Top

Published in:

Open Access 01-11-2018 | Clinical Study

Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors

Authors: Takahiro Sasaki, Junya Fukai, Yoshinori Kodama, Takanori Hirose, Yoshiko Okita, Shusuke Moriuchi, Masahiro Nonaka, Naohiro Tsuyuguchi, Yuzo Terakawa, Takehiro Uda, Yusuke Tomogane, Manabu Kinoshita, Namiko Nishida, Shuichi Izumoto, Yoshikazu Nakajima, Hideyuki Arita, Kenichi Ishibashi, Tomoko Shofuda, Daisuke Kanematsu, Ema Yoshioka, Masayuki Mano, Koji Fujita, Yuji Uematsu, Naoyuki Nakao, Kanji Mori, Yonehiro Kanemura

Published in: Journal of Neuro-Oncology | Issue 2/2018

Abstract

Introduction

This study investigates the current state of clinical practice and molecular analysis for elderly patients with diffuse gliomas and aims to elucidate treatment outcomes and prognostic factors of patients with glioblastomas.

Methods

We collected elderly cases (≥ 70 years) diagnosed with primary diffuse gliomas and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and pathological characteristics were analyzed retrospectively. Various factors were evaluated in univariate and multivariate models to examine their effects on overall survival.

Results

Included in the study were 140 elderly patients (WHO grade II: 7, III: 19, IV: 114), median age was 75 years. Sixty-seven patients (47.9%) had preoperative Karnofsky Performance Status score of ≥ 80. All patients underwent resection (gross-total: 20.0%, subtotal: 14.3%, partial: 39.3%, biopsy: 26.4%). Ninety-six of the patients (68.6%) received adjuvant treatment consisting of radiotherapy (RT) with temozolomide (TMZ). Seventy-eight of the patients (75.0%) received radiation dose of ≥ 50 Gy. MGMT promoter was methylated in 68 tumors (48.6%), IDH1/2 was wild-type in 129 tumors (92.1%), and TERT promoter was mutated in 78 of 128 tumors (60.9%). Median progression-free and overall survival of grade IV cases was 8.2 and 13.6 months, respectively. Higher age (≥ 80 years) and TERT promoter mutated were associated with shorter survival. Resection and adjuvant RT + TMZ were identified as independent factors for good prognosis.

Conclusions

This community-based study reveals characteristics and outcomes of elderly glioma patients in a real-world setting. Elderly patients have several potential factors for poor prognosis, but resection followed by RT + TMZ could lengthen duration of survival.

Available only for authorised users

Committee of Brain Tumor Registry of Japan (2017) Report of Brain Tumor Registry of Japan (2005–2008). Neurol Med Chir (Tokyo) 57(suppl-1):1–102

Committee of Brain Tumor Registry of Japan (2014) Report of Brain Tumor Registry of Japan (2001–2004). Neurol Med Chir (Tokyo) 54(suppl.):1–102

Perry JR, Laperriere N, O’Callaghan CJ et al (2017) Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 376:1027–1037CrossRefPubMed

Álvarez de Eulate-Beramendi S, Álvarez-Vega MA, Balbin M et al (2016) Prognostic factors and survival study in high-grade glioma in the elderly. Br J Neurosurg 30:330–336CrossRefPubMed

Jordan JT, Gerstner ER, Batchelor TT, Cahill DP, Plotkin SR (2016) Glioblastoma care in the elderly. Cancer 122:189–197CrossRefPubMed

Zarnett OJ, Sahgal A, Gosio J et al (2015) Treatment of elderly patients with glioblastoma: a systematic evidence-based analysis. JAMA Neurol 72:589–596CrossRefPubMed

Arvold ND, Reardon DA (2014) Treatment options and outcomes for glioblastoma in the elderly patient. Clin Interv Aging 9:357–367PubMedPubMedCentral

Wick W, Platten M, Meisner C et al (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13:707–715CrossRefPubMed

The Cancer Genome Atlas Research Network (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498CrossRefPubMedCentral

10.

Eckel-Passow JE, Lachance DH, Molinaro AM et al (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372:2499–2508CrossRefPubMedPubMedCentral

11.

Suzuki H, Aoki K, Chiba K et al (2015) Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 47:458–468CrossRefPubMed

12.

Arita H, Yamasaki K, Matsushita Y et al (2016) A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas. Acta Neuropathol Commun 4:79CrossRefPubMedPubMedCentral

13.

