title: Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes.
abstract: BACKGROUND
  Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects.
  
  
  METHODS
  Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments.
  
  
  RESULTS
  Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects.
  
  
  CONCLUSIONS
  After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.
authors.affiliation: Servicio de Oncología Radioterápica, Hospital Universitario Virgen de las Nieves, Granada, Spain. jaghgr@supercable.es
authors.forename: Escarlata
authors.initials: E
authors.lastname: López
authors.forename: Rosario
authors.initials: R
authors.lastname: Guerrero
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Núñez
authors.forename: Rosario
authors.initials: R
authors.lastname: del Moral
authors.forename: Mercedes
authors.initials: M
authors.lastname: Villalobos
authors.forename: Joaquina
authors.initials: J
authors.lastname: Martínez-Galán
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Valenzuela
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Muñoz-Gámez
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Oliver
authors.forename: David
authors.initials: D
authors.lastname: Martín-Oliva
authors.forename: José Mariano
authors.initials: JM
authors.lastname: Ruiz de Almodóvar
mesh_terms: D001918:Brachytherapy; D001943:Breast Neoplasms / Q000532:radiotherapy*; D003037:Cobalt Radioisotopes / Q000627:therapeutic use; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics*; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007496:Iridium Radioisotopes / Q000627:therapeutic use; D008214:Lymphocytes / Q000528:radiation effects*; D010315:Particle Accelerators; D012867:Skin / Q000528:radiation effects*; D013997:Time Factors
chemical_list: D003037:Cobalt Radioisotopes; D004273:DNA, Neoplasm; D007496:Iridium Radioisotopes