Different Approaches in Radiation Therapy of Craniopharyngioma

Radiation therapy is a cornerstone in the therapeutic management of craniopharyngioma. The close proximity to neighboring eloquent structures pose a particular challenge to radiation therapy. Modern treatment technologies including fractionated 3-D conformal radiotherapy, intensity modulated radiation therapy, and recently proton therapy are able to precisely cover the target while preserving surrounding tissue, Tumor controls between 80 and in access of 90% can be achieved. Alternative treatments consisting of radiosurgery, intracavitary application of isotopes, and brachytherapy also offer an acceptable tumor control and might be given in selected cases. More research is needed to establish the role of each treatment modality

Standardisierung im E-Learning oder Vom schleichenden Untergang der Didaktik

Die Autoren diskutieren die Vor- und Nachteile einer Standardisierung von E-Learning Formaten. Ähnlich wie der Standard Rich Text zum Datenaustausch von Textdateien standardisiert wurde, können Lerneinheiten (learning objects) als standardisierte, wieder verwendbare Objekte gespeichert und vielseitig eingesetzt werden. Eine Möglichkeit besteht im Ablegen in zentralen Pools in Hochschulen, wo sie in unterschiedliche Plattformen eingebunden werden. Die Autoren stellen in Frage, ob hierbei wegen der Fokussierung auf Effizienz und Atomisierung von Information mediendidaktische Überlegungen vernachlässigt werden und der Begriff des Wissens reduziert wird auf abrufbare Informationen. In einem Exkurs verdeutlichen sie die Problematik am Beispiel von Studierenden der Medizin, die über ein gutes Faktenwissen verfügen, häufig aber Schwierigkeiten bei der Anwendung haben. In diesem Zusammenhang stellen sie die Kliniksimulation "Prometheus" vor, die wegen ihrer Handlungsorientierung die Studierenden zur Expertise anleiten soll

Is There an Indication for First Line Radiotherapy in Primary CNS Lymphoma?

Background: Primary CNS Lymphoma is a rare and severe but potentially curable disease. In the last thirty years treatment has changed significantly. Survival times increased due to high-dose methotrexate-based chemotherapy. With intensive regimens involving autologous stem cell transplantation (ASCT), 4-year survival rates of more than 80% can be reached. However, this treatment regimen is not feasible in all patients, and is associated with some mortality. Methods: In this review, current evidence regarding the efficacy and toxicity of radiotherapy in PCNSL shall be summarized and discussed mainly based on data of controlled trials. Results: Being the first feasible treatment whole brain radiotherapy (WBRT) was initially used alone, and later as a consolidating treatment after high-dose methotrexate-based chemotherapy. More recently, concerns regarding activity and neurotoxicity of standard dose WBRT limited its use. On the contrary, latest evidence of some phase II trials suggests efficacy of consolidating WBRT is comparable to ASCT. After complete remission reduced dose WBRT appears as a feasible concept with decreased neurotoxicity. Evidence for use of local stereotactic radiotherapy is very limited. Conclusion: Radiotherapy has a role in the treatment of PCNSL patients not suitable to ASCT, e.g., as consolidating reduced dose WBRT after complete response. Local stereotactic radiotherapy for residual disease should be examined in future trials

Radiotherapy in Medulloblastoma—Evolution of Treatment, Current Concepts and Future Perspectives

Medulloblastoma is the most frequent malignant brain tumor in children. During the last decades, the therapeutic landscape has changed significantly with craniospinal irradiation as the backbone of treatment. Survival times have increased and treatments were stratified according to clinical and later molecular risk factors. In this review, current evidence regarding the efficacy and toxicity of radiotherapy in medulloblastoma is summarized and discussed mainly based on data of controlled trials. Current concepts and future perspectives based on current risk classification are outlined. With the introduction of CSI, medulloblastoma has become a curable disease. Due to combination with chemotherapy, survival rates have increased significantly, allowing for a reduction in radiation dose and a decrease of toxicity in low- and standard-risk patients. Furthermore, modern radiotherapy techniques are able to avoid side effects in a fragile patient population. However, high-risk patients remain with relevant mortality and many patients still suffer from treatment related toxicity. Treatment needs to be continually refined with regard to more efficacious combinatorial treatment in the future

Novel Technique of Craniospinal Axis Proton Therapy with the Spot-Scanning System: Avoidance of Patching Multiple Fields and Optimized Ventral Dose Distribution

Background and Purpose:: Conventional craniospinal irradiation (CSI) is a complex procedure carrying a high risk of adverse side effects. Still, it is indispensable for cure in a number of pediatric brain tumors. In this study, the feasibility and the potential advantage of spot-scanning proton therapy for CSI are investigated. Material and Methods:: A boy (5.5 years of age) with a recurrent medulloblastoma received CSI with a single posterior field using the spot-scanning system at Paul Scherrer Institute. Dose distribution to the targets and the organs at risk, treatment time, reproducibility of patient positioning, toxicity (according to EORTC/RTOG score), and treatment outcome were evaluated. Results:: The plan achieved a homogeneous coverage of the target volume, even using a single field. The doses to the organs ventral to the target were minimized. During treatment, grade 1 skin reaction and grade 2 central nervous system toxicity were observed. After 2 months, the boy presented with a transitory fatigue. After 24 months, he is alive and free of disease. Growth hormones and thyroid hormones are reduced. Conclusion:: These results, based on a single patient, suggest that spot-scanning proton therapy for craniospinal treatment is feasible and safe. By applying a single dorsal field, difficulties of multiple-field patching can be avoided and the ventral dose spread can be minimize

Enhanced Survival of High-Risk Medulloblastoma-Bearing Mice after Multimodal Treatment with Radiotherapy, Decitabine, and Abacavir

Children with high-risk SHH/TP53-mut and Group 3 medulloblastoma (MB) have a 5-year overall survival of only 40%. Innovative approaches to enhance survival while preventing adverse effects are urgently needed. We investigated an innovative therapy approach combining irradia- tion (RT), decitabine (DEC), and abacavir (ABC) in a patient-derived orthotopic SHH/TP53-mut and Group 3 MB mouse model. MB-bearing mice were treated with DEC, ABC and RT. Mouse survival, tumor growth (BLI, MRT) tumor histology (H/E), proliferation (Ki-67), and endothelial (CD31) staining were analyzed. Gene expression was examined by microarray and RT-PCR (Ki-67, VEGF, CD31, CD15, CD133, nestin, CD68, IBA). The RT/DEC/ABC therapy inhibited tumor growth and enhanced mouse survival. Ki-67 decreased in SHH/TP53-mut MBs after RT, DEC, RT/ABC, and RT/DEC/ABC therapy. CD31 was higher in SHH/TP53-mut compared to Group 3 MBs and decreased after RT/DEC/ABC. Microarray analyses showed a therapy-induced downregulation of cell cycle genes. By RT-PCR, no therapy-induced effect on stem cell fraction or immune cell inva- sion/activation could be shown. We showed for the first time that RT/DEC/ABC therapy improves survival of orthotopic SHH/TP53-mut and Group 3 MB-bearing mice without inducing adverse effects suggesting the potential for an adjuvant application of this multimodal therapy approach in the human clinic

Reirradiation as part of a salvage treatment approach for progressive non-pontine pediatric high-grade gliomas: preliminary experiences from the German HIT-HGG study group

Background and purpose: The aim of the present analysis was to assess the feasibility, toxicity, and the tumor control of reirradiation as a salvage treatment for progressive pediatric non-pontine high-grade gliomas (HGG). Patients and methods: The database of the Reference Center for Radiation Oncology of the German HIT (HIT = German acronym for brain tumor) treatment network for childhood brain tumors was screened for children who were reirradiated for progressive non-pontine HGG. Results: We identified eight patients (WHO grade III: n = 5; WHO grade IV: n = 3) who underwent reirradiation between April 2006 and July 2012. Median age was 13.5 years at primary diagnosis and 14.8 years at first progression. All patients initially underwent surgery (incomplete resection, n = 7; biopsy, n = 1) followed by radiochemotherapy. Relapses occurred inside (n = 2), at the margin (n = 4), and outside of the preirradiated area (n = 2). In all patients, reirradiation was tolerated well without significant acute toxicity. Temporary clinical improvement and tumor regression on magnetic resonance imaging (MRI) following reirradiation was reported (n = 3). However, all patients finally died by disease progression. Median survival time was 26.2 months from initial diagnosis and 11.4 months after first progression. Median time interval between initial radiotherapy and first reirradiation was 9.0 months. In six patients, all macroscopic tumor deposits were reirradiated. In these patients, median progression-free (overall) survival from the start of reirradiation was 2.4 (4.6) months. Conclusion: Our analysis, although based on a limited patient number, suggests that reirradiation of progressive non-pontine HGG is feasible in children. Benefit in terms of quality of life and/or survival needs to be assessed in a prospective and ideally in a randomized manner

