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

다국어 초록 (Multilingual 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.

참고문헌 (Reference)

1 Wen PY, "Updated response assessment criteria for high-grade gliomas : response assessment in neurooncology working group" 28 : 1963-1972, 2010

2 Park CK, "The value of temozolomide in combination with radiotherapy during standard treatment for newly diagnosed glioblastoma" 112 : 277-283, 2013

3 Yang H, "The prognosis of MGMT promoter methylation in glioblastoma patients of different race : a meta-analysis" 39 : 2277-2287, 2014

4 주진덕, "Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas : A Prospective Multicenter Study of Korean Patients" 대한신경외과학회 52 (52): 92-97, 2012

5 Laws ER, "Survival following surgery and prognostic factors for recently diagnosed malignant glioma : data from the Glioma Outcomes Project" 99 : 467-473, 2003

6 Curran WJ Jr, "Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials" 85 : 704-710, 1993

7 Stupp R, "Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma" 352 : 987-996, 2005

8 Oike T, "Radiotherapy plus concomitant adjuvant temozolomide for glioblastoma: Japanese mono-institutional results" 8 : e78943-, 2013

9 Lamborn KR, "Prognostic factors for survival of patients with glioblastoma : recursive partitioning analysis" 6 : 227-235, 2004

10 Rivera AL, "MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma" 12 : 116-121, 2010

11 Criniere E, "MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities" 83 : 173-179, 2007

12 Hegi ME, "MGMT gene silencing and benefit from temozolomide in glioblastoma" 352 : 997-1003, 2005

13 Seiz M, "Long-term adjuvant administration of temozolomide in patients with glioblastoma multiforme : experience of a single institution" 136 : 1691-1695, 2010

14 Senft C, "Intraoperative MRI guidance and extent of resection in glioma surgery : a randomised, controlled trial" 12 : 997-1003, 2011

15 Esteller M, "Inactivation of the DNArepair gene MGMT and the clinical response of gliomas to alkylating agents" 343 : 1350-1354, 2000

16 Esteller M, "Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia" 59 : 793-797, 1999

17 Suzuki Y, "Higher pAkt expression predicts a significant worse prognosis in glioblastomas" 51 : 343-348, 2010

18 Kreth FW, "Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy" 24 : 3117-3123, 2013

19 Buckner JC, "Factors influencing survival in high-grade gliomas" 30 (30): 10-14, 2003

20 Stummer W, "Extent of resection and survival in glioblastoma multiforme : identification of and adjustment for bias" 62 : 564-576, 2008

21 Stupp R, "Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study : 5-year analysis of the EORTC-NCIC trial" 10 : 459-466, 2009

22 Lawrence YR, "Delayed initiation of radiotherapy for glioblastoma: how important is it to push to the front (or the back) of the line" 105 : 1-7, 2011

23 Irwin C, "Delay in radiotherapy shortens survival in patients with high grade glioma" 85 : 339-343, 2007

24 DeAngelis LM, "Brain tumors" 344 : 114-123, 2001

25 Lacroix M, "A multivariate analysis of 416 patients with glioblastoma multiforme : prognosis, extent of resection, and survival" 95 : 190-198, 2001