A Phase II Trial of Concurrent Temozolomide and Hypofractionated Stereotactic Radiotherapy for Complex Brain Metastases

Nan Bi, Yuchao Ma, Jianping Xiao, Hongmei Zhang, Yingjie Xu, Yuan Tian, Junling Li, Ye Zhang, Qingfeng Liu, Kai Wang, Lei Deng, Wenqing Wang, Xuesong Chen, Feng Liu, Ruizhi Zhao, Siran Yang, Xiaodong Huang, Junlin Yi, Chen Hu, Yexiong Li

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Complex brain metastases (BMs), such as large lesions, lesions within or close to eloquent locations, or multiple recurrent/progressive BMs, remain the most challenging forms of brain cancer because of decreased intracranial control rates and poor survival. In the present study, we report the results from a single institutional phase II trial of concurrent temozolomide (TMZ) with hypofractionated stereotactic radiotherapy (HFSRT) in patients with complex brain metastases, including assessment of its feasibility and toxicity. Patients and Methods: Fifty-four patients with histologically proven primary cancer and complex BMs were enrolled between 2010 and 2015. All the patients were treated with concurrent HFSRT and TMZ (administrated orally at a dosage of 75 mg/m2 per day for at least 20 days). The primary endpoint was overall survival (OS). Results: The median follow-up time was 30.6 months. The local control rates at 1 and 2 years were 96% and 82%, respectively. The median OS was 17.4 months (95% confidence interval [CI], 12.6–22.2), and the OS rates at 1 and 2 years were 65% (95% CI, 52%–78%) and 33% (19%–47%). Only six patients (15.8%) died of intracranial disease. The median brain metastasis-specific survival was 46.9 months (95% CI, 35.5–58.4). Treatment-related grade 3–4 adverse events were rare and included one grade 3 hematological toxicity and two grade 3 liver dysfunctions. Conclusion: Treatment using HFSRT concurrent with TMZ was well tolerated and could significantly extend OS compared with historical controls in complex BMs. Large randomized clinical trials are warranted. Trial registration ID: NCT02654106. Implications for Practice: The treatment using hypofractionated stereotactic radiotherapy concurrent with temozolomide appeared to be safe and could significantly extend overall survival compared with historical control in complex brain metastases. Large randomized clinical trials are warranted to verify our results.

Original languageEnglish (US)
Pages (from-to)e914-e920
JournalOncologist
Volume24
Issue number9
DOIs
StatePublished - Sep 1 2019

Keywords

  • Complex brain metastasis
  • Concurrent chemoradiotherapy
  • Hypofractionated stereotactic radiotherapy
  • Temozolomide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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