The apparent diffusion coefficient may be predictive of tumor classification and may be a useful tool in characterizing tumor cellularity and total nuclear area. These parameters are not available in standard MR imaging. Therefore, diffusion-tensor imaging may enhance the diagnostic process in pediatric CNS malignancies.

PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy ( P < .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively ( P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas.

CMBs are common and associated with neurocognitive dysfunction in pediatric brain tumor survivors treated with radiation.

CONCLUSION. Administration of the H3.3K27M-specific vaccine was well tolerated. Patients with H3.3K27M-specific CD8 + immunological responses demonstrated prolonged OS compared with nonresponders. TRIAL REGISTRATION. ClinicalTrials.gov NCT02960230.

Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.

The National Institute of Nursing Research launched the campaign "Palliative Care Conversations Matter" to promote awareness of palliative care (PC) benefits to support family members and to foster early PC discussions by providers with patients and family members (National Institute of Nursing Research, 2014). Research indicates that PC contributes to effective symptom management in children with a poor prognosis and may minimize emotional distress experienced by affected family members (Grady, 2014). Studies also indicate that integration of early PC, advanced-care planning and end-of-life care (EOL) support may minimize negative responses among parents (Broom, Kirby, Good, Wootton, & Adams, 2014). Research on PC/EOL Communication and Support Pediatric providers often struggle with initiating early discussions about PC/EOL options and prognosis with parents due to having limited or no PC/EOL communication training and perceptions about parents' preferences and readiness to receive difficult information about their child's condition. Providers have reported their fear that early PC/EOL discussions with parents may take away hope (Almack, Cox, Moghaddam, Pollock, & Seymour, 2012; Granek, Krzyzanowska, Tozer, & Mazzotta, 2013) and increase emotional distress among parents (Mack & Joffe, 2014). Also, a gap exists in prospective studies to evaluate parental PC/EOL information preferences and coping responses after receiving PC/EOL information during the child's early diagnosis and prognosis period. Conflicting philosophies exist about the purpose of PC/ EOL and timing of PC consultation for children with cancer (Dalberg et al., 2013). In one study, 44.2% of pediatric 676836J POXXX10.

10009 Background: Entrectinib is a CNS-penetrant oral inhibitor of TrkA/B/C, ROS1 and ALK tyrosine kinases. We report the efficacy of entrectinib in children with recurrent/refractory solid or CNS tumors. Methods: Patients ≤ 20y old with recurrent/refractory solid tumors were eligible. After determination of the recommended dose in all-comers, disease-specific expansion cohorts of CNS and solid tumors harboring target aberrations in NTRK1/2/3, ROS1 or ALK, and neuroblastoma (NBL), regardless of mutation spectrum, were enrolled. Response, assessed by Investigator, was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) using RANO for CNS tumors, RECIST for solid tumors, and Curie score for NBL. Results: Between May 2016 and October 2018, 29 patients aged 4.9m–20y (median 7y) were enrolled and 28 were evaluated for response. Entrectinib was well tolerated. Dose limiting toxicities were elevated creatinine, dysgeusia, fatigue and pulmonary edema. The recommended dose was 550 mg/m2 daily. All responses occurred at doses ≥ 400 mg/m2. In CNS tumors (n = 6), all high-grade with gene fusions: 1 achieved a CR ( ETV6-NTRK3); 3 achieved a PR ( TPR-NTRK1, EEF1G-ROS1, EML1-NTRK2); 1 achieved an unconfirmed PR ( GOPC-ROS1); and 1 has yet to be evaluated ( KANK1-NTRK2). In extracranial solid tumors (n = 8), 6 had a fusion of whom 1 achieved a CR ( DCTN1-ALK) and 5 achieved a PR ( TFG1-ROS1, EML4-NTRK3, ETV6-NTRK3, KIF5B-ALK, ETV6-NTRK3). In NBL (n = 15): 1 achieved a CR ( ALK F1174L). Median duration of therapy was 85d (6–592d) for all patients; 56d (6–338d) for non-responders; and 281d (56–592d) for responders. Median time to response was 57d (30–58d). Conclusions: Entrectinib produced striking, rapid and durable responses in all children with refractory CNS and solid tumors harboring NTRK1/2/3, ROS1 or ALK fusions (11 out of 11) as well as in an ALK-mutated NBL. No responses were seen in tumors lacking aberrations in target kinases. These results support the continued evaluation of entrectinib as a targeted therapeutic in solid tumors with NTRK1/2/3, ROS1 and ALK fusions, especially in high-grade CNS neoplasms. Clinical trial information: NCT02650401.

Background Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non-small cell lung cancer. We report analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors. Methods STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose escalation of oral, once-daily entrectinib, enrolled patients aged &lt;22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions, or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D. Results At data cut-off, 43 patients, median age 7 years, were response-evaluable. In phase 1, four patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9–76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2–18.4). Conclusions Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions.