RARE-30. PEDIATRIC GLIOBLASTOMA IN THE POST-TEMOZOLOMIDE ERA: OUTCOMES AND CHARACTERISTICS

Abstract INTRODUCTION Glioblastoma (GBM) is the most common brain tumor, however, is a rare occurrence in children and is poorly characterized. We evaluated the characteristics and outcomes of pediatric GBM (pGBM). METHODS Retrospective analysis of pediatric (age< 18) patients diagnosed with GBM undergoing first glioblastoma resection at our brain tumor center (2005- 2016). RESULTS From 1457 GBM patients, we identified twenty-four (1.65%) pGBMs (Median Age=9 years, Females=45.8%). Median overall survival (OS) was 32.1 months, while the median progression-free survival was 11.5 months. The commonest symptoms at presentation were headaches (54.2%,n=13) and motor symptoms (50%,n=12). Mean tumor diameter was 4.5 cm and 25% of the cohort underwent gross total resection (GTR) of their tumor. Univariate analysis revealed median OS significantly associated with tumor extent of resection (GTR=56.4 months; STR/Biopsy=13.7 months, p=0.001), age at surgery (>10 years=43.9 months, < 10 years= 17.2 months, p=0.01), tumor size (> 4cm= 9.1 months, < 4cm=56.9 months, p=0.01),motor symptoms at presentation (present=14.9 months, absent=41.04 months, p=0.02) and infratentorial tumors (infratentorial=17.4 vs supratentorial=53.4 months, p=0.02). Multivariate analysis revealed GTR (HR 0.2[95% CI 0.07–0.72]; p=0.03), Age >10 years (HR 0.6[95% CI 0.02–0.64]; p=0.002), tumor >4 cm (HR 2.89[95% CI 1.88–4.11]; p=0.001) and EGFR amplification (HR 3.48[95% CI 0.82–17.4]; p=0.005) to be independent predictors of OS. Comparing patients under and over 10 years, we found that older patients had smaller tumors at presentation (4.9 vs 3.6 cms, p=0.03), greater rates of preoperative temozolomide (n=1,7.7% vs n=6, 54.5%) and bevacizumab (n=1,7.7% vs n=4, 36.4%) treatment, and lower rates of EGFR amplification (66.7% vs 11.1%) that could explain survival disparities between groups. CONCLUSION Motor symptoms, larger tumors at presentation and tumor EGFR amplification may be indictive of poorer outcomes in pGBM. However, maximal tumor resection, aggressive chemoradiation and tumor presentation at age >10 years may confer better prognosis in these patients

Gliosarcoma with neuroaxis metastases.

Gliosarcomas are rare tumours of the central nervous system, with a well-known capacity for metastasis. When they metastasise, the dissemination occurs more frequently via the haematogenous route to extraneural sites. Metastasis-spread through the cerebrospinal fluid is extremely rare. We present the case of a 58-year-old man who underwent a gross total resection of a lesion in the left temporal lobe. The histological findings revealed a gliosarcoma and the patient received radiotherapy followed by chemotherapy. Seven months after surgery, while the patient remained neurologically intact, brain and spinal cord MRI revealed tumour recurrence and neuroaxis metastases through the traffic routes of the cerebrospinal fluid. The patient died 8 months after the diagnosis. A PubMed search regarding metastatic gliosarcoma up to June 2015 was also carried out. To the best of our knowledge, this is the first case report of gliosarcoma metastases to the brain and spinal cord leptomeninges

Is surgical spinal decompression for supratentorial GBM symptomatic drop down metastasis warranted? A case report and review of literature

Background: Symptomatic spinal metastasis from an intracranial primaryglioblastoma multiforme (GBM) is very rare. Our literature search identified a totalof 42 such patients of which 11 were treated with surgical decompression for spinal metastasis with only one such report from the pediatric age group. Previous studies have reported variable outcomes after surgical management. Case Description: We report the case of a 16‑year‑old boy who underwentsurgical spinal decompression for spinal metastasis after intracranial GBM. Thepatient regained motor and autonomic function following surgery and reportedimprovement in pain. We also present findings from a literature review using thePubMed database from 1985 to June 2013 on this subject and compare radiation therapy with surgical decompression as palliative modalities in such patients. Conclusion: There are no evidence‑based guidelines available on the subjectand no treatment regimen has yet demonstrated survival benefit in these patients. Surgical decompression may be a better option for patients with focal resectable lesions and who are medically stable to tolerate the procedur

