The Effect of the Addition of Chemotherapy to Radiotherapy on Cognitive Function in Patients with Low Grade Glioma: Secondary Analysis of RTOG 98-02 Open Access

Abstract

Purpose: The addition of PCV (procarbazine, CCNU, vincristine) chemotherapy to radiotherapy (RT) for patients with WHO grade II glioma improves progression free survival (PFS), without a significant improvement in overall survival (OS). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long term survival.

Methods: Two hundred fifty-one patients with World Health Organization (WHO) grade II glioma and age >40 with any extent of resection, or age <40 with subtotal resection/biopsy were randomized to RT (54 Gy) or RT + PCV. One hundred eleven patients with age <40 and gross total resection were observed on a related phase II study. CF was assessed by mini-mental status exam (MMSE) at baseline and years 1, 2, 3, and 5. The primary analysis was between the RT and RT + PCV randomized arms. All MMSE score changes were comparisons between the key evaluation score to baseline MMSE score. The proportion of patients with MMSE decline (defined as score decrease >3 points) as a categorical variable was analyzed using the Fisher exact test. MMSE score change over time as a continuous measure was analyzed using linear mixed effects model, utilizing both univariate and multivariate models to adjust for potential confounding variables.

Results: Overall, very few patients experienced significant decline in MMSE score, with a median follow-up time of 9.7 years for alive patients. There were no significant differences in the proportion of patients experiencing MMSE decline between study arms at any time point or longitudinally over time. Patients in both randomized arms experienced a statistically significant average MMSE score increase over time, with no difference between arms. Patients with baseline MMSE score <27 were numerically more likely to experience significant MMSE gain than decline.

Conclusions: The MMSE is a relatively insensitive tool and subtle changes in CF may have been missed. However, the addition of PCV to RT did not result in significantly higher rates of MMSE decline than RT alone. The addition of PCV chemotherapy to RT significantly improves PFS without excessive CF detriment over RT alone for patients with low grade glioma.

Table of Contents

Table of Contents

Introduction pages 1-2

Background pages 3-4

Methods pages 5-9

Results pages 10-13

Discussion pages 14-18

References pages 19-22

Tables pages 23-46

List of Tables:

Table 1. Randomized Patient Characteristics from RTOG 98-02 Table 2. MMSE Assessment Compliance Table 3. Characteristics for Eligible Patients With and Without MMSE at Year 1 Table 4. Characteristics for Eligible Patients With and Without MMSE at Year 2 Table 5. Characteristics for Eligible Patients With and Without MMSE at Year 3 Table 6. Characteristics for Eligible Patients With and Without MMSE at Year 5 Table 7. Characteristics of Eligible Patients with MMSE by Treatment Arm at Year 1 Table 8. Characteristics of Eligible Patients with MMSE by Treatment Arm at Year 2 Table 9. Characteristics of Eligible Patients with MMSE by Treatment Arm at Year 3 Table 10. Characteristics of Eligible Patients with MMSE by Treatment Arm at Year 5 Table 11. Patient Characteristics by Baseline MMSE Score Table 12. Categorical Change in MMSE Score by Baseline MMSE Table 13. Categorical Change in MMSE Score by Treatment Arm Table 14. Univariate Mixed Effects Model for MMSE Change Over Time for Randomized Patients (n=238) Table 15. Multivariate Mixed Effects Model for MMSE Change Over Time for Randomized Patients (n=238)

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research Curriculum Program
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Oncology
Keyword	radiation therapy low grade glioma cognitive function glioma chemotherapy
Committee Chair / Thesis Advisor	Shu, Hui-Kuo, Emory University Manatunga, Amita, Emory University
Committee Members	Ziegler, Thomas R, Emory University Bruce, Beau Benjamin, Emory University

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