Search

Background Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. Methods Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. Results Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. Conclusions Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.

Background Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential. Methods Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, Results Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival. Conclusions The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.

BackgroundDiffuse intrinsic pontine gliomas (DIPG) generally occur in young school-age children, although can occur in adolescents and young adults. The purpose of this study was to describe clinical, radiological, pathologic, and molecular characteristics in patients ≥10 years of age with DIPG enrolled in the International DIPG Registry (IDIPGR).MethodsPatients ≥10 years of age at diagnosis enrolled in the IDIPGR with imaging confirmed DIPG diagnosis were included. The primary outcome was overall survival (OS) categorized as long-term survivors (LTS) (≥24 months) or short-term survivors (STS) (ResultsAmong 1010 patients, 208 (21%) were ≥10 years of age at diagnosis; 152 were eligible with a median age of 12 years (range 10-26.8). Median OS was 13 (2-82) months. The 1-, 3-, and 5-year OS was 59.2%, 5.3%, and 3.3%, respectively. The 18/152 (11.8%) LTS were more likely to be older (P < .01) and present with longer symptom duration (P < .01). Biopsy and/or autopsy were performed in 50 (33%) patients; 77%, 61%, 33%, and 6% of patients tested had H3K27M (H3F3A or HIST1H3B), TP53, ATRX, and ACVR1 mutations/genome alterations, respectively. Two of 18 patients with IDH1 testing were IDH1-mutant and 1 was a LTS. The presence or absence of H3 alterations did not affect survival.ConclusionPatients ≥10 years old with DIPG have a median survival of 13 months. LTS present with longer symptom duration and are likely to be older at presentation compared to STS. ATRX mutation rates were higher in this population than the general DIPG population.

BACKGROUND: There are no standard practice guidelines for cerebrospinal (CSF) diversion for diffuse intrinsic pontine glioma (DIPG), nor clear understanding of potential for palliation and life-prolongation. We evaluated CSF diversion characteristics in children with DIPG to determine incidence, indications, symptom effects, and survival. METHODS: Data were extracted from subjects registered in the International DIPG registry (IDIPGR). Univariable analyses was performed using the Fisher’s exact test or Wilcoxon rank sum test. Survival was estimated using the Kaplan-Meier method. RESULTS: Evaluable patients (n=542) met criteria for DIPG diagnosis by central radiologic review; of those, 126 (23%) had permanent CSF diversion. Median time from diagnosis to diversion was 0.5 months (IQR 0.1-4.5 months). Those with permanent diversion were significantly younger (median 5.4 years vs 7.0 years, p

INTRODUCTION The role of diagnostic biopsy in diffuse intrinsic pontine glioma (DIPG) remains in question. Distinguishing radiographically between DIPG and other pontine tumors with more favorable prognosis and different therapy is critically important. METHODS Cases submitted to the International DIPG registry with histopathologic data were analyzed. Central imaging review was performed by two neuro-radiologists; all cases with imaging features or histopathology suggestive of alternative diagnoses were re-reviewed. Imaging features suggestive of alternative diagnoses included non-pontine origin, RESULTS Among 297 patients with pathology from biopsy and/or autopsy available, 27 (9%) had histologic diagnoses not consistent with DIPG, commonly embryonal tumors (n=9) and pilocytic astrocytomas (n=11). 163 patients had diagnostic MRI available for central neuroimaging review. Among 81 patients classified as characteristic of DIPG, 80 (99%) had histopathology consistent with DIPG (diffuse midline glioma, H3K27M-mutant, glioblastoma, anaplastic astrocytoma, diffuse astrocytoma). Among 63 patients classified as likely DIPG, but with unusual imaging features, 59 (94%) had histopathology consistent with DIPG. 19 patients had imaging features suggestive of another diagnosis, including 13 with non-pontine tumor origin; the remaining 6 all had histopathology not consistent with DIPG. Association between central imaging review and histopathology was significant (p CONCLUSIONS The important role and accuracy of central neuroimaging review in diagnosing or excluding DIPG is demonstrated. In patients with pontine tumors for which DIPG is felt unlikely radiographically, biopsy may be considered to guide diagnosis and treatment.

Diffuse intrinsic pontine glioma (DIPG) is aggressive brainstem tumor with median survival of < 1 year. We queried data from the International DIPG Registry to define clinical, radiological, histological, and molecular characteristics of DIPG patients who survived < 3 months from diagnosis. Among 909 patients enrolled on the registry, 59 (6.5%) had overall survival (OS) of < 3 months. Median age at diagnosis was 5.8 years (range 0–13 years), and 12 (20%) were age < 3 years at diagnosis. Most presented with short duration of symptoms (< 6 weeks, 50/58; 86%) and at least one cranial nerve palsy, cerebellar sign, and/or pyramidal tract sign (52/54; 96%). Twenty-two (41%) presented with hydrocephalus, including 10 who required CSF diversion. All had extra-pontine extension on diagnostic imaging. Less than half of patients (25/56, 45%) received therapy; of these, 11 received radiation (RT) only, 12 received RT and chemotherapy, and 2 received chemotherapy only. Most received steroids (48/52; 92%), including 27 who received palliative steroids at the end of life. Biopsy and autopsy were performed in 11/57 (19%) and 13/58 (22%) cases, respectively. Of 22 for whom histology was known, 19 represented high-grade glioma subtypes, 2 low-grade gliomas, and 1 embryonal tumor. Six were molecularly characterized, and 3 harbored H3K27M mutations. Ongoing work will aim to further characterize the molecular features of these tumors with exceptional poor outcomes despite therapy.

