螺旋断层治疗用于全骨髓照射的初步结果

目的：评估全骨髓照射作为异基因外周血干细胞移植（ Allo－PBSCT）前预处理方式的疗效及安全性。方法2014—2015年6例患者Allo－PBSCT前均采用HT联合环磷酰胺（60 mg／kg1次／d共2 d）的预处理方式。采用HT技术实施。结果6例患者中位年龄18．5岁。处方剂量（12 Gy分3次3 d完成）精确覆盖全部骨骼区域,OAR受量较全身照射降低13％～60％。头颈、胸腹、盆腔部位剂量验证通过率分别为（95．8±1．2）％、（96．2±1．1）％、（98．9±0．8）％。上、下部分的HI和平均治疗时间分别为1．18、1．17和39．2、14．3 min。放疗期间5例患者出现1—2级恶心、呕吐,2例患者出现1—2级疼痛,1例患者出现1级腹泻,1例患者出现2级肠炎。所有患者均未出现3—4级非血液学不良反应,并且成功植入骨髓。结论 HT技术应用于全骨髓照射是可行的,靶区适形度高,剂量均匀性好,安全性高且不良反应较传统TBI明显减低,可作为新的骨髓移植前预处理方式。     

基于螺旋断层治疗的全身皮肤照射体位固定新技术初步观察

目的 初步观察不同体位固定技术在螺旋断层治疗技术下进行全身皮肤照射(TSI)的可行性。方法 对中山大学肿瘤防治中心接受TSI治疗的 3例蕈样霉菌病患者分别采用低温热塑高分子材料俯卧位固定、潜水衣结合负压真空袋仰卧位固定、低温热塑高分子材料结合真空袋仰卧位固定方法,观察固定效果并计算平均摆位误差、靶区适形指数(CI)、靶区均匀性指数(HI)和靶区 Dmean。结果 3种体位固定方式均起到良好固定效果,设计的放疗计划各参数均能达到临床要求。3例患者平均摆位误差在左右、头脚、腹背方向分别为(0.26±3.40)、(-2.63±4.63)、(6.13±4.86)mm,靶区CI为 0.56±0.09、HI为 1.186±0.059、Dmean为(2586.56±63.28)cGy。结论 低温热塑高分子材料或潜水衣都可以联合真空袋进行TSI治疗的体位固定。通过补偿膜剂量建成效应提高表皮剂量达临床要求,为螺旋断层治疗技术进行TSI提供了安全可靠的体位固定方法。     

螺旋断层IMRT全骨髓照射流程可行性探讨

目的 探讨应用螺旋断层IMRT实施全骨髓照射(TMI)的流程可行性。方法 12例患者骨髓移植前1周均实施TMI预处理,处方剂量12 Gy分3次,1 次/d。按照TMI流程依次完成体位固定、CT定位、靶区勾画、计划设计及剂量验证等步骤,并实施治疗。统计靶区和正常组织的剂量参数,观察剂量验证结果与图像引导结果的相关性。结果 与全身照射(TBI)相比,TMI可显著降低正常组织受量,正常组织除口腔外中位数均<6.0 Gy,其中晶体D50(1.8±0.1) Gy,脑D50(5.7±0.2) Gy,双肺D50(5.2±0.2) Gy,肝D50(4.6±0.2) Gy。3 mm/3%标准下各部位γ通过率>95%,头颈段x轴摆位误差小于盆腔段,而z轴摆位误差则大于盆腔段。结论 应用螺旋断层IMRT可顺利实施TMI,剂量学优势明显,治疗流程合理可行。     

全骨髓照射中基于黏膜保护的HT-TMI计划参数选择研究

目的:通过对比不同螺距、调制因子组合的螺旋断层放射治疗全骨髓照射(total marrow irradiation,TMI)计划,评估其剂量学参数,寻求黏膜保护的最优参数组合。方法:勾画全骨髓临床靶区（含上、下颌骨）及危及器官,放疗计划优化时将射野宽度、螺距及调制因子三种计划参数固定,并对黏膜相关器官限量,评估器官受量的降低程度及该方案对整体计划质量的影响。固定射野宽度为5 cm,采用不同螺距和不同调制因子制定计划,通过非参数检验比较不同计划的剂量学指标、出束时间,分析不同参数组合对改善黏膜剂量分布的差异,以获取最优组合。结果:黏膜相关器官限量后平均中位剂量较不限量减少52%~64%,且对整体计划质量无显著影响;螺距(0.287)和调制因子(3或3.5)改善黏膜相关器官剂量分布更具优势。结论:通过计划优化减低黏膜相关器官剂量是可行的。     

