title: Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): a multicentre, randomised controlled trial.
abstract: BACKGROUND
  Breast-conserving surgery for palpable breast cancer is associated with tumour-involved margins in up to 41% of cases and excessively large excision volumes. Ultrasound-guided surgery has the potential to resolve both of these problems, thereby improving surgical accuracy for palpable breast cancer. We aimed to compare ultrasound-guided surgery with the standard for palpable breast cancer-palpation-guided surgery-with respect to margin status and extent of healthy breast tissue resection.
  
  
  METHODS
  In this randomised controlled trial, patients with palpable T1-T2 invasive breast cancer were recruited from six medical centres in the Netherlands between October, 2010, and March, 2012. Eligible participants were randomly assigned to either ultrasound-guided surgery or palpation-guided surgery in a 1:1 ratio via a computer-generated random sequence and were stratified by study centre. Patients and investigators were aware of treatment assignments. Primary outcomes were surgical margin involvement, need for additional treatment, and excess healthy tissue resection (defined with a calculated resection ratio derived from excision volume and tumour diameter). Data were analysed by intention to treat. This trial is registered at http://www.TrialRegister.nl, number NTR2579.
  
  
  RESULTS
  134 patients were eligible for random allocation. Two (3%) of 65 patients allocated ultrasound-guided surgery had tumour-involved margins compared with 12 (17%) of 69 who were assigned palpation-guided surgery (difference 14%, 95% CI 4-25; p=0·0093). Seven (11%) patients who received ultrasound-guided surgery and 19 (28%) of those who received palpation-guided surgery required additional treatment (17%, 3-30; p=0·015). Ultrasound-guided surgery also resulted in smaller excision volumes (38 [SD 26] vs 57 [41] cm(3); difference 19 cm(3), 95% CI 7-31; p=0·002) and a reduced calculated resection ratio (1·0 [SD 0·5] vs 1·7 [1·2]; difference 0·7, 95% CI 0·4-1·0; p=0·0001) compared with palpation-guided surgery.
  
  
  CONCLUSIONS
  Compared with palpation-guided surgery, ultrasound-guided surgery can significantly lower the proportion of tumour-involved resection margins, thus reducing the need for re-excision, mastectomy, and radiotherapy boost. By achieving optimum resection volumes, ultrasound-guided surgery reduces unnecessary resection of healthy breast tissue and could contribute to improved cosmetic results and quality of life.
  
  
  BACKGROUND
  Dutch Pink Ribbon Foundation, Osinga-Kluis Foundation, Toshiba Medical Systems.
authors.affiliation: Department of Surgical Oncology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: Krekel
authors.forename: Max H
authors.initials: MH
authors.lastname: Haloua
authors.forename: Alexander M F
authors.initials: AM
authors.lastname: Lopes Cardozo
authors.forename: Roos H
authors.initials: RH
authors.lastname: de Wit
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Bosch
authors.forename: Louise M
authors.initials: LM
authors.lastname: de Widt-Levert
authors.forename: Sandra
authors.initials: S
authors.lastname: Muller
authors.forename: Henk
authors.initials: H
authors.lastname: van der Veen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bergers
authors.forename: Elly S M
authors.initials: ES
authors.lastname: de Lange de Klerk
authors.forename: Sybren
authors.initials: S
authors.lastname: Meijer
authors.forename: M Petrousjka
authors.initials: MP
authors.lastname: van den Tol
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology / Q000601:surgery*; D005260:Female; D006801:Humans; D007432:Intraoperative Period; D015412:Mastectomy, Segmental / Q000379:methods*; D008875:Middle Aged; D009367:Neoplasm Staging; D010173:Palpation; D016896:Treatment Outcome; D016217:Ultrasonography, Mammary