title: Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: Local tumour control and survival.
abstract: OBJECTIVE
  Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique.
  
  
  METHODS
  Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D98% to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI.
  
  
  RESULTS
  Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73%. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3%. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60%. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. Dmean to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance.
  
  
  CONCLUSIONS
  HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration.
authors.affiliation: Department of Radiation Oncology, University Medical Center Freiburg, Robert-Koch-Str. 3, 79106, Freiburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Oehlke
authors.forename: David
authors.initials: D
authors.lastname: Wucherpfennig
authors.forename: Franziska
authors.initials: F
authors.lastname: Fels
authors.forename: Lars
authors.initials: L
authors.lastname: Frings
authors.forename: Karl
authors.initials: K
authors.lastname: Egger
authors.forename: Astrid
authors.initials: A
authors.lastname: Weyerbrock
authors.forename: Vesna
authors.initials: V
authors.lastname: Prokic
authors.forename: Carsten
authors.initials: C
authors.lastname: Nieder
authors.forename: Anca-Ligia
authors.initials: AL
authors.lastname: Grosu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001930:Brain Injuries / Q000175:diagnosis / Q000209:etiology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000532:radiotherapy* / Q000556:secondary*; D016371:Cranial Irradiation / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D006624:Hippocampus / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000517:prevention & control*; D059351:Organ Sparing Treatments / Q000009:adverse effects / Q000379:methods*; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology; D015996:Survival Rate; D016896:Treatment Outcome