Barbara Fazeny-Dörner

Glioblastoma with spinal seeding

Background:Extracranial seeding of glioblastoma multiforme (GBM) is very rare and its development depends on several factors. This case report describes two patients suffering from GBM with spinal seeding. In both cases, the anatomic localization of the primary tumor close to the cerebrospinal fluid (CSF) was the main factor for spinal seeding.Case Reports:Two patients with GBM and spinal seeding are presented. After diagnosis of spinal seeding, both patients were highly symptomatic from their spinal lesions. Case 1 experienced severe pain requiring opiates, and case 2 had paresis of lower limbs as well as urinary retention/incontinence. Both patients were treated with spinal radiation therapy. Nevertheless, they died 3 months after diagnosis of spinal seeding.Results:In both patients the diagnosis of spinal seeding was made at the time of cranial recurrence. Both tumors showed close contact to the CSF initially. Even though the patients underwent intensive treatment, it was not possible to keep them in a symptom-free state.Conclusion:Because of short survival periods, patients deserve optimal pain management and dedicated palliative care.Hintergrund:Die extrakraniale Ausbreitung eines Glioblastoma multiforme (GBM) ist sehr selten und hängt von mehreren Faktoren ab. Dieser Fallbericht schildert zwei Patienten mit spinalen Absiedelungen eines GBM. In beiden Fällen war die anatomische Lokalisation des GBM nahe den Liquorräumen der ausschlaggebende Faktor für die Absiedelungen.Fallberichte:Zwei Patienten mit GBM und spinalen Absiedelungen via Liquor werden vorgestellt. Bei der Diagnose der spinalen Absiedelungen waren beide Patienten aufgrund ihrer spinalen Läsionen hochgradig symptomatisch. Die erste Patientin hatte starke Schmerzen, welche mit Opiaten teilweise beherrscht werden konnten, der zweite Patient litt an einer Parese der unteren Extremitäten sowie Blasenstörungen. Beide Patienten wurden einer spinalen Bestrahlung unterzogen. Sie verstarben 3 Monate nach Diagnose der spinalen Absiedelungen.Ergebnisse:Bei beiden Patienten fiel die Diagnose der spinalen Absiedelungen mit dem Auftreten eines kranialen Rezidivs zusammen. Beide Tumoren zeigten initial einen nahen Kontakt zu den Liquorräumen. Trotz intensiver Therapie gelang es nicht, die Patienten in einem symptomarmen Zustand zu halten.Schlussfolgerung:Im Vordergrund sollte wegen der kurzen Überlebenszeit die symptomorientierte Therapie stehen.

Stabilization of a progressive hemangioblastoma under treatment with thalidomide.

After the second recurrence of spinal seeding in hemangioblastoma not associated to von-Hippel–Lindau disease, we treated an adult female patient with thalidomide 200 mg orally/day at night for longer than 1 year. The patient reported subjective relief of symptoms after 1 month. Magnetic resonance imaging (MRI) controls 1, 6 and 11 months after begin of thalidomide treatment did not show further tumor progression. She remained wheelchair-bound, but mobility of her arms continuously improved. There was no thalidomide associated side-effect in this patient until her death from pneumonia due to legionnaires disease.Antiangiogenic treatment with interferon (IFN) α-2a and IFN α-2b and with SU 5416 has been reported to be effective and well tolerated in several patients with previously progressive angioblastomas and hemangioblastomas. This case adds further evidence of the efficacy of an antiangiogenic treatment concept in a progressive hemangioblastoma.

Unexpected out-of-hospital deaths in persons aged 85 years or older: an autopsy study of 1886 patients

PURPOSE The aim of this study was to determine the causes of death in the very elderly. METHODS We reviewed 24,081 consecutive autopsies performed over 10 years (1989 to 1998) at the Institute of Forensic Medicine, Vienna, Austria. We focused on autopsies of people aged 85 years or older who died unexpectedly out of hospital. RESULTS The mean age of the 1886 patients (561 men and 1325 women) at the time of death was 88 +/- 3 years (range, 85 to 108 years). Thirty-one percent (n = 588) of those who died were described as having been previously healthy. Cardiovascular disease was the most common cause of death (n = 1465 [77%]). Thirteen percent (n = 246) died of respiratory illness, 5% (n = 94) of gastrointestinal disorders, and 3% (n = 53) of diseases of the central nervous system. Genitourinary and metabolic diseases were uncommon. CONCLUSION Although this out-of-hospital sample is not representative of the entire elderly population, postmortem examinations emphasize the importance of cardiovascular diseases in causing unexpected deaths in older persons.

