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BACKGROUND: Brain tumours are the most common solid tumours in childhood. Half of these tumours occur in the posterior fossa, where surgical removal is complicated by the risk of cerebellar mutism syndrome, of which postoperative speech impairment (POSI) is a cardinal symptom, in up to 25% of patients. The surgical approach to midline tumours, mostly undertaken by transvermian or telovelar routes, has been proposed to influence the risk of POSI. We aimed to investigate the risk of developing POSI, the time course of its resolution, and its association with surgical approach and other clinical factors. METHODS: In this observational prospective multicentre cohort study, we included children (aged

Pediatric very rare tumors (VRTs) represent a heterogeneous subset of childhood cancers, with reliable survival estimates depending dramatically on each (un)registered case. The current study aimed to evaluate the number of VRTs among Lithuanian children, to assess the impact of the registration status on survival rates and to track changes in treatment outcomes over the 16-year study period. We performed a population-based retrospective study across children below 18 years old diagnosed with VRTs in Lithuania between the years 2000 and 2015. The identified cases were cross-checked with the Lithuanian Cancer Registry—a population-based epidemiology cancer registry—for the fact of registration and survival status. The overall survival was calculated in relation to the registration status and treatment period. Thirty-seven children with VRTs were identified within the defined time frame. Six of them (16.2%) were not reported to the Lithuanian Cancer Registry at diagnosis. The probability of overall survival at 5 years (OS5y) differed significantly between the registered (n = 31) and unregistered (n = 6) cohorts: 51.6% versus 100%, respectively (p = 0.049). A 5-year survival estimate for children diagnosed with a VRT at the age of 0–14 years differed by 10 percentage points according to the registration completeness: 52.1% calculated for the entire cohort versus 42.1% for registered patients only. The OS5y has not improved over the analyzed period: 61.1% in 2000–2007 versus 57.9% in 2008–2015 (p = 0.805). The survival continued to decline beyond 5 years post-diagnosis due to late cancer-related adverse events: 59.5% of patients were alive at 5 years as compared to 44.3% at 10 years. The OS5y of children affected by VRT was lower than in more common childhood cancers. The survival rate of the unregistered patients may lead to misinterpretation of treatment outcomes. Meticulous registration of VRTs is crucial for correct evaluation of treatment outcomes, especially across small countries with few cases.

Background. Pediatric very rare tumors (VRTs) represent a heterogeneous subset of childhood cancers, with reliable survival estimates depending dramatically on each (un)registered case. The current study aimed to evaluate the number of VRTs among Lithuanian children, to assess the impact of the registration status on survival rate and to track changes in treatment outcome over the 16-year study period. Methods. We performed a population-based retrospective study across children below 18 years old diagnosed with a VRT in Lithuania between the years 2000 and 2015. The identified cases were cross-checked with the Lithuanian Cancer Registry – a population-based epidemiology cancer registry – for the fact of registration and survival status. The overall survival was calculated according to the registration status and treatment period. Results. Thirty-seven children with VRTs were identified within the defined time frame. Six of them (16.2%) were not reported to the Lithuanian Cancer Registry at diagnosis. The probability of overall survival at 5 years (OS5y) differed significantly between the registered (n = 31) and unregistered (n = 6) cohorts: 51.6% vs 100%, respectively (p = 0.049). A 5-year survival estimate for children diagnosed with a VRT at the age of 0-14 years differed by 10% according to the registration completeness: 52.1% calculated for the entire cohort vs 42.1% for registered patients only. The OS5y did not improve over the analyzed period: 61.1% in 2000-2007 vs 57.9% in 2008-2015 (p = 0.805). The survival continued to decline beyond 5 years due to late cancer-related adverse events: 59.5% of patients were alive at 5 years as compared to 44.3% at 10 years. Conclusions. The OS5y of children affected by VRT was lower than in more common childhood cancers. The survival rate of the unregistered patients was superior that mislead interpretation of treatment outcome. Meticulous registration of VRTs is crucial for correct evaluation of treatment outcome, especially across small countries with few cases.

Background: Pediatric very rare tumors (VRTs) represent a heterogeneous subset of childhood malignancies, with reliable survival rate estimations depending dramatically on each (un)registered case. The current study aimed to evaluate the number of VRTs among Lithuanian children and the change in treatment outcome over the 16 year study period as well as to assess the impact of the registration status on survival estimation. Methods . We performed a population-based retrospective analysis across children below 18 years old diagnosed with VRTs in Lithuania between the years 2000 to 2015. The identified cases were then crosschecked with the Lithuanian Cancer Registry (a population-based epidemiology cancer registry) for the registration and survival status. A five year overall survival (OS 5y ) was calculated using Kaplan-Meier estimation method. Results . Forty-four children affected by VRTs were identified within the defined time frame. Nine of them (20.5%) were not reported to the Lithuanian Cancer Registry at the time of diagnosis. The OS 5y of the entire cohort was 55.8%. The cure rate did not improve over the analyzed time periods – 54.2% in 2000-2007 vs 49.4% in 2008-2015. The OS 5y differed significantly between registered (n=35) and unregistered (n=9) cohorts: 45.1% vs 100%, respectively (p=0.016). The tumor progression was responsible for treatment failure in 95% of cases. Conclusions. The OS 5y of all analyzed children affected by VRT was lower as compared to the other childhood cancers. The survival rate of the unregistered patients was significantly superior that mislead interpretation of treatment outcome. Meticulous registration of VRTs is crucial for correct evaluation of treatment outcome, especially across small countries with fewer numbers of cases.