Weller M, Weber RG, Willscher E et al (2015) Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups. Acta Neuropathol 129:679–693CrossRefPubMed

14.

Louis DN, von Deimling A, Cavenee WK (2016) Diffuse astrocytic and oligodendroglial tumours. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO classification of tumours of the central nervous system, revised, 4th edn. IARC, Lyon, pp 16–77

15.

Wick W, Weller M, van den Bent M et al (2014) MGMT testing—the challenges for biomarker-based glioma treatment. Nat Rev Neurol 10:372–385CrossRefPubMed

16.

National Comprehensive Cancer Network® (2016) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Central Nervous System Cancers. Version I. https://www.nccn.org. Accessed 25 Dec 2016

17.

Malmström A, Grønberg BH, Marosi C et al (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 13:916–926CrossRefPubMed

18.

Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRef

19.

Kinoshita M, Sakai M, Arita H et al (2016) Introduction of high throughput magnetic resonance T2-weighted image texture analysis for WHO grade 2 and 3 gliomas. PLoS ONE 11:e0164268CrossRefPubMedPubMedCentral

20.

Okita Y, Nonaka M, Shofuda T et al (2014) (11)C-methinine uptake correlates with MGMT promoter methylation in nonenhancing gliomas. Clin Neurol Neurosurg 125:212–216CrossRefPubMed

21.

Uzuka T, Asano K, Sasajima T et al (2014) Treatment outcomes in glioblastoma patients aged 76 years or older: a multicenter retrospective cohort study. J Neurooncol 116:299–306CrossRefPubMed

22.

Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820CrossRefPubMed

23.

Arita H, Narita Y, Fukushima S et al (2013) Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol 126:267–276CrossRefPubMed

24.

Wiestler B, Claus R, Hartlieb SA et al (2013) Malignant astrocytomas of elderly patients lack favorable molecular markers: an analysis of the NOA-08 study collective. Neuro Oncol 15:1017–1026CrossRefPubMedPubMedCentral

25.

Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535CrossRefPubMed

26.

Arvold ND, Tanguturi SK, Aizer AA et al (2015) Hypofractionated versus standard radiation therapy with or without temozolomide for older glioblastoma patients. Int J Radiat Oncol Biol Phys 92:384–389CrossRefPubMed

27.

Fukai J, Nishibayashi H, Uematsu Y et al (2016) Rapid regression of glioblastoma following carmustine wafer implantation: a case report. Mol Clin Oncol 5:153–157CrossRefPubMedPubMedCentral

28.

Arvold ND, Cefalu M, Wang Y, Zigler C, Schrag D, Dominici F (2017) Comparative effectiveness of radiotherapy with vs. without temozolomide in older patients with glioblastoma. J Neurooncol 131:301–311CrossRefPubMed

29.

Franceschi E, Depenni R, Paccapelo A et al (2016) Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study. J Neurooncol 128:157–162CrossRefPubMed

30.

Babu R, Komisarow JM, Agarwal VJ et al (2016) Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival. J Neurosurg 124(4):998–1007CrossRefPubMed

Title: Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors
Authors: Takahiro Sasaki
Junya Fukai
Yoshinori Kodama
Takanori Hirose
Yoshiko Okita
Shusuke Moriuchi
Masahiro Nonaka
Naohiro Tsuyuguchi
Yuzo Terakawa
Takehiro Uda
Yusuke Tomogane
Manabu Kinoshita
Namiko Nishida
Shuichi Izumoto
Yoshikazu Nakajima
Hideyuki Arita
Kenichi Ishibashi
Tomoko Shofuda
Daisuke Kanematsu
Ema Yoshioka
Masayuki Mano
Koji Fujita
Yuji Uematsu
Naoyuki Nakao
Kanji Mori
Yonehiro Kanemura
Publication date: 01-11-2018
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-2957-7

2024 ASCO Annual Meeting

Springer Medicine

Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors

Abstract

Introduction

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2018

Postoperative stereotactic radiosurgery for patients with resected brain metastases: a volumetric analysis

Trametinib for progressive pediatric low-grade gliomas

Prediction value of unmeasurable MR enhancement at early stage after gross-total resection on the survival state of patients with high-grade glioma

Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery

Neurocognitive evaluation of brain metastases patients treated with post-resection stereotactic radiosurgery: a prospective single arm clinical trial

Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma