Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study

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Object

Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome. However, extended surgery may increase morbidity. The randomized Phase III 5-aminolevulinic acid (ALA) study investigated 5-ALA–induced fluorescence as a tool for improving resections. An interim analysis demonstrated more frequent complete resections with longer progression-free survival (PFS). However, marginal differences were found regarding neurological deterioration and the frequency of additional therapies. Presently, the authors focus on the latter aspects in the final study population, and attempt to determine how safety might be affected by cytoreductive surgery.

Methods

Patients with malignant gliomas were randomized for fluorescence-guided (ALA group) or conventional white light (WL) (WL group) microsurgery. The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group. Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS. Among secondary outcome measures, the National Institutes of Health Stroke Scale (NIH-SS) score and the Karnofsky Performance Scale (KPS) score were used for assessing neurological function.

Results

More frequent complete resections and improved PFS were confirmed, with higher median residual tumor volumes in the WL group (0.5 vs 0 cm3, p = 0.001). Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours. Patients at risk were those with deficits unresponsive to steroids. No differences were found in the KPS score. Regarding outcome, a combined end point of risks and neurological deficits was attempted, which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group. Interestingly, the cumulative incidence of repeat surgery was significantly reduced in ALA patients. When stratified by completeness of resection, patients with incomplete resections were quicker to deteriorate neurologically (p = 0.0036).

Conclusions

Extended resections performed using a tool such as 5-ALA–derived tumor fluorescence, carries the risk of temporary impairment of neurological function. However, risks are higher in patients with deficits unresponsive to steroids.

Abbreviations used in this paper: AE = adverse event; KPS = Karnofsky Performance Scale; NIH-SS = National Institutes of Health Stroke Scale; PFS = progression-free survival; SAE = serious AE; WL = white light; 5-ALA = 5-aminolevulinic acid.

Article Information

* See Appendix 2 for a complete list of study participants.

Address correspondence to: Walter Stummer, M.D., Department of Neurosurgery, University of Münster, Albert-Schweitzer Strasse 33, 48149 Münster, Germany. email: walter.stummer@ukmuenster.de.

Please include this information when citing this paper: published online April 16, 2010; DOI: 10.3171/2010.3.JNS097.

© AANS, except where prohibited by US copyright law."

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Figures

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    Chart showing the cumulative incidence of repeat surgery. m = month; n.a. = not applicable.

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    Kaplan-Meier curves showing PFS by using a combined end point analysis adapted from Macdonald et al. Progression is defined as a > 25% increase in size of enhancing tumor or any new tumor on MR imaging studies, or neurological worsening (that is, increase in the NIH-SS score of ≥ 1 compared with the preceding visit) in case of stable or increased use of steroids.

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    Time from randomization to NIH-SS deterioration (≥ 1 point) with stable/increased use of steroids—event-free survival—Kaplan-Meier estimates (death/radiological progression censored). CR = complete resection; IR = incomplete resection.

References

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