Surgery Followed by Hypofractionated Radiosurgery on the Tumor Bed in Oligometastatic Patients With Large Brain Metastases. Results of a Phase 2 Study

Pierina Navarria, Federico Pessina, Elena Clerici, Davide Franceschini, Lorenzo Gabriel Gay, Fiorenza De Rose, Ilaria Renna, Giuseppe D'Agostino, Ciro Franzese, Tiziana Comito, Stefano Tomatis, Marco Conti Nibali, Antonella Leonetti, Guglielmo Puglisi, Lorenzo Bello, Marta Scorsetti

Research output: Contribution to journalArticlepeer-review


PURPOSE: This prospective phase II study assessed safety and feasibility of surgery followed by hypofractionated radiosurgery (HSRS) on the tumor bed in oligometastatic patients with single large brain metastases (BMs).

METHODS AND MATERIALS: Between June 2015 and May 2018, 101 patients were enrolled. Oligometastatic disease was defined by a maximum of 5 extracranial metastatic lesions. HSRS was performed within 1 month of surgery and consisted of 30 Gy in 3 fractions. Local control, occurrence of new BMs, overall survival, and treatment-related toxicities were assessed.

RESULTS: At a median follow-up time of 26 months, local recurrence occurred in 6 patients (5.9%). Six-month, 1-year, and 2-year local control rates were 100%, 98.9% ± 1.1%, and 85.9% ± 0.6%, respectively. New BMs occurred in 39 patients (38.6%); median brain distant progression time and 6-month, 1-year, and 2-year brain distant progression rates were 39 months (95% CI, 19-39 months), 17% ± 3.7%, 31.4% ± 4.8%, and 42.5% ± 5.9%, respectively. At the last observation time, 50 patients (49.5%) were alive and 51 (50.5%) were dead; 10 patients died owing to neurologic causes and 40 as a result of systemic progression. Median overall survival time and 6-month, 1-year, and 2-year overall survival rates were 22 months (95% CI, 20-30 months), 95% ± 2.1%, 81.9% ± 3.8%, and 46.6% ± 6%, respectively. Infratentorial site, residual tumor volume, longer interval time between primary diagnosis and occurrence of BMs, and oligometastatic disease status significantly influenced outcome. Grade 2 to 3 radionecrosis occurred in 26 patients. Neurocognitive functions remained stable or, in some cases, improved.

CONCLUSIONS: Surgery followed by HSRS on the tumor bed is a safe and effective approach, affording good brain control with acceptable toxicities. As for extracranial metastatic sites, patients with BMs can benefit from local ablative treatment in the context of an oligometastatic disease.

Original languageEnglish
Pages (from-to)1095-1105
Number of pages11
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number5
Publication statusPublished - Dec 1 2019


  • Adult
  • Aged
  • Brain Neoplasms/mortality
  • Cause of Death
  • Combined Modality Therapy/methods
  • Disease Progression
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm, Residual
  • Neurocognitive Disorders/diagnosis
  • Postoperative Complications/etiology
  • Prospective Studies
  • Radiation Dose Hypofractionation
  • Radiation Injuries/etiology
  • Radiosurgery/methods
  • Survival Rate
  • Time Factors
  • Tumor Burden


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