Body region-specific 3D age-scaling functions for scaling whole-body computed tomography anatomy for pediatric late effects studies.

Radiation epidemiology studies of childhood cancer survivors treated in the pre-computed tomography (CT) era reconstruct the patients' treatment fields on computational phantoms. For such studies, the phantoms are commonly scaled to age at the time of radiotherapy treatment because age is the generally available anthropometric parameter. Several reference size phantoms are used in such studies, but reference size phantoms are only available at discrete ages (e.

Development of an age-scalable 3D computational phantom in DICOM standard for late effects studies of childhood cancer survivors.

Purpose: We previously developed an age-scalable 3D computational phantom that has been widely used for retrospective whole-body dose reconstructions of conventional two-dimensional historic radiation therapy (RT) treatments in late effects studies of childhood cancer survivors. This phantom is modeled in the FORTRAN programming language and is not readily applicable for dose reconstructions for survivors treated with contemporary RT whose treatment plans were designed using computed tomography images and complex treatment fields. The goal of this work was to adapt the current FORTRAN model of our age-scalable computational phantom into Digital Imaging and Communications in Medicine (DICOM) standard so that it can be used with any treatment planning system (TPS) to reconstruct contemporary RT.

Radiation therapy related cardiac disease risk in childhood cancer survivors: Updated dosimetry analysis from the Childhood Cancer Survivor Study.

Background And Purpose: We previously evaluated late cardiac disease in long-term survivors in the Childhood Cancer Survivor Study (CCSS) based on heart radiation therapy (RT) doses estimated from an age-scaled phantom with a simple atlas-based heart model (H). We enhanced our phantom with a high-resolution CT-based anatomically realistic and validated age-scalable cardiac model (H). We aimed to evaluate how this update would impact our prior estimates of RT-related late cardiac disease risk in the CCSS cohort.

Development and validation of an age-scalable cardiac model with substructures for dosimetry in late-effects studies of childhood cancer survivors.

Background And Purpose: Radiation therapy is a risk factor for late cardiac disease in childhood cancer survivors. Several pediatric cohort studies have established whole heart dose and dose-volume response models. Emerging data suggest that dose to cardiac substructures may be more predictive than whole heart metrics.

Subsequent Neoplasm Risk Associated With Rare Variants in DNA Damage Response and Clinical Radiation Sensitivity Syndrome Genes in the Childhood Cancer Survivor Study.

Purpose: Radiotherapy for childhood cancer is associated with elevated subsequent neoplasm (SN) risk, but the contribution of rare variants in DNA damage response and radiation sensitivity genes to SN risk is unknown.

Patients And Methods: We conducted whole-exome sequencing in a cohort of childhood cancer survivors originally diagnosed during 1970 to 1986 (mean follow-up, 32.7 years), with reconstruction of doses to body regions from radiotherapy records.

Association of Breast Cancer Risk After Childhood Cancer With Radiation Dose to the Breast and Anthracycline Use: A Report From the Childhood Cancer Survivor Study.

Importance: Chest irradiation for childhood cancer is associated with increases in breast cancer risk. Growing evidence suggests that anthracyclines increase this risk, but the outcome of combined anthracycline use and radiotherapy has not been studied.

Objectives: To evaluate breast cancer risk in childhood cancer survivors following radiotherapy and chemotherapy and assess whether risks varied by estrogen receptor (ER) status.

Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus: A Report from the Childhood Cancer Survivor Study.

Background: Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus, but the association between risk and radiation dose and volume is unclear.

Methods: Participants included 20 762 5-year survivors of childhood cancer (4568 exposed to abdRT) and 4853 siblings. For abdRT, we estimated maximum dose to abdomen; mean doses for whole pancreas, pancreatic head, body, tail; and percent pancreas volume receiving no less than 10, 20, and 30 Gy.

Adaptations to a Generalized Radiation Dose Reconstruction Methodology for Use in Epidemiologic Studies: An Update from the MD Anderson Late Effect Group.

Epidemiologic studies that include patients who underwent radiation therapy for the treatment of cancer aim to quantify the relationship between radiotherapy and the risk of subsequent late effects. Because of the long follow-up period required to observe late effects, these studies are conducted retrospectively. The studies routinely include patients treated across numerous institutions using a wide range of technologies and represent treatments over several decades.

Hypothyroidism after Radiation Therapy for Childhood Cancer: A Report from the Childhood Cancer Survivor Study.

While thyroid cancer risks from exposure to ionizing radiation early in life are well characterized quantitatively, the association of radiation with nonmalignant, functional thyroid disorders has been less studied. Here, we report on a risk analysis study of hypothyroidism with radiation dose to the thyroid gland and the hypothalamic-pituitary axis among survivors of childhood cancer. Utilizing data from the Childhood Cancer Survivor Study, a cohort of 14,364 five-year survivors of childhood cancer diagnosed at 26 hospitals in the U.

Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer.

Purpose We aimed to predict individual risk of ischemic heart disease and stroke in 5-year survivors of childhood cancer. Patients and Methods Participants in the Childhood Cancer Survivor Study (CCSS; n = 13,060) were observed through age 50 years for the development of ischemic heart disease and stroke. Siblings (n = 4,023) established the baseline population risk.

