title: Postmastectomy hypofractionated and accelerated radiation therapy with (and without) subcutaneous amifostine cytoprotection.
abstract: OBJECTIVE
  Postmastectomy radiation therapy (PMRT) provides major local control and survival benefits. More aggressive radiation therapy schemes may, however, be necessary in specific subgroups, provided they are safely administered. We report the tolerance and efficacy of a highly accelerated and hypofractionated regimen (HypoARC).
  
  
  METHODS
  One hundred twelve high-risk patients who had undergone mastectomy received 10 consecutive fractions of 3.5 Gy in 12 days (thoracic wall and axillary/supraclavicular areas). Two consecutive additional fractions of 4 Gy were given to the surgical scar area (electrons 8-10 MeV) and 1 3.5-Gy fraction to the axilla (in cases with extensive nodal involvement). A minimum follow-up of 24 months (median, 44 months) was allowed before analysis. Of 112 patients, 21 (18.7%) refused to receive amifostine, the remaining receiving tolerance-based individualized doses (500-1000 mg/day subcutaneously).
  
  
  RESULTS
  By use of a dose individualization algorithm, 68.1%, 11%, and 18.7% of patients received 1000 mg, 750 mg, and 500 mg/day of amifostine. Patchy moist skin desquamation outside and inside the booster fields was noted in 14 of 112 (12.5%) and 26 of 112 (23.2%) patients, respectively. No case of acute pneumonitis was recorded. High amifostine dose offered a significant skin protection. Within a median follow-up time of 44 months, moderate subcutaneous edema outside and within the booster thoracic area was noted in 5 of 112 (4.4%) and 8 of 112 (7.1%) cases, respectively. Intense asymptomatic radiographic findings of in field lung fibrosis were noted in 4 of 112 (3.6%) patients. Amifostine showed a significant protection against lung and soft tissue fibrosis. A 97% projected 5-year local relapse free survival and 84% 5-year disease-specific survival were recorded. Lack of steroid receptor expression, simple human epidermal growth factor 2 positivity, or triple negative phenotype defined higher metastasis rates but had no effect on local control.
  
  
  CONCLUSIONS
  PMRT with HypoARC showed an excellent early and short-term late toxicity profile, and amifostine further reduced early and late radiation sequelae. Encouraging local control rates are obtained in high-risk subgroups.
authors.affiliation: Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: Marianthi
authors.initials: M
authors.lastname: Panteliadou
authors.forename: Ioannis M
authors.initials: IM
authors.lastname: Abatzoglou
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Sismanidou
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004999:Amifostine / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016022:Case-Control Studies; D003131:Combined Modality Therapy / Q000379:methods; D019610:Cytoprotection; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D015182:Lymphatic Irradiation / Q000379:methods; D015411:Mastectomy, Modified Radical; D008875:Middle Aged; D017564:Radiation Pneumonitis / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011855:Radiodermatitis / Q000517:prevention & control; D020893:Receptor, ErbB-3 / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016019:Survival Analysis
chemical_list: D011837:Radiation-Protective Agents; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020893:Receptor, ErbB-3; D004999:Amifostine