Franz Payer

NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality

PURPOSEnNovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division.nnnMETHODSnPhase III trial of chemotherapy-free treatment of NovoTTF (20-24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival.nnnRESULTSnPatients (median age 54 years (range 23-80), Karnofsky performance status 80% (range 50-100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1-6). Median survival was 6.6 versus 6.0 months (hazard ratio 0.86 [95% CI 0.66-1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6 months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains.nnnCONCLUSIONSnThis is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.

Brain stem infarction and diaschisis. A SPECT cerebral perfusion study.

Background and Purpose We studied six patients suffering from pure, unilateral brain stem infarction to explore the association of remote cerebral and cerebellar blood flow changes with damage at different sites of this region of the bra. Methods We used single-photon emission computed tomography and [123I]iodoamphetamine to measure regional differences in tracer uptake. Qualitative image analysis and calculated asymmetry indexes were correlated to the location of the infarcted area on magnetic resonance imaging and to the patients clinical findings. Results Significant perfusion asymmetries were noted in the two patients with infarction in the upper pons but not in those with lesions below this level. They comprised a contralateral cerebellar and ipsilateral supratentorial hypoactivity that was most marked in the frontoparietal cortex. There was no clear relation between the patterns of cerebral or cerebellar tracer uptake and specific neurological findings. Conclusions Remote perfusion changes after pure brain stem infarction may be seen both infratentorially and supratentorially and depend on the lesion site rather than on the neurological deficit. In this context, our study confirmed damage to the corticopontocerebellar pathways as the key event in the genesis of a crossed cerebellar diaschisis. The exact mechanisms causing ipsilateral cerebral hemispheric diaschisis await further clarification.

Cerebral Hemodynamic Changes following Treatment with Erythropoietin

Adverse hemorheologic effects induced by erythropoietin (EPO) treatment of renal anemia may pose a cerebrovascular risk. We therefore investigated the changes in cerebral perfusion, cerebral blood flow velocity (BFV) and neuropsychologic performance in 11 patients (mean age 37 years) receiving EPO. In response to EPO there was a significant (p less than 0.01) increase in hematocrit (35%), hemoglobin (43%) and whole-blood viscosity (50% at high and 90% at low shear rate). The initially increased blood flow velocity dropped significantly (p less than 0.05) and returned toward normal values in the middle cerebral arteries and the basilar artery (22 and 19% decrease, respectively). Global cerebral blood flow (CBF) decreased by 10% (not significant). The score of the Wechsler Adult Intelligence Scale digit symbol test improved significantly (p less than 0.01) after EPO treatment. None of the patients developed cerebrovascular symptoms or side effects. We conclude that the hematologic and rheologic changes following EPO treatment cause CBF and BFV to return toward normal and improve neuropsychologic performance in patients with end-stage renal disease.

Temozolomide for recurrent or progressive high-grade malignant glioma : Results of an Austrian multicenter observational study

ZusammenfassungHINTERGRUND: Chemotherapie bei Patienten mit hochgradigen Gliomen (HGG) wurde auch nach Veröffentlichung günstiger Daten und von zwei Metaanalysen kontroversiell diskutiert. Die vorliegende Anwendungsbeobachtung wurde durchgeführt, um die Behandlung von Patienten mit HGG mit Chemotherapie zu unterstützen. PATIENTEN UND METHODEN: 6 österreichische Zentren schlossen 43 Patienten mit histologisch verifizierten rezidivierten HGG ein. Zwölf chemotherapie-naive Patienten erhielten orales Temozolomide (Tmz) in einer Dosis von 200 mg/m2 einmal täglich an fünf aufeinanderfolgenden Tagen, bei 26 Patienten, die unterschiedliche Erstlinienchemotherapien erhalten hatten, wurde eine Tagesdosis von 150 mg/m2 angewendet. Die Therapie wurde nach jeweils 28 Tagen insgesamt 6 Mal wiederholt. ERGEBNISSE: Einundzwanzig Patienten (52,5 %) erhielten 6 Zyklen Chemotherapie. Zwei komplette sowie 8 partielle Remissionen wurden erzielt. Einundzwanzig Patienten überlebten ein Jahr nach Therapiebeginn, 8 Patienten überlebten 3 Jahre. Folgende Toxizitäten wurden beobachtet: 3 Thrombozytopenien WHO Grad 4 und 35 Lymphozytopenien G3 und G4, diese führten weder zu interstitiellen Pneumonien noch zu stationärer Behandlung. Nicht-hämatologische Toxizitäten waren selten und von untergeordneter klinischer Bedeutung. Die Lebensqualität der Patienten konnte während der Behandlung aufrechterhalten werden. SCHLUSSFOLGERUNG: Diese Ergebnisse bestätigen die Verträglichkeit und Wirksamkeit der Chemotherapie mit Temozolomide bei Patienten mit rezidivierten/progredienten HGG.SummaryBACKGROUND: The use of chemotherapy in patients with malignant gliomas has remained a controversial issue even after the publication of favorable study data and a meta-analysis. The present study was initiated to support the use of chemotherapy in patients with relapsed high-grade gliomas (HGG). PATIENTS AND METHODS: Six Austrian centers recruited 43 patients with histologically confirmed HGG at first recurrence. Twelve chemotherapy-naïve patients received oral temozolomide at a dose of 200 mg/m2 once a day for five consecutive days and 26 patients a dose of 150 mg/m2 also for five days after various first-line chemotherapies. TMZ treatment was repeated every four weeks for a total of six cycles. RESULTS: Twenty-one patients (52.5 %) received at least six cycles of therapy. Two patients experienced complete remission and eight patients a partial response. Twenty patients survived at one year after enrolment in the study; eight patients survived beyond three years of follow-up. Hematological toxicities consisted of three thrombocytopenias G4 and 35 lymphocytopenias G3 and G4; these did not cause interstitial pneumonia or require inpatient treatment. Non-hematological toxicities were rare and without clinical relevance. Patients quality of life was maintained during treatment. CONCLUSION: The study data confirm the feasibility and efficacy of chemotherapy with temozolomide in patients with relapsed/progressive HGG.

