Predicted risks of second malignant neoplasm incidence and mortality due to secondary neutrons in a girl and boy receiving proton craniospinal irradiation

Department of Radiation Physics, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.
Physics in Medicine and Biology (Impact Factor: 2.76). 11/2010; 55(23):7067-80. DOI: 10.1088/0031-9155/55/23/S08
Source: PubMed


The purpose of this study was to compare the predicted risks of second malignant neoplasm (SMN) incidence and mortality from secondary neutrons for a 9-year-old girl and a 10-year-old boy who received proton craniospinal irradiation (CSI). SMN incidence and mortality from neutrons were predicted from equivalent doses to radiosensitive organs for cranial, spinal and intracranial boost fields. Therapeutic proton absorbed dose and equivalent dose from neutrons were calculated using Monte Carlo simulations. Risks of SMN incidence and mortality in most organs and tissues were predicted by applying risks models from the National Research Council of the National Academies to the equivalent dose from neutrons; for non-melanoma skin cancer, risk models from the International Commission on Radiological Protection were applied. The lifetime absolute risks of SMN incidence due to neutrons were 14.8% and 8.5%, for the girl and boy, respectively. The risks of a fatal SMN were 5.3% and 3.4% for the girl and boy, respectively. The girl had a greater risk for any SMN except colon and liver cancers, indicating that the girl's higher risks were not attributable solely to greater susceptibility to breast cancer. Lung cancer predominated the risk of SMN mortality for both patients. This study suggests that the risks of SMN incidence and mortality from neutrons may be greater for girls than for boys treated with proton CSI.

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Available from: Shiao Woo, Oct 04, 2015
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    • "Realistic calculations of stray radiation dose within a patient are computationally complex and have only recently been accomplished for proton therapy [8-10]. Recently, there has been much progress in research to compare the risks of second cancers after photon and proton radiotherapies [8,10-13]. In contrast, relatively little attention has been paid in the literature to predictive comparisons of other late effects, such as cardiac toxicity [11], for pediatric patients who received radiotherapy. "
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    ABSTRACT: Hodgkin disease (HD) and medulloblastoma (MB) are common malignancies found in children and young adults, and radiotherapy is part of the standard treatment. It was reported that these patients who received radiation therapy have an increased risk of cardiovascular late effects. We compared the predicted risk of developing radiogenic cardiac toxicity after photon versus proton radiotherapies for a pediatric patient with HD and a pediatric patient with MB. In the treatment plans, each patient's heart was contoured in fine detail, including substructures of the pericardium and myocardium. Risk calculations took into account both therapeutic and stray radiation doses. We calculated the relative risk (RR) of cardiac toxicity using a linear risk model and the normal tissue complication probability (NTCP) values using relative seriality and Lyman models. Uncertainty analyses were also performed. The RR values of cardiac toxicity for the HD patient were 7.27 (proton) and 8.37 (photon), respectively; the RR values for the MB patient were 1.28 (proton) and 8.39 (photon), respectively. The predicted NTCP values for the HD patient were 2.17% (proton) and 2.67% (photon) for the myocardium, and were 2.11% (proton) and 1.92% (photon) for the whole heart. The predicted ratios of NTCP values (proton/photon) for the MB patient were much less than unity. Uncertainty analyses revealed that the predicted ratio of risk between proton and photon therapies was sensitive to uncertainties in the NTCP model parameters and the mean radiation weighting factor for neutrons, but was not sensitive to heart structure contours. The qualitative findings of the study were not sensitive to uncertainties in these factors. We conclude that proton and photon radiotherapies confer similar predicted risks of cardiac toxicity for the HD patient in this study, and that proton therapy reduced the predicted risk for the MB patient in this study.
    Radiation Oncology 07/2013; 8(1):184. DOI:10.1186/1748-717X-8-184 · 2.55 Impact Factor
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    • "energy, spread-out Bragg peak width, gantry angle and collimator dimensions. The treatment plan was similar to that from Taddei et al (2010); except that two junction shifts were added to enhance clinical realism. "
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    ABSTRACT: In girls and young women, irradiation of the ovaries can reduce the number of viable ovarian primordial follicles, which may lead to premature ovarian failure (POF) and subsequently to sterility. One strategy to minimize this late effect is to reduce the radiation dose to the ovaries. A primary means of reducing dose is to choose a radiotherapy technique that avoids irradiating nearby normal tissue; however, the relative risk of POF (RRPOF) due to the various therapeutic options has not been assessed. This study compared the predicted RRPOF after craniospinal proton radiotherapy, conventional photon radiotherapy (CRT) and intensity-modulated photon radiotherapy (IMRT). We calculated the equivalent dose delivered to the ovaries of an 11-year-old girl from therapeutic and stray radiation. We then predicted the percentage of ovarian primordial follicles killed by radiation and used this as a measure of the RRPOF; we also calculated the ratio of the relative risk of POF (RRRPOF) among the three radiotherapies. Proton radiotherapy had a lower RRPOF than either of the other two types. We also tested the sensitivity of the RRRPOF between photon and proton therapies to the anatomic position of the ovaries, i.e., proximity to the treatment field (2 ≤ RRRPOF ≤ 10). We found that CRT and IMRT have higher risks of POF than passive-scattering proton radiotherapy (PRT) does, regardless of uncertainties in the ovarian location. Overall, PRT represents a lower RRPOF over the two other modalities.
    Physics in Medicine and Biology 04/2013; 58(10):3107-3123. DOI:10.1088/0031-9155/58/10/3107 · 2.76 Impact Factor
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    • "As previously discussed, the clinical significance is of whole-body low-dose neutron exposure is unclear, but putatively has a high potential for carcinogenesis [Brenner and Hall, 2008; National Council on Radiation Protection and Measurements (NCRP), 1990]. Large volume exposures typical of craniospinal dosimetric models suggest an attributable lifetime risk of SMN up to 14.8% (fatal SMN risk of 5.3%), for passively scattered proton therapy (Taddei et al., 2009, 2010). Thus, it is the neutron-producing external scatter dose that is thought to be an “avoidable” contributor to this substantial risk of SMN (Schneider et al., 2001). "
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    ABSTRACT: One of the most significant effects of radiation therapy on normal tissues is mutagenesis, which is the basis for radiation-induced malignancies. Radiation-induced malignancies are late complications arising after radiotherapy, increasing in frequency among survivors of both pediatric and adult cancers. Genetic backgrounds harboring germline mutations in tumor suppressor genes are recognized risk factors. Some success has been found with using genome wide association studies to identify germline polymorphisms associated with susceptibility. The insights generated by genetics, epidemiology, and the development of experimental models are defining potential strategies to offer to individuals at risk for radiation-induced malignancies. Concurrent technological efforts are developing novel radiotherapy delivery to reduce irradiation of normal tissues, and thereby, to mitigate the risk of radiation-induced malignancies. The goal of this review is to discuss epidemiologic, modeling, and radiotherapy delivery data, where these lines of research intersect and their potential impact on patient care.
    Frontiers in Oncology 04/2013; 3:73. DOI:10.3389/fonc.2013.00073
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