title: Stereotactic radiosurgery (SRS) with volumetric modulated arc therapy (VMAT): interim results of a multi-arm phase I trial (DESTROY-2).
abstract: OBJECTIVE
  To present the interim results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumours in different extracranial sites.
  
  
  METHODS
  Patients were enrolled in different arms according to tumour site and clinical stage, and sequentially assigned to a given dose level. Acute toxicity, tumour response and early local control were investigated and reported.
  
  
  RESULTS
  One hundred lesions in 65 consecutive patients (male/female: 30/35, median age: 66 years; range: 40-89) were treated. Of these 100 lesions, 21 were primary or metastatic lung tumours, 24 were liver metastases, 30 were bone metastases, 24 were nodal metastases and one was a primary vulvar melanoma. The prescribed dose ranged from 12 (BED(2Gy,α/β:10) = 26.4 Gy) to 28 Gy (BED(2Gy,α/β:10) = 106.4 Gy) to the planning target volume. Twenty-one patients (32.3%) experienced grade 1-2 acute toxicity, which was grade 2 in only two cases. The overall response rate based on computed tomography/magnetic resonance imaging was 52% (95% confidence interval 40.1-63.2%) and based on positron emission tomography scan was 90% (95% confidence interval 76.2-96.4%). As of November 2013, the median duration of follow-up was 11 months (range = 1-38). Recurrence/progression within the SRS-VMAT treated field was observed in nine patients (total lesions = 18): the inside SRS-VMAT field local control expressed on a per lesion basis was 87.8% at 12 months and 71.9% at 24 months.
  
  
  CONCLUSIONS
  The maximum tolerable dose has not yet been reached in any study arm. SRS-VMAT resulted in positive early clinical results in terms of tumour response, local control rate and acute toxicity.
authors.affiliation: Radiation Oncology Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Deodato
authors.affiliation: Medical Physics Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cilla
authors.affiliation: Radiation Oncology Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy. Electronic address: gmacchia@rm.unicatt.it.
authors.forename: G
authors.initials: G
authors.lastname: Macchia
authors.affiliation: Palliative Therapies Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Torre
authors.affiliation: Radiation Oncology Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Caravatta
authors.affiliation: Radiation Oncology Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mariano
authors.affiliation: Palliative Therapies Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mignogna
authors.affiliation: Radiation Oncology Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ferro
authors.affiliation: Radiation Oncology Department, Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: G C
authors.initials: GC
authors.lastname: Mattiucci
authors.affiliation: Radiation Oncology Department, Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Balducci
authors.affiliation: Radiation Oncology Department, Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Frascino
authors.affiliation: Medical Physics Department, Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Piermattei
authors.affiliation: Gynaecologic Oncology Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ferrandina
authors.affiliation: Radiation Oncology Department, Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Valentini
authors.affiliation: Radiation Oncology Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy; Palliative Therapies Unit, Fondazione di Ricerca e Cura "Giovanni Paolo II", Università Cattolica del Sacro Cuore, Campobasso, Italy; Radiation Oncology Department, Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: A G
authors.initials: AG
authors.lastname: Morganti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000601:surgery*; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods
keywords: Extracranial radiosurgery; SABR; SBRT; SRS; VMAT; phase I