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

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          Abstract

          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. In order to develop substructure dose-response models, the heart model previously used for pediatric cohort dosimetry needed enhancement and substructure delineation.

          Methods:

          To enhance our heart model, we combined the age-scalable capability of our computational phantom with the anatomically-delineated (with substructures) heart models from an international humanoid phantom series. We examined cardiac volume similarity/overlap between registered age-scaled phantoms (1, 5, 10, and 15 years) with the enhanced heart model and the reference phantoms of the same age; dice similarity coefficient (DSC) and overlap coefficient (OC) were calculated for each matched pair. To assess the accuracy of our enhanced heart model, we compared doses from computed tomography-based planning (ground truth) with reconstructed heart doses. We also compared doses calculated with the prior and enhanced heart models for a cohort of nearly 5000 childhood cancer survivors.

          Results:

          We developed a realistic cardiac model with 14-substructures, scalable across a broad age range (1–15 years); average DSC and OC were 0.84 ± 0.05 and 0.90 ± 0.05, respectively. The average percent difference between reconstructed and ground truth mean heart doses was 4.2%. In the cohort dosimetry analysis, dose and dose-volume metrics were approximately 10% lower on average when the enhanced heart model was used for dose reconstructions.

          Conclusion:

          We successfully developed and validated an anatomically realistic age-scalable cardiac model that can be used to establish substructure dose-response models for late cardiac disease in childhood cancer survivor cohorts.

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          Most cited references29

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          Chronic health conditions in adult survivors of childhood cancer.

          Only a few small studies have assessed the long-term morbidity that follows the treatment of childhood cancer. We determined the incidence and severity of chronic health conditions in adult survivors. The Childhood Cancer Survivor Study is a retrospective cohort study that tracks the health status of adults who received a diagnosis of childhood cancer between 1970 and 1986 and compares the results with those of siblings. We calculated the frequencies of chronic conditions in 10,397 survivors and 3034 siblings. A severity score (grades 1 through 4, ranging from mild to life-threatening or disabling) was assigned to each condition. Cox proportional-hazards models were used to estimate hazard ratios, reported as relative risks and 95% confidence intervals (CIs), for a chronic condition. Survivors and siblings had mean ages of 26.6 years (range, 18.0 to 48.0) and 29.2 years (range, 18.0 to 56.0), respectively, at the time of the study. Among 10,397 survivors, 62.3% had at least one chronic condition; 27.5% had a severe or life-threatening condition (grade 3 or 4). The adjusted relative risk of a chronic condition in a survivor, as compared with siblings, was 3.3 (95% CI, 3.0 to 3.5); for a severe or life-threatening condition, the risk was 8.2 (95% CI, 6.9 to 9.7). Among survivors, the cumulative incidence of a chronic health condition reached 73.4% (95% CI, 69.0 to 77.9) 30 years after the cancer diagnosis, with a cumulative incidence of 42.4% (95% CI, 33.7 to 51.2) for severe, disabling, or life-threatening conditions or death due to a chronic condition. Survivors of childhood cancer have a high rate of illness owing to chronic health conditions. Copyright 2006 Massachusetts Medical Society.
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            The Childhood Cancer Survivor Study: a National Cancer Institute-supported resource for outcome and intervention research.

            Survival for childhood cancer has increased dramatically over the last 40 years with 5-year survival rates now approaching 80%. For many diagnostic groups, rapid increases in survival began in the 1970s with the broader introduction of multimodality approaches, often including combination chemotherapy with or without radiation therapy. With this increase in rates of survivorship has come the recognition that survivors are at risk for adverse health and quality-of-life outcomes, with risk being influenced by host-, disease-, and treatment-related factors. In 1994, the US National Cancer Institute funded the Childhood Cancer Survivor Study, a multi-institutional research initiative designed to establish a large and extensively characterized cohort of more than 14,000 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. This ongoing study, which reflects the single most comprehensive body of information ever assembled on childhood and adolescent cancer survivors, provides a dynamic framework and resource to investigate current and future questions about childhood cancer survivors.
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              Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer.

              Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance. A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test. The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses. This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                8407192
                6944
                Radiother Oncol
                Radiother Oncol
                Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
                0167-8140
                1879-0887
                9 May 2021
                17 October 2020
                December 2020
                19 May 2021
                : 153
                : 163-171
                Affiliations
                [a ]Department of Radiation Physics, The University of Texas MD Anderson Cancer Center
                [b ]The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
                [c ]Department of Radiation Oncology, Winship Cancer Institute, Emory University, United States
                [d ]Division of Cancer Epidemiology and Genetics, National Cancer Institute
                [e ]Department of Radiation Oncology, Mayo Clinic Florida
                [f ]Department of Radiation Oncology and Pediatrics, University of Rochester Medical Center, United States
                [g ]Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital
                [h ]Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, United States
                Author notes
                [* ]Corresponding author at: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, United States. rhowell@ 123456mdanderson.org (R.M. Howell).
                Article
                NIHMS1640013
                10.1016/j.radonc.2020.10.017
                8132170
                33075392
                ef3cf002-62b9-43db-8187-7451b1ea4914

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Article

                Oncology & Radiotherapy
                late effects,radiation therapy,cardiac toxicity,computational phantom,childhood cancer

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