title: Accelerated partial breast irradiation with low-dose-rate interstitial implant brachytherapy after wide local excision: 12-year outcomes from a prospective trial.
abstract: OBJECTIVE
  To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa).
  
  
  METHODS
  Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall's tau (τ(β)) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy.
  
  
  RESULTS
  The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome (τ(β) 0.6, p < .0001), lower patient satisfaction (τ(β) 0.5, p < .001), and worse fibrosis (τ(β) 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias ≥1 cm(2). Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose (τ(β) 0.3-0.5, p ≤ .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence-free survival, and overall survival rate was 85% (95% confidence interval, 70-97%), 72% (95% confidence interval, 54-86%), and 87% (95% confidence interval, 73-99%), respectively.
  
  
  CONCLUSIONS
  Low-dose-rate accelerated partial breast irradiation with implant brachytherapy provides acceptable local control in select early-stage BCa patients. However, treatment-related toxicity and cosmetic complications were significant with longer follow-up and at higher doses.
authors.affiliation: Harvard Radiation Oncology Program, Boston, MA, USA.
authors.forename: Jona A
authors.initials: JA
authors.lastname: Hattangadi
authors.forename: Simon N
authors.initials: SN
authors.lastname: Powell
authors.forename: Shannon M
authors.initials: SM
authors.lastname: MacDonald
authors.forename: Thomas
authors.initials: T
authors.lastname: Mauceri
authors.forename: Marek
authors.initials: M
authors.lastname: Ancukiewicz
authors.forename: Phoebe
authors.initials: P
authors.lastname: Freer
authors.forename: Brian
authors.initials: B
authors.lastname: Lawenda
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Alm El-Din
authors.forename: Michele A
authors.initials: MA
authors.lastname: Gadd
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Smith
authors.forename: Alphonse G
authors.initials: AG
authors.lastname: Taghian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D001940:Breast / Q000473:pathology / Q000528:radiation effects; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy / Q000379:methods; D004954:Esthetics; D005218:Fat Necrosis / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D008197:Lymph Node Excision; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D017060:Patient Satisfaction; D011446:Prospective Studies; D011832:Radiation Injuries / Q000473:pathology; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D016896:Treatment Outcome
references.citation: J Natl Cancer Inst. 2003 Aug 20;95(16):1205-10
references.pmid: 12928345
references.citation: Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):45-51
references.pmid: 16503383
references.citation: Brachytherapy. 2005;4(1):10-7
references.pmid: 15737901
references.citation: Radiother Oncol. 2010 Mar;94(3):274-9
references.pmid: 20181401
references.citation: Int J Radiat Oncol Biol Phys. 2009 Jun 1;74(2):447-52
references.pmid: 19058921
references.citation: Int J Radiat Oncol Biol Phys. 2011 May 1;80(1):17-24
references.pmid: 20605365
references.citation: Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):671-80
references.pmid: 12788172
references.citation: Eur J Cancer. 1996 Apr;32A(4):608-11
references.pmid: 8695261
references.citation: Radiother Oncol. 2007 Mar;82(3):281-6
references.pmid: 17126940
references.citation: Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1239-46
references.pmid: 14630257
references.citation: Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1393-404
references.pmid: 15590170
references.citation: Am J Surg. 2000 Oct;180(4):299-304
references.pmid: 11113440
references.citation: Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):489-95
references.pmid: 16246495
references.citation: Int J Radiat Oncol Biol Phys. 2003 Mar 15;55(4):1013-8
references.pmid: 12605981
references.citation: Radiother Oncol. 2004 Jun;71(3):281-5
references.pmid: 15172143
references.citation: Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):694-702
references.pmid: 17531400
references.citation: Brachytherapy. 2007 Oct-Dec;6(4):286-92
references.pmid: 17991625
references.citation: Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):681-9
references.pmid: 12788173
references.citation: Radiother Oncol. 2009 Jan;90(1):1-13
references.pmid: 18783840