INTRODUCTION: Patients ≥10 years of age with a DIPG are reported to have a higher rate of long-term survival (≥24 months). The purpose of this study was to compare clinical, radiological, pathological and molecular characteristics between patients ≥10 years old with DIPG who were long-term survivors (LTS) vs short-term survivors (STS) and assess biological differences in this age group compared to patients

BACKGROUND: Children

Objectives. We aimed to quantify children's levels of pain and fear during needle puncture procedures in a context where intravenous sedation-analgesia seems to be effective for pain and anxiety relief. The relevance of a nonpharmacological intervention in the pharmacological regimen was evaluated. Design. Fear and pain were assessed by children, parents and physicians, on a visual analog scale (VAS, 0–10 cm), before and during puncture procedures. Higher scores represented more intense pain/fear. Results. During 4 consecutive months, 18 children were recruited, but four were excluded from analyses because they did not receive the full sedation regimen (midazolam/ketamine) (N = 14, mean age ± SD: 9.9 ± 3.4 years). Parents self-reported their own anxiety before the procedure (4.69 ± 3.17), but no correlation was found with their children's self-reported fear. Before procedures, the children's fear was self-reported on a VAS by children (2.93 ± 2.93), parents (4.45 ± 2.87), and physicians (3.67 ± 2.48). During procedures under sedation, the children's pain (1.71 ± 2.74) did not correlate with the parents' (4.01 ± 3.23) and physicians' (1.83 ± 2.32) ratings. Children anticipating high levels of pain and fear on the VAS experienced higher levels of pain (r = 0.65, P

MB-23. RECURRENT SHH/TP53 MUTANT MEDULLOBLASTOMA TREATED WITH A COMBINATION OF LITHIUM AND RADIATION THERAPY Anne-Sophie Carret1, Louis Crevier2, Yvan Samson1, Benjamin Ellezam3, and Anne-Marie Charpentier4; Department of Pediatrics, Division of Hematology-Oncology, CHU Sainte-Justine/Universite de Montreal, Montreal, QC, Canada; Department of Neurosurgery, CHU Sainte-Justine/ Universite de Montreal, Montreal, QC, Canada; Department of Pathology, CHU Sainte-Justine/Universite de Montreal, Montreal, QC, Canada; Department of Radiation Oncology, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada INTRODUCTION: TP53 mutations remain a poor prognotic factor and account for a high proportion of the treatment failure in SHH subgroup medulloblatoma. Poor survival of patients with P53 mutant medulloblastoma may be related to radiation/chemotherapy resistance. Lithium, an activator of the WNT pathway, sensitizes TP53 mutant medulloblastoma to radiation. CASE REPORT: a 12-yo boy presented with left localized hemispheric medulloblastoma. After a complete excision of the tumour he was randomized and treated according to COGACNS0331 and received a standard-dose craniospinal radiation with a boost to the entire posterior fossa, followed by maintenance chemotherapy. Patient was considered in complete remission. 15 months post-end of treatment, MRI showed a local recurrence. After 2 cycles of temozolomide, irinotecan and bevacizumab chemotherapy, patient had tumor progression. He then underwent a complete resection of the tumour. Pathology showed anaplastic type, SHH/TP53 mutant medulloblastoma. Due to the expected poor survival and the lackof known and consensual curative treatment, the patient was treated with a combination of therapeutic dose of lithium and focal radiation therapy to a dose of 54 Gy. One year later, the patient remains asymptomatic and, in complete remission. CONCLUSION: Lithium combined to radiation therapy may represent an interesting therapeutic avenue for higher risk groups of medulloblastoma in a context of a pilot study. Neuro-Oncology 18:iii97–iii122, 2016. doi:10.1093/neuonc/now076.21 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Despite all recent advances in cancer's treatment, 18% of children will die from their cancer. New tools that enable better individual tumor characterization and classification are required to improve patient care and outcomes on children. Personalized targeted therapy has proven to be a promising strategy for first line treatment in adult cancer. Given the high heterogeneity in childhood cancers, access to histopathology-based clinical trials for targeted therapy is challenging and facilitated by the capacity to sequence individual childhood tumors in real time. A feasibility study is currently underway at the CHU Sainte-Justine, Montreal, where 30 relapse or refractory cancer patients between 0 and 21 years, are being offered in-depth genomic and transcriptomic investigation to identify patient-specific alterations that may be targetable with alternative therapies. This pilot study will allow us to address the following questions: 1) determine the number of children with cancer who are suitable candidates for targeted therapy at our institution each year, 2) determine the number and type of driver mutation(s) found in our population of recurrent or refractory cancers, 3) determine the number of cancer patients who harbour actionable driver mutation(s) that can be targeted with a Health Canada approved targeted drug, 4) assess the feasibility of obtaining high quality/quantity biospecimen, performing genomic sequencing and data analysis, identifying a drug based on the genomic data and offering this information to the medical team, the patient and the family within a 10-week time frame. The following step toward translating our results into novel personalized therapeutic approaches will then be the development of phase II clinical trials to evaluate the efficacy of these targeted therapies in terms of therapeutic response, survival, and overall quality of life. Our overreaching goal is to be able to offer personalized targeted therapy options to all patients upon primary diagnosis of their cancer.