Survival improvement in patients with glioblastoma multiforme during the last 20 years in a single tertiary-care center

ZusammenfassungStudienzielZiel der retrospektiven Analyse war es, die Überlebensdauer und einen eventuellen Fortschritt von 357 konsekutiven Patienten mit Gliob lastoma multiforme (GBM) innerhalb von 3 Gruppen aus unterschiedlichen Diagnose-Zeiträumen (Gruppe A: 1982–1984, B: 1994/1995; C: 1996–1998), die während der letzten 20 Jahre an unserem tertiärem Zentrum behandelt wurden, zu untersuchen.Patienten und MethodenPatienten der Gruppe A (n=100) wurden zwischen 1982 und 1984 diagnostiziert und dienten als historische Kontrolle. Patienten der Gruppe B (n=93) wurden 1994/1995 und Patienten der Gruppe C (n=164) zwischen 1996 und 1998 diagnostiziert.Die Überlebens-Analyse wurde durchgeführt in Bezug auf die drei Patientengruppen (A versus B versus C), in Bezug auf die applizierten Therapiemodalitäten nach neurochirurgischer Intervention (keine spezifische Therapie versus Radiotherapie versus kombinierte Radio-/Chemotherapie), in Bezug auf die unterschiedlichen first-line Chemotherapien, in Bezug auf Alter, Geschlecht und Tumorlokalisation. Die non-parametrische Kaplan-Meier Methode wurde angewandt. Ein p-Wert <0,05 wurde als statistisch signifikant angesehen.Patienten der Gruppen A und B erhielten Radio- und/oder Chemotherapie in einem unterschiedlichen Ausmaß (Radiotherapie: Gruppe A: 22%, Gruppe B: 62%; Chemotherapie: Gruppe A: 6%, Gruppe B: 33%). Die Chemotherapie wurde in beiden Gruppen nach Abschluss der Radiotherapie appliziert. In Gruppe C erhielten 96% der Patienten eine kombinierte Radio-/Chemotherapie innerhalb von 3 Wochen nach der neurochriurgischen Intervention.ErgbnisseDas mediane Überleben betrug in Gruppe A 5,2 Monate, in Gruppe B 5, 1 Monate und in Gruppe C 14,5 Monate (p<0,0001). Länger als 18 Monate lebten 9% der Patienten in Gruppe A, 10% der Patienten in Gruppe B und 25% der Patienten in Gruppe C (p<0,05).SchlussfolgerungDie Überlebenszeitverbesserung in Gruppe C ist auf die frühzeitige und kombineierte Applikation von Radio-/Chemotherapie zurückzuführen. Die Therapie wurde ambulant durchgeführt; dies wurde durch ein interdisziplinäres neuro-onkologisches Team ermöglicht. Die Nebenwirkungen waren mild und die Akzeptanz bei den Patienten hervorragend.SummaryMethodologyThe survival of 357 consecutive patients with newly diagnosed glioblastoma multiforme (GBM) in three treatment groups reflecting different time-periods of diagnosis (A: 1982–1984; B: 1994/1995; C: 1996–1998) was analysed to assess the impact and the potential improvement of changing treatment strategies in our tertiary-care center.Patients and methodsGroup A (n=100) included all consecutive patients diagnosed from 1982 to 1984 and served as the historical control. Group B (n=93) included all consecutive patients diagnosed in 1994/1995 and group C (n=164) those diagnosed from 1996 to 1998. Survival in the three treatment groups (A vs. B vs. C) was analysed according to treatment given after neurosurgical intervention (i.e. no specific therapy versus radiotherapy versus combined radio-/chemotherapy), and according to first-line chemotherapy, age (<40, 40–60, ≥60), sex, and tumor location (hemispheric versus bilateral or multifocal tumors, and tumors involving eloquent brain areas). Survival was analysed using Kaplan-Meier’s non-parametric method. A p-value <0.05 was considered statistically significant.ResultsPatients in groups A and B received radio-and/or chemotherapy to a varying extent (radiotherapy: group A: 22%, group B: 62%; chemotherapy: group A: 6%, group B: 33%). Chemotherapy was administered after termination of radiotherapy in both groups. In group C, 96% of patients received combined radio-/chemotherapy which was administered concomitantly and started within three weeks after surgery.Median survival was 5.2 months in group A, 5.1 months in group B and 14.5 months in C (p<0.0001). Nine patients in group A (9%), 9 in group B (10%) and 40 in group C (25%) survived more than 18 months (p<0.05).ConclusionsSurvival improvement in group C might be attributable to the early start of combined radio-/chemotherapy. Therapy was administered on a complete outpatient basis, enabled by a dedicated interdisciplinary neuro-oncologic team caring for group C. Toxicity was mild and patients’ acceptance excellent.

Cytogenetic and comparative genomic hybridization findings in four cases of breast cancer after neoadjuvant chemotherapy

To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH analysis, the patients showed typical imbalances for ductal breast cancer: gains of 1q (3 patients), 5q (2 patients), 8q (3 patients), and X (4 patients) and losses of 1p33 approximately p36 (3 patients), 16q (3 patients), 17p (3 patients), 19 (4 patients), and 22q (4 patients). Other recurrent imbalances of atypical pattern for ductal breast cancer were gain of 4q21 approximately q32 (2 patients), 20q21 approximately q22 (2 patients), and 21 (2 patients) and loss of 20p (3 patients). Three patients showed involvement of several regions bearing genes of drug resistance (MDR1 [HUGO symbol: ABCB1], BCRP [HUGO symbol: ABCG2], MRP1 [HUGO symbol: ABCC1], RFC1); the fourth patient displayed an amplification in the region of MYC (alias c-myc), thus providing--at the level of the light microscope--an explanatory background for the ability of their tumors to survive anthracycline-, taxane- and cyclophosphamide-based chemotherapy. Conventional cytogenetic analysis and CGH displayed highly coincidental findings in the tumors of four patients after neoadjuvant chemotherapy for breast cancer.