title: Redefining radiotherapy for early-stage breast cancer with single dose ablative treatment: a study protocol.
abstract: A shift towards less burdening and more patient friendly treatments for breast cancer is currently ongoing. In low-risk patients with early-stage disease, accelerated partial breast irradiation (APBI) is an alternative for whole breast irradiation following breast-conserving surgery. MRI-guided single dose ablative APBI has the potential to offer a minimally burdening, non-invasive treatment that could replace current breast-conserving therapy.
  
  
  
  The ABLATIVE study is a prospective, single arm, multicenter study evaluating preoperative, single dose, ablative radiation treatment in patients with early-stage breast cancer. Patients with core biopsy proven non-lobular invasive breast cancer, (estrogen receptor positive, Her2 negative, maximum tumor size 3.0 cm on diagnostic MRI) and a negative sentinel node biopsy are eligible. Radiotherapy (RT) planning will be performed using a contrast enhanced (CE) planning CT-scan, co-registered with a CE-MRI, both in supine RT position. A total of twenty-five consecutive patients will be treated with a single ablative RT dose of 20 Gy to the tumor and 15 Gy to the tumorbed. Follow-up MRIs are scheduled within 1 week, 2, 4 and 6 months after single-dose RT. Breast-conserving surgery is scheduled at six months following RT. Primary study endpoint is pathological complete response. Secondary study endpoints are the radiological response and toxicity. Furthermore, patients will fill out questionnaires on quality of life and functional status. Cosmetic outcome will be evaluated by the treating radiation oncologist, patient and 'Breast Cancer Conservation Treatment cosmetic results' software. Recurrence and survival rates will be assessed. The patients will be followed up to 10 years after diagnosis. If patients give additional informed consent, a biopsy and a part of the irradiated specimen will be stored at the local Biobank and used for future research on radiotherapy response associated genotyping.
  
  
  
  The ABLATIVE study evaluates MRI-guided single dose ablative RT in patients with early-stage breast cancer, aiming at a less burdening and non-invasive alternative for current breast-conserving treatment.
  
  
  
  ClinicalTrials.gov registration number NCT02316561 . The trial was registrated prospectively on October 10th 2014.
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands. r.charaghvandi@umcutrecht.nl.
authors.forename: R K
authors.initials: RK
authors.lastname: Charaghvandi
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: van Asselen
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M E P
authors.initials: ME
authors.lastname: Philippens
authors.affiliation: Imaging Division, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Verkooijen
authors.affiliation: Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C H
authors.initials: CH
authors.lastname: van Gils
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: Imaging Division, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: Pijnappel
authors.affiliation: Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M G G
authors.initials: MG
authors.lastname: Hobbelink
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: A J
authors.initials: AJ
authors.lastname: Witkamp
authors.affiliation: Department of Surgery, Diakonessenhuis, Utrecht, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van Dalen
authors.affiliation: Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van der Wall
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: T C
authors.initials: TC
authors.lastname: van Heijst
authors.affiliation: Department of Surgery, St. Antonius, Nieuwegein, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Koelemij
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Vulpen
authors.affiliation: Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H J G D
authors.initials: HJ
authors.lastname: van den Bongard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D011446:Prospective Studies; D011788:Quality of Life; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
keywords: Ablative; Breast cancer; MRI-guidance; Partial breast irradiation; Radiosurgery