This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, P. Articles by Buckner, J. Search for Related Content PubMed Articles by Brown, P. Articles by Buckner, J. Related Articles Related Editorial Related Correspondence

In Reply:

Mayo Clinic, Rochester, MN

We appreciate the opportunity to respond and are pleased to see our manuscript generated such interest, including this letter and a guest editorial [1]. We agree with the correspondents, as clearly stated in our manuscript, that the mini-mental state examination (MMSE) is an insensitive screening tool [2]. Nonetheless, decreased MMSE scores do indicate dementia, are sensitive enough to predict tumor progression before changes are noted on imaging [3], and predict a worse survival in brain tumor patients [4,5]. In addition, our results, using MMSE to evaluate for neurocognitive deterioration, are consistent with the literature finding devastating neurocognitive deficits caused by radiation to be quite rare after focal, conventionally fractionated radiotherapy using modern techniques in adults. Several studies have prospectively performed extensive neuropsychologic testing (as advocated by the correspondents) on adult patients with low-grade brain tumors after radiotherapy and have not found significant neurocognitive deficits when compared with either baseline or a cohort of patients with low-grade brain tumors not treated with radiotherapy [6–9]. We also performed extensive neuropsychologic testing at baseline and serial evaluations on an initial cohort of 20 patients from the same group of patients followed with MMSE alone [10]. Concordant with the results we obtained with the MMSE, we found no evidence of significant neurocognitive deficits even with extensive testing. The primary cause of cognitive deficits in patients with brain tumors seems to be the tumor itself and tumor progression rather than conventional radiotherapy delivered with modern techniques [3,7,11].

Klein and Heimans questioned the absence of analysis of dose fraction. Although the randomization of total dose was analyzed, the dose fraction was 1.8 Gy for both the 50.4- and 64.8-Gy arms, and therefore, dose fraction was not analyzed. Interestingly, this relatively smaller dose fraction, along with the comparatively more advanced radiotherapy techniques in practice (three-dimensional conformal, or magnetic resonance imaging-based or computed tomography-based planning) at that time, could account for the low incidence of neurocognitive decline seen in our patients [11].

We do agree with the correspondents that more extensive "neurocognitive test batteries" are needed [1]. However, when formulating this test battery it needs to be in the context of a hurried, busy clinical practice of an oncologist, who is typically without extensive training in delivering these neurocognitive tests. Often clinical expertise in neurocognitive testing is not readily available to many patients, because of either geography or financial considerations. Therefore, we strongly encourage our neuro-oncology colleagues to draft and prospectively test these batteries, striking a balance between the need for sophisticated and discriminating neurocognitive tests, financial and geographical constraints, and the practice of a busy clinician [12].

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Meyers CA, Wefel JS: The use of the mini-mental state examination to assess cognitive functioning in cancer trials: No ifs, ands, buts, or sensitivity. J Clin Oncol 21:3557–3558, 2003[Free Full Text]

2. Brown PD, Buckner JC, O'Fallon JR, et al: Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the Folstein mini-mental state examination. J Clin Oncol 21:2519–2524, 2003[Abstract/Free Full Text]

3. Taylor BV, Buckner JC, Cascino TL, et al: Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma. J Clin Oncol 16:2195–2201, 1998[Abstract]

4. Shaw E, Arusell R, Scheithauer B, et al: Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: Initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol 20:2267–2276, 2002[Abstract/Free Full Text]

5. Murray KJ, Scott C, Zachariah B, et al: Importance of the mini-mental status examination in the treatment of patients with brain metastases: A report from the Radiation Therapy Oncology Group protocol 91–04. Int J Radiat Oncol Biol Phys 48:59–64, 2000[CrossRef][Medline]

6. Vigliani MC, Sichez N, Poisson M, et al: A prospective study of cognitive functions following conventional radiotherapy for supratentorial gliomas in young adults: 4-year results. Int J Radiat Oncol Biol Phys 35:527–533, 1996[CrossRef][Medline]

7. Torres IJ, Mundt AJ, Sweeney PJ, et al: A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors. Neurology 60:1113–1118, 2003[Abstract/Free Full Text]

8. Armstrong CL, Hunter JV, Ledakis GE, et al: Late cognitive and radiographic changes related to radiotherapy: Initial prospective findings. Neurology 59:40–48, 2002[Abstract/Free Full Text]

9. Steinvorth S, Welzel G, Fuss M, et al: Neuropsychological outcome after fractionated stereotactic radiotherapy (FRST) for base of skull meningiomas: A prospective 1-year follow-up. Radiother Oncol 69:177–182, 2003[CrossRef][Medline]

10. Laack N, Brown P, Furth A, et al: Neurocognitive function after radiotherapy (RT) for supratentorial low-grade gliomas (LGG): Results of a North Central Cancer Treatment Group (NCCTG) prospective study. Int J Radiat Oncol Biol Phys 57:S134, 2003 (suppl 2)[Medline]

11. Klein M, Heimans JJ, Aaronson NK, et al: Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: A comparative study. Lancet 360:1361–1368, 2002[CrossRef][Medline]

12. Regine WF, Schmitt FA, Scott C, et al: Feasibility of neurocognitive outcome evaluations in patients with brain metastases in a multi-institutional cooperative group setting: Results of Radiation Therapy Oncology Group (RTOG) Trial BR-0018. Int J Radiat Oncol Biol Phys 54:49, 2002 (abstr 79)

Related Editorial

• The Use of the Mini-Mental State Examination to Assess Cognitive Functioning in Cancer Trials: No Ifs, Ands, Buts, or Sensitivity
  Christina A. Meyers and Jeffrey S. Wefel
  JCO 2003 21: 3557-3558 [Full Text]

Related Correspondence

• The Measurement of Cognitive Functioning in Low-Grade Glioma Patients After Radiotherapy
  Martin Klein and Jan J. Heimans
  JCO 2004 22: 966-967 [Full Text]

This article has been cited by other articles:

				C. A. Meyers and P. D. Brown Role and Relevance of Neurocognitive Assessment in Clinical Trials of Patients With CNS Tumors J. Clin. Oncol., March 10, 2006; 24(8): 1305 - 1309. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, P. Articles by Buckner, J. Search for Related Content PubMed Articles by Brown, P. Articles by Buckner, J. Related Articles Related Editorial Related Correspondence