ABSTRACT
BACKGROUND: The use of radiotherapy (RT) is debated for pediatric patients with Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to the thyroid, heart, lungs, and breasts are compared with the extensive mantle field (MF), Involved Field RT(IFRT), Modified IFRT (mIFRT), and Involved Node RT (INRT) and the risk of radiation-induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique. PROCEDURE: INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were simulated for 10 supradiaphragmatic, clinical stage III classical HL patients <18 years old, total of 4 x 2 plans for each patient. The lifetime excess risks of cardiac morbidity, cardiac mortality, lung, breast, and thyroid cancer with each technique were estimated. The estimated excess risks attributable to RT were based on HL series with long-term follow-up, treating death from other causes as competing risks. The corresponding LYL were derived from the estimated excess risks. Statistical analyses were performed with repeated measures ANOVA. RESULTS: Both a reduction in field size and in prescribed radiation dose significantly lowered the estimated dose to the heart, lungs, breasts, and thyroid compared to past,extended fields, even for patients with mediastinal disease. This translated into a significantly reduced estimated risk of cardiovascular disease, secondary cancers, and LYL. CONCLUSIONS: Involved Node Radiotherapy should be considered for pediatric patients with Hodgkin lymphoma since it is estimated to substantially lower the risk of severe long-term complications.
Subject(s)
Hodgkin Disease/complications , Lymph Nodes/radiation effects , Neoplasms, Second Primary/etiology , Radiation Injuries/etiology , Radiotherapy Planning, Computer-Assisted/adverse effects , Radiotherapy/adverse effects , Adolescent , Breast/radiation effects , Child , Female , Follow-Up Studies , Heart/radiation effects , Hodgkin Disease/radiotherapy , Humans , Lung/radiation effects , Male , Organs at Risk , Prognosis , Risk Assessment , Thyroid Gland/radiation effectsABSTRACT
Recent studies have suggested that development of childhood acute lymphoblastic leukaemia may often be initiated in utero. To provide further evidence of an prenatal origin of childhood leukaemia, we conducted a molecular biological investigation of nine children with B-precursor acute lymphoblastic leukaemia carrying the chromosomal translocation t(12;21), the most common subtype of all childhood acute lymphoblastic leukaemia. Specifically, for each child we identified the non-constitutive chromosomal sequences made up by the t(12;21) fusion gene. From these, leukaemia clone-specific DNA primers were constructed and applied in nested polymerase chain reaction analyses of DNA extracted from the patients' Guthrie cards obtained at birth. Leukaemia clone-specific fusion gene regions were demonstrated in Guthrie card DNA of three patients, age 2 years 11 months, 3 years 4 months, and 5 years 8 months at leukaemia diagnosis. Our findings are consistent with previous observations, and thus provide further evidence that the development of t(12;21) B-precursor acute lymphoblastic leukaemia may be initiated in utero. Review of the current literature moreover indicates that age at leukaemia may be inversely correlated with the burden of cells with leukaemia clonal markers, i.e. leukaemia predisposed cells at birth, and that certain types of childhood acute lymphoblastic leukaemia develop as a multiple step process involving both pre- and postnatal genetic events.
Subject(s)
Biomarkers, Tumor/genetics , Genetic Predisposition to Disease , Neoplasm Proteins/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Base Sequence , Blood Specimen Collection , Child , Child, Preschool , Chromosomes, Human, Pair 12/genetics , Chromosomes, Human, Pair 21/genetics , Core Binding Factor Alpha 2 Subunit , DNA Primers/chemistry , DNA, Neoplasm/analysis , Female , Gene Rearrangement , Genes, Immunoglobulin , Humans , Infant , Infant, Newborn , Male , Mannose-Binding Lectin/genetics , Mannose-Binding Lectin/metabolism , Molecular Sequence Data , Oncogene Proteins, Fusion/genetics , Polymerase Chain Reaction , Translocation, Genetic/geneticsSubject(s)
Chromosomes, Human, Pair 12 , Chromosomes, Human, Pair 21 , DNA-Binding Proteins/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Proto-Oncogene Proteins , Repressor Proteins , Transcription Factors/genetics , Translocation, Genetic , Base Sequence , Core Binding Factor Alpha 2 Subunit , Humans , Molecular Sequence Data , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Proteins c-ets , ETS Translocation Variant 6 ProteinABSTRACT
One of the more consistent findings in leukemia research is the association between birth weight and childhood leukemia. Because thyroid hormones are critically involved in growth and differentiation, we speculated that hormone levels could be of significance to the development of leukemia in early life. Specifically, we hypothesized that high levels of thyroid-stimulating hormone (TSH) would be associated with a low risk of leukemia. Accordingly, high TSH (low free thyroid hormone) early after birth most likely reflects low function of the thyroid accompanied by low rate of cell turnover and so lower risk of faulty cell divisions leading to cancer. In a matched case-control study nested from all singleton children born in Denmark between 1986 and 1998, we compared levels of TSH (as measured in a neonatal screening program for congenital hypothyroidism) in 188 cases of acute lymphoblastic leukemia (ALL) and 28 of acute myeloid leukemia (AML) with levels in 1,450 and 216 matched controls, respectively. Data were analyzed using conditional logistic regression and odds ratios (OR) were adjusted for birth weight. As hypothesized, we found a decreased risk of ALL and AML associated with high TSH (OR(ALL) = 0.7 [0.5-1.0]; OR(AML) = 0.3 [0.1-1.0]). However, both conditions were also associated with low levels of TSH (OR(ALL) = 0.4 [0.2-0.7]; OR(AML) = 0.3 [0.1-1.4]). In conclusion, extreme TSH levels a few days after birth appears to be associated with a decreased risk of acute childhood leukemia.
