Jesse Courtier

Imaging of Müllerian Duct Anomalies

The müllerian ducts are paired embryologic structures that undergo fusion and resorption in utero to give rise to the uterus, fallopian tubes, cervix, and upper two-thirds of the vagina. Interruption of normal development of the müllerian ducts can result in formation of müllerian duct anomalies (MDAs). MDAs are a broad and complex spectrum of abnormalities that are often associated with primary amenorrhea, infertility, obstetric complications, and endometriosis. MDAs are commonly associated with renal and other anomalies; thus, identification of both kidneys is important. However, MDAs are not associated with ovarian anomalies. Hysterosalpingography (HSG) is routinely used in evaluation of infertility. Because a key component of MDA characterization is the external uterine fundal contour, HSG is limited for this purpose. Patients suspected of having an MDA are often initially referred for pelvic ultrasonography (US). Magnetic resonance (MR) imaging is typically reserved for complex or indeterminate cases. MR imaging is the imaging standard of reference because it is noninvasive, does not involve ionizing radiation, has multiplanar capability, allows excellent soft-tissue characterization, and permits a greater field of interrogation than does US. Use of MR imaging for evaluation of MDAs reduces the number of invasive procedures and related costs by guiding management decisions.

Fetal tracheolaryngeal airway obstruction: prenatal evaluation by sonography and MRI.

We reviewed the sonographic and MRI findings of tracheolaryngeal obstruction in the fetus. Conditions that can cause tracheolaryngeal obstruction include extrinsic causes such as lymphatic malformation, cervical teratoma and vascular rings and intrinsic causes such as congenital high airway obstruction syndrome (CHAOS). Accurate distinction of these conditions by sonography or MRI can help facilitate parental counseling and management, including the decision to utilize the ex utero intrapartum treatment (EXIT) procedure.

Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma: A NANT (New Approaches to Neuroblastoma Therapy) Trial

PURPOSE Alisertib is an oral Aurora A kinase inhibitor with preclinical activity in neuroblastoma. Irinotecan and temozolomide have activity in patients with advanced neuroblastoma. The goal of this phase I study was to determine the maximum tolerated dose (MTD) of alisertib with irinotecan and temozolomide in this population. PATIENTS AND METHODS Patients age 1 to 30 years with relapsed or refractory neuroblastoma were eligible. Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m(2) per day on days 1 to 7 along with irinotecan 50 mg/m(2) intravenously and temozolomide 100 mg/m(2) orally on days 1 to 5. Dose escalation of alisertib followed the rolling six design. Samples for pharmacokinetic and pharmacogenomic testing were obtained. RESULTS Twenty-three patients enrolled, and 22 were eligible and evaluable for dose escalation. A total of 244 courses were administered. The MTD for alisertib was 60 mg/m(2), with mandatory myeloid growth factor support and cephalosporin prophylaxis for diarrhea. Thrombocytopenia and neutropenia of any grade were seen in the majority of courses (84% and 69%, respectively). Diarrhea in 55% of courses and nausea in 54% of courses were the most common nonhematologic toxicities. The overall response rate was 31.8%, with a 50% response rate observed at the MTD. The median number of courses per patient was eight (range, two to 32). Progression-free survival rate at 2 years was 52.4%. Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib. CONCLUSION Alisertib 60 mg/m(2) per dose for 7 days is tolerable with a standard irinotecan and temozolomide backbone and has promising response and progression-free survival rates. A phase II trial of this regimen is ongoing.

Imaging of nontraumatic adrenal hemorrhage.

OBJECTIVE The purpose of this pictorial essay is to review the imaging findings of acute, chronic, and tumor-related nontraumatic adrenal hemorrhage. CONCLUSION Rapid development or evolution of a nonenhancing adrenal mass or masses with an adreniform shape or high T1 signal intensity on MR images of a patient under stress or with a bleeding diathesis, including anticoagulant use, suggests acute adrenal hemorrhage. Chronic hemorrhage appears as a thin-walled pseudocyst or atrophy. Imaging findings that may indicate underlying tumor include intralesional calcification, enhancement, and hypermetabolic activity on PET images.

131I-Metaiodobenzylguanidine with Intensive Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Neuroblastoma. A New Approaches to Neuroblastoma Therapy (NANT) Phase II Study

(131)I-Metaiodobenzylguanidine ((131)I-MIBG) has been used as a single agent or in combination with chemotherapy for the treatment of high-risk neuroblastoma. The activity and toxicity of (131)I-MIBG when combined with carboplatin, etoposide, and melphalan (CEM) and autologous stem cell transplantation (SCT) are now investigated in a phase II multicenter study. Fifty patients with MIBG-avid disease were enrolled into 2 cohorts, stratified by response to induction therapy. The primary study endpoint was response of patients with refractory (n = 27) or progressive disease (n = 15). A second cohort of patients (n = 8) with a partial response (PR) to induction therapy was included to obtain preliminary response data. (131)I-MIBG was administered on day -21 to all patients, with CEM given days -7 to -4, and SCT given on day 0. (131)I-MIBG dosing was determined by pre-therapy glomerular filtration rate (GFR), with 8 mCi/kg given if GFR was 60 to 99 mL/minute/1.73 m(2) (n = 13) and 12 mCi/kg if GFR ≥ 100 mL/minute/1.73 m(2) (n = 37). External beam radiotherapy was delivered to the primary and metastatic sites, beginning approximately 6 weeks after SCT. Responses (complete response + PR) were seen in 4 of 41 (10%) evaluable patients with primary refractory or progressive disease. At 3 years after SCT, the event-free survival (EFS) was 20% ± 7%, with overall survival (OS) 62% ± 8% for this cohort of patients. Responses were noted in 3 of 8 (38%) of patients with a PR to induction, with 3-year EFS 38% ± 17% and OS 75% ± 15%. No statistically significant difference was found comparing EFS or OS based upon pre-therapy GFR or disease cohort. Six of 50 patients had nonhematologic dose-limiting toxicity (DLT); 1 of 13 in the low GFR and 5 of 37 in the normal GFR cohorts. Hepatic sinusoidal obstructive syndrome (SOS) was seen in 6 patients (12%), with 5 events defined as dose-limiting SOS. The median times to neutrophil and platelet engraftment were 10 and 15 days, respectively. Patients received a median 163 cGy (61 to 846 cGy) with (131)I-MIBG administration, with 2 of 3 patients receiving >500 cGy experiencing DLT. The addition of (131)I-MIBG to a myeloablative CEM regimen is tolerable and active therapy for patients with high-risk neuroblastoma.

Phase I Study of Vorinostat as a Radiation Sensitizer with 131I-Metaiodobenzylguanidine (131I-MIBG) for Patients with Relapsed or Refractory Neuroblastoma

Purpose: 131I-metaiodobenzylguanidine (MIBG) is a radiopharmaceutical with activity in neuroblastoma. Vorinostat is a histone deacetylase inhibitor that has radiosensitizing properties. The goal of this phase I study was to determine the MTDs of vorinostat and MIBG in combination. Experimental Design: Patients ≤ 30 years with relapsed/refractory MIBG-avid neuroblastoma were eligible. Patients received oral vorinostat (dose levels 180 and 230 mg/m2) daily days 1 to 14. MIBG (dose levels 8, 12, 15, and 18 mCi/kg) was given on day 3 and peripheral blood stem cells on day 17. Alternating dose escalation of vorinostat and MIBG was performed using a 3+3 design. Results: Twenty-seven patients enrolled to six dose levels, with 23 evaluable for dose escalation. No dose-limiting toxicities (DLT) were seen in the first three dose levels. At dose level 4 (15 mCi/kg MIBG/230 mg/m2 vorinostat), 1 of 6 patients had DLT with grade 4 hypokalemia. At dose level 5 (18 mCi/kg MIBG/230 mg/m2 vorinostat), 2 patients had dose-limiting bleeding (one grade 3 and one grade 5). At dose level 5a (18 mCi/kg MIBG/180 mg/m2 vorinostat), 0 of 6 patients had DLT. The most common toxicities were neutropenia and thrombocytopenia. The response rate was 12% across all dose levels and 17% at dose level 5a. Histone acetylation increased from baseline in peripheral blood mononuclear cells collected on days 3 and 12 to 14. Conclusions: Vorinostat at 180 mg/m2/dose is tolerable with 18 mCi/kg MIBG. A phase II trial comparing this regimen to single-agent MIBG is ongoing. Clin Cancer Res; 21(12); 2715–21. ©2015 AACR.

