We developed a DIPG survival prediction tool that can be used to predict the outcome of patients and for stratification in trials. Validation of the model is needed in a prospective cohort.

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BackgroundStandards for residual tumour measurement after resection of gliomas with no or minimal enhancement have not yet been established. In this study residual volumes on early and late postoperative T2-/FLAIR-weighted MRI are compared.MethodsA retrospective cohort included 58 consecutive glioma patients with no or minimal preoperative gadolinium enhancement. Inclusion criteria were first-time resection between 2007 and 2009 with a T2-/FLAIR-based target volume and availability of preoperative, early (<48 h) and late (1–7 months) postoperative MRI. The volumes of non-enhancing T2/FLAIR tissue and diffusion restriction areas were measured.ResultsResidual tumour volumes were 22% smaller on late postoperative compared with early postoperative T2-weighted MRI and 49% smaller for FLAIR-weighted imaging. Postoperative restricted diffusion volume correlated with the difference between early and late postoperative FLAIR volumes and with the difference between T2 and FLAIR volumes on early postoperative MRI.ConclusionWe observed a systematic and substantial overestimation of residual non-enhancing volume on MRI within 48 h of resection compared with months postoperatively, in particular for FLAIR imaging. Resection-induced ischaemia contributes to this overestimation, as may other operative effects. This indicates that early postoperative MRI is less reliable to determine the extent of non-enhancing residual glioma and restricted diffusion volumes are imperative.

Given the rarity of DIPG, we emphasize the need for (inter-)national trials to facilitate the identification of potentially effective therapeutics in the future. This can be supported by the recent development of a European DIPG registry enabling international study collaborations.

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6–6.4 months) and the median overall survival is 11.0 months (95% CI 10.5–11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-016-2363-y) contains supplementary material, which is available to authorized users.

The availability of various first-line treatment modalities for acromegaly and evolving surgical techniques emphasize the need for accurately defined predictors of surgical outcome. We retrospectively analysed the outcome of 30 patients with acromegaly after initial endoscopic transsphenoidal surgery in two university hospitals from 2001 until 2009, and reviewed comparable literature investigating predictive tumor characteristics. Medical records were monitored for patient characteristics. Each pituitary magnetic resonance imaging (MRI) scan was revised independently by two neuroradiologists using a standardised analysis form to record distinctive predefined tumor characteristics. All characteristics were independently analysed as predictors for persistent disease, and a multivariable predictive model was created. Literature from 2000 onwards was searched for studies describing tumor characteristics predictive for surgical outcome. The cohort consisted of 27 macroadenomas with 90 % demonstrating signs of parasellar extension. The surgical cure rate overall was 30 %. Independently, next to male sex and increasing tumor size, infrasellar and parasellar extension based on MRI staging tended to increase the risk of persistent disease. In a multivariable analysis, sex and parasellar extension of the tumor were demonstrated to be the variables allowing for the best fitted predictive model for persistent disease. Earlier studies on preoperative tumor characteristics showed comparable results, although these were based on several different tumor classification systems. This retrospective study demonstrates that accurately defined tumor characteristics based on imaging, especially for cavernous sinus invasion, can be helpful in predicting surgical outcome. Comparative studies on different treatment modalities are essential for clinical practice within the scope of re-evaluation of the role of surgery in GH-secreting adenomas.

The purpose of this phase I/II, open-label, single-arm trial is to investigate the safety, tolerability, maximum tolerated dose and preliminary efficacy of the potential radiosensitizer gemcitabine, administered concomitantly to radiotherapy, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Six doses of weekly gemcitabine were administered intravenously, concomitantly to 6 weeks of hyperfractionated radiotherapy. Successive cohorts received increasing doses of 140, 175 and 200 mg/m2 gemcitabine, respectively, following a 3 + 3 dose-escalation schedule without expansion cohort. Dose-limiting toxicities (DLT) were monitored during treatment period. Clinical response was assessed using predefined case report forms and radiological response was assessed using the modified RANO criteria. Quality of life (QoL) was assessed using PedsQL questionnaires. Between June 2012 and December 2016, nine patients were enrolled. Treatment was well tolerated, and no DLTs were observed up to the maximum dose of 200 mg/m2. All patients experienced reduction of tumor-related symptoms. QoL tended to improve during treatment. PFS and MOS were 4.8 months (95% CI 4.0–5.7) and 8.7 months (95% CI 7.0–10.4). Classifying patients according to the recently developed DIPG survival prediction model, intermediate risk patients (n = 4), showed a PFS and MOS of 6.4 and 12.4 months, respectively, versus a PFS and MOS of 4.5 and 8.1 months, respectively, in high risk patient (n = 5). Gemcitabine up to 200 mg/m2/once weekly, added to radiotherapy, is safe and well tolerated in children with newly diagnosed DIPG. PFS and MOS were not significantly different from literature.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-017-2575-9) contains supplementary material, which is available to authorized users.

BACKGROUND: Pediatric Diffuse intrinsic pediatric glioma (DIPG) remained dismal regardless of the new therapeutic and technical attempts. PURPOSE: To investigate the efficacy and toxicity of hypofractionated radiotherapy in pediatric DIPG compared to conventional radiotherapy and to determine the prognostic factors for its overall (OS) and progressionfree survival (PFS). PATIENTS AND METHODS: Sixty four children, below the age of 18 years, who presented to Children's Cancer Hospital, Egypt (CCHE) during the period July 2007 and July 2011 were randomized into 2 groups. The hypofractionated group received 39 Gy in 13 fractions in 21/2 weeks and the conventional arm receiving 55.8 Gy in 31 fractions in 6 weeks using conformal radiotherapy technique. The two arms were not different in age, gender, performance status and tumor volume. RESULTS: Thirty two children were randomized in each arm. The median OS for the whole group was 9.5 + 1.0 months: 7.4 + 1.0 months for the hypofractionated arm and 9.9 + 1.0 months for the conventional arm. The whole group has median PFS of 7.3 + 0.8 months; 7.0 + 1.4 months for the hypofractionated and 7.7 + 1.1 for the conventional arm. On the other hand, the 1-year and 2-year OS were 41.4 + 9.2% and 28.4 + 8,8% in the hypofractionated arm and 36.2 + 8.7% and 32.3 + 7.8% in the conventional arm. None of these differences was statistically significant. Furthermore, none of the tested factors (age, gender, performance status, tumor volume, radiation volume or tumor extension) proved to have statistically significant influence on OS or PFS. All patients showed marked degree of improvement in symptoms and signs with earlier response in the hypofractionated arm. The immediate and delayed side effects were not different between the 2 arms. CONCLUSIONS: Hypofractionated radiotherapy had similar overall, progression-free survival and delayed effect (in the long survivors) to conventional fractionation. It offers less burden on the patients, their families and the treating machines and departments.