Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: An alternative to standard total body irradiation
Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: An alternative to standard total body irradiation
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DOI：
10.1016/j.bbmt.2005.10.026
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发表时间：
2006-03-01
影响因子：
4.3
通讯作者：
Somlo, G
中科院分区：
文献类型：
--
作者：
Wong, JYC;Liu, A;Somlo, G
全身照射是骨髓移植预适应方案的重要组成部分。在脑外伤中，由于相关的正常器官毒性，剂量递增是困难的。为了减少对正常器官的剂量，减少毒性，并允许剂量递增，需要一种方法来优先将更有针对性的剂量输送到肿瘤负担最大的部位。这项研究的目的是通过剂量学分析，评估使用最近开发的图像引导断层扫描调强放射治疗递送系统(螺旋断层放射治疗)选择性地将靶向清髓剂量的辐射输送到骨髓和骨髓的潜在优势和可行性。3名年龄分别为5岁、20岁和53岁的患者的全身CT数据被用于治疗计划研究，以评估两种靶向TBI策略：全骨髓照射(TMI)，靶区定义为骨骼；全骨髓和淋巴照射(TMLI)，靶区定义为骨、主要淋巴结链、肝、脾和避难所，如脑。并与常规脑损伤的器官剂量和剂量分布进行比较。与传统的TBI相比，TMI和TMLI的平均器官剂量减少了1.7到7.5倍。通过这种更有针对性的方法，剂量-体积直方图分析预测了将骨骼(和包含骨髓)的剂量提高到20GY的可能性，同时将正常器官的剂量维持在低于常规TBI的12GY水平。成人和儿童患者的结果相似，表明这种形式的靶向TBI将适用于大多数患者，无论框架大小。作为串联移植方案的一部分，53岁的多发性骨髓瘤患者接受了TMI至10GY的治疗。临床结果证实了治疗计划的预测。TMI后，患者经历了预期的血细胞计数最低点，随后成功植入。2级恶心和I级呕吐仅在TMI的第2天发生。未观察到皮肤红斑、口腔粘膜炎、食管炎和肠炎。这份报告证明了使用图像引导的断层扫描强度调制放射治疗传递系统选择性地将清髓剂量的辐射传递到骨骼和骨髓的可行性和潜在的剂量学优势。器官剂量大大低于与标准TBI相关的剂量，并预测有可能显著减少相关毒性并允许剂量上升。结果还表明，这种形式的靶向脑损伤可能比其他形式的靶向脑损伤具有潜在的优势，如放射免疫治疗或寻骨放射性核素治疗。正在进行的临床试验将确定可达到的最大TMI和TMLI剂量，并确定这种新方法对接受造血干细胞移植的患者的潜在优势和局限性。(C)2006年美国血液和骨髓移植学会。
Total body irradiation (TBI) is an important part of bone marrow transplantation conditioning regimens. In TBI, dose escalation is difficult, because of associated normal organ toxicities. A method to deliver a more targeted dose of TBI preferentially to sites of greatest tumor burden is needed to reduce the dose to normal organs, reduce toxicities, and permit dose escalation. The purpose of this study was to evaluate, through a dosimetric analysis, the potential advantages and feasibility of selectively delivering targeted myeloablative doses of radiation to bone and marrow using a recently developed image-guided tomographic intensity-modulated radiation therapy delivery system (helical tomotherapy). Whole-body computed tomography datasets from 3 patients, age 5, 20, and 53 years, were used for treatment planning studies to evaluate 2 targeted TBI strategies: total marrow irradiation (TMI), in which the target region was defined as the skeletal bone, and total marrow and lymphoid irradiation (TMLI), in which the target regions were defined as bone, major lymph node chains, liver, spleen, and sanctuary sites, such as brain. Organ doses and dose distributions were compared with those in conventional TBI. A 1.7- to 7.5-fold reduction in median organ doses was observed with TMI and TMLI compared with conventional TBI. With this more targeted approach, a dose-volume histogram analysis predicted the potential to escalate the dose to bone (and containing marrow) up to 20 Gy, while maintaining doses to normal organs at lower levels than in conventional TBI to 12 Gy. Results were similar for the adult and pediatric patients, indicating that this form of targeted TBI will be applicable to most patients regardless of frame size. TMI to 10 Gy was delivered as part of a tandem transplant regimen to the 53-year-old patient with multiple myeloma. Clinical results confirmed the treatment planning predictions. After TMI, the patient experienced the expected blood count nadir, followed by successful engraftment. Grade 2 nausea and grade I emesis occurred only briefly on day 2 of TMI. Skin erythema, oral mucositis, esophagitis, and enteritis were not observed. This report demonstrates the feasibility and potential dosimetric advantages of selectively delivering myeloablative doses of radiation to bone and marrow using an image-guided tomographic intensity-modulated radiation therapy delivery system. Organ doses are substantially lower than those associated with standard TBI and predict the potential to significantly reduce associated toxicities and allow for dose escalation. The results also suggest that this form of targeted TBI may have potential advantages over other forms of targeted TBI, such as radioimmunotherapy or bone-seeking radionuclide therapy. Ongoing clinical trials will define the maximum TMI and TMLI doses achievable and define the potential advantages and limitations of this new approach for patients undergoing hematopoietic stem cell transplantation. (C) 2006 American Society for Blood and Marrow Transplantation.