Retrospective NCI Phantom-Monte Carlo Dosimetry for Late Effects in Wilms Tumor

项目摘要 放射治疗是儿童晚期毒性的最重要因素。与成年人不同， 关于儿童三维（3D）正常组织辐射耐受性的大量数据。这项回顾性 剂量测定研究将使用患者匹配的NCI计算儿科体模模型进行Monte Carlo剂量学分析。本研究将在所有5000名Wilms儿童的匹配模型上进行 根据五项国家Wilms肿瘤研究（NWTS）方案接受放射治疗（RT）的肿瘤（WT）， 1969-2002. WT的高生存率（90%）和NWTS晚期效应数据库的许多优势 使其成为治疗晚期效应的详细剂量测定研究的理想平台。1例患者匹配 基于每名NWTS患者的身高、体重、年龄和性别的体模，已预先勾画出目标轮廓 器官将从NCI的Lee博士的模型库中选择。此体模将导入到 用于重建NWTS辐射野的放射治疗计划系统。虽然现代RT治疗 计划系统（TPS）对于估计场内和近场位置的剂量是相当准确的， 方法不适用于野外剂量测量。蒙特卡罗（MC）剂量计算算法 克服了TPS的这一缺陷，更准确地测量了野外剂量。在这项研究中，两者 剂量测定模型将用于估计现场剂量，基于MC的剂量计算将用于 估计野外剂量对于本研究的AIM 1，我们将收集13个靶器官的3D剂量学数据， 器官包括甲状腺、心脏（整个心脏、心室和心肌）、肺、肾、肝、胸壁， 胃、结肠、乳房、子宫、卵巢、骨盆和睾丸。对于AIM 2，我们将审查和验证 西北地区试验记录的雄性和雌性生殖晚期效应（性腺功能减退和不育） 数据库，并进行一项基于前瞻性队列研究，以确定其患病率 NWTS幸存者。对于AIM 3，我们将研究RT剂量与靶器官之间的相关性， NCI Phantom MC剂量测定模型和NWTS确定的六种晚期效应，包括：充血性 心力衰竭（心脏、心室、心肌）、限制性肺病（肺、胸壁）、第二次 恶性肿瘤（肺、甲状腺、乳腺、肝、胃、结肠）、终末期肾病（肾脏）、不良反应 妊娠结局（卵巢、子宫、骨盆）和其他生殖结局（性腺功能减退和 不孕症-女性的卵巢、子宫和男性的睾丸）。全面了解3D器官 耐受性将有助于降低RT诱导的晚期毒性的发生率，并将其对 现在和未来的儿童癌症幸存者。

PROJECT SUMMARY Radiation therapy is the most important contributor to late toxicity in children. Unlike in adults, there is not much data on three-dimensional (3D) normal tissue radiation tolerance in children. This retrospective dosimetry study will use the patient-matched NCI computational pediatric phantom model for conducting Monte Carlo dosimetry analysis. This study will be performed on matched phantoms of all 5000 children with Wilms tumor (WT) who received radiation therapy (RT) on five National Wilms Tumor Study (NWTS) protocols during 1969-2002. The high survivorship (90%) of WT and the many advantages of the NWTS late effects database makes this an ideal platform for a detailed dosimetry study of late effects of therapy. One patient-matched phantom based on height, weight, age and sex of each NWTS patient, with already pre-contoured target organs will be selected from the phantom library of Dr. Lee at the NCI. This phantom will be imported into the radiation treatment planning system for reconstruction of NWTS radiation fields. While modern RT treatment planning systems (TPS) are fairly accurate for estimating doses both in-field and near-field locations, this method is not suitable for out-of-field dose measurements. The Monte Carlo (MC) dose calculation algorithm has overcome this deficiency of TPS and measures out-of-field doses more accurately. In this study, both dosimetry models will be used for estimating doses in-field, and MC-based dose calculations will be used for estimating out-of-field doses. For AIM 1 of this study, we will collect target organ 3D dosimetry data for 13 organs including thyroid, heart (total heart, ventricles and myocardium), lungs, kidneys, liver, chest wall, stomach, colon, breasts, uterus, ovaries, pelvis and testicles. For AIM 2 we will review and validate reproductive late effects (hypogonadism and infertility) among males and females recorded in the NWTS database and conduct a prospective questionnaire-based cohort study to determine their prevalence among NWTS survivors. For AIM 3 we will study the association between RT dose to target organs estimated using the NCI Phantom MC dosimetry model and six late effects ascertained by the NWTS including: congestive heart failure (heart, ventricles, myocardium), restrictive pulmonary disease (lungs, chest wall), second malignant neoplasms (lung, thyroid, breasts, liver stomach, colon), end stage renal disease (kidney/s), adverse pregnancy outcomes (ovaries, uterus, pelvis) and additional reproductive outcomes (hypogonadism and infertility – ovaries, uterus in females and testicles in males). A comprehensive knowledge of 3D organ tolerance will help reduce the incidence of RT induced late toxicity and minimize their adverse impact on current and future childhood cancer survivors.