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Is There a Tumor Volume Threshold for Postradiosurgical Symptoms? A Single-Institution Analysis

Kuhn, Elizabeth N. MD*,‡; Taksler, Glen B. PhD§; Dayton, Orrin MD; Loganathan, Amritraj MD; Bourland, Daniel PhD; Tatter, Stephen B. MD, PhD; Laxton, Adrian W. MD; Chan, Michael D. MD

doi: 10.1227/NEU.0000000000000519
Research-Human-Clinical Studies

BACKGROUND: Single-fraction radiosurgery may carry a higher risk of symptomatic peritumoral edema than conventionally fractionated radiotherapy, with a reported incidence of 2.5% to 37%. Previous research has shown that larger tumor volume and margin dose >14 Gy are associated with increased risk of toxicity. Parasagittal location has been associated with toxicity in some studies, but not in others.

OBJECTIVE: To determine risk factors for and patterns of postradiosurgical symptoms (PRS).

METHODS: This single-institution retrospective chart review included 282 stereotactic radiosurgery procedures for an intracranial meningioma from January 1999 to March 2011. PRS were assessed by using the Common Terminology Criteria for Adverse Events (Version 4.0). Statistical analyses were conducted by using the 194 procedures for which treatment plans were available.

RESULTS: PRS were observed after 65 procedures (23%); 35 (12%) were grade 2 or higher. Posttreatment edema occurred in 21% of grade I PRS, 68% of grade II PRS, and 71% of grade III PRS. Tumor volume ≥7.1 cc (adjusted hazards ratio = 4.9, P = .02), prior external beam radiotherapy (adjusted hazards ratio = 2.6, P = .03), and histological grade (P = .005) predicted PRS. On multivariate analysis, parasagittal location was not predictive of PRS, although skull base location predicted a lower risk of symptomatic posttreatment edema (adjusted hazards ratio = 0.133, P = .02).

CONCLUSION: In our series, prior external beam radiotherapy, tumor volume, and tumor grade are risk factors for PRS, while pretreatment edema approached statistical significance. Peritumoral edema is the predominant mechanism of significant PRS, and skull base tumors have a lower risk of posttreatment edema.

ABBREVIATIONS: CI, confidence interval

CTCAE, Common Terminology Criteria for Adverse Events

EBRT, external beam radiotherapy

PRS, postradiosurgical symptoms

SRS, stereotactic radiosurgery

WHO, World Health Organization

*Department of Neurosurgery, University of Alabama at Birmingham Medical Center, Birmingham, Alabama;

Department of Neurosurgery, Wake Forest School of Medicine, Winston–Salem, North Carolina;

§Medicine Institute, Cleveland Clinic, Cleveland, Ohio;

Department of Neurosurgery, University of Florida Health, Gainesville, Florida; and

Department of Radiation Oncology, Wake Forest School of Medicine, Winston–Salem, North Carolina

Correspondence: Elizabeth N. Kuhn, MD, 1720 2nd Ave S, FOT 1062, Birmingham, AL 35294-3410. E-mail:

Received January 31, 2014

Accepted June 18, 2014

Copyright © by the Congress of Neurological Surgeons