BackgroundGlioblastoma patients show a great variability in progression free survival (PFS) and overall survival (OS). To gain additional pretherapeutic information, we explored the potential of O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET as an independent prognostic biomarker.MethodsWe retrospectively analyzed 146 consecutively treated, newly diagnosed glioblastoma patients. All patients were treated with temozolomide and radiation therapy (RT). CT/MR and FET PET scans were obtained postoperatively for RT planning. We used Cox proportional hazards models with OS and PFS as endpoints, to test the prognostic value of FET PET biological tumor volume (BTV).ResultsMedian follow-up time was 14 months, and median OS and PFS were 16.5 and 6.5 months, respectively. In the multivariate analysis, increasing BTV (HR = 1.17, P < 0.001), poor performance status (HR = 2.35, P < 0.001), O(6)-methylguanine-DNA methyltransferase protein status (HR = 1.61, P = 0.024) and higher age (HR = 1.32, P = 0.013) were independent prognostic factors of poor OS. For poor PFS, only increasing BTV (HR = 1.18; P = 0.002) was prognostic. A prognostic index for OS was created based on the identified prognostic factors.ConclusionLarge BTV on FET PET is an independent prognostic factor of poor OS and PFS in glioblastoma patients. With the introduction of FET PET, we obtain a prognostic index that can help in glioblastoma treatment planning.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-016-3494-2) contains supplementary material which is available to authorized users.
Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-β-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age- and sex-matched controls treated with paclitaxel and low-dose aspirin. By a cumulative dose of 1,500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% confidence interval, 0.9-3.0). Among those receiving a high-dose paclitaxel regimen, the hazard ratio was 2.3 (95% confidence interval, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy in patients treated with high-dose paclitaxel.
The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been treated with irinotecan 125 mg/m and bevacizumab 10 mg/kg every 2 weeks. The response rate was 37.1% for lom-bev and 30.1% for iri-bev. Median progression-free survival (PFS) was 23 weeks for lom-bev and 21 weeks for iri-bev (p = 0.9). Overall survival (OS) was 37 weeks for lom-bev and 32 weeks for iri-bev (p = 0.5). Lom-bev caused a significantly higher frequency of thrombocytopenia (11.4% grade 3-4) compared to iri-bev (3.5% grade 3-4). Iri-bev patients had more gastrointestinal toxicity with regard to nausea, vomiting, diarrhea, constipation and stomatitis. Within the limitations of the study lom-bev is a well-tolerated treatment for recurrent GBM, although hematological toxicity may be a dose limiting factor. No significant differences between lom-bev and iri-bev were observed with regard to PFS or OS. The differences in toxicity profiles between lom-bev and iri-bev could guide treatment decision in recurrent GBM therapy as efficacy is equal and no predictive factors for efficacy exist.
BACKGOUND: Patients with glioblastoma (GBM) show a variable disease course ranging from rapid progression to prolonged progression free survival (PFS). Despite aggressive standard therapy consisting of radiotherapy plus concomitant and adjuvant temozolomide (RCX) the prognoses is poor with a median overall survival (OS) less than 15 months and 5-year overall survival less than 10%. To maximize patient survival and optimize quality of life, it is relevant to identify prognostic biomarkers for treatment stratification. Positron emission tomography (PET) scanning using radiolabeled amino acids has been introduced in the radiation therapy planning of GBM. Therefore this study will evaluate whether postoperative FET PET in newly diagnosed GBM can provide additional prognostic information on outcome. MATERIALS AND METHODS: 147 patients from our GBM database treated with RCX and evaluated with FET PET postoperatively (1-2 weeks) in the period November 2011 -February 2014 were included retrospectively. With OS as the primary endpoint, and PFS as a secondary endpoint, the prognostic value of postoperative biological tumor volume (BTV) in FET PET, mean tumor to background ratio (TBRmean) and maximum tumor to background ratio (TBRmax) was estimated using Cox proportional hazards model. The analysis was adjusted for the known prognostic factors, performance status (PS), age and corticosteroid therapy status, by multivariate analysis. RESULTS: Median OS and PFS were 14.0 and 6.54 months respectively. In the univariate analysis, increasing BTV and higher values of TBRmean and TBRmax correlated significantly (,0.0001) with poor OS and PFS. In the multivariate analysis increasing BTV, poor PS and high age was independent prognostic factors for poor OS and PFS with p-values , 0.0001. CONCLUSION: Increasing postoperative FET PET tumor volume is an important independent prognostic factor of poor OS and PFS for GBM patients. Underlining the importance, of maximal tumor resection, on OS.
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