Carbohydrate metabolism in children after complex treatment of medulloblastoma

BACKGROUND: Disorders of carbohydrate metabolism are frequent complications after complex treatment of cancer. Early detection of these disorders allows to modify lifestyle, if necessary, apply drug therapy and correct the identified changes in time, which will subsequently lead to a decrease in cardiovascular risks, an improvement in the quality and an increase in the life expectancy of this group of patients.AIM: To identify the frequency of occurrence and determine the optimal methods for early diagnosis of carbohydrate metabolism disorders in children after complex treatment of medulloblastoma.MATERIALS AND METHODS: 97 patients (64 boys) were examined after complex treatment of medulloblastoma (surgical treatment, craniospinal radiation therapy [CSI], chemotherapy). The median age at the time of the survey was 11.2  (5.29 -17.9) years. The average follow-up period after the end of all types of treatment is 4.7 (0.59 - 11.94) years. At the time of examination, all patients were compensated for hypothyroidism and hypocorticism (if any), and no one was on growth hormone therapy. All patients underwent a standard oral glucose tolerance test (OGTT) and determination of the level of glycated hemoglobin (HbA1c).RESULTS: None of the patients had a basal glycemic level higher than 5.5 mmol / L. Impaired glucose tolerance ( glycemia at the 120th minute ≥7.8 mmol / L <11.09 mmol / L) was detected in 10 out of 97 patients (10.3%). 7 patients with IGT had insulin resistance (according to MATSUDA index), while 1 of them had normal HOMA-IR index. Only one patient with IGT had an increase in the level of glycated hemoglobin up to 6.2%. Insulin resistance (using the MATSUDA index) was present in 30 patients, and 11 of them had a normal HOMA-IR index. Thus, 34 out of 97 patients (35.1%) had disorders of carbohydrate metabolism (IGT and / or insulin resistance). At the same time, the level of glycated hemoglobin reflected disturbances in only one case, and the basal level of glycemia was not informative in any case.CONCLUSION: Assessment of basal levels of glycemia and insulin, as well as glycated hemoglobin, is insufficient to exclude disorders of carbohydrate metabolism in patients after complex treatment of medulloblastoma. It is advisable to carry out a standard OGTT

Growth hormone deficiency in childhood brain tumors and acute lymphoblastic leukemia survivors

Thanks to modern treatment protocols, childhood cancer survivors (CCS) are a very fast-growing population nowadays. Cancer therapy inevitably leads to different late adverse effects, where endocrine disorders are highly prevalent, including growth hormone deficiency (GHD) which is the most common endocrine outcome after cancer treatment in childhood and contributes to impaired growth. Short stature is a big issue, which leads to problems in psychological and social adaptation of patients and reduces their quality of life. Impact of GH treatment on various physiological processes and global outcome of CCS is of great interest. Several studies have demonstrated an influence of GH and IGF-1 on the development/tumour growth, cell proliferation. In this regard, the issue of increasing the risk of cancer recurrence and/or the development of secondary neoplasms in CCS, causes a lot of controversy and is the subject of continuous evaluation. In this review, we went through the available data on the prevalence and pathogenesis of GHD following chemo- and radiotherapy, in particular after treatment of brain tumors and acute lymphoblastic leukaemia in childhood. In addition, here we discuss the existing problems in the diagnosis of GHD, the safety of GH replacement therapy, as well as the treatment algorithm of the GHD in adults

Метастатический почечно-клеточный рак почки у ребенка 10 лет. Возможности таргетной терапии (клиническое наблюдение)

Renal cell carcinoma (RCC) is rare in children, its metastatic form is even rarer. At present there is no treatment protocol for children with RCC. This clinical observation presented the patient 10 year old with RCC metastases to the lungs. After radical surgery, after targeted sorafenib therapy the patient has a positive dynamics. At present his progression-free survival is 30 months.Почечно-клеточный рак (ПКР) редко встречается у детей, а его метастатическая форма еще реже. На настоящий момент не существует протоколов лечения для детей с ПКР, не изучены возможности современной таргетной терапии. В данной статье представлено клиническое наблюдение пациента 10 лет с ПКР и метастазами в легкие. После тотального удаления опухоли почки на фоне проведения таргетной терапии сорафенибом у пациента достигнута положительная динамика. В настоящий момент выживаемость без прогрессирования составляет 30 мес

Вторичная анапластическая астроцитома у ребенка после лечения медуллобластомы. Клинический случай

The development of secondary tumors is a rare but well-known late effect of radiation therapy of lesions of the central nervous system. At the same time, malignant gliomas most often occur.This article presents a rare clinical case of secondary anaplastic astrocytoma in a child who received chemoradia-tion therapy for medulloblastoma after surgical treatment.Purpose. Demonstration of a rare occurrence of anaplastic astrocytoma after surgical and chemoradiation treatment of medulloblastoma.Развитие вторичных новообразований является редким, но хорошо известным поздним эффектом лучевой терапии опухолей центральной нервной системы. При этом чаще всего возникают злокачественные глиомы.В данной статье представлен редкий клинический случай вторичной анапластической астроцитомы у ребенка, получившего после хирургического лечения химиолучевую терапию по поводу медуллобластомы.Цель исследования: демонстрация редкого случая возникновения анапластической астроцитомы после хирургического и химиолучевого лечения медуллобластомы

Risk factors for cardiovascular diseases in patients received complex treatment for cranial and craniospinal tumors in childhood

Aim. To study the traditional risk factors for cardiovascular disease (CVD), indicators of endothelial function and exercise tolerance in patients received complex treatment for cranial and craniospinal tumors in childhood, including radiation therapy.Material and methods. We compared examination data of 48 patients who underwent treatment for brain tumors using cranial and craniospinal irradiation in childhood (mean age, 21,7±4,3 years, mean period after the end of treatment, 6,9±5,4 years), and 20 healthy volunteers. Examination methods included assessment of lipid profile, vascular stiffness and endothelial function using the Photoplethysmography and occlusion test, cardiopulmonary test, and in patients who underwent craniospinal irradiation, also echocardiography and duplex ultrasound of extracranial arteries.Results. Compared to healthy individuals, patients after a brain tumor were found to have lower blood pressure, higher heart rate (HR), significantly lower exercise performance (peak oxygen consumption, 19,8±6,4 ml×min-1×kg vs 30,3±5,8 ml×min-1×kg, p<0,0001) and a higher prevalence of dyslipidemia (56% vs 5%, p<0,0001), as well as an increase in the augmentation index, indicating higher stiffness of large vessels (-7,3±16,3 vs -20,3±7,9, p=0,001), and a trend towards a decrease in the occlusion index (p=0,051). Echocardiography and duplex ultrasound revealed no radiation-associated abnormalities.Conclusion. Determining the mechanisms and prognostic significance of the identified risk factors for CVD (dyslipidemia, decreased exercise tolerance, increased heart rate and vascular stiffness) in this category of patients requires further research. Regular monitoring of risk factors, primarily the lipid profile, and the use of preventive measures for individuals with an increased risk of CVD should be recommended

Therapeutic implications of improved molecular diagnostics for rare CNS-embryonal tumor entities: results of an international, retrospective study

BACKGROUND: Only few data are available on treatment-associated behavior of distinct rare CNS-embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumor with multi-layered rosettes (ETMR) are needed for development of differentiated treatment strategies. METHODS: Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n=307). Additional cases (n=66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n=292) were descriptively analyzed. RESULTS: DNA methylation profiling of "CNS-PNET" classified 58(19%) cases as ETMR, 57(19%) as HGG, 36(12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns similar to established CNS tumor reference classes. Best treatment results were achieved for CNS NB-FOXR2 patients (5-year PFS: 63%±7%, OS: 85%±5%, n=63), with 35/42 progression-free survivors after upfront craniospinal irradiation (CSI) and chemotherapy. The worst outcome was seen for ETMR and HGG patients with 5-year PFS of 18%±6% and 22%±7%, and 5-year OS of 24%±6% and 25%±7%, respectively. CONCLUSION: The historically reported poor outcome of CNS-PNET patients becomes highly variable when tumors are molecularly classified based on DNA methylation profiling. Patients with CNS NB-FOXR2 responded well to current treatments and a standard-risk-CSI based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments

Development of the SIOPE DIPG network, registry and imaging repository : a collaborative effort to optimize research into a rare and lethal disease

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.Peer reviewe

Metastatic renal cell carcinoma kidney in children 10 years old – possibility of targeted therapy

Renal cell carcinoma (RCC) is rare in children, its metastatic form is even rarer. At present there is no treatment protocol for children with RCC. This clinical observation presented the patient 10 year old with RCC metastases to the lungs. After radical surgery, after targeted sorafenib therapy the patient has a positive dynamics. At present his progression-free survival is 30 months