Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index

Abstract

Background: The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB).

Methods and materials: We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field).

Results: The median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not.

Conclusions: MIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease.

Figure 1

Kaplan-Meier curves of overall survival and progression-free survival for each histological grade. Kaplan-Meier curves of progression-free survival (PFS) and overall survival (OS) according to histology grade: (A) anaplastic astrocytoma (n = 26), (B) glioblastoma (n = 105).

Figure 2

Representative images for the case of GB with lower MIB-1 LI. A 76-years female patient with GB showing a lower MIB-1 LI (21%) that recurred in the central region. (A) A postcontrast MR image (T1 weighted) before surgery. (B) A postcontrast MR image (T1 weighted) after a gross total removal. (C) Treatment planning CT image showing the 95% isodose curve (yellow), the 80% isodose curve (green), and the 20% isodose curve (blue). (D) A postcontrast MR image (T1 weighted) at 4 months after completing radiotherapy showing a recurrence tumor that developed in the central. (E) Immunohistochemical analyses (×200).

Figure 3

Representative images for the case of GB with higher MIB-1 LI. A 24-years male patient with GB showing a higher MIB-1 LI (79%) that recurred in the distant region. (A) A postcontrast MR image (T1 weighted) before surgery (B) A postcontrast MR image (T1 weighted) after a gross total removal. (C) Treatment planning CT image showing the 95% isodose curve (yellow), 80% isodose curve (green), and the 20% isodose curve (blue). (D) A postcontrast MR image (T1 weighted) at 11 months after completion of radiation showing a recurrence tumor that developed in the distant. (E) Immunohistochemical analyses (×200).

Figure 4

Distributions of MIB-1 LI. Distributions of MIB-1 LI in patients with AA (n = 22) and in patients with GB (n = 79).