Adaptive radiation therapy of breast cancer by repeated imaging during irradiation

Breast cancer is the most frequent cancer among females and also a leading cause of cancer related mortality worldwide. A multimodality treatment approach may be utilized for optimal management of patients with combinations of surgery, radiation therapy (RT) and systemic treatment. RT composes an integral part of breast conserving treatment, and is typically used after breast conserving surgery to improve local control. Recent years have witnessed significant improvements in the discipline of radiation oncology which allow for more focused and precise treatment delivery. Adaptive radiation therapy (ART) is among the most important RT techniques which may be utilized for redesigning of treatment plans to account for dynamic changes in tumor size and anatomy during the course of irradiation. In the context of breast cancer, ART may serve as an excellent tool for patients receiving breast irradiation followed by a sequential boost to the tumor bed. Primary benefits of ART include more precise boost localization and potential for improved normal tissue sparing with adapted boost target volumes particularly in the setting of seroma reduction during the course of irradiation. Herein, we provide a concise review of ART for breast cancer in light of the literature.     

鼻咽癌调强放疗中解剖及剂量学改变再次计划必要性研究

目的 探讨鼻咽癌调强放疗(IMRT)中解剖学动态变化规律,以及这些变化对剂量学分布的影响,客观评价放疗重新修改物理计划的必要性.方法搜集12例Ⅲ～Ⅳ期鼻咽癌患者进行相关临床前瞻性研究,所有患者均接受同步放化疗.疗前常规螺旋CT扫描,由临床医生进行靶区及危及器官勾画.IMRT计划完成后再次螺旋CT扫描校正治疗中心,开始治疗后的每周按治疗中心重复进行螺旋CT扫描,然后将获取的CT图像和原计划CT图像融合.首先在系统融合界面就变化的PTV1及正常器官(腮腺、轮廓)进行重新修改,并计算出靶区及正常器官体积变化范围,从中寻找再次计划的最佳时间段.其次按照首次计划条件在重新修改的靶区上再次计算,得出靶区及正常器官剂量学参数后与首次计划对比观察其变化.结果 IMRT治疗中头颈部外轮廓、腮腺体积逐步缩小,放疗至5周左右腮腺及轮廓体积变化达顶峰,因而选择第5周CT和首次CT作为剂量学研究对象.再次计算及配对设计比较发现治疗中和治疗前PTV1,D99、D95,脊髓Dmax、Dmean,脑干Dmax、Dmean,下颌骨Dmax、Dmean相似(P值均＞0.05),而双侧腮腺D50不同(P左=0.03,P右=0.01).结论 IMRT治疗过程中鼻咽癌患者出现腮腺缩小、轮廓改变和PTV缩小.放疗至5周左右相关体积变化达顶峰.第5周再次计划与原计划相比脊髓、脑干、下颌骨、PTV1各项剂量学参数值变化不大,但腮腺剂量增加较为明显.     

头颈部肿瘤自适应放疗的研究进展

调强放射治疗(intensity-modulated radiation therapy,IMRT)是头颈部恶性肿瘤的重要治疗方法之一。但在IMRT过程中,摆位误差、解剖结构的移位及变形、肿瘤退缩或进展及形状改变等,可导致靶区和危及器官的照射剂量和体积出现“偏差”,影响IMRT的精确性。图像引导的放射治疗(image-guidedradiotherapy,IGRT)可部分纠正摆位误差,从而提高放疗精度,但不能解决非刚性误差以及解剖结构变化带来的剂量差异。自适应放射治疗(adaptive radiation therapy,ART)是在IMRT和IGRT基础上出现的新型放疗技术,能修正IMRT和IGRT靶区和危及器官的偏差。通过患者图像、剂量等反馈信息对原治疗计划重新优化和调整,这是一种基于反馈控制理论的治疗策略。其目的是使放射治疗更加精确化、个体化。     

The role of replanning in fractionated intensity modulated radiotherapy for nasopharyngeal carcinoma

Background and purpose

Anatomic changing frequently occurred during fractionated radiotherapy. The aims of this study were to model the potential benefit of adaptive IMRT replanning during fractionated radiotherapy and its potential advantage over clinical outcome in patients with nasopharyngeal carcinoma.

Materials and methods

Thirty-three patients with repeat CT imaging and replanning were retrospectively analyzed. 66 case-matched control patients without replanning were identified by matching for AJCC stage, gender, and age. Hybrid IMRT plans were generated to evaluate the dosimetric changing. Mann-Whitney-Wilcoxon tests were used to evaluate the effect of replanning on volumetric and dosimetric outcomes within individuals. Kaplan-Meier estimators were used to estimate the survival function of patients with or without replanning.

Results

The mean volume of the ipsilateral and contralateral parotid glands decreased during the treatment. The hybrid IMRT plans showed decreased doses to target volumes and increased doses to normal structures in replanning. The clinical outcome comparison indicated that the IMRT replanning improved the 3 years local progression-free survival for patients who had AJCC staged more than T₃ (T_3,4N_x) and ease the late effects for patients who had large lymph nodes (AJCC stage T_xN_2,3).

Conclusion

Repeat CT imaging and IMRT replanning were recommendatory for specific nasopharyngeal carcinoma patients.     

局部晚期鼻咽癌调强放疗中解剖结构改变及剂量分布变化研究

目的 探讨局部晚期鼻咽癌患者在调强放疗（IMRT）期间的解剖结构体积改变及剂量分布变化。方法 选取18例局部晚期鼻咽癌患者,利用每周锥形束CT （CBCT）分析患者的解剖结构体积变化,并在放疗20次后再次进行IMRT计划设计,探讨二程IMRT计划的剂量学。结果 GTV_nx每周平均缩小3.15%,共缩小22.03%;GTV_nd每周平均缩小5.67%,共缩小39.68%;左右腮腺每周分别缩小4.93%和5.26%,总共缩小29.60%和31.56%。GTV_nd和腮腺在放疗前4周有较大退缩,放疗4周后体积改变趋于平缓。与初始Plan 1相比,Plan 2中PGTV_nd的D₉₅下降2.20%（t=2.382,P<0.05）,而PGTV_nx、PTV₁和PTV₂的D₉₅没有显著变化;左腮腺D_mean、D₅₀和V₃₀分别增加7.34%、12.68%和10.90%,与放疗前比较差异均有统计学意义（t=-3.376、-3.738、-3.679,P<0.05）;右腮腺D_mean、D₅₀和V₃₀分别增加6.13%、11.17%和9.72%,与放疗前比较差异均有统计学意义（t=-2.550、-2.446、-2.673,P<0.05）;喉的D_mean平均增加8.69%,与放疗前比较差异均有统计学意义（t=-3.099,P<0.05）。相比较于Plan 2,综合计划Plan （1+2）中PGTV_nd的D₉₅增加1.37%,差异有统计学意义（t=-3.555,P<0.05）,左腮腺D_mean、D₅₀和V₃₀分别平均降低了2.90%、2.73%和4.62%,差异有统计学意义（t=3.089、2.718、2.705,P<0.05）;右腮腺D_mean、D₅₀和V₃₀分别降低3.49%、3.44%和3.80%,与放疗前比较,差异均有统计学意义（t=2.781、2.958、4.275,P<0.05）;喉的D_mean平均降低3.29%（t=2.747,P<0.05）。结论 局部晚期鼻咽癌患者在IMRT期间靶区和腮腺体积均会显著缩小;放疗中期有必要设计二程放疗计划,以此来提高靶区剂量并一定程度上降低靶区周围危及器官的剂量。     

鼻咽癌IMRT再计划的研究进展

IMRT是目前鼻咽癌最主要的治疗手段。研究表明鼻咽癌放疗过程中由于原发肿瘤及转移淋巴结退缩、体重下降导致正常器官及头颈部轮廓缩小,这些变化可能引起原发肿瘤剂量不足和OAR剂量过高,从而影响治疗疗效。放疗中修改计划可保证靶区剂量、降低OAR剂量,部分患者从中获益。但对于IMRT中再计划的优势、时机及频率还未达成共识,需要继续探索。对于如何挑选放疗中需要修改计划的患者目前缺乏相应的规范,有待继续研究。     

Evaluation of the effectiveness of novel single-intervention adaptive radiotherapy strategies based on daily dose accumulation

Parotid gland (PG) shrinkage and neck volume reduction during radiotherapy of head and neck (H&N) cancer patients is a clinical issue that has prompted interest in adaptive radiotherapy (ART). This study focuses on the difference between planned dose and delivered dose and the possible effects of an efficient replanning strategy during the course of treatment. Six patients with H&N cancer treated by tomotherapy were retrospectively enrolled. Thirty daily dose distributions (D_MVCT) were calculated on pretreatment megavoltage computed tomography (MVCT) scans. Deformable Image Registration which matched daily MVCT with treatment planning kilovoltage computed tomography was performed. Using the resulting deformation vector field, all daily D_MVCT were deformed to the planning kilovoltage computed tomography and resulting doses were accumulated voxel per voxel. Cumulative D_MVCT was compared to planned dose distribution performing γ-analysis (2 mm, 2% of 2.2 Gy). Two single-intervention ART strategies were executed on the 18th fraction whose previous data had suggested to be a suitable timepoint for a single replanning intervention: (1) replanning on the original target and deformed organ at risks (OARs) (a “safer” approach regarding tumor coverage) and (2) replanning on both deformed target and deformed OARs. D_MVCT showed differences between planned and delivered doses (3D-γ 2mm/2%-passing rate = 85 ± 1%, p < 0.001). Voxel by voxel dose accumulation showed an increase in average dose of warped PG of 3.0 Gy ± 3.3 Gy. With ART the average dose of warped PG decreased by 3.2 Gy ± 1.7 Gy in comparison to delivered dose without replanning when both target and OARs were deformed. Average dose of warped PG decreased by 2.0 Gy ± 1.4 Gy when only OARs were deformed. Anatomical variations lead to increased doses to PGs. Efficient single-intervention ART-strategies with replanning on the 18th MVCT result a reduced PG dose. A strategy with deformation of both target and OAR resulted in the lowest PG dose, while formally maintaining PTV coverage. Deformation of only OAR nevertheless reduces PG dose and has less uncertainties regarding PTV coverage.     

食管癌简化调强放疗中靶体积变化及对初始计划剂量学影响

目的 探讨食管癌简化调强放疗(sIMRT)中解剖学动态变化规律和靶体积变化,以及这些变化对初始计划剂量学分布影响,评价重新修改放疗计划的必要性和时机.方法 29例接受单纯放疗的食管癌患者常规模拟CT扫描,其中11例在放疗开始后每2周扫描(每例4次),18例在放疗第4周进行第2次扫描(每例2次).将CT模拟图像与初始计划CT图像融合后由同一医生重新勾画靶区及正常器官,将初始计划导入新勾画的靶区,得出靶区及正常器官剂量学参数后与初始计划比较.结果 每2周扫描的11例忠者疗前和疗后第2、4、6周胸部轮廓体积变化平均值分别为13948cm3和13245、12789、11837 cm3(6周时t=2.07,P=0.043),每2周体积缩小平均值为425 cm3.0～6周中大体肿瘤体积平均值逐渐降低,其中0周与4、6周比较下降最明显(47.22 cm3:37.78 cm3,t=2.44,P=0.035;47.22 cm3:33.55 cm3,t=2.55,P=0.029),而4周和6周变化不明显(t=-0.75,P=0.261).0～6周靶区适行指数逐渐降低和不均匀指数依次增加,分别为0.70、0.68、0.67、0.61(4周时t=3.20,P=0.013)和1.13、1.22、1.23、1.27(4周时t=-4.56,P=0.001).全组患者sIMRT 4周时100%大体肿瘤受照剂量增加至62.57 Gy(t=-2.93,P=0.007),99%临床靶体积受照剂量和95%计划靶体积受照剂量分别下降至58.24 Gy(t=1.49,P=0.147;2例＜54 Gy)和57.44 Gy(t=2.07,P=0.048);正常组织中只有脊髓最大剂量和双肺V30的增加有统计学意义(41.52 Gy∶43.53Gy,t=-2.42,P=0.022;11.4%∶12.2%,t=-2.26,P=0.032).结论 食管癌sIMRT4周时肿瘤体积变化最明显,是CT-CT融合观察靶体积变化的最佳时机.部分患者需要做二次计划的修改使肿瘤靶区获得合理剂量.