The cellular composition of H3K27M gliomas: Diffuse midline gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) are an aggressive type of childhood cancer with few options for treatment. Filbin et al. used a single-cell sequencing approach to study the oncogenic programs, genetics, and cellular hierarchies of H3K27M-glioma. Tumors were mainly composed of cells resembling oligodendrocyte precursor cells, whereas differentiated malignant cells were a smaller fraction. In comparison with other gliomas, these cancers had distinct oncogenic programs and stem cell–like profiles that contributed to their stable tumor-propagating potential. The analysis also identified a lineage-specific marker that may be useful in developing therapies. Science , this issue p. 331

Atypical teratoid rhabdoid tumors (ATRTs) are recently defined highly aggressive embryonal central nervous system tumors with a poor prognosis and no definitive guidelines for treatment. We report on the importance of an initial correct diagnosis and disease‐specific therapy on outcome in 22 consecutive patients and propose a new treatment strategy. From 1992 to 2012, nine patients initially diagnosed correctly as ATRT (cohort A, median age 24 months) were treated according to an intensive multimodal regimen (MUV‐ATRT) consisting of three 9‐week courses of a dose‐dense regimen including doxorubicin, cyclophosphamide, vincristine, ifosfamide, cisplatin, etoposide, and methotrexate augmented with intrathecal therapy, followed by high‐dose chemotherapy (HDCT) and completed with local radiotherapy. Thirteen patients were treated differently (cohort B, median age 30 months) most of whom according to protocols in use for their respective diagnoses. As of July 2013, 5‐year overall survival (OS) and event‐free survival (EFS) for all 22 consecutive patients was 56.3 ± 11.3% and 52.9 ± 11.0%, respectively. For MUV‐ATRT regimen‐treated patients (cohort A) 5‐year OS was 100% and EFS was 88.9 ± 10.5%. For patients treated differently (cohort B) 5‐year OS and EFS were 28.8 ± 13.1%. All nine MUV‐ATRT regimen‐treated patients are alive for a median of 76 months (range: 16–197), eight in first complete remission. Our results compare favorably to previously published data. The drug combination and sequence used in the proposed MUV‐ATRT regimen appear to be efficacious in preventing early relapses also in young children with M1–M3 stage disease allowing postponement of radiotherapy until after HDCT.

Background: Coil instability possibly translating into higher delayed rebleeding rates remains a concern in the endovascular management of cerebral aneurysms. Objective: To report on 127 patients with endovascular aneurysmal remnants who underwent re-treatment over an 18 year period. Methods: Patients presenting with aneurysm residuals >20% of the original lesion, unstable neck remnants, aneurysmal regrowth, or new aneurysmal daughter sacs were treated by an individualized approach, using both endovascular and surgical techniques. Results: Seventy-five aneurysmal remnants (59.1%) were treated by further re-embolization. Standard coil embolization was used in 65 cases, stent-protected coiling in 9 cases, and balloon remodeled coiling in 1 case, respectively. Fifty-two (40.9%) aneurysmal remnants were treated surgically. Standard microsurgical clipping was used in 44 patients, parent artery occlusion or trapping under bypass protection in 5 cases, deliberate clipping of the basilar artery trunk in 2 cases, and aneurysm wrapping in one case, respectively. Mechanisms of aneurysm recurrence were coil compaction in 93 cases and regrowth in 34 cases. A single reembolization was sufficient to occlude 78.7% of recurrences from coil compaction, but only 14.3% of recurrences from aneurysm regrowth. Conclusion: The individualized approach resulted in complete occlusion of 114 aneurysms (89.7%), with neck remnants and residual aneurysms detectable in 11 (8.7%) and 2 (1.6%) cases, respectively. Treatment morbidity was 11.9%, without significant differences between surgical (15.6%) and endovascular (9.3%) patients (P = .09). Recurrences from coil compaction were safely treated by re-embolization, whereas recurrences from aneurysmal regrowth may best be managed surgically when technically feasible.

Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. European Société Internationale d’Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3–17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0–8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8–9.7) years. Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities—important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted.

BACKGROUND:. Microscope integrated intraoperative near-infrared indocyanine green angiography (ICGA) provides assessment of the cerebral vasculature in