A phase I study of short-course accelerated whole brain radiation therapy for multiple brain metastases

Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e463-8. doi: 10.1016/j.ijrobp.2012.06.023. Epub 2012 Aug 18.


Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases.

Methods and materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded.

Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%).

Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / radiation effects
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / secondary*
  • Cohort Studies
  • Dose Fractionation, Radiation
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose*
  • Middle Aged
  • Multivariate Analysis
  • Quality of Life
  • Radiation Injuries / complications
  • Radiation Injuries / pathology
  • Radiotherapy Planning, Computer-Assisted / methods
  • Severity of Illness Index
  • Skin / radiation effects
  • Young Adult