Genome-Wide Association Study to Identify Susceptibility Loci That Modify Radiation-Related Risk for Breast Cancer After Childhood Cancer.

Background: Childhood cancer survivors treated with chest-directed radiotherapy have substantially elevated risk for developing breast cancer. Although genetic susceptibility to breast cancer in the general population is well studied, large-scale evaluation of breast cancer susceptibility after chest-directed radiotherapy for childhood cancer is lacking.

Methods: We conducted a genome-wide association study of breast cancer in female survivors of childhood cancer, pooling two cohorts with detailed treatment data and systematic, long-term follow-up: the Childhood Cancer Survivor Study and St.

Temporal Trends in Treatment and Subsequent Neoplasm Risk Among 5-Year Survivors of Childhood Cancer, 1970-2015.

Importance: Cancer treatments are associated with subsequent neoplasms in survivors of childhood cancer. It is unknown whether temporal changes in therapy are associated with changes in subsequent neoplasm risk.

Objective: To quantify the association between temporal changes in treatment dosing and subsequent neoplasm risk.

Stomach Cancer Following Hodgkin Lymphoma, Testicular Cancer and Cervical Cancer: A Pooled Analysis of Three International Studies with a Focus on Radiation Effects.

To further understand the risk of stomach cancer after fractionated high-dose radiotherapy, we pooled individual-level data from three recent stomach cancer case-control studies. These studies were nested in cohorts of five-year survivors of first primary Hodgkin lymphoma (HL), testicular cancer (TC) or cervical cancer (CX) from seven countries. Detailed data were abstracted from patient records and radiation doses were reconstructed to the site of the stomach cancer for cases and to the corresponding sites for matched controls.

Increased pancreatic cancer risk following radiotherapy for testicular cancer.

Background: Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear.

Methods: Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls.

Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

Purpose: The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures.

Patients And Methods: We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, < 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up.

The Risk of Cataract among Survivors of Childhood and Adolescent Cancer: A Report from the Childhood Cancer Survivor Study.

With therapeutic successes and improved survival after a cancer diagnosis in childhood, increasing numbers of cancer survivors are at risk of subsequent treatment-related morbidities, including cataracts. While it is well known that the lens of the eye is one of the most radiosensitive tissues in the human body, the risks associated with radiation doses less than 2 Gy are less understood, as are the long- and short-term cataract risks from exposure to ionizing radiation at a young age. In this study, we followed 13,902 five-year survivors of childhood cancer in the Childhood Cancer Survivor Study cohort an average of 21.

Breast cancer following spinal irradiation for a childhood cancer: A report from the Childhood Cancer Survivor Study.

It has been suggested that pediatric patients treated with spinal irradiation may have an elevated risk of breast cancer. Among a cohort of 363 long-term survivors of a pediatric central nervous system tumor or leukemia treated with spinal irradiation, there was little evidence of an increased breast cancer risk.

Recurrent stroke in childhood cancer survivors.

Objective: To estimate the rates and predictors of recurrent stroke among survivors of pediatric cancer who have had a first stroke.

Methods: The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up that enrolled 14,358 survivors (<21 years old at diagnosis; diagnosed 1970-1986; survived ≥5 years after cancer diagnosis) and followed them prospectively since 1994. We surveyed 443 survivors who reported a first stroke to identify recurrent stroke, and estimated recurrent stroke rates ≥5 years after cancer diagnosis.

Intestinal Obstruction in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

Purpose: For adult survivors of childhood cancer, knowledge about the long-term risk of intestinal obstruction from surgery, chemotherapy, and radiotherapy is limited.

Methods: Intestinal obstruction requiring surgery (IOS) occurring 5 or more years after cancer diagnosis was evaluated in 12,316 5-year survivors in the Childhood Cancer Survivor Study (2,002 with and 10,314 without abdominopelvic tumors) and 4,023 sibling participants. Cumulative incidence of IOS was calculated with second malignant neoplasm, late recurrence, and death as competing risks.

Characterization of genomic alterations in radiation-associated breast cancer among childhood cancer survivors, using comparative genomic hybridization (CGH) arrays.

Ionizing radiation is an established risk factor for breast cancer. Epidemiologic studies of radiation-exposed cohorts have been primarily descriptive; molecular events responsible for the development of radiation-associated breast cancer have not been elucidated. In this study, we used array comparative genomic hybridization (array-CGH) to characterize genome-wide copy number changes in breast tumors collected in the Childhood Cancer Survivor Study (CCSS).

Individual prediction of heart failure among childhood cancer survivors.

Purpose: To create clinically useful models that incorporate readily available demographic and cancer treatment characteristics to predict individual risk of heart failure among 5-year survivors of childhood cancer.

Patients And Methods: Survivors in the Childhood Cancer Survivor Study (CCSS) free of significant cardiovascular disease 5 years after cancer diagnosis (n = 13,060) were observed through age 40 years for the development of heart failure (ie, requiring medications or heart transplantation or leading to death). Siblings (n = 4,023) established the baseline population risk.