Sakthivel Vasanthan, Ganesh Kadirampatti M, McKenzie Craig, Boopathy Raghavendiran, Selvaraj Jothybasu
Advanced Medical Physics, Houston, USA.
Research and Development Centre, Bharathiar University, Coimbatore, India.
Australas Phys Eng Sci Med. 2019 Mar;42(1):201-209. doi: 10.1007/s13246-019-00731-y. Epub 2019 Feb 6.
Cranio-spinal irradiation (CSI) is widely used for treating medulloblastoma cases in children. Radiation-induced second malignancy is of grave concern; especially in children due to their long-life expectancy and higher radiosensitivity of tissues at young age. Several techniques can be employed for CSI including 3DCRT, IMRT, VMAT and tomotherapy. However, these techniques are associated with higher risk of second malