Preoperative stereotactic radiosurgery before planned resection of brain metastases: updated analysis of efficacy and toxicity of a novel treatment paradigm

Restricted access

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.

ABBREVIATIONS DBF = distant brain failure; GPA = graded prognostic index; GTR = gross-total resection; GTV = gross tumor volume; HR = hazard ratio; IQR = interquartile range; LMD = leptomeningeal disease; LR = local recurrence; NSCLC = non–small cell lung cancer; OS = overall survival; RCC = renal cell carcinoma; RN = radiation necrosis; RT = radiotherapy; SRS = stereotactic radiosurgery; STR = subtotal resection; WBRT = whole-brain RT.

Downloadable materials

  • Supplemental Figs. 1 and 2 (PDF 475 KB)

Article Information

Correspondence Roshan S. Prabhu: Southeast Radiation Oncology Group, Levine Cancer Institute, Charlotte, NC. roshansprabhu@gmail.com.

INCLUDE WHEN CITING Published online December 14, 2018; DOI: 10.3171/2018.7.JNS181293.

Disclosures Dr. Ward reports receipt of financial compensation (paid to Southeast Radiation Oncology Group) for participation on the AstraZeneca Advisory Board.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    SRS dose versus gross tumor volume. The best-fit regression was logarithmic. R2 = coefficient of determination.

  • View in gallery

    Cumulative incidence of cavity local recurrence with competing risk of death. Curve truncated at 3 years.

  • View in gallery

    Cumulative incidence of the composite endpoint of cavity local recurrence, leptomeningeal disease recurrence, or symptomatic radiation necrosis with competing risk of death. Curve truncated at 3 years.

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 362 362 72
Full Text Views 194 194 34
PDF Downloads 137 137 18
EPUB Downloads 0 0 0

PubMed

Google Scholar