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Malmström, A., Lysiak, M., Winther Kristensen, B., Hovey, E., Henriksson, R. & Söderkvist, P. (2019). Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma. Neuro-Oncology Practice, 1-9
Open this publication in new window or tab >>Do we really know who has an MGMT methylated glioma?: Results of an international survey regarding use of MGMT analyses for glioma
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2019 (English)In: Neuro-Oncology Practice, ISSN 2054-2577, p. 1-9Article in journal (Refereed) Published
Abstract [en]

Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.

Place, publisher, year, edition, pages
Oxford: Oxford University Press, 2019
National Category
Medical Bioscience Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-160808 (URN)10.1093/nop/npz039 (DOI)
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-11-06Bibliographically approved
Ellegård, S., Veenstra, C., Pérez-Tenorio, G., Fagerström, V., Garsjo, J., Gert, K., . . . Stål, O. (2019). ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2-positive metastatic breast cancer treated with trastuzumab. Oncology Letters, 17(3), 3371-3381
Open this publication in new window or tab >>ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2-positive metastatic breast cancer treated with trastuzumab
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2019 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 17, no 3, p. 3371-3381Article in journal (Refereed) Published
Abstract [en]

Trastuzumab has markedly improved the treatment and long-term prognosis of patients with HER2-positive breast cancer. A frequent clinical challenge in patients with relapsing and/or metastatic disease is de novo or acquired trastuzumab resistance, and to date no predictive biomarkers for palliative trastuzumab have been established. In the present study, the prognostic values of factors involved in the HER2-associated PI3K/Akt signalling pathway were explored. The first 46 consecutive patients treated at the Department of Oncology, Linkoping University Hospital between 2000 and 2007 with trastuzumab for HER2-positive metastatic breast cancer were retrospectively included. The gene copy number variation and protein expression of several components of the PI3K/Akt pathway were assessed in the tumour tissue and biopsy samples using droplet digital polymerase chain reaction and immunohistochemistry. Patients with tumours displaying a high-grade ERBB2 (HER2) amplification level of amp;gt;= 6 copies had a significantly improved overall survival hazard ratio [(HR)=0.4; 95%, confidence interval (CI): 0.2-0.9] and progression-free survival (HR=0.3; 95% CI: 0.1-0.7) compared with patients with tumours harbouring fewer ERBB2 copies. High-grade ERBB2 amplification was significantly associated with the development of central nervous system metastases during palliative treatment. Copy gain (amp;gt;= 3 copies) of the gene encoding the tyrosine phosphatase PTPN2 was associated with a shorter overall survival (HR=2.0; 95% CI: 1.0-4.0) and shorter progression-free survival (HR=2.1; 95% CI: 1.0-4.1). In conclusion, high ERBB2 amplification level is a potential positive prognostic factor in trastuzumab-treated HER2-positive metastatic breast cancer, whereas PTPN2 gain is a potential negative prognostic factor. Further studies are warranted on the role of PTPN2 in HER2 signalling.

Place, publisher, year, edition, pages
Athens, Greece: Spandidos Publications, 2019
Keywords
HER2; brain metastasis; protein tyrosine phosphatase non-receptor type 2; ribosomal protein S6 kinase B1; PI3K; phosphatase and tensin homolog
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-155540 (URN)10.3892/ol.2019.9998 (DOI)000460555900098 ()30867772 (PubMedID)2-s2.0-85062153648 (Scopus ID)
Note

Funding Agencies|Swedish Cancer Society [17-0479]; Medical Research Council of Southeast Sweden [FORSS-757671]; ALF Grants Region Ostergotland [LIO-795201]; Stiftelsen Onkologiska Klinikernas Forskningsfond i Linkoping [2016-06-21]

Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-08-27Bibliographically approved
Malmström, A. (2019). Studies for Better Treatment of Patients with Glioma. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Studies for Better Treatment of Patients with Glioma
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.

The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.

The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).

The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.

The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.

In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2019. p. 73
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1709
National Category
Medical Bioscience Clinical Laboratory Medicine Cancer and Oncology Surgery Nursing Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-161677 (URN)10.3384/diss.diva-161677 (DOI)9789179299798 (ISBN)
Public defence
2019-11-22, Linden, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Funder
Medical Research Council of Southeast Sweden (FORSS)Swedish Cancer SocietyRegion Östergötland
Note

Supporter of this thesis not mentioned above are LiUCancer and NSC research grant; Linköping University Hospital for Neuro-research, Lion's Cancer Foundation, Cancer Foundation Norrland and Rotary Borgholm research grant.

Available from: 2019-11-06 Created: 2019-11-06 Last updated: 2020-02-06Bibliographically approved
Coomans, M., Dirven, L., Aaronson, N. K., Baumert, B. G., van den Bent, M., Bottomley, A., . . . Taphoorn, M. J. B. (2019). The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials. European Journal of Cancer, 116, 190-198
Open this publication in new window or tab >>The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials
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2019 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 116, p. 190-198Article in journal (Refereed) Published
Abstract [en]

Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small. (C) 2019 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2019
Keywords
Glioma; Health-related quality of life (HRQoL); Prognostic factor; Brain tumour; Survival
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:liu:diva-158938 (URN)10.1016/j.ejca.2019.05.012 (DOI)000473270800022 ()31203194 (PubMedID)
Note

Funding Agencies|European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group

Available from: 2019-07-20 Created: 2019-07-20 Last updated: 2019-07-20
van Thuijl, H. F., Mazor, T., Johnson, B. E., Fouse, S. D., Aihara, K., Hong, C., . . . Costello, J. F. (2015). Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment. Acta Neuropathologica, 129(4), 597-607
Open this publication in new window or tab >>Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment
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2015 (English)In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 129, no 4, p. 597-607Article in journal (Refereed) Published
Abstract [en]

Temozolomide (TMZ) increases the overall survival of patients with glioblastoma (GBM), but its role in the clinical management of diffuse low-grade gliomas (LGG) is still being defined. DNA hypermethylation of the O (6) -methylguanine-DNA methyltransferase (MGMT) promoter is associated with an improved response to TMZ treatment, while inactivation of the DNA mismatch repair (MMR) pathway is associated with therapeutic resistance and TMZ-induced mutagenesis. We previously demonstrated that TMZ treatment of LGG induces driver mutations in the RB and AKT-mTOR pathways, which may drive malignant progression to secondary GBM. To better understand the mechanisms underlying TMZ-induced mutagenesis and malignant progression, we explored the evolution of MGMT methylation and genetic alterations affecting MMR genes in a cohort of 34 treatment-na less than ve LGGs and their recurrences. Recurrences with TMZ-associated hypermutation had increased MGMT methylation compared to their untreated initial tumors and higher overall MGMT methylation compared to TMZ-treated non-hypermutated recurrences. A TMZ-associated mutation in one or more MMR genes was observed in five out of six TMZ-treated hypermutated recurrences. In two cases, pre-existing heterozygous deletions encompassing MGMT, or an MMR gene, were followed by TMZ-associated mutations in one of the genes of interest. These results suggest that tumor cells with methylated MGMT may undergo positive selection during TMZ treatment in the context of MMR deficiency.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2015
Keywords
Low-grade glioma; Temozolomide; Hypermutator; Mismatch repair; MGMT
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-117202 (URN)10.1007/s00401-015-1403-6 (DOI)000351517200008 ()25724300 (PubMedID)
Note

Funding Agencies|Accelerate Brain Cancer Cure; Grove Foundation; TDC Foundation; Anne and Jason Farber Foundation; UCSF Brain Tumor SPORE grant [NIH P50CA097257]; Dutch Cancer Society (KWF) [2009-4470]; foundation STOPHersentumoren; Edli foundation; LiU Cancer Research Network; Medical Research Council of Southeast Sweden; National Institute Of General Medical Sciences [T32GM008568]; National Institutes of Health [1T32CA15102201]; National Cancer Institute [R01CA169316]; Sontag Foundation; NCI RO1 [R01 CA163687]; Project for Development of Innovative Research on Cancer Therapeutics (P-Direct); Ministry of Education, Culture, Sports, Science and Technology of Japan [23134501, 24221011]

Available from: 2015-04-22 Created: 2015-04-21 Last updated: 2019-10-14
Mosrati, M. A., Malmström, A., Lysiak, M., Krysztofiak, A., Hallbeck, M., Milos, P., . . . Söderkvist, P. (2015). TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma. OncoTarget, 6(18), 16663-16673
Open this publication in new window or tab >>TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma
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2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 18, p. 16663-16673Article in journal (Refereed) Published
Abstract [en]

Telomerase reverse transcriptase (TERT) activity is up-regulated in several types of tumors including glioblastoma (GBM). In the present study, 128 primary glioblastoma patients were examined for single nucleotide polymorphisms of TERT in blood and in 92 cases for TERT promoter mutations in tumors. TERT promoter mutations were observed in 86% of the tumors and of these, C228T (-124 bp upstream start codon) was detected in 75% and C250T (-146 bp) in 25% of cases. TERT promoter mutations were associated with shorter overall survival (11 vs. 20 months p = 0.002 and 12 vs. 20, p = 0.04 for C228T and C250T, respectively). The minor alleles of rs2736100 and rs10069690 SNPs, located in intron 2 and the promotor regions, respectively, were associated with an increased risk of developing GBM (p = 0.004 and 0.001). GBM patients having both TERT promoter mutations and being homozygous carriers of the rs2853669 C-allele displayed significantly shorter overall survival than those with the wild type allele. The rs2853669 SNP is located in a putative Ets2 binding site in the promoter (-246 bp upstream start codon) close to the C228T and C250T mutation hot spots. Interleukin-6 (IL-6) expression regulated by TERT promoter status and polymorphism, what leads us to think that TERT and IL-6 plays a significant role in GBM, where specific SNPs increase the risk of developing GBM while the rs2853669 SNP and specific mutations in the TERT promoter of the tumor lead to shorter survival.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC, 2015
Keywords
TERT polymorphism; TERT promoter mutations; IDH1 mutation; glioblastoma; IL-6
National Category
Medical Genetics
Identifiers
urn:nbn:se:liu:diva-120882 (URN)10.18632/oncotarget.4389 (DOI)000359012000088 ()26143636 (PubMedID)
Note

Funding Agencies|Swedish Cancer foundation; Region Ostergotland research fund; FORSS

Available from: 2015-08-28 Created: 2015-08-28 Last updated: 2019-10-14
Asklund, T., Malmström, A., Bergqvist, M., Björ, O. & Henriksson, R. (2014). Brain tumors in Sweden: Data from a population-based registry 1999-2012.. Acta Oncologica
Open this publication in new window or tab >>Brain tumors in Sweden: Data from a population-based registry 1999-2012.
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2014 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226XArticle in journal (Refereed) Published
Abstract [en]

Background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research. Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre- and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse. Results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables. Conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.

Place, publisher, year, edition, pages
Informa Healthcare, 2014
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-112207 (URN)10.3109/0284186X.2014.975369 (DOI)000350646400011 ()25383446 (PubMedID)
Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2018-01-03
Asklund, T., Malmström, A., Björ, O., Blomquist, E. & Henriksson, R. (2013). Considerable improvement in survival for patients aged 60-84 years with high grade malignant gliomas - Data from the Swedish Brain Tumour Population-based Registry [Letter to the editor]. Acta Oncologica, 52(5), 1043-1046
Open this publication in new window or tab >>Considerable improvement in survival for patients aged 60-84 years with high grade malignant gliomas - Data from the Swedish Brain Tumour Population-based Registry
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2013 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 1043-1046Article in journal, Letter (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-89909 (URN)10.3109/0284186X.2012.754993 (DOI)000318655300023 ()23398620 (PubMedID)
Available from: 2013-03-11 Created: 2013-03-11 Last updated: 2018-01-03
Malmström, A., Henning Gronberg, B., Marosi, C., Stupp, R., Frappaz, D., Schultz, H., . . . Henriksson, R. (2012). Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. The Lancet Oncology, 13(9), 916-926
Open this publication in new window or tab >>Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
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2012 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, no 9, p. 916-926Article in journal (Refereed) Published
Abstract [en]

Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. less thanbrgreater than less thanbrgreater thanMethods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. less thanbrgreater than less thanbrgreater thanFindings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5; n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52-0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6; n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06; p=0.12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0.35 [0.21-0.56], pandlt;0.0001; HR for hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9.7 months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93], p=0.02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38]; p=0.81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. less thanbrgreater than less thanbrgreater thanInterpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.

Place, publisher, year, edition, pages
Elsevier, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84333 (URN)10.1016/S1470-2045(12)70265-6 (DOI)000308425600019 ()
Note

Funding Agencies|Merck||Lions Cancer Research Foundation||University of Umea||Swedish Cancer Society||Schering-Plough||University of Umea, Sweden||Cancer Fonden, Sweden||

Available from: 2012-10-05 Created: 2012-10-05 Last updated: 2019-11-06
Malmström, A., Stupp, R., Hegi, M., Rosell, J. & Henriksson, R. (2012). Treatment options in elderly patients with glioblastoma - Authors' reply [Letter to the editor]. The Lancet Oncology, 13(11), E461-E462
Open this publication in new window or tab >>Treatment options in elderly patients with glioblastoma - Authors' reply
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2012 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, no 11, p. E461-E462Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Elsevier: Lancet, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-86116 (URN)10.1016/S1470-2045(12)70467-9 (DOI)000310570900003 ()
Available from: 2012-12-07 Created: 2012-12-07 Last updated: 2018-01-03
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8410-4939

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