title: Long-term follow-up of a prospective policy of margin-directed radiation dose escalation in breast-conserving therapy.
abstract: BACKGROUND
  A prospectively applied treatment policy for breast-conserving therapy used margin assessment as the exclusive guide to the intensity of radiation therapy directed at the tumor bed.
  
  
  METHODS
  From 1982 to 1994, 498 women with 509 Stage I/II breast carcinomas with a median follow-up of 121 months were treated. Final margin status (FMS) categories were defined as greater than 5 mm, greater than 2-5 mm, greater than 0-2 mm, and positive. For margins less than or equal to 2 mm or indeterminate, reexcisions were performed if feasible. All patients received whole breast irradiation to 50.0-50.4 Gy. Final tumor bed boosts as a function of FMS were as follows: no residual on reexcision, no boost performed; FMS greater than 5 mm, boost of 10 Gy; FMS greater than 2-5 mm, boost of 14 Gy; FMS greater than 0-2 mm or positive, boost of 20 Gy. Cases were analyzed for local failure with respect to histology, age, tumor size, excision volume, reexcision, and total dose.
  
  
  RESULTS
  FMS was positive, greater than 0-2 mm, greater than 2-5 mm, and greater than 5 mm, and no residual tumor on reexcision in 21%, 20%, 17%, 14%, and 28% of cases, respectively. At 12 years, Kaplan-Meier local failure rates were 17% for FMS positive, 9% for FMS greater than 0-2 mm, 5% for FMS greater than 2-5 mm, 0% for FMS greater than 5 mm, and 6% for specimens without evidence of residuum on reexcision (P = 0.009). Patients 45 years old and younger had a 12-year local failure rate of 15% whereas patients older than 45 years had a 12-year local failure rate of 6% (P = 0.01). On multivariate analysis, young age (P = 0.03) predicted increased local failure rate, whereas margins that were less than or equal to 2 mm or positive predicted late (> 5 years) but not early (< or = 5 years) recurrence (P = 0.003).
  
  
  CONCLUSIONS
  Graded tumor bed dose escalation in response to FMS results in very low rates of local failure over the first 5 years for all FMS categories. However, tumors with close/positive margins have significantly increased local failure rates after 5 years of follow-up even with increased radiation boost dose. In addition, graded tumor bed dose escalation does not fully overcome the adverse influence of young age.
authors.affiliation: Department of Radiation Oncology #359, Tufts-New England Medical Center, Boston, MA 02111, USA. aneuschatz@lifespan.org
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Neuschatz
authors.forename: Thomas
authors.initials: T
authors.lastname: DiPetrillo
authors.forename: Homa
authors.initials: H
authors.lastname: Safaii
authors.forename: Lori Lyn
authors.initials: LL
authors.lastname: Price
authors.forename: Rupert K
authors.initials: RK
authors.lastname: Schmidt-Ullrich
authors.forename: David E
authors.initials: DE
authors.lastname: Wazer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000532:radiotherapy* / Q000601:surgery; D018275:Carcinoma, Lobular / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D011829:Radiation Dosage