Phase I/II study of (131)I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma.

Background:131I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan.Methods:Patients 1–30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days −1 to +6, irinotecan (50 mg m−2 per dose IV) on days 0–4, vincristine (2 mg m−2) on day 0, MIBG (555 or 666 MBq kg−1) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients.Results:Thirty-two patients (12 phase I ; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg−1. Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80% vs 37%; P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients.Conclusions:MIBG (666 MBq kg−1) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan.

Pediatric inflammatory bowel disease: imaging issues with targeted solutions

To date, there have been many advances in inflammatory bowel disease (IBD) imaging in every cross-sectional imaging modality, particularly in children. The main emphasis in pediatric IBD imaging is on robust and reproducible measures of small bowel Crohn’s disease inflammation, accurate diagnosis of IBD-related complications, and minimizing radiation burden to the patient, as repeat imaging is necessary over the course of their disease. In this article, we discuss the current state-of-the-art imaging techniques, in addition to routine fluoroscopy, including MR and CT enterography and bowel ultrasound. We also present the emerging use of new methods to characterize disease severity and distinguish active inflammation from fibrosis such as diffusion-weighted imaging, bowel elastography, and contrast-enhanced ultrasound. The diagnostic performance of particular examinations, their strengths and weaknesses, and role in IBD management will be discussed. Although these advanced imaging techniques applied to children are similar to those performed in adults, special considerations related to their application in pediatric patients will also be reviewed.

Radiation dose reduction in pediatric CT-guided musculoskeletal procedures.

BackgroundComputed-tomography-guided interventions are attractive for tissue sampling of pediatric bone lesions; however, it comes with exposure to ionizing radiation, inherent to CT and magnified by multiple passes during needle localization.ObjectiveWe evaluate a method of CT-guided bone biopsy that minimizes ionizing radiation exposure by lowering CT scanner tube current (mAs) and voltage (kVp) during each localization scan.Materials and methodsWe retrospectively reviewed all CT-guided bone biopsies (n = 13) over a 1-year period in 12 children. Three blinded readers identified the needle tip on the reduced-dose CT images (mAs = 50, kVp = 80) during the final localization scan at biopsy and rated the image quality as high, moderate or low.ResultsThe image quality of the reduced-dose scans during biopsy was rated as either high or moderate, with needle tip visualized in 12 out of 13 biopsies. Twelve of 13 biopsies also returned sufficient sample for a pathological diagnosis. The average savings in exposure using the dose-reduction technique was 87%.ConclusionOur results suggest that a low mAs and kVp strategy for needle localization during CT-guided bone biopsy yields a large dose reduction and produces acceptable image quality without sacrificing yield for biopsy diagnosis.

Magnetic resonance enterography: inflammatory bowel disease and beyond.

This article addresses the current technique and protocols for magnetic resonance (MR) enterography, with a primary focus on inflammatory bowel disease (IBD) and a secondary detailed discussion of other diseases of the small bowel beyond IBD. A brief discussion of MR imaging for appendicitis is included, but the evaluation of appendicitis does not require an enterographic protocol. The focused key points and approach presented in this article are intended to enhance the readers understanding to help improve patient compliance with the MR enterographic studies, overcome challenges, and improve interpretation.