Despite decades of intense research, the complex biology of glioblastoma (GBM) is not completely understood. Progression-free survival and overall survival have remained unchanged since the implementation of the STUPP regimen in 2005 with concomitant radio-/chemotherapy and adjuvant chemotherapy with temozolomide.In the context of Hanahan and Weinberg's six hallmarks and two emerging hallmarks of cancer, we discuss up-to-date status and recent research in the biology of GBM. We discuss the clinical impact of the research results with the most promising being in the hallmarks ‘enabling replicative immortality’, ‘inducing angiogenesis’, ‘reprogramming cellular energetics’ and ‘evading immune destruction’.This includes the importance of molecular diagnostics according to the new WHO classification and how next generation sequencing is being implemented in the clinical daily life. Molecular results linked together with clinical outcome have revealed the importance of the prognostic biomarker isocitratedehydrogenase (IDH), which is now part of the diagnostic criteria in brain tumours. IDH is discussed in the context of the hallmark ‘reprogramming cellular energetics’. O-6-methylguanine-DNA methyltransferase status predicts a more favourable response to treatment and is thus a predictive marker. Based on genomic aberrations, Verhaak et al have suggested a division of GBM into three subgroups, namely, proneural, classical and mesenchymal, which could be meaningful in the clinic and could help guide and differentiate treatment decisions according to the specific subgroup.The information achieved will develop and improve precision medicine in the future.
Background: Glioblastoma (GB) is an incurable brain cancer with limited treatment options. The aim was to test the feasibility of using cell-free DNA (cfDNA) to support evaluation of treatment response, pseudo-progression and whether progression could be found before clinical and/or radiologic progression. Results: CfDNA fluctuated during treatment with the highest levels before diagnostic surgery and at progression. An increase was seen in 3 out of 4 patients at the time of progression while no increase was seen in 3 out of 4 patients without progression. CfDNA levels could aid in 3 out of 3 questionable cases of pseudo-progression. Methods: Eight newly diagnosed GB patients were included. Blood samples were collected prior to diagnosis, before start and during oncologic treatment until progression. Seven patients received concurrent radiotherapy/Temozolomide with adjuvant Temozolomide with one of the patients included in a clinical trial with either immunotherapy or placebo as add-on. One patient received radiation alone. CfDNA concentration was determined for each blood sample. Conclusions: It was feasible to measure cfDNA concentration. Despite the limited cohort size, there was a good tendency between cfDNA and treatment course and -response, respectively with the highest levels at progression.
Glioblastoma (GBM) is an incurable brain tumor for which new treatment strategies are urgently needed. Next-generation sequencing of GBM has most often been performed retrospectively and on archival tissue from both diagnostic and relapse surgeries with limited knowledge of clinical information, including treatment given. We sought to investigate the genomic composition prospectively in treatment-na€ ıve patients, searched for possible targetable aberrations, and investigated for prognostic and/or predictive factors. A total of 108 newly diagnosed GBM patients were included. Clinical information, progression-free survival, and overall survival (OS) were noted. Tissues were analyzed by whole-exome sequencing, single nucleotide polymorphism (SNP) and transcriptome arrays, and RNA sequencing; assessed for mutations, fusions, tumor mutational burden (TMB), and chromosomal instability (CI); and classified into GBM subgroups. Each genomic report was discussed at a multidisciplinary tumor board meeting to evaluate for matching trials. From 111 consecutive patients, 97.3% accepted inclusion in this study. Eighty-six (77%) were treated with radiation therapy/temozolomide (TMZ) and adjuvant TMZ. One NTRK2 and three FGFR3-TACC3 fusions were identified. Copy number alterations in GRB2 and SMYD4 were significantly correlated with worse median OS together with known clinical variables like age, performance status, steroid dose, and O6-methyl-guanine-DNA-methyl-transferase status. Patients with CI-median or TMB-high had significantly worse median OS compared to CI-low/high or TMB-low/median. In conclusion, performing genomic profiling at diagnosis enables evaluation of genomic-driven therapy at the first progression. Furthermore, TMB-high or CI-median patients had worse median OS, which can support the possibility of offering experimental treatment already at the first line for this group.
BackgroundPalliative thoracic radiotherapy (PTR) can relieve symptoms originating from intra-thoracic disease. The optimal timing and fractionation of PTR is unknown. Time to effect is 2 months. The primary aim of this retrospective study was to investigate survival after PTR, hypothesizing that a significant number of patients received futile fractionated PTR. The secondary aim was to find prognostic factors to guide treatment decisions.MethodsPatients with non-small-cell lung cancer (NSCLC) planned for PTR in the period of 2010-2011 at the University Hospital of Copenhagen were included. We noted pathology, tumor, node and metastasis (TNM) classification of malignant tumors, stage, indication, start date, schedule for PTR, completed y/n, performance status (PS) and time of death. Analyses were performed as an intention-to-treat using Cox regression, Fishers exact test and Kaplan Meier.ResultsA total of 159 patients were included. Median overall survival (OS) was 4.2 months. Sixteen patients (10%) did either not begin or finish PTR. Of these, eight (5%) died prior to or during PTR. Of the 151 patients receiving PTR, sixteen patients (11%) died within 14 days, thirty-three (22%) within 30 days and fifty (33%) within 2 months. PS 0-1 and squamous cell carcinoma were correlated with a better survival.ConclusionsOur study show that a significant number of patients who received PTR died before they could achieve optimal effect of the treatment. PS and histology were significant prognostic factors favoring PS 0-1 and squamous cell carcinoma. Based on our study, we suggest that patients with PS 0-1 should be considered for fractionated PTR whereas patients with PS ≥ 2 should be considered for high dose single fraction only or supportive palliative care.Electronic supplementary materialThe online version of this article (10.1186/s12904-017-0270-4) contains supplementary material, which is available to authorized users.
Key Clinical Message The clinician should always consider extracranial metastases in glioblastoma. Increased risk factors are young age at diagnosis, histology of gliosarcoma, and prior intracranial tumor surgery. Clinical guidelines are needed for this rare event, including consideration for prophylactic intervention.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.