title: Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in Patients With Brain Oligometastases: A Phase 1 Study (ISIDE-BM-1).
abstract: To investigate the maximum tolerated dose of intensity modulated radiation therapy simultaneous integrated boost whole-brain radiation therapy for palliative treatment of patients with <5 brain metastases using a standard linear accelerator.
  
  
  
  The whole brain plus 3-mm margin was defined as the planning target volume (PTVwb), whereas each brain metastasis, defined as the contrast-enhancing tumor on MRI T1 scans, plus a 3-mm isotropic margin, was defined as metastases PTV (PTVm). Radiation therapy was delivered in 10 daily fractions (2 weeks). Only the dose to PTVmwas progressively increased in the patient cohorts (35 Gy, 40 Gy, 45 Gy, 50 Gy), whereas the PTVwbwas always treated with 30 Gy (3 Gy per fraction) in all patients. The dose-limiting toxicity was evaluated providing that 3 months of follow-up had occurred after the treatment of a 6-patient cohort.
  
  
  
  Thirty patients were enrolled in the study (dose PTVm: 35 Gy, 8 patients; 40 Gy, 6 patients; 45 Gy, 6 patients; 50 Gy, 10 patients). The number of treated brain metastases was 1 in 18 patients, 2 in 5 patients, 3 in 6 patients, and 4 in 1 patient. Three patients experienced dose-limiting toxicity: 1 patient at dose level 2 presented grade 3 (G3) skin toxicity; 1 patient at dose level 4 presented G3 neurologic toxicity; and 1 patient at the same level showed brain hemorrhage. Most patients showed G1 to 2 acute toxicity, in most cases skin (n=19) or neurologic (n=10). Twenty-seven were evaluable for response: 6 (22%) stable disease, 18 (67%) partial response, and 3 (11%) complete response. Median survival and 1-year overall survival were 12 months and 53%, respectively. No patient showed late toxicity.
  
  
  
  In this first prospective trial on the use of intensity modulated radiation therapy simultaneous integrated boost delivered with a standard linear accelerator in patients with brain oligometastases, a boost dose up to 50 Gy in 10 fractions was tolerable according to the study design.
authors.affiliation: Radiotherapy Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II," Catholic University of Sacred Heart, Campobasso, Italy.
authors.forename: Marica
authors.initials: M
authors.lastname: Ferro
authors.affiliation: Department of Radiotherapy, Fondazione Policlinico Universitario "A. Gemelli," Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Chiesa
authors.affiliation: Radiotherapy Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II," Catholic University of Sacred Heart, Campobasso, Italy. Electronic address: gmacchia@rm.unicatt.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Macchia
authors.affiliation: Medical Physics Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II," Catholic University of Sacred Heart, Campobasso, Italy.
authors.forename: Savino
authors.initials: S
authors.lastname: Cilla
authors.affiliation: Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bertini
authors.affiliation: Radiotherapy Department, Ospedale Bellaria, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Frezza
authors.affiliation: Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Farioli
authors.affiliation: Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cammelli
authors.affiliation: Department of Radiotherapy, Fondazione Policlinico Universitario "A. Gemelli," Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Balducci
authors.affiliation: Medical Physics Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II," Catholic University of Sacred Heart, Campobasso, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ianiro
authors.affiliation: Medical Physics Unit, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Angelini
authors.affiliation: Medical Physics Unit, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Compagnone
authors.affiliation: Department of Radiotherapy, Fondazione Policlinico Universitario "A. Gemelli," Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.affiliation: Radiotherapy Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II," Catholic University of Sacred Heart, Campobasso, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.affiliation: Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary*; D003287:Contrast Media; D016371:Cranial Irradiation / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010166:Palliative Care / Q000379:methods; D010315:Particle Accelerators; D056888:Patient Positioning; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D003287:Contrast Media