Glioblastoma multiforme of the pineal region

ManuscriptGlioblastoma multiforme (GBMs) tumors are exceedingly rare tumors in the pineal region. We present three cases in which patients presented with a pineal/posterior third ventricular region mass and review all the previously reported cases in the literature. Pineal region GBM seems to be a very aggressive tumor with a high rate of leptomeningeal and ependymal metastatic disease. Patients usually present with signs and symptoms of hydrocephalus and Parinaud's syndrome. The clinical and radiological characteristics of pineal GBM do not differentiate it from other malignancies of this region, thus surgical biopsy is generally required for definitive diagnosis. Glioblastoma should be considered in the differential diagnosis of the pineal region tumors, especially when evidence of leptomeningeal or ependymal metastatic disease is present

Breaking boundaries: A rare case of glioblastoma with uncommon extraneural metastases: A case report and literature review

Introduction Extraneural metastases (ENM) from glioblastoma (GBM) remain extremely rare with only a scarce number of cases described in the literature. The lack of cases leads to no consensus on the optimal treatment and follow-up of these patients. Research question Do patient or tumor characteristics describe risk factors for ENM in GBM patients, and is it possible to identify mechanisms of action? Material and methods This study presents a 55-year-old man with diagnosed GBM who was referred to a CT due to reduced general condition and mild back pain which revealed extensive systemic metastases. A literature review was conducted to identify potential patient or tumor characteristics that may serve as risk factors for metastasis. Results ENM from GBM are likely underreported, with limited examples in the literature and low survival rates of only a few months. Certain clinical and histopathological factors, such as male sex, younger age, temporal lobe location, and specific biological markers, have been associated with a higher likelihood of metastasis formation. Bone and/or bone marrow metastases are the most common sites. Despite various treatment regimens being attempted, there is no consensus on the optimal therapeutic approach for this patient group. Conclusion Clinical and histopathological factors can aid clinicians in recognizing the potential for ENM in GBM patients. Our review identifies some of the possible patient- and tumor-related risk factors. However, further research is crucial to identify specific molecular markers and elucidate the underlying biological mechanisms that is essential for development of targeted therapies.publishedVersio

Molecular Diagnostics and Pathology of Major Brain Tumors

Tumors of central nervous system (CNS) account for a small portion of tumors of human body, which include tumors occurring in the parenchyma of brain and spinal cord as well as their coverings. The following chapter covers some new development in some major brain tumors in both pediatric and adult populations, as well as some uncommon but diagnostic and management challenging tumors

Neurosurgery for brain metastasis from breast cancer

Breast cancer is the most common malignancy among women worldwide, and the main cause of death in patients with breast cancer is metastasis. Metastasis to the central nervous system occurs in 10% to 16% of patients with metastatic breast cancer, and this rate has increased because of recent advancements in systemic chemotherapy. Because of the various treatments available for brain metastasis, accurate diagnosis and evaluation for treatment are important. Magnetic resonance imaging (MRI) is one of the most reliable preoperative examinations not only for diagnosis of metastatic brain tumors but also for estimation of the molecular characteristics of the tumor based on radiographic information such as the number of lesions, solid or ring enhancement, and cyst formation. Surgical resection continues to play an important role in patients with a limited number of brain metastases and a relatively good performance status. A single brain metastasis is a good indication for surgical treatment followed by radiation therapy to obtain longer survival. Surgical removal is also considered for two or more lesions if neurological symptoms are caused by brain lesions of >3 cm with a mass effect or associated hydrocephalus. Although maximal safe resection with minimal morbidity is ideal in the surgical treatment of brain tumors, supramarginal resection can be achieved in select cases. With respect to the resection technique, en bloc resection is generally recommended to avoid leptomeningeal dissemination induced by piecemeal resection. An operating microscope, neuronavigation, and intraoperative neurophysiological monitoring are essential in modern neurosurgical procedures, including tumor resection. More recently, supporting surgical instruments have been introduced. The use of endoscopic surgery has dramatically increased, especially for intraventricular lesions and in transsphenoidal surgery. An exoscope helps neurosurgeons to comfortably operate regardless of patient positioning or anatomy. A tubular retractor can prevent damage to the surrounding brain tissue during surgery and is a useful instrument in combination with both an endoscope and exoscope. Additionally, 5-aminolevulinic acid (5-ALA) is a promising reagent for photodynamic detection of residual tumor tissue. In the near future, novel treatment options such as high-intensity focused ultrasound (HIFU), laser interstitial thermal therapy (LITT), oncolytic virus therapy, and gene therapy will be introduced

Charakteristika, Therapie und Prognose von Patienten mit metastasierten WHO Grad IV Gliomen - Eine Metaanalyse individueller Patientendaten: Charakteristika, Therapie und Prognose von Patienten mit metastasierten WHO Grad IV Gliomen-Eine Metaanalyse individueller Patientendaten

Da hochgradige Gliome nur eine geringe Tendenz zur Metastasierung aufweisen, beschränkte sich das klinische Wissen über diesen seltenen Krankheitsverlauf bisher im Wesentlichen auf die Erkenntnisse aus Einzelfallberichten und kleineren Fallserien. Eine detaillierte Analyse der beschriebenen Fälle war bisher nicht verfügbar. Die vorliegende Arbeit stellt eine systematische Auswertung der wissenschaftlichen Literatur über Patienten mit metastasierten Glioblastomen oder Gliosarkomen dar. Unser Ziel war es, sämtliche Publikationen zu berücksichtigen, welche bis April 2013 veröffentlicht worden sind. Mit Hilfe einer systematischen Literaturrecherche in den beiden Datenbanken PubMed und Web of Science konnten 215 Arbeiten identifiziert werden, welche insgesamt 357 Fallberichte enthielten. Die Prognose nach Diagnose einer Metastasierung ist infaust. In der untersuchten Patientenkohorte betrug die mediane Überlebenszeit lediglich 3.0 ± 0.4 Monate. Eine univariate Datenanalyse ergab, dass Geschlecht, Alter, der histologische Subtyp und das Zeitintervall zwischen der Diagnose des Primärtumors und der Metastasen die Überlebenszeit nicht beeinflussten. Im Gegensatz dazu war eine Metastasierung, die ausschließlich außerhalb des zentralen Nervensystems (ZNS) auftrat, mit längeren Überlebenszeiten verbunden. In den letzten Jahrzehnten wurden offenbar keine entscheidenden therapeutischen Fortschritte erzielt. Fälle, die in Publikationen bis zum Jahr 2000 Erwähnung fanden, wiesen keine schlechteren Überlebenszeiten auf als die nach der Jahrtausendwende publizierten Fälle. Aktuell gibt es keinen Datensatz, der geeignet wäre, die vielfältigen Therapieansätze systematisch auf ihre Wirksamkeit hin zu überprüfen. Wir sehen hier die Notwendigkeit, ein zentrales Register zu etablieren.:1. Bibliographische Beschreibung 2 2. Abkürzungsverzeichnis 3 3. Tabellenverzeichnis 4 4. Abbildungsverzeichnis 4 5. Einführung 5 5.1.1. Klassifikation und Epidemiologie 5 5.1.2. Ätiologie 5 5.1.3. Diagnose 5 5.1.4. Molekularpathologie 7 5.1.5. Therapie 7 5.2. Metastasierung 9 5.2.1. Wege der Metastasierung eines Glioblastoms 9 5.2.2. Therapie im Fall einer Metastasierung 12 5.3. Zielsetzung 13 6. Publikationen in Originalsprache 15 6.1 An individual patient data meta-analysis on characteristics, treatments and outcomes of the glioblastoma/ gliosarcoma patients with central nervous system metastases reported in literature until 2013 15 6.2 An individual patient data meta-analysis on characteristics, treatments and outcomes of glioblastoma/ gliosarcoma patients with metastases outside of the central nervous system 23 7. Zusammenfassung der Arbeit 38 8. Anhang I 8.1. Übersicht über klinische Charakteristika I 8.2. Übersicht über die Prozedur der Literaturrecherche V 8.3. Literaturverzeichnis der Publikationspromotion VI 8.4. Verzeichnis der Patientenkohorte XI 8.5. Literaturverzeichnis der individuellen Patientendaten-Metaanalyse XXIII 8.6. Danksagung XXXIII 8.7. Lebenslauf XXXIV 8.8. Publikationen XXXVI 8.8.1 Erstautorenschaften XXXVI 8.8.2 Coautorenschaften XXXVI 8.8.3 Kongressbeiträge XXXVI 8.9. Erklärung über die eigenständige Abfassung der Arbeit XXXVI