Stereotactic radiosurgery (SRS) with volumetric modulated arc therapy (VMAT): interim results of a multi-arm phase I trial (DESTROY-2)

Clin Oncol (R Coll Radiol). 2014 Dec;26(12):748-56. doi: 10.1016/j.clon.2014.08.005. Epub 2014 Aug 29.

Abstract

Aims: 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.

Materials and 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.

Keywords: Extracranial radiosurgery; SABR; SBRT; SRS; VMAT; phase I.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / surgery*
  • Radiosurgery / adverse effects
  • Radiosurgery / methods*
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Radiotherapy, Intensity-Modulated / methods