Background: The addition of PCV chemotherapy to radiotherapy (RT) for patients with WHO grade II glioma improves progression free survival (PFS) and overall survival (OS), for patients surviving at least 2 years (Shaw, J Clin Oncol 26: 2008). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long term survival. Methods: 251patients with WHO grade II glioma and age > 40 with any extent of resection, or age < 40 with subtotal resection/biopsy were randomized to RT (54Gy) or RT + PCV. 111 patients with age < 40 and gross total resection were observed. CF was assessed by mini-mental status exam (MMSE)at baseline and years 1, 3, and 5 for patients without progression. Change in MMSE score from baseline of > 3 points was considered clinically significant. 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. The table below summarizes MMSE change from baseline over time. Neither baseline MMSE score nor change in MMSE at year 1 significantly predicted for OS or PFS, but there was a trend towards worse OS for patients with MMSE loss of ≥ 2 points [HR 1.73, 95% CI (0.86, 3.47), p=0.12]. Conclusions: The MMSE is a relatively insensitive tool that has not been validated in patients receiving cranial RT, and subtle changes in CF may have been missed. However, the addition of PCV to RT for low grade glioma did not result in significantly higher rates of MMSE decline than RT alone or observation. There was a trend towards an MMSE decline of ≥ 2 points at year 1 predicting for worse OS.   

	Observation (%)	RT (%)	RT + PCV (%)
Significant MMSE decline
Year 1	0 / 62 (0)	5 / 74 (6.8)	2 / 51 (3.9)
Year 3	0 / 44 (0)	1 / 48 (2.1)	0 / 43 (0)
Year 5	0 / 27 (0)	0 / 22 (0)	2 / 25 (8)
No MMSE change
Year 1	60 / 62 (96.8)	66 / 74 (89.2)	44 / 51 (86.3)
Year 3	44 / 44 (100)	45 / 48 (93.8)	38 / 43 (88.4)
Year 5	27 / 27 (100)	21 / 22 (95.5)	20 / 25 (80)
Significant MMSE gain
Year 1	2 / 62 (3.2)	3 / 74 (4.1)	5 / 51 (9.8)
Year 3	0 / 44 (0)	2 / 48 (4.2)	5 / 43 (11.6)
Year 5	0 / 27 (0)	1 / 22 (4.5)	3 / 25 (12)