title: Factors determining outcome for breast-conserving irradiation with margin-directed dose escalation to the tumor bed.
abstract: OBJECTIVE
  A prospectively applied treatment policy for breast-conserving therapy used margin assessment as the exclusive guide to the intensity of therapy directed at the tumor-bearing quadrant.
  
  
  METHODS
  From 1982-1994, there were 509 treated Stage I and II breast carcinomas with a median follow-up of 72 months. For operational purposes, tumor excision margins were prospectively defined as: > 5 mm, 2.1-5 mm, > 0 < or = 2 mm, and positive. If a margin was assessed as < or = 2 mm or indeterminate, and it was deemed cosmetically feasible, a reexcision of the tumor bed would be performed. All patients received whole breast irradiation to 50-50.4 Gy. The following scheme for tumor bed boost irradiation as a function of final margin status (FMS) was observed: (a) Minimal risk = no tumor found on reexcision, no boost performed; (b) low risk = FMS > 5 mm, boost of 10 Gy; intermediate risk = FMS 2.1-5 mm, boost to 14 Gy; high risk = FMS < or = 2 mm or positive, boost to 20 Gy. Cases were analyzed for local failure (LF) with respect to histology (invasive ductal (IDC), IDC with associated DCIS (IDC/DCIS), invasive lobular (ILC)), age, tumor size, total excision volume, reexcision, total dose, tamoxifen therapy, and chemotherapy.
  
  
  RESULTS
  There were 19 breast recurrences for a Kaplan-Meier local failure rate for all cases at 5 and 10 years of 2.7% and 7.1%, respectively. Local failure in the first 4 years of follow-up was rare, with a mean annual incidence rate of 0.25% that rose to a mean of 1.1% in subsequent years. Univariate results of Cox proportional hazards regression survival models found positive FMS (p = 0.02), IDC/DCIS (p = 0.04) and age (0.0006) as significantly associated with local failure. In a multivariable model of FMS and IDC/DCIS, FMS retained significance (p = 0.01) but IDC/DCIS was borderline (p = 0.06). When FMS and age were included in a multivariable model, there was a significant interaction (p = 0.01) between the two variables. There was a significant increase in the relative risk of LF for age < or = 45 years (range 11.1-17.4), irrespective of FMS category. Although excellent overall control rates were achieved for patients > 45 years, for younger patients LF rates appeared to remain proportional to the relative closeness of the FMS, despite rigorous dose escalation.
  
  
  CONCLUSIONS
  Graded tumor-bed dose escalation in response to FMS results in an exceptionally low risk of "early" local recurrence within the first 5 years of follow-up. However, this strategy is unable to completely overcome the longer term adverse influence of young age and positive FMS.
authors.affiliation: Department of Radiation Oncology, New England Medical Center, Boston, MA 02111, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Wazer
authors.forename: R K
authors.initials: RK
authors.lastname: Schmidt-Ullrich
authors.forename: R
authors.initials: R
authors.lastname: Ruthazer
authors.forename: C H
authors.initials: CH
authors.lastname: Schmid
authors.forename: R
authors.initials: R
authors.lastname: Graham
authors.forename: H
authors.initials: H
authors.lastname: Safaii
authors.forename: J
authors.initials: J
authors.lastname: Rothschild
authors.forename: J
authors.initials: J
authors.lastname: McGrath
authors.forename: J K
authors.initials: JK
authors.lastname: Erban
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D017211:Treatment Failure