Pseudoprogression oder Pseudorespons: Herausforderung an die Bildgebung des Glioblastoma multiforme

SummaryThis methodological paper on magnetic resonance tomography imaging recalls the assessment criteria on therapy response of Glioblastoma multiforme as defined by David Macdonald in 1990 that have remained State of the Art since their first publication. It defines the terms pseudoprogression, radiation induced necrosis and pseudoresponse. These phenomena are seen increasingly since the introduction of radiochemotherapy with Temozolomide as treatment standard in glioblastoma and since the use of antiangiogenetic therapy in malignant gliomas. Therefore, the assessment criteria have been recently updated with the newly proposed RANO criteria (Response assessment in Neuro-Oncology). Furthermore, the potential of additional information to conventional MR by MR perfusion, MR diffusion and MR spectroscopy is briefly discussed.ZusammenfassungAusgehend von der Beurteilung des Therapieerfolgs bei Glioblastomen durch bildgebende Untersuchungen nach den Kriterien, die David Macdonald 1990 vorgeschlagen hatte und die seither unangefochten Standardinstrumente blieben, werden in diesem Beitrag die Begriffe Pseudoprogression, Radionekrose und Pseudorespons definiert und anhand von Beispielen erklärt. Diese Phänomene werden im Zuge der Verbreitung der kombinierten Radiochemotherapie und der Einführung anti-angiogenetisch wirksamer Substanzen in die Therapie maligner Gliome häufiger beobachtet. Dies hat ein Update der Beurteilungskriterien maligner Gliome, den RANO-Kriterien, notwendig gemacht. Außerdem werden mögliche Zusatzinformationen zur konventionellen MR-Untersuchung, die aus MR-Perfusion, MR-Diffusion und MR-Spektroskopie bei malignen Gliomen gewonnen werden kurz erläutert.This methodological paper on magnetic resonance tomography imaging recalls the assessment criteria on therapy response of Glioblastoma multiforme as defined by David Macdonald in 1990 that have remained State of the Art since their first publication. It defines the terms pseudoprogression, radiation induced necrosis and pseudoresponse. These phenomena are seen increasingly since the introduction of radiochemotherapy with Temozolomide as treatment standard in glioblastoma and since the use of antiangiogenetic therapy in malignant gliomas. Therefore, the assessment criteria have been recently updated with the newly proposed RANO criteria (Response assessment in Neuro-Oncology). Furthermore, the potential of additional information to conventional MR by MR perfusion, MR diffusion and MR spectroscopy is briefly discussed.

Pseudoprogression oder Pseudorespons: Herausforderung an die Bildgebung des Glioblastoma multiforme@@@Pseudoprogression or pseudoresponse: a challenge for the diagnostic imaging in Glioblastoma multiforme

SummaryThis methodological paper on magnetic resonance tomography imaging recalls the assessment criteria on therapy response of Glioblastoma multiforme as defined by David Macdonald in 1990 that have remained State of the Art since their first publication. It defines the terms pseudoprogression, radiation induced necrosis and pseudoresponse. These phenomena are seen increasingly since the introduction of radiochemotherapy with Temozolomide as treatment standard in glioblastoma and since the use of antiangiogenetic therapy in malignant gliomas. Therefore, the assessment criteria have been recently updated with the newly proposed RANO criteria (Response assessment in Neuro-Oncology). Furthermore, the potential of additional information to conventional MR by MR perfusion, MR diffusion and MR spectroscopy is briefly discussed.ZusammenfassungAusgehend von der Beurteilung des Therapieerfolgs bei Glioblastomen durch bildgebende Untersuchungen nach den Kriterien, die David Macdonald 1990 vorgeschlagen hatte und die seither unangefochten Standardinstrumente blieben, werden in diesem Beitrag die Begriffe Pseudoprogression, Radionekrose und Pseudorespons definiert und anhand von Beispielen erklärt. Diese Phänomene werden im Zuge der Verbreitung der kombinierten Radiochemotherapie und der Einführung anti-angiogenetisch wirksamer Substanzen in die Therapie maligner Gliome häufiger beobachtet. Dies hat ein Update der Beurteilungskriterien maligner Gliome, den RANO-Kriterien, notwendig gemacht. Außerdem werden mögliche Zusatzinformationen zur konventionellen MR-Untersuchung, die aus MR-Perfusion, MR-Diffusion und MR-Spektroskopie bei malignen Gliomen gewonnen werden kurz erläutert.This methodological paper on magnetic resonance tomography imaging recalls the assessment criteria on therapy response of Glioblastoma multiforme as defined by David Macdonald in 1990 that have remained State of the Art since their first publication. It defines the terms pseudoprogression, radiation induced necrosis and pseudoresponse. These phenomena are seen increasingly since the introduction of radiochemotherapy with Temozolomide as treatment standard in glioblastoma and since the use of antiangiogenetic therapy in malignant gliomas. Therefore, the assessment criteria have been recently updated with the newly proposed RANO criteria (Response assessment in Neuro-Oncology). Furthermore, the potential of additional information to conventional MR by MR perfusion, MR diffusion and MR spectroscopy is briefly discussed.