Cancer Res Treat.  2017 Jan;49(1):193-203. 10.4143/crt.2015.473.

Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea

Affiliations
  • 1Department of Neurosurgery, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea.
  • 2Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 3Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • 4Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • 5Division of Hematology/Oncology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
  • 6Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 7Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 8Department of Neurosurgery, Brain Tumor Center, Yonsei University Health System, Seoul, Korea.
  • 9Department of Radiation Oncology, Brain Tumor Center, Yonsei University Health System, Seoul, Korea.
  • 10Department of Neurosurgery, Chonnam National University Hwasun Hospital, Hwasun, Korea.
  • 11Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun, Korea.
  • 12Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 13Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 14Department of Neurosurgery, Gangnam Severance Hospital, Yonsei University College of Health Science, Seoul, Korea.
  • 15Department of Neuro-Oncology Clinic, Center for Specific Organs Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea.
  • 16Department of Radiation Oncology, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea.
  • 17Department of Neurosurgery, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
  • 18Department of Radiation Oncology, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea.
  • 19Department of Neurosurgery, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.
  • 20Department of Neurosurgery, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea.
  • 21Department of Neurosurgery, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.
  • 22Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
  • 23Department of Neurosurgery, Hallym University Sacred Heart Hospital, Anyang, Korea.
  • 24Department of Neurosurgery, Soonchunhyang University Hospital, Seoul, Korea.
  • 25Department of Neurosurgery, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
  • 26Department of Pathology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 27Department of Radiation, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 28Department of Pathology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.
  • 29Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 30Department of Systemic Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea. nsghs@ncc.re.kr
  • 31Division of Hematotology/Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. sehoon.lee119@gmail.com
  • 32Department of Neurosurgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Abstract

PURPOSE
The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample.
MATERIALS AND METHODS
A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively.
RESULTS
After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period.
CONCLUSION
Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

Keyword

Glioblastoma; Temozolomide; MGMT; Chemoradiotherapy

MeSH Terms

Biopsy
Chemoradiotherapy*
Disease-Free Survival
Follow-Up Studies
Glioblastoma*
Humans
Korea*
Methylation
Radiotherapy
Retrospective Studies*
Survival Rate

Figure

  • Fig. 1. Kaplan-Meier curves showing overall survival (OS) (A) and progression-free survival (PFS) (B) according to the extent of the resection. Patients who received gross total resection (GTR) showed a significantly longer OS (21.0 months vs. 15.8 months) and PFS (10.9 months vs. 9.1 months) than those who received subtotal resection (STR), partial resection (PR), or biopsy (Bx) alone.

  • Fig. 2. Kaplan-Meier curves showing overall survival (OS) (A) and progression-free survival (PFS) (B) according to the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Patients with the methylated MGMT promoter had a longer OS (23.9 months vs. 16.7 months) and longer PFS (13.2 months vs. 9.3 months) than those with the unmethylated MGMT promoter.

  • Fig. 3. Kaplan-Meier curves showing overall survival (OS) (A) and progression-free survival (PFS) (B) according to the extent of the resection in patients with the methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter. Kaplan-Meier curves showing OS (C) and PFS (D) according to the extent of resection in patients with unmethylated MGMT promoter. Patients receiving gross total resection (GTR) demonstrated a significantly longer OS than those receiving subtotal resection (STR), partial resection (PR), or biopsy (Bx) alone in both groups with methylated (28.6 months vs. 16.7 months) and unmethylated MGMT promoter (19.0 months vs. 14.8 months). For OS, patients receiving GTR demonstrated a significantly longer PFS than those receiving STR, PR, or Bx alone in both groups with methylated (20.7 months vs. 11.1 months) and unmethylated MGMT promoter (10.6 months vs. 7.2 months).

  • Fig. 4. Kaplan-Meier curves showing overall survival (OS) (A) and progression-free survival (PFS) (B) according to the completion of six cycles of adjuvant temozolomide (TMZ) in patients with the methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter. Kaplan-Meier curves showing OS (C) and PFS (D) according to completion of six cycles of adjuvant TMZ in patients with the unmethylated MGMT promoter. Patients with the methylated MGMT promoter had a longer OS and longer PFS as the number of adjuvant TMZ cycles approached six compared to those with the unmethylated MGMT promoter.


Cited by  2 articles

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Yong Wonn Kwon, Won-Jin Moon, Mina Park, Hong Gee Roh, Young Cho Koh, Sang Woo Song, Jin Woo Choi
Investig Magn Reson Imaging. 2018;22(3):158-167.    doi: 10.13104/imri.2018.22.3.158.

Risk Factors for Cognitive Impairment in High-Grade Glioma Patients Treated with Postoperative Radiochemotherapy
Qiang Wang, Fengxia Xiao, Fei Qi, Xiaopeng Song, Yonghua Yu
Cancer Res Treat. 2020;52(2):586-593.    doi: 10.4143/crt.2019.242.


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