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  • Journal of Neurosurgery x
  • By Author: Asher, Anthony L. x
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Roshan S. Prabhu, Katherine R. Miller, Anthony L. Asher, John H. Heinzerling, Benjamin J. Moeller, Scott P. Lankford, Robert J. McCammon, Carolina E. Fasola, Kirtesh R. Patel, Robert H. Press, Ashley L. Sumrall, Matthew C. Ward and Stuart H. Burri

OBJECTIVE

Preoperative stereotactic radiosurgery (SRS) is a feasible alternative to postoperative SRS and may lower the risk of radiation necrosis (RN) and leptomeningeal disease (LMD) recurrence. The study goal was to report the efficacy and toxicity of preoperative SRS in an expanded patient cohort with longer follow-up period relative to prior reports.

METHODS

The records for patients with brain metastases treated with preoperative SRS and planned resection were reviewed. Patients with classically radiosensitive tumors, planned adjuvant whole brain radiotherapy, or no cranial imaging at least 1 month after surgery were excluded. Preoperative SRS dose was based on lesion size and was reduced approximately 10–20% from standard dosing. Surgery generally followed within 48 hours.

RESULTS

The study cohort consisted of 117 patients with 125 lesions treated with single-fraction preoperative SRS and planned resection. Of the 117 patients, 24 patients were enrolled in an initial prospective trial; the remaining 93 cases were consecutively treated patients who were retrospectively reviewed. Most patients had a single brain metastasis (70.1%); 42.7% had non–small cell lung cancer, 18.8% had breast cancer, 15.4% had melanoma, and 11.1% had renal cell carcinoma. Gross total resection was performed in 95.2% of lesions. The median time from SRS to surgery was 2 days, the median SRS dose was 15 Gy, and the median gross tumor volume was 8.3 cm3. Event cumulative incidence at 2 years was as follows: cavity local recurrence (LR), 25.1%; distant brain failure, 60.2%; LMD, 4.3%; and symptomatic RN, 4.8%. The median overall survival (OS) and 2-year OS rate were 17.2 months and 36.7%, respectively. Subtotal resection (STR, n = 6) was significantly associated with increased risk of cavity LR (hazard ratio [HR] 6.67, p = 0.008) and worsened OS (HR 2.63, p = 0.05) in multivariable analyses.

CONCLUSIONS

This expanded and updated analysis confirms that single-fraction preoperative SRS confers excellent cavity local control with very low risk of RN or LMD. Preoperative SRS has several potential advantages compared to postoperative SRS, including reduced risk of RN due to smaller irradiated volume without need for cavity margin expansion and reduced risk of LMD due to sterilization of tumor cells prior to spillage at the time of surgery. Subtotal resection, though infrequent, is associated with significantly worse cavity LR and OS. Based on these results, a randomized trial of preoperative versus postoperative SRS is being designed.

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Editorial

Clinical data simplified

John H. Sampson, James E. Herndon II, Roger E. McLendon, Vic Hasselblad, Anthony L. Asher, Matthew J. McGirt and Eric D. Peterson

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Lisa R. Rogers, Jack P. Rock, Allen K. Sills, Michael A. Vogelbaum, John H. Suh, Thomas L. Ellis, Volker W. Stieber, Anthony L. Asher, Robert W. Fraser, Judith S. Billingsley, Paul Lewis, Dawid Schellingerhout, Brain Metastasis Study Group and Edward G. Shaw

Object

The aim of this study was to evaluate the effectiveness of brachytherapy using the GliaSite Radiation Therapy System in patients with a newly diagnosed resected single brain metastasis. The primary end point of the study was local tumor control. The secondary end points included patient survival, distant brain recurrence, quality of life, and treatment toxicity.

Methods

The authors conducted a prospective multiinstitutional phase II study of GliaSite brachytherapy prescribed at a 60-Gy dose administered to a 1-cm depth after resection of a single brain metastasis. No whole-brain radiation therapy was given. Patients were assessed at 1 and 3 months after brachytherapy and every 3 months thereafter for up to 2 years.

Seventy-one patients were enrolled at 13 centers. A GliaSite balloon catheter was implanted in 62 patients. Fifty-four patients received brachytherapy. The median patient age was 60 years. The most common tumor (54%) was non–small cell lung cancer. Fifty-seven percent of patients had brain metastasis only, whereas 43% had extracranial metastasis. The median final administered dose was 60 Gy. The magnetic resonance imaging–determined local control rate, based on several different methods, was 82 to 87%. Both the median patient survival time and the median duration of functional independence were 40 weeks. Among the 35 patients who died, the cause of death was neurological in 11%. Thirteen patients underwent reoperation for suspected tumor recurrence or radiation necrosis, and histological diagnoses included radiation necrosis without tumor (nine patients), radiation necrosis mixed with tumor (two patients), and tumor only (two patients). Extracranial metastasis, tumor size, and radiation necrosis were significant factors affecting patient survival.

Conclusions

In patients with a resected single brain metastasis, GliaSite brachytherapy leads to a local control rate, median patient survival time, and duration of functional independence similar to those achieved with resection plus whole-brain radiation therapy.