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

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.

Outcome of gamma knife radiosurgery for metastatic brain tumors derived from non-small cell lung cancer.

The purpose of this study was to analyze outcomes in patients treated with gamma knife radiosurgery (GKS) for brain metastases from non-small cell lung cancer (NSCLC). We retrospectively reviewed the medical records of 817 patients who underwent GKS for brain metastases from NSCLC between January 2002 and December 2012. A total of 1363 GKS procedures were performed for 2970 lesions. The median overall survival time from the initial GKS was 13 months and the salvage treatment-free survival from the first GKS was 6.5 months. Younger age (≤65 years), female sex, better RPA class, higher DS-GPA score, adenocarcinoma, synchronous onset, and lower integrated value of the "numbers and cumulative volume of tumors" were associated with better outcomes. Among the 601 patients with an available follow up image, the pattern of the first progression after initial GKS was the development of new lesions in 356 patients (59.2 %), regrowth of treated lesions in 106 patients (17.6 %), and leptomeningeal seeding (LMS) in 51 patients (8.5 %). Among the deceased, the last MRI performed prior to death was evaluated in 409 patients and showed progression in 263 patients (64.3 %), despite multiple salvage treatments. LMS was identified in 63 patients (15.4 %); a rate much higher than the incidence at first progression. Intracranial tumor burden, defined as the integrated value of the "number of the lesions and cumulative tumor volume", is a new prognostic factor of greater significance than tumor volume or number alone when analyzed as separate factors. Although the cause of death was not progression of brain lesions in the majority of patients, the brain lesions tended to have been persistently progressive in most patients, despite repeated salvage treatment. LMS is an important pattern of treatment failure, in addition to local progression or development of new lesions, particularly in the terminal phase of the disease.

Clinical outcome of concomitant chemoradiotherapy followed by adjuvant temozolomide therapy for glioblastaomas: single-center experience.

INTRODUCTION: The use of radiotherapy plus temozolomide administered concomitantly with and after radiotherapy for glioblastoma was recently shown to improve median and 2-year survival in a large international multicenter study. To compare this result in routine clinical practice, an audit of the management and outcome of patients with glioblastoma at our institute was performed. METHODS: A total of 79 patients with pathologically confirmed glioblastoma were treated with radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m(2) per day, followed by 6 cycles of adjuvant temozolomide (150-200 mg/m(2), 5 consecutive days per month). The primary end point was overall survival (OS). Secondary endpoints included progression-free survival (PFS) and toxicity. We evaluated the clinical outcome of concomitant chemoradiotherapy for newly diagnosed glioblastomas at a single institute in Korea. RESULTS: The median age was 52 years (15-76 years), 47 patients were male and 32 patients were female. 92.4% of the patients had undergone debulking surgery. The median overall survival (OS) was 18.3 months (95% CI, 16.3-20.1 months), and the time to progression was 6.7 months (95% CI, 5.2-8.3 months). The 1-year and 2-year survival rates were 70.1% and 37.1%, respectively. In the retrospective analysis, the patients with a post-operative KPS over 80 showed more prolonged survival than those who had a KPS less 80 (23.1 months vs. 13.4 months; p<0.001). Age and extent of surgery did not emerge as significant factors. Twenty-four patients (30%) were treated with low-dose continuous temozolomide therapy after the tumor had recurred. Hematologic toxicity was the main adverse effect, occurring in seven patients (8.8%). Patients with lymphopenia were not reported. CONCLUSIONS: This study is the largest study of radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in Korean patients, who share a common genetic feature. The median and 2-year survival outcomes in this study are comparable to the previous reports. However, for the recurrent glioblastomas refractory to temozolomide, further clinical trials using other agents should be studied continuously in the future.