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.

Imaging of pediatric head and neck masses.

Medical imaging is an important tool in the evaluation and classification of pediatric head and neck masses. Such lesions may include congenital, inflammatory, infectious, vascular, or neoplastic processes. Ultrasound is often the first line modality in the workup of a neck mass in a child, followed by MRI or CT depending on the scenario. This information must be interpreted in the context of the patient's clinical history, physical examination, and demographics. The medical imaging workup of a neck mass in a child must be focused to yield the maximum information possible while minimizing the risks of radiation and sedation.

MR assessment of left ventricular function: quantitative comparison of fast imaging employing steady-state acquisition (FIESTA) with fast gradient echo cine technique.

PURPOSE: To evaluate the agreement of fast imaging employing steady-state acquisition (FIESTA) cine technique with segmented k-space fast gradient echo (GRE) cine technique when using them for assessment of cardiac function. MATERIALS AND METHODS: Eleven MR cine studies were performed on six healthy volunteers and five patients, using FIESTA and fast GRE techniques. The quantitative measurements of ventricular function obtained from the two techniques were compared. The data analysis was performed by two observers independently. RESULTS: Compared to fast GRE cine technique, FIESTA cine technique consistently resulted in higher end-diastolic volume (10.2%) and end-systolic volume (21.6%), but lower myocardial mass of left ventricle (19.2%) and ejection fraction (9.9%). The stroke volume obtained from the two techniques was very close. The primary explanation for this variability is that the two techniques have different mechanisms on establishing signal contrast. CONCLUSION: Compared to fast GRE technique, FIESTA provides significantly different results when using it for assessment of left ventricular function. It is important to consider this difference in the assessment of cardiac function.