<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_raon-2016-0041_s_333_w2aab3b8c12b1b7b1aab1c15b1Aa"><h3>Background</h3><p>In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma.</p></sec><sec id="j_raon-2016-0041_s_334_w2aab3b8c12b1b7b1aab1c15b2Aa"><h3>Patients and methods</h3><p>Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent <italic>in situ</italic> hybridization).</p></sec><sec id="j_raon-2016-0041_s_335_w2aab3b8c12b1b7b1aab1c15b3Aa"><h3>Results</h3><p>Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p &lt; 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p = 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups.</p></sec><sec id="j_raon-2016-0041_s_336_w2aab3b8c12b1b7b1aab1c15b4Aa"><h3>Conclusions</h3><p>Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored.</p></sec></abstract>

BackgroundIn spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma.Patients and methodsLong-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization).ResultsMethylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p = 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups.ConclusionsMolecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored.

Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factor

Department of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana,

Faculty of Medicine, University of Maribor,

Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana,

Institute of Pathology, Faculty of Medicine, University of Ljubljana,

Department of Mathematics and Computer Science, Faculty of Natural Sciences and Mathematics, University of Maribor,

Radiology and Oncology

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

BackgroundIn spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical...

Variable		LTS group	Control group
Mean age (range)		47,5 (21–74)	49, 6 (23–74)
Gender	Male	24	31
	Female	16	9
Surgery	Gross total	22	23
	Reduction	15	15
	Biopsy	3	2
WHO PS	0	9	5
	1	25	26
	2	4	9
	3	2	0
Mean RT dose (Gy)		58	57,9
RT technique	1D	1	0
	2D	3	3
	3D	36	37
No. of fractions		25–33	25–33
Chemotherapy	Yes	37	39
	Adjuvant only	3	1

	LTS group	Control group	P value
IDH1(immunohistochemistry)	6/40	1/34	0.043
IDH1 (genetic)	6/38	1/33	0.043
IDH2 (genetic)	0/38	0/33	n.s.
1p/19q	0/38	1/34	n.s.
1p	3/38	1/34	n.s.
19q	10/38	6/34	n.s.
MGMT methylation	36/38	12/33	< 0.001
CDKN2A (deletion)	29/39	25/34	n.s.
CDKN2B (deletion)	27/39	24/34	n.s.

	LTS group	Control group	P value
Complete response* Includes patients reported by surgeon as gross total resection; LTS = long term survivor	24	4	< 0.001
Partial response	5	2	n.s.
Stable disease	4	13	0.013
Progression	7	20	0.002
Overall response	31/40	19/40	< 0.001
Non evaluable	0	1

Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factor

Article Category: Research Article

Pubblicato online: 10 nov 2016

Pagine: 394 - 401

Ricevuto: 15 lug 2015

Accettato: 06 ago 2015

DOI: https://doi.org/10.1515/raon-2015-0041

© 2016 Radiol Oncol

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Demographics, standard prognostic factors and treatment for long-term survivor (LTS) group and control group

Molecular and genetic markers

Response to primary treatment