bleeding or go undetected in the acute setting. In some cases, the patient may come to medical attention due to femoral nerve palsy rather than hip or groin pain. In this report, we describe a case of femoral nerve palsy caused by acute post-traumatic subperiosteal hematoma of the iliac bone using MRI to highlight the subperiosteal location. Anatomy of the femoral nerve is also discussed.