BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The core of standard of care for newly diagnosed GBM was established in 2005 and includes maximum feasible surgical resection followed by radiation and temozolomide, with subsequent temozolomide with or without tumor-treating fields. Unfortunately, nearly all patients experience a recurrence. Bevacizumab (BV) is a commonly used second-line agent for such recurrences, but it has not been shown to impact overall survival, and short-term response is variable. METHODS: We collected MRI perfusion and diffusion images from 54 subjects with recurrent GBM treated only with radiation and temozolomide. They were subsequently treated with BV. Using machine learning, we created a model to predict short term response (6 months) and overall survival. We set time thresholds to maximize the separation of responders/survivors versus non-responders/short survivors. RESULTS: We were able to segregate 21 (68%) of 31 subjects into unlikely to respond categories based on Progression Free Survival at 6 months (PFS6) criteria. Twenty-two (69%) of 32 subjects could similarly be identified as unlikely to survive long using the machine learning algorithm. CONCLUSION: With the use of machine learning techniques to evaluate imaging features derived from pre- and post-treatment multimodal MRI, it is possible to identify an important fraction of patients who are either highly unlikely to respond, or highly likely to respond. This can be helpful is selecting patients that either should or should not be treated with BV.

• MeSH
• alkylační protinádorové látky terapeutické užití   MeSH
• bevacizumab terapeutické užití   MeSH
• časové faktory MeSH
• difuzní magnetická rezonance MeSH
• dospělí MeSH
• glioblastom farmakoterapie   patologie   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• nádory mozku farmakoterapie   patologie   MeSH
• objem krve v mozku účinky léků   fyziologie   MeSH
• prediktivní hodnota testů * MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• radioterapie MeSH
• retrospektivní studie MeSH
• strojové učení MeSH
• temozolomid terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Molecular screening plays a major role in prognostic categorization and subsequent definition of treatment strategies for acute myeloid leukemia. The possibility of using IDH1/2 mutations as a marker for the monitoring of minimal residual disease (MRD) is still under investigation and remains unclear. METHODS: In this retrospective study, we evaluated 90 patients with de novo AML using Sanger sequencing (exon 4, IDH1 and IDH2). For subsequent MRD monitoring were used both methods, massive parallel sequencing and droplet digital PCR (ddPCR). RESULTS: We identified 22 patients (24%) who harboured mutations in IDH1 or IDH2 genes. Fourteen (64%) of them had other commonly used MRD markers (insertion in NPM1 and partial tandem duplication of MLL, MLL-PTD). Eight of the 22 patients had IDH1 mutations, 13 had IDH2 mutations and 1 had both IDH1 and IDH2 mutations. In our cohort, this IDH1/2 marker responded to the treatment in all of the patients and reflected the onset of the relapse very well. NPM1 mutation based MRD monitoring was more sensitive and predicted relapse earlier but IDH1/2 based monitoring was more sensitive than a method based on MLL-PTD. Both massive parallel sequencing and ddPCR were competent to monitor MRD using IDH1/2. Nevertheless, ddPCR was able to achieve a higher sensitivity in some cases and moreover this method can analyse a single sample without significant price increases. CONCLUSION: Given these data, we conclude that IDH1/2 mutations can be used as a reliable and cost-effective marker for MRD monitoring.

• MeSH
• akutní myeloidní leukemie diagnóza   enzymologie   genetika   terapie   MeSH
• dospělí MeSH
• exony MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie MeSH
• indukce remise MeSH
• isocitrátdehydrogenasa chemie   genetika   metabolismus   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• následné studie MeSH
• nemocnice univerzitní MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• reziduální nádor MeSH
• senioři MeSH
• substituce aminokyselin MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH