title: Risk of a second malignant neoplasm after cancer in childhood treated with radiotherapy: correlation with the integral dose restricted to the irradiated fields.
abstract: OBJECTIVE
  After successful treatment of cancers in childhood, the occurrence of second malignant neoplasm (SMN) came to the fore. Few studies have considered the relationship between the radiation dose received and the risk of developing an SMN. To take into account the heterogeneity of the dose distribution so as to evaluate the overall risk of an SMN after a childhood cancer, we therefore focused on the integral dose restricted to the irradiated fields.
  
  
  METHODS
  The study was performed in a cohort of 4,401 patients who were 3-year survivors of all types of childhood cancer treated between 1947 and 1986 in France and Great Britain. For each patient, the integral dose was estimated for the volume inside the beam edges.
  
  
  RESULTS
  We found a significant dose-response relationship between the overall risk of an SMN and the estimated integral dose. The excess relative risk for each incremental unit of the integral dose was only 0.008 in a linear model and 0.017 when a negative exponential term was considered, when adjusted for chemotherapy. The risk of SMN occurrence was 2.6 times higher in the case of irradiation. However among patients who had received radiotherapy, only those who had received the highest integral dose actually had a higher risk.
  
  
  CONCLUSIONS
  The integral dose in our study cannot be considered as a good predictor of later risks. However other studies with the same study design are obviously needed to evaluate the use of the integral dose as a tool for decision making concerning different radiotherapy techniques.
authors.affiliation: INSERM U 605, Villejuif, France; Institut Gustave Roussy, Villejuif cedex, France. rubino@igr.fr
authors.forename: France
authors.initials: F
authors.lastname: Nguyen
authors.forename: Carole
authors.initials: C
authors.lastname: Rubino
authors.forename: Sylvie
authors.initials: S
authors.lastname: Guerin
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diallo
authors.forename: Akthar
authors.initials: A
authors.lastname: Samand
authors.forename: Mike
authors.initials: M
authors.lastname: Hawkins
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lefkopoulos
authors.forename: Florent
authors.initials: F
authors.lastname: De Vathaire
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004307:Dose-Response Relationship, Radiation; D004739:England / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology*; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D012306:Risk; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000532:radiotherapy; D017741:Survivors
chemical_list: D000970:Antineoplastic Agents