Introduction Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. Methods Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. Results Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. Conclusion This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

Thiamine responsive megaloblastic anemia syndrome (TRMAS) is a rare autosomal recessive disorder especially in countries where consanguinity is uncommon. Three main features are characteristic of the disease – megaloblastic anemia, early onset deafness, and non-type I diabetes. TRMAS is a Mendelian disorder; a gene SLC19A2 coding high affinity thiamine transporter mediating vitamin B1 uptake through cell membrane has been identified. We present the first patient with TRMAS in Lithuania – a 3-year-old boy born to a non-consanguineous family with a novel homozygous SLC19A2 gene mutation. The patient had insulin dependent diabetes (onset 11 months), respiratory illness (onset 11 months), bilateral profound hearing loss (onset at 7 months, verified at 20 months), refractory anemia (onset 2 years), and decreased vision acuity and photophobia (onset 2.5 years). The psychomotor abilities developed according to age. Phenotypic evaluation did not reveal any dysmorphic features. The clinical diagnosis of TRMAS was suspected and daily supplementation with thiamine 100 mg was started. The condition of the patient markedly improved several days after the initiation of treatment. The results of SLC19A2 gene molecular testing confirmed the clinical diagnosis – novel homozygous c.[205G>T], p.[(Val69Phe)] mutation changing conserved amino acid residue or even interfering the mRNA splicing. Clinical heterogeneity, diverse dynamics, and wide spectrum of symptoms are aggravating factors in the diagnosis. The possibility of treatment demands early recognition of disorder to facilitate the improvement of the patient's condition. © 2015 Wiley Periodicals, Inc.

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 material The online version of this article (doi:10.1007/s11060-016-2363-y) contains supplementary material, which is available to authorized users.

Medulloblastoma, a primitive neuroectodermal tumor growing in cerebellum, is one of the most sensitive to radiation therapy childhood brain tumors, therefore, this method of treatments is justly considered to be the standard for the treatment of medulloblastoma. The outcome of this malignant brain tumor differs in standard and high-risk groups of patients. The aim of the work was to evaluate the survival rate for children with medulloblastoma according to two risk groups.Eighteen patients aged from 3 to 18 years with histological proven medulloblastoma treated with standard craniospinal and additional posterior fossa radiotherapy were investigated in our study. Nine patients with disseminated and partial removed medulloblastoma were assigned to the high-risk group and other 9 patients with local ant totally removed medulloblastoma were allocated to the standard risk group.Radiological response of medulloblastoma to the radiation therapy was observed in 15 (83.3%) out of 18 patients: complete radiological response was observed in 6 (67%) out of 9 standard-risk patients and in only 1 (11.1%) out of 9 high-risk patients (p0.05). Medulloblastoma progressed in 15 (83.3%) patients treated with radiation therapy: relapse rate in the high-risk group was 100% and in the standard-risk group--66.7% (p0.05). The mean time to progression for all patients was 18.2 months: 28.9 months in standard and 7.4 months in high-risk group (p=0.02). The overall survival for all investigated patients was 25.8 months: 37.2 and 14.3 months in the standard and high-risk groups, respectively (p=0.01). Five years progression-free and overall survival rate for all patients was 16.7%: 0% in the high-risk group and 33.3 % in the standard-risk group (p0.05).In our study the difference in survival rate between standard and high-risk patients with medulloblastoma was shown. We observed a statistically significant longer time to progression and better overall survival in the standard-risk group. However, we did not find any significant differences in other survival indices (response, relapse rates, mortality, five years progression- free and overall survival) between those two risk groups.

The prognosis of children with medulloblastoma, primitive neuroectodermal tumor of cerebella, is poor especially in case of disseminated disease. Bad outcome of this disease encouraged the investigators to look for new more effective and safer ways of medulloblastoma treatment that would be able to improve the prognosis and quality of live for children with medulloblastoma. Adjuvant chemotherapy administered after radiotherapy prolongs the time to progression as well as overall survival for high-risk group of medulloblastoma patients, while such results vary little in standard-risk medulloblastoma group.To evaluate effectiveness of adjuvant chemotherapy while treating high-risk medulloblastoma patients.A total of 18 patients with disseminated and non-totally removed medulloblastoma admitted to high-risk group aged from 3 to 18 years were enrolled in this study. Nine of these patients were treated by radiotherapy alone and the adjuvant chemotherapy with CCNU (lomustine), cisplatinum, and vincristine after radiotherapy was administered to the other nine patients.Full response was determined in all patients of adjuvant chemotherapy group and only in 3 children out of 9 in radiotherapy group (33.3%) (p0.01). The rate of the relapse was 100% in radiotherapy and 11.1% in adjuvant chemotherapy group that differed statistically reliably in both group patients (p0.001). Mean time to progression among patients of radiotherapy group was 9+/-2 months and 47+/-8 months among of the patients of adjuvant chemotherapy group (p0.01). Two years free to progression survival in adjuvant chemotherapy group was 88.9%, in radiotherapy group - 0%. Two-year overall survival in these groups was 71.1 and 22.2%, respectively (p0.01).With this research we proved that adjuvant chemotherapy, prescribed after standard radial (craniospinal and local) treatment, statistically reliably improves survival indices of patients from high risk group and has to be prescribed to all patients from this risk group.