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glioblastoma_multiforme_treatment [2018/12/10 08:06]
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glioblastoma_multiforme_treatment [2018/12/20 07:44] (current)
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 ====== Glioblastoma multiforme treatment ====== ====== Glioblastoma multiforme treatment ======
  
-The standard of care management for newly diagnosed ​[[glioblastoma multiforme]] (GBM) includes [[surgery]],​ [[radiation]],​ [[temozolomide]] (TMZ) [[chemotherapy]],​ and [[tumor treating fields]] +see [[High Grade glioma treatment]]
-((Stupp R, Taillibert S, Kanner A et al (2017) Effect of tumortreating +
-fields plus maintenance temozolomide vs maintenance +
-temozolomide alone on survival in patients with glioblastoma:​ a +
-randomized clinical trial. JAMA 318:​2306–2316)). ​+
  
-First therapeutic report of [[temozolomide]] to treat human [[glioma]]s 
-((Friedman HS, McLendon RE, Kerby T, et al. [[DNA mismatch repair]] 
-and O6-alkylguanine-DNA alkyltransferase analysis and response to 
-Temodal in newly diagnosed malignant glioma. J Clin Oncol 1998;16: 
-3851–7)). 
----- 
  
-The recommended treatment for MGMT promoter unmethylated [[glioblastoma]] (GBM) is [[radiation therapy]] with concurrent/​adjuvant [[temozolomide]] (TMZ). 
- 
-From [[2005]], state-of-the-art therapy in [[glioblastoma multiforme]] consists of [[maximal safe resection]] ​ followed by combined [[radiotherapy]] and [[chemotherapy]] with [[temozolomide]],​ according to [[Stupp regimen]] ​ 
-((Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy 
-Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;​352(10):​987-96. PubMed PMID: 15758009.)) 
-, particularly in patients that demonstrate [[MGMT promoter methylation]]. ​ 
- 
-Conflicting reports have emerged regarding the importance of the time interval between these 2 treatments and there is no clear association between duration from surgery to initiation of chemoradiation on [[overall survival]] (OS). 
-((Osborn VW, Lee A, Garay E, Safdieh J, Schreiber D. Impact of Timing of 
-Adjuvant Chemoradiation for Glioblastoma in a Large Hospital Database. 
-Neurosurgery. 2018 Nov 1;​83(5):​915-921. doi: 10.1093/​neuros/​nyx497. PubMed PMID:  
-29092047. 
-)). 
- 
-Although [[overall survival]] (OS) is the standard for determining GBM treatment efficacy, using OS as an endpoint when studying new therapeutic strategies can be problematic because of potential influence of therapies prior to or subsequently following the therapy being studied. For example, it is difficult to definitively conclude that [[bevacizumab]] has no efficacy in GBM when a large percentage of patients in the placebo arms in both III trials studying efficacy of bevacizumab (i.e. AVAglio and [[RTOG 0825]]) eventually crossed over and received bevacizumab (31% in AVAglio) 
-((Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, 
-Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. 
-Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N 
-Engl J Med. 2014 Feb 20;​370(8):​709-22. doi: 10.1056/​NEJMoa1308345. PubMed PMID: 
-24552318. 
-)) 
-and 48% in RTOG-0825 
-((Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, 
-Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D,  
-Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, 
-Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed 
-glioblastoma. N Engl J Med. 2014 Feb 20;​370(8):​699-708. doi: 
-10.1056/​NEJMoa1308573. PubMed PMID: 24552317; PubMed Central PMCID: PMC4201043. 
-)). 
-If bevacizumab increased OS when given at any time during treatment, we may expect both treatment arms to have similar median OS since most patients eventually were treated with bevacizumab,​ disguising any therapeutic effects of the drug. Together, these results suggest OS may not be a suitable endpoint when studying new therapeutics or when there is a high chance of cross over in the control arm 
-((Ellingson BM, Wen PY, Cloughesy TF. Modified Criteria for Radiographic 
-Response Assessment in Glioblastoma Clinical Trials. Neurotherapeutics. 2017 
-Apr;​14(2):​307-320. doi: 10.1007/​s13311-016-0507-6. Review. PubMed PMID: 28108885; 
-PubMed Central PMCID: PMC5398984. 
-)). 
- 
-To overcome the limitations associated with using OS as the primary endpoint in studies involving new therapeutics,​ [[progression free survival]] (PFS) and [[objective response rate]] (ORR) should be considered important end points ​ 
-((Lamborn KR, Yung WK, Chang SM, Wen PY, Cloughesy TF, DeAngelis LM, Robins HI,  
-Lieberman FS, Fine HA, Fink KL, Junck L, Abrey L, Gilbert MR, Mehta M, Kuhn JG, 
-Aldape KD, Hibberts J, Peterson PM, Prados MD; North American Brain Tumor 
-Consortium. Progression-free survival: an important end point in evaluating 
