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

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Abstract

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/m2 per day, followed by 6 cycles of adjuvant temozolomide (150–200 mg/m2, 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.

Introduction

Glioblastoma (GBM) is the most common and aggressive neoplasm of the brain in adults. These tumors account for 45–50% of all gliomas [6]. The median survival is generally less than 1 year from the time of diagnosis, and most patients die within 2 years, even under the most favorable circumstances. Despite the use of macroscopic debulking and effective adjuvant radiation therapy (RT), the median survival (MS) of patients who present with GBM is generally only 9–12 months, with less than 15% of patients alive at 2 years post-diagnosis [7], [8]. Temozolomide (TMZ) is an oral alkylating agent with considerable antitumor activity in brain tumors [14]. Concomitant TMZ along with radiotherapy (RT) followed by 6 cycles of adjuvant TMZ has become the standard treatment for such patients in accordance with the randomized European and Canadian trial, which demonstrated a significant improvement in the median and 2-year survival of patients receiving or not receiving TMZ [1], [4], [5]. However, it is important to assess whether the same results can be replicated in clinical practice and in patients from different populations. We hereby report the analysis of the first 79 patients with GBM treated uniformly in accordance with the protocol of Stupp et al. [1], [15] with a focus on the safety, tolerability and survival benefits of this protocol in a Korean population. We believe that this study is the first to investigate the efficacy of radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma in a Korean population, and we believe that this study included more cases than any other such study in an Asian population.

Section snippets

Materials and methods

Between May 2004 and December 2007, we experienced a total of 79 patients with newly diagnosed glioblastomas in our institute. All patients were histopathologically confirmed with glioblastomas according to the WHO classification (ref. 2007 WHO).

Patient characteristics

The age range of the patient population was from 15 to 76 years, with a median of 52 years. Only one patient, aged 15 years, was below 18 years of age. Seventy-four percent of the patients underwent gross total resection of the tumor prior to radiotherapy, while 18% underwent subtotal or partial resection, and the rest (8%) underwent open or stereotactic biopsy. All patients had pathology categorized as WHO grade IV or GBM. The patient details are outlined in Table 1. Prior to surgery, 35% of

Discussion

The results of this local cohort of patients managed with adjuvant TMZ demonstrated a MS of 18.3 months and a 2-year survival rate of 37.1%. Outcome results of high-grade gliomas are quite dependent upon pre-treatment factors such as age, performance status, histology and extent of surgical resection [12]. It is therefore important to critically analyze the impact of these factors on the outcome results in order to evaluate and compare the results of any therapy. The median age of our patient

Conclusion

The median and 2-year survival outcomes of this study population of Asian patients with GBM are comparable to the results of the large European Multicentre Study and justify the continued use of TMZ in routine clinical practice. Although TMZ therapy has now become the standard of care for patients with newly diagnosed GBM, numerous unanswered questions remain, and larger randomized trials should be conducted to guide clinical decision making in the management of patients with glioblastoma.

Acknowledgements

This work was supported by the Sungkyunkwan University School of Medicine and the Samsung Medical Center.

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