Reirradiation as part of a salvage treatment approach for progressive non-pontine pediatric high-grade gliomas: preliminary experiences from the German HIT-HGG study group

Background and purpose: The aim of the present analysis was to assess the feasibility, toxicity, and the tumor control of reirradiation as a salvage treatment for progressive pediatric non-pontine high-grade gliomas (HGG). Patients and methods: The database of the Reference Center for Radiation Oncology of the German HIT (HIT = German acronym for brain tumor) treatment network for childhood brain tumors was screened for children who were reirradiated for progressive non-pontine HGG. Results: We identified eight patients (WHO grade III: n = 5; WHO grade IV: n = 3) who underwent reirradiation between April 2006 and July 2012. Median age was 13.5 years at primary diagnosis and 14.8 years at first progression. All patients initially underwent surgery (incomplete resection, n = 7; biopsy, n = 1) followed by radiochemotherapy. Relapses occurred inside (n = 2), at the margin (n = 4), and outside of the preirradiated area (n = 2). In all patients, reirradiation was tolerated well without significant acute toxicity. Temporary clinical improvement and tumor regression on magnetic resonance imaging (MRI) following reirradiation was reported (n = 3). However, all patients finally died by disease progression. Median survival time was 26.2 months from initial diagnosis and 11.4 months after first progression. Median time interval between initial radiotherapy and first reirradiation was 9.0 months. In six patients, all macroscopic tumor deposits were reirradiated. In these patients, median progression-free (overall) survival from the start of reirradiation was 2.4 (4.6) months. Conclusion: Our analysis, although based on a limited patient number, suggests that reirradiation of progressive non-pontine HGG is feasible in children. Benefit in terms of quality of life and/or survival needs to be assessed in a prospective and ideally in a randomized manner

QOL-04. Histology, treatment, and extent of pretreatment hydrocephalus are major determents of neurocognitive outcome for survivors of pediatric posterior fossa tumors - report from the German HIT-studies [Abstract]

BACKGROUND: Cognitive impairments following pediatric brain tumors are generally attributed to tumor site, surgical intervention, complications as well as to nonsurgical treatment. We investigated impairments for patients with medulloblastoma (MB), ependymoma (EP) and low-grade glioma (LGG) of the cerebellum treated within the German pediatric brain tumor network to compare and rank major determents. PATIENTS+METHODS: Following protocol treatment, 245 patients with MB (n=106), EP (n=32), and cerebellar LGG (n=107, surgery only) were examined 2 + 5 years after diagnosis using the German “Neuropsychological-Basic-Diagnostic” (NBD) tool based on the Cattell-Horn-Carroll model for intelligence. Within this retrospective study, multiple linear regression models were applied. RESULTS: The MB+EP vs. LGG-cohort differed slightly in median age at diagnosis (8.7/6.1 years) and location (cerebellar hemispheres: 8%MB+EP/49.5%LGG), while sex-ratio, grade of resection, extent of pre-operative hydrocephalus were comparable. With smaller median tumor-volume in the MB+EP vs. LGG-cohort (34.1/44.1cm3), ranges broadly overlapped. Median scores of age-appropriate tests were in the lower normal range for all patients for fluid and crystallized intelligence, selective attention, visual-spatial processing (VSP) and verbal short-term memory (median=93-103), but distinctly below for processing speed (PS), and psychomotor speed abilities (PMS) (median=65-84). Higher doses of craniospinal irradiation (>23.4Gy/23.4Gy) resulted in lower scores for most domains for MB-patients compared to LGG-patients (e.g., PS-estimate: >23.4Gy:-27.71, p=0.026/23.4Gy:-9.93, p=0.286). EP-patients (surgery+54Gy local radiation) scored better than LGG-patients except for PS (estimate:-15.65, p=0.111). Impairments were accentuated with higher degrees of hydrocephalus (estimate:-7.64, p=0.103) in patients with incomplete resection (estimate:12.23, p=0.006) for PMS both hands. CONCLUSION: Following age-adapted comprehensive treatment, survivors of a cerebellar tumor show significant impairments of PMS abilities in our trials. Our data suggest that slow growing LGG impair neurocognitive development more than local radiotherapy for ependymoma, while craniospinal irradiation compromises VSP and PS in MB. Initial symptomatic intracranial pressure remains a strong predictor for general neuropsychological impairment