-therapy for recurrent high-grade gliomas. Neuro Oncol. 2008 Apr;​10(2):​162-70. 
-doi: 10.1215/​15228517-2007-062. Epub 2008 Mar 4. PubMed PMID: 18356283; PubMed 
-Central PMCID: PMC2613818. 
-)). 
-===== Surgery ===== 
-see [[Glioblastoma surgery]]. 
- 
-===== Radiochemotherapy ===== 
-The recommended treatment for O6-methylguanine-DNA methyltransferase (MGMT) promoter unmethylated glioblastoma (GBM) is radiation therapy with concurrent/​adjuvant [[temozolomide]] (TMZ). However, it is well known that the clinical benefit from TMZ is lower in these patients. 
- 
-Waiting time after surgery and overall time data do not indicate a relevant time factor in the treatment of [[glioblastoma multiforme]] in a large contemporary single-centre cohort. Although a study was limited by its retrospective nature, its results indicate that short delays of postoperative radiochemotherapy,​ e.g. for screening of a patient for a clinical trial, may be uncritical 
-((Seidlitz A, Siepmann T, Löck S, Juratli T, Baumann M, Krause M. Impact of 
-waiting time after surgery and overall time of postoperative radiochemotherapy on 
-treatment outcome in glioblastoma multiforme. Radiat Oncol. 2015 Aug 
-16;​10(1):​172. PubMed PMID: 26276734. 
-)). 
- 
-====Glioblastoma multiforme antiangiogenic therapy==== 
-see [[Glioblastoma multiforme antiangiogenic therapy]]. 
- 
- 
-====Future Direction==== 
-GBM is one of the most active areas of [[research]]. Significant efforts are being made to look beyond basic morphology. ​ 
- 
-The retrospective analysis of the [[AVAglio trial]] reported 4.3 months incremental survival in the [[proneural glioblastoma]] subgroup 
-(( Sandmann T, Bourgon R, Garcia J, Li C, Cloughesy T, Chinot OL, et al. Patients with proneural glioblastoma may derive overall survival benefit from the addition of bevacizumab to first line radiotherapy and temozolomide:​ Retrospective analysis of the AV Aglio trial. J Clin Oncol. 2015:​pii–JCO.2015.61.5005. Epub ahead of print. )). 
- 
-Hence, patient selection and personalization of treatment should be done with more appropriateness in future. However, the complexity of performing these molecular assays in the lab appears to be labor and cost intensive and may limit routine use. In this context, a simplified model incorporating [[MGMT]] [[methylation]],​ human telomerase (TERT) methylation,​ and IDH mutation may be formulated to dictate the optimum treatment. Treatment personalization may further be refined with the incorporation of these molecular factors along with patient factors like age, performance status, etc., (molecular-clinical profiling). A Large number of newer drugs and virus based therapy are being evaluated in different phase III and phase II trials as well.  
- 
-The [[subventricular zone]] (SVZ) forms the lining the lateral ventricles and represents the origin of neural and some cancer stem cells. Gupta et al. reported on dose volume parameters of SVZ in 40 patients of adult GBM. Dose to the ipsilateral SVZ dose was found to be an independent predictor of survival in multivariate analysis in this study. Although a novel finding, this requires further validation in a prospective study 
-((Mallick S, Gandhi AK, Rath GK. Therapeutic approach beyond conventional 
-temozolomide for newly diagnosed glioblastoma:​ Review of the present evidence and 
-future direction. Indian J Med Paediatr Oncol. 2015 Oct-Dec;​36(4):​229-37. doi: 
-10.4103/​0971-5851.171543. Review. PubMed PMID: 26811592; PubMed Central PMCID: 
-PMC4711221. 
-)). 
----- 
- 
-[[Citalopram]] with standard RT and [[Temozolomide]] TMZ 
- 
-RT alone versus RT and TMZ for elderly 
- 
-[[CCNU]]/​TMZ combination therapy versus standard TMZ (MGMT-methylated cases) 
- 
-Standard RT plus concomitant and adjuvant OSAG 101 (Theraloc°) plusTMZ versus standard RT plus 
-concomitant and adjuvant TMZ 
- 
-Rindopepimut/​GM-CSF with adjuvantTMZ in EGFvall-positive GBM CDX110-04 
- 
-[[DCVax-L]],​ autologous dendritic cells pulsed with tumor Iysate antigen 020221 
- 
-Adjuvant TMZ with or without Interferon-alpha NCT 01765088 
- 
-Adjuvant RT and temozolomide with or without Velipari b NCT 02152982 
- 
-CCNU - Lomustine; TMZ -Temozolomide;​ MGMT - O‘-methylguanine—DNA methyltransferase;​ GBM - Glioblastoma multiforme; RT - Radiotherapy,​- 
- 
-GM-CSF -Granulocyte-monocyte colony stimulating factor,- EGFRvIII - Epidermal growth factor receptor variant III. 
- 
-====Immunotherapy==== 
-see [[Glioblastoma immunotherapy]] 
- 
-===Not good candidates for surgery==== 
- 
-Extensive dominant lobe glioblastoma 
- 
-[[Butterfly glioblastoma]]. 
- 
-[[Glioblastoma in elderly patients]] 
- 
-[[Karnofsky performance score]] < 70 
- 
-[[Multicentric glioblastoma]]. 
----- 
-see also [[recurrent glioblastoma treatment]]. 
glioblastoma_multiforme_treatment.txt · Last modified: 2018/12/20 07:44 by administrador