title: Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy.
abstract: OBJECTIVE
  To evaluate toxicity in breast cancer patients treated with anthracycline and taxane based chemotherapy and whole breast hypofractionated radiotherapy, and to identify the risk factors for toxicity.
  
  
  METHODS
  537 early breast cancer patients receiving hypofractionated radiotherapy after conservative surgery were enrolled from April 2009 to December 2014, in an Italian cancer institute. The dose was 42.4 Gy in 16 daily fractions, 2.65 Gy per fraction. The boost to the tumor bed was administered only in grade III breast cancer patients and in patients with close or positive margins. Acute and late toxicity were prospectively assessed during and after radiotherapy according to RTOG scale. The impact of patients clinical characteristics, performed treatments and dose inhomogeneities on the occurrence of an higher level of acute skin toxicity and late fibrosis has been evaluated by univariate and multivariate analysis.
  
  
  RESULTS
  The mean age was 74 (range 46-91 yrs). 27% of patients received boost. 22% of cases (n = 119) received also chemotherapy. The median follow-up was 32 months. G1 and G2/G3 acute skin toxicity were 61.3% and 20.5% and G1 and G2/G3 late fibrosis 12.6% and 4.3% respectively. Chemotherapy (p = 0.04), diabetes (p = 0.04) and boost administration (p < 0.01) were found to be statistically significant on the occurrence of late fibrosis, but a multivariate analysis did not show any factors connected. The boost administration (p < 0.01), the breast volume (p = 0.05), dose inhomogeneities (p < 0.01) and boost volume (p = 0.04) were found to be statistically significant as concerns the occurrence of acute skin reaction at the univariate analysis, but only the boost administration (p = 0.02), at multivariate analysis.
  
  
  CONCLUSIONS
  The results of our study, according to the large randomized trials, confirmed that hypofractionated whole breast irradiation is safe, and only the boost administration seems to be an important predictor for toxicity. Chemotherapy does not impact on acute and late skin toxicity.
authors.affiliation: Radiotherapy Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: mariacarmen.desantis@istitutotumori.mi.it.
authors.forename: M C
authors.initials: MC
authors.lastname: De Santis
authors.affiliation: Medical Physics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bonfantini
authors.affiliation: Analytic Epidemiology and Health Impact Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Di Salvo
authors.affiliation: Radiotherapy Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Dispinzieri
authors.affiliation: Radiotherapy Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Mantero
authors.affiliation: Radiotherapy Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Soncini
authors.affiliation: Analytic Epidemiology and Health Impact Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Baili
authors.affiliation: Analytic Epidemiology and Health Impact Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sant
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bianchi
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Maggi
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Di Cosimo
authors.affiliation: Breast Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Agresti
authors.affiliation: Medical Physics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pignoli
authors.affiliation: Department of Oncology and Hemato-oncology, Università degli Studi di Milano.Director, Radiation Oncology 1 and Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Valdagni
authors.affiliation: Radiotherapy Unit 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Lozza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001940:Breast / Q000473:pathology / Q000528:radiation effects; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D001952:Bridged-Ring Compounds / Q000009:adverse effects; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011446:Prospective Studies; D000069473:Radiation Dose Hypofractionation; D011832:Radiation Injuries / Q000209:etiology*; D000069475:Re-Irradiation / Q000009:adverse effects; D012307:Risk Factors; D012867:Skin / Q000528:radiation effects; D043823:Taxoids / Q000009:adverse effects
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane
keywords: Breast cancer; Chemotherapy; Hypofractionated radiotherapy; RTOG scale; Toxicity