Diagnostics and treatment of diffuse intrinsic pontine glioma: where do we stand?

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.

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.

[Chronic disease and health condition prevention in childhood--2nd part: emphases from the 14th Symposium of Preventive Pediatrics]. / Prevencija kronicnih bolesti i stanja u djece--2. dio: naglasci s xiv. Simpozija Preventivne Pedijatrije.

Chronically ill children nowdays in developed countries are more prevalent than before, and thanks to modern therapeutic modalities more children are surviving into adulthood. Increased survival cannot be assumed to be associated with increased quality of life. With the chronically ill child holistic approach is important, which incorporates not only realisation of the highest possible standards in diagnostics and treatment, but also special care for disease prevention. All this is very important in so called integrative approach in the care of a chronically ill child, with the aim of achieving as high as possible quality of life and complete social integration. At the 14th Preventive Pediatrics Symposium, which took place in Skrad, June 1' 2013, from preventive standpoint, the following chronic childhood illnesses were discussed: attention deficit hyperactivity disorder--ADHD, migraine, thyroid gland diseases, leukemia, cystic fibrosis, chronic renal disease, chronic inflammatory liver disease, chronic inflammatory bowel disease, juvenile idiopathic arthritis, and chronic otitis media with effusion. It is emphasized that talking about a disease prevention, there are three levels of it--primary, second- ary and tertiary prevention: how to avoid occurrence of disease, how to diagnose and treat existent disease in early stages, before it causes significant morbidity, and finally how to reduce the negative impact of existent disease by restoring function and reducing disease-related complications--how to improve quality of life of children with chronic diseases. Quaternary prevention describes methods to mitigate or avoid results of unnecessary or excessive interventions of the health system. An important process is also transition of care from child-oriented to adult-oriented care. Adults with chronic health conditions should continue to be evaluated periodically for possible late consequences of their childhood illness and previ- ous medical treatments.

[Chronic disease and health condition prevention in childhood: emphases from the 13th Symposium of Preventive Pediatrics]. / Prevencija kronicnih bolesti i stanja u djece: naglasci s XIII. simpozija preventivne pedijatrije.

Chronic diseases in childhood have become an important priority, especially in developed countries, because of higher prevalence, relatively and absolutely. Besides that, inappropriate procedures a chronically ill child can result in child's growth and development disorder. According to literature data, 15-20% of children have chronic disease with the impact on their physical, mental and emotional status. Disease prevention strategies are described at the primary, secondary and tertiary level: how to avoid occurrence of disease, how to diagnose and treat existent disease in early stages, before it causes significant morbidity, and finally how to reduce negative impact of existent disease by restoring function and reducing disease-related complications - how to improve quality of life of children with chronic diseases. The new term of quaternary prevention describes methods to mitigate or avoid results of unnecessary or excessive interventions in the health system. In this paper the authors present recent attitudes about chronic diseases prevention modalities in childhood, which, at the beggining of the 21st century, have become more intriguing and represent a new challenge for pediatric health care. Thus, from preventive standpoint, the following chronic illnesses are discussed: asthma, malignant diseases, autism, epilepsy, cerebral palsy, tuberculosis, diabetes type 1, congenital heart diseases, arterial hypertension, celiac disease, and eating disorders. These emphases are from the 13th Preventive Pediatrics Symposium, which took place in Skrad, June 2nd, 2012. Further activities are planned with the aim of continuation of health care furtherance for children with other chronic illnesses.

Papillary tumor of the pineal region in pediatric patient - A case report.

Background: Papillary tumor of the pineal region (PTPR) represents a rare and histologically distinct subgroup of tumors originating in the pineal region. Few pediatric cases have been reported so far in the literature; therefore, clinical data are scarce. Case Description: We describe a case of PTPR in a 9-year-old girl who presented with a 5-month history of excessive appetite and weight gain. The patient underwent neuroimaging procedures and total gross surgical resection with postoperative adjuvant local radiotherapy, which from our experience was the best treatment choice as an attempt to avoid local recurrence. During 78-month follow-up, the patient from our study manifested no disease recurrence. Conclusion: PTPR should be included in the differential diagnosis of pineal region masses.

A challenging case of an adolescent and young adult patient with high-risk acute lymphoblastic leukemia: the need for a multidisciplinary approach: a case report.

BACKGROUND: Adolescents and young adults diagnosed with acute lymphoblastic leukemia are treated according to pediatric-based regimens to achieve better results. However, implementation of intensive chemotherapy protocols in this age group is associated with increased treatment-related toxicities, affecting almost every organ and system. In this case, the focus of our interest was on rather rare entities: steroid-induced psychosis that seldom develops in children and adolescents, and choroid plexus hemosiderosis, infrequently identified as a first sign of iron overload. CASE PRESENTATION: The aim of this paper is to present a challenging case of a 15-year-old Caucasian male patient treated for high-risk acute lymphoblastic leukemia and who experienced various adverse incidents during intensive chemotherapy, thus necessitating a high-quality multidisciplinary approach. Slow minimal residual disease clearance was an additional concerning issue. Induction and re-induction were complicated by steroid-induced hyperglycemia that required multiple-week insulin. During consolidation, acute kidney injury on the basis of chronic kidney disease was verified, demanding subsequent drug dose modifications. By the end of re-induction, after dexamethasone cessation, infrequent steroid-induced psychosis, presented as incoherent speech, aggressive behavior, and mood swings, required intensive psychiatric support. Neurological evaluation of seizures revealed uncommon choroid plexus hemosiderosis by brain magnetic resonance imaging, warranting appropriate selection of iron chelation therapy in the context of preexisting nephropathy. Ultimately, iron deposits of moderate intensity were verified by liver magnetic resonance imaging, while heart tissue remained intact. The early diagnosis and adequate treatment of aforementioned difficult toxicities resulted in complete recovery of the patient. CONCLUSIONS: Treating adolescents with high-risk acute leukemia and multiple therapy-related morbidities remains a challenge, even in the era of extensive and effective supportive therapy. Superior survival rates might be achieved by prompt recognition of both frequent and rarely encountered adverse episodes, as well as well-timed and appropriate management by a well-coordinated multidisciplinary team.