title: A minimally invasive treatment option for large metastatic brain tumors: long-term results of two-session Gamma Knife stereotactic radiosurgery.
abstract: BACKGROUND
  Large brain metastases (BM) remain a significant cause of morbidity and death for cancer patients despite current advances in multimodality therapies. The goal of the present study was to evaluate the efficacy and limitations of 2-session Gamma Knife stereotactic radiosurgery (SRS) for patients with large BM.
  
  
  METHODS
  This is a prospective, open-label and single arm study analyzing 58 consecutive patients who received 2-session SRS for large BM (≥ 10 mL). The median age was 66 years, and the median Karnofsky performance status (KPS) score was 70. SRS was the initial treatment in 51 large tumors (84%) and was used as salvage after failed prior treatments for 10 tumors (16%). The fraction protocol was 20-30 Gy given in 2 fractions with 3-4 weeks between fractions. Overall survival (OS) and neurological death (ND), local tumor control and KPS were analyzed.
  
  
  RESULTS
  The median follow-up time was 9.0 months. One- and 2-year OS rates were 47% and 20%, respectively. The median OS time was 11.8 months (95% CI: 5.5-15.6). The causes of death were intracranial local progression in 5 cases, meningeal carcinomatosis in 3 and progression of the primary lesion in 39. One- and 2-year ND-free survival rates were 91% and 84%, respectively. In 52 of 61 large BM (85%) with sufficient radiological follow-up data, 6- and 12-month local tumor control rates were 85% and 64%, respectively. The mean KPS improved from 70 at the 1st SRS to 82 at the 2nd; the first follow-up mean KPS was 87 (P < 0.001). Symptomatic radiation injury developed and required conservative treatment in 3 patients (5%).
  
  
  CONCLUSIONS
  Long-term follow-up showed that two-session Gamma Knife SRS achieved durable tumor control rates as well as acceptable treatment-related morbidity. This treatment method may potentially merit being offered to patients with large BM who are in poor condition or are otherwise ineligible for standard care.
authors.affiliation: Division of Radiation Oncology, Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan. yomoshoji@gmail.com.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yomo
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D019060:Minimally Invasive Surgical Procedures; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D009367:Neoplasm Staging; D009369:Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011379:Prognosis; D011446:Prospective Studies; D016634:Radiosurgery; D011879:Radiotherapy Dosage; D015996:Survival Rate