新型体位固定系统在全骨髓照射中的应用

目的 应用MVCT分析新型体位固定系统在全骨髓照射(TMI)中的应用效果。方法 回顾分析2016-2017年武汉大学中南医院接受TMI治疗的22例患者的资料。新型体位固定组12例,组合式固定组10例。分析2个组患者头颈部、胸部、腹盆部、下肢的摆位误差数据,采用两独立样本t检验分析差异。结果 在头颈部新型体位固定组患者在左右、头脚、前后和沿长轴旋转方向摆位误差分别为(1.06±0.79)、(1.34±0.66)、(2.45±1.48)mm和(0.63°±0.65°),在胸部分别为(1.58±1.13)、(2.38±1.99)、(2.05±1.68)mm和(0.31°±0.32°),在腹盆部分别为(1.67±1.24)、(3.88±2.20)、(1.96±1.32)mm和(0.48°±0.53°),在下肢分别为(0.95±0.73)、(1.99±1.35)、(3.66±2.13)mm和(0.24°±0.31°);组合式固定组患者分别为(2.59±2.58)、(3.28±1.85)、(3.71±2.43)mm和(1.15°±1.18°),在胸部分别为(4.38±3.69)、(5.64±3.78)、(2.72±1.91)mm和(1.55°±0.86°),在腹盆部分别为(4.14±2.97)、(6.97±3.68)、(2.21±2.26)mm和(1.23°±0.74°),在下肢分别为(2.28±1.15)、(5.97±3.00)、(3.44±1.93)mm和(1.09°±0.94°)。2个组患者各部位摆位误差在左右、头脚及旋转方向上不同(P<0.05),而在胸腹部位分次间摆位稳定性在左右、头脚及旋转方向上也不同(P<0.05)。结论 新型体位固定系统可显著提高摆位精度和摆位稳定性,提高患者的治疗精度。     

螺旋断层全身皮肤照射治疗的研究进展

皮肤T细胞淋巴瘤是一组相对罕见的主要表现在皮肤的成熟T细胞淋巴瘤,其常见的亚型是蕈样肉芽肿（俗称蕈样霉菌病）。电子线全身照射作为重要的常规治疗手段之一,却存在着剂量分布不均、体位重复差、治疗时间过长等诸多缺点,从而影响疗效及患者预后。近年随着螺旋断层放疗系统的出现与逐步普及,越来越多的单位凭借其能治疗超长靶区和实现剂量雕刻式分布的特点,正逐步扩展其在全身皮肤照射治疗中的应用,以便进一步探讨其优劣并确认是否能取代传统电子线全身照射。本文对螺旋断层全身皮肤照射治疗的研究进展做一综述,介绍其治疗技术的发展、临床治疗效果及目前存在的顾虑和争议。     

螺旋断层放疗与常规放疗在全脑全脊髓放疗中的急性血液学毒性比较北大核心CSCD

目的比较螺旋断层放疗和常规放疗在全脑全脊髓放疗中引起的急性血液学毒性。方法回顾性分析70例全脑全脊髓放疗患者放疗期间的急性血液学资料,按治疗技术分为螺旋断层放疗组(HT组14例)和常规放疗组(CRT组56例),参照CTCAE v3.0不良反应评价标准观察患者放疗期间急性血液学毒性情况并比较两组骨髓抑制情况,组间差异性比较采用χ2检验。结果放疗期间HT组和CRT组白细胞、血小板及血红蛋白下降发生率分别为100%、100%、78.6%及91.1%、67.9%、32.1%(P<0.05);两组Ⅲ~Ⅳ度白细胞、血小板、血红蛋白减低的发生率分别为85.7%、50%、14.2%及35.8%、10.7%、0(P<0.05);HT组和CRT组各有92.8%(10/14)和10.7%(6/56)的患者因骨髓抑制延误放疗(P<0.05);HT组平均出现骨髓抑制时间为11.50天,CRT组为17.37天(P<0.05)。放疗前化疗患者较未化疗患者骨髓抑制严重。结论全脑全脊髓螺旋断层放疗骨髓抑制较常规放疗发生率高、程度重,临床需引起重视,可能与骨髓、全身低剂量照射范围及剂量、化疗等因素相关,需进一步研究。     

全脑全脊髓放疗骨髓保护的初步研究

目的 分析全脑全脊髓放疗患者骨髓受量与血液学毒性的关系,并初步探索HT及VMAT在全脑全脊髓放疗中骨髓的剂量学差异。方法 收集我院螺旋断层全脑全脊髓放疗20例患者临床资料及HT计划,将计划回传至MIM系统。在CT上依次勾画患者的颅骨、下颌骨、锁骨、胸骨、肩胛骨、肋骨、椎体骨、盆骨,在DVH图上读出上述骨结构及总骨的V2、V5、V10、V15、V20、V25、V30、V35、Dmean、Dmax值,分析上述指标与患者≥2级血液学毒性相关性。再从中选取6例患者为对象,将图像传输至Monaco计划系统并完成VMAT计划,对比两种计划上述骨结构剂量体积差异。采用Spearman相关性分析及Wilcoxon符号秩和检验。结果 患者≥2级白细胞减低与盆骨V25、总骨V5呈正相关(P=0.038、0.025),≥2级血小板减少与盆骨V20呈正相关(P=0.041),≥2级中性粒细胞减低与椎骨V10呈正相关(P=0.036)。患者VMAT与HT计划相比,椎骨、盆骨的各剂量体积指标相近(P>0.05)。结论 全脑全脊髓放疗中患者≥2级白细胞减低与盆骨V25、总骨V5呈正相关,≥2级血小板减少与盆骨V20呈正相关,≥2级中性粒细胞减低与椎骨V10呈正相关。全脑全脊髓放疗患者VMAT与HT计划相比椎骨、盆骨各剂量体积相近。     

鼻咽癌螺旋断层治疗中口腔黏膜勾画方法探索

目的 评价两种口腔黏膜勾画方法在鼻咽癌患者中预测急性放射性口腔黏膜炎(A-ROM)价值。方法 前瞻性观察分析2017-2019年间浙江省肿瘤医院收治的局部中晚期鼻咽癌150例,所有患者均接受根治性螺旋断层治疗并采用全口腔勾画法(OCC法)和表面黏膜勾画法(MSC法)勾画口腔黏膜。根据RTOG急性放射损伤分级标准每周评估并记录患者的A-ROM分级,比较两种方法对A-ROM的价值。结果 所有患者≥3级A-ROM发生率为33.3%。单因素分析≥3级A-ROM发生的相关剂量学参数包括OCC法的V5、V10、V15、V45、V50、V55、V60、V65、V70和MSC法的V5、V10、V50、V55、V60、V65、V70、Dmean(P均<0.05)。二分类Logistic回归分析发现OCC法的性别、吸烟是≥3级A-ROM的危险因素(男/女:OR=0.141,95%CI为0.037~0.538,P=0.004;吸烟/不吸烟:OR=5.109,95%CI为1.413~18.470,P=0.013)。MSC法的性别、吸烟、N分期、V55是≥3级A-ROM的危险因素(男/女:OR=0.129,95%CI为0.032~0.519,P=0.004;吸烟/不吸烟:OR=4.448,95%CI为1.224~16.164,P=0.023;N分期:OR=2.291,95%CI为1.268~4.137,P=0.006;V55:OR=1.432,95%CI为1.008~2.033,P=0.045)。MSC的V55阈值为7.70%,曲线下面积为0.754,敏感性为0.680,特异性为0.740(P<0.001)。结论 采用螺旋断层治疗鼻咽癌时,MSC法相比OCC法可以更加准确地预测A-ROM的严重程度。     

鼻咽癌螺旋断层治疗中口腔黏膜勾画方法探索

目的 评价两种口腔黏膜勾画方法在鼻咽癌患者中预测急性放射性口腔黏膜炎(A-ROM)价值。方法 前瞻性观察分析2017-2019年间浙江省肿瘤医院收治的局部中晚期鼻咽癌150例,所有患者均接受根治性螺旋断层治疗并采用全口腔勾画法(OCC法)和表面黏膜勾画法(MSC法)勾画口腔黏膜。根据RTOG急性放射损伤分级标准每周评估并记录患者的A-ROM分级,比较两种方法对A-ROM的价值。结果 所有患者≥3级A-ROM发生率为33.3%。单因素分析≥3级A-ROM发生的相关剂量学参数包括OCC法的V5、V10、V15、V45、V50、V55、V60、V65、V70和MSC法的V5、V10、V50、V55、V60、V65、V70、Dmean(P均<0.05)。二分类Logistic回归分析发现OCC法的性别、吸烟是≥3级A-ROM的危险因素(男/女:OR=0.141,95%CI为0.037~0.538,P=0.004;吸烟/不吸烟:OR=5.109,95%CI为1.413~18.470,P=0.013)。MSC法的性别、吸烟、N分期、V55是≥3级A-ROM的危险因素(男/女:OR=0.129,95%CI为0.032~0.519,P=0.004;吸烟/不吸烟:OR=4.448,95%CI为1.224~16.164,P=0.023;N分期:OR=2.291,95%CI为1.268~4.137,P=0.006;V55:OR=1.432,95%CI为1.008~2.033,P=0.045)。MSC的V55阈值为7.70%,曲线下面积为0.754,敏感性为0.680,特异性为0.740(P<0.001)。结论 采用螺旋断层治疗鼻咽癌时,MSC法相比OCC法可以更加准确地预测A-ROM的严重程度。     

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

PURPOSE: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. METHODS AND MATERIALS: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. RESULTS: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. CONCLUSION: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.     

HT在分段TBI中上下靶区间距研究

目的 选取8例急性白血病HT的TBI患者,将其分两段照射的上下靶区按不同间距设计的计划依次对应叠加在一起,分析不同间距下衔接处靶区剂量分布情况,寻找最佳靶区间隔距离。方法 选取8例身高约120 cm急性白血病患者作为研究对象,使用Siemens定位CT进行扫描,图像层厚5 mm,从颅顶扫描至脚趾,同时在髌骨上方10 cm附近放置铅丝,作为上下两段靶区分割线。在瓦里安Eclipse 10.0医生工作站进行靶区和OAR勾画,其中上下靶区在铅丝分割处依次分别内收不同距离,然后传至HT计划工作站进行计划设计,其中铅门宽度5 cm,调制因子1.8,螺距0.43,其余计划参数都保持一致。将设计好的计划分别对应叠加在一起,依次分析不同间隔距离所对应衔接处靶区剂量分布情况,从而选择出最佳靶区间隔距离。结果 比较不同间隔距离时所对应的衔接处靶区剂量分布,发现间隔为5 cm时衔接处靶区的剂量分布最佳,当间隔距离>5 cm时衔接处靶区剂量明显不足,当间隔<5 cm且逐渐变小时衔接处靶区的剂量明显超过处方剂量且逐步增大。结论 对于HT进行分段式TBI治疗时,采用铅门宽度5 cm,调制因子1.8,螺距0.43及扫描层厚5 mm的设计参数,在勾画上下靶区时应距铅丝分割线各内收2.5 cm距离,即靶区间距为5 cm时,能保证在进行分段TBI治疗时靶区衔接处不会出现剂量冷热点,确保治疗的精确与安全。     

Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant

Background and purpose

To report our clinical experience in planning and delivering total marrow irradiation (TMI) after total body irradiation (TBI) in patients with relapsed acute leukemia undergoing an allogeneic stem-cell transplant (SCT).

Materials and Methods

Patients received conventional TBI as 2 Gy BID/day for 3 days boosted the next day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT).

Results

Fifteen patients were treated from July 2009 till May 2010, ten with acute myeloid leukemia, and five with acute lymphoid leukemia. At the time of radiotherapy eight patients were in relapse and seven in second or third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases and an unrelated donor in 8 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%-65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up is short ranging from 180 to 510 days (median 310 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Three patients have died (2 for severe GvHD, 1 for infection) and 2 patients showed relapsed leukemia. Twelve patients are alive with ten survivors in clinical remission of disease.

Conclusions

This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. For patients with advanced leukemia targeted TMI after TBI may be a novel approach to increase radiation dose with low risk of severe toxicity.     

Total body irradiation using helical tomotherapy: Set-up experience and in-vivo dosimetric evaluation

PurposeHelical Tomotherapy (HT) appears as a valuable technique for total body irradiation (TBI) to create highly homogeneous and conformal dose distributions with more precise repositioning than conventional TBI techniques. The aim of this work is to describe the technique implementation, including treatment preparation, planning and dosimetric monitoring of TBI delivered in our institution from October 2016 to March 2019.Material and methodPrior to patient care, irradiation protocol was set up using physical phantoms. Gafchromic films were used to assess dose distribution homogeneity and evaluate imprecise patient positioning impact. Sixteen patients’ irradiations with a prescribed dose of 12 Gy were delivered in 6 fractions of 2 Gy over 3 days. Pre-treatment quality assurance (QA) was performed for the verification of dose distributions at selected positions. In addition, in-vivo dosimetry was carried out using optically stimulated luminescence dosimeters (OSLD).ResultsPlanning evaluation, as well as results of pre-treatment verifications, are presented. In-vivo dosimetry showed the strong consistency of OSLD measured doses. OSLD mean relative dose differences between measurement and calculation were respectively +0,96% and ?2% for armpit and hands locations, suggesting better reliability for armpit OSLD positioning. Repercussion of both longitudinal and transversal positioning inaccuracies on phantoms is depicted up to 2 cm shifts.ConclusionThe full methodology to set up TBI protocol, as well as dosimetric evaluation and pre-treatment QA, were presented. Our investigations reveal strong correspondence between planned and delivered doses shedding light on the dose reliability of OSLD for HT based TBI in-vivo dosimetry.