title: Concomitant chemo-radiotherapy and local dose of radiation as risk factors for second malignant neoplasms after solid cancer in childhood: a case-control study.
abstract: Radiotherapy and chemotherapy are associated with an increased risk of a second malignant neoplasm (SMN) after a cancer during childhood. This study specified the dose-effect relationship between radiotherapy, chemotherapy and the risk of a SMN, and investigated the effect of chemo-radiotherapy on the risk of SMN. A case-control study nested in a European cohort of 4,581 patients treated for a solid cancer during childhood was conducted. One hundred and fifty three cases with a SMN and 442 controls were matched according to sex, age at first cancer, calendar year, type of first cancer and follow-up. The local radiation dose was estimated at the site of the SMN, for each case and at the same site, for the matched controls. The local dose of radiation significantly increased the risk of a SMN. The best model was linear with an excess relative risk per Gray equal to 0.13 (95% CI, 0.06; 0.26). Any chemotherapy significantly increased the risk of a SMN, odd ratio(adjusted) (OR(adjusted)) = 2.4 (95% confidence interval (95% CI), 1.4-4.1), but no dose-effect relationship was observed between any drug category and the risk of a SMN. Patients who had received concomitant chemo-radiotherapy were significantly more at risk of developing a SMN than patients who had been treated with sequential chemo-radiotherapy, even after adjustment for the local dose of radiation and the 6 most frequently administered drugs, OR(adjusted) = 2.3 (95%CI, 1.1-4.8). Radiation was found to be the foremost treatment-related risk factor for the occurrence of a SMN. Compared to sequential treatment, concomitant chemo-radiotherapy may lead to a higher risk of a SMN.
authors.affiliation: National Institute of Public Health and Medical Research (INSERM), Unit 605, Villejuif, France. guerin@igr.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Guérin
authors.forename: Catherine
authors.initials: C
authors.lastname: Guibout
authors.forename: Akthar
authors.initials: A
authors.lastname: Shamsaldin
authors.forename: Marie-Gabrielle
authors.initials: MG
authors.lastname: Dondon
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diallo
authors.forename: Mike
authors.initials: M
authors.lastname: Hawkins
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.forename: Olivier
authors.initials: O
authors.lastname: Hartmann
authors.forename: Jean
authors.initials: J
authors.lastname: Michon
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.forename: Florent
authors.initials: F
authors.lastname: de Vathaire
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents