title: Second malignancies following breast cancer treatment: a case-control study based on the Peridose methodology. Allegro project (task 5.4).
abstract: OBJECTIVE
  To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies. MATERIAL AND STUDY DESIGN: A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed. Minimum 5-year follow-up was required. Each index case was matched with 5 controls by 1) year of birth, 2) year of radiotherapy and 3) follow-up duration. Peridose-software was used to calculate peripheral dose.
  
  
  RESULTS
  195 second cancers were registered (19% [corrected] of all patients treated with adjuvant irradiation). Several methodological limitations of the Peridose calculation were encountered including impossibility to calculate the peripheral dose in the patients treated with intraoperative or external electron beam radiotherapy, in case of second tumors located at <15 cm from the radiotherapy field etc. Moreover, Peridose requires full radiotherapy data and the distance between radiotherapy field and second primary site. Due to these intrinsic limitations, only 6 index cases were eligible for dose calculation. Calculated doses at the second cancer site in index cases and in an analogous site in controls ranged between 7.5 and 145 cGy. The mean index-control dose difference was -3.15 cGy (range, -15.8 cGy and +2.7 cGy).
  
  
  CONCLUSIONS
  The calculated peripheral doses were low and the index-control differences were small. However, the small number of eligible patients precludes a reliable analysis of a potential dose-response relationship. Large patient series followed for a long period and further improvement in the methodology of the peripheral dose calculation are necessary in order to overcome the methodological challenges of the study.
authors: Dept of Radiation Oncology, European Institute of Oncology, via Ripamonti 435, Milan, Italy.
authors: Roberto
authors: R
authors: Orecchia
authors: Barbara A
authors: BA
authors: Jereczek-Fossa
authors: Elena
authors: E
authors: Rondi
authors: Isa
authors: I
authors: Bossi-Zanetti
authors: Ilaria
authors: I
authors: Meaglia
authors: Rosa
authors: R
authors: Luraschi
authors: Maria Cristina
authors: MC
authors: Leonardi
authors: Nicole
authors: N
authors: Rotmensz
authors: Edoardo
authors: E
authors: Botteri
authors: Cristiana
authors: C
authors: Fodor
authors: Agnese
authors: A
authors: Cecconi
authors: Anna
authors: A
authors: Morra
authors: Roberta
authors: R
authors: Lazzari
authors: Annamaria
authors: A
authors: Ferrari
authors: Federica
authors: F
authors: Cattani
authors: Viviana
authors: V
authors: Galimberti
authors: Alberto
authors: A
authors: Luini
authors: Paolo
authors: P
authors: Veronesi
authors: Stefano
authors: S
authors: Zurrida
authors: Stefano
authors: S
authors: Magrini
authors: Wolfgang
authors: W
authors: Doerr
authors: Nicole
authors: N
authors: Humble
authors: Klaus R
authors: KR
authors: Trott
authors: Andrea
authors: A
authors: Ottolenghi
authors: Vere
authors: V
authors: Smyth
authors: Umberto
authors: U
authors: Veronesi
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D016022:Case-Control Studies; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000517:prevention & control*; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D011881:Radiotherapy, Computer-Assisted / Q000009:adverse effects; D012189:Retrospective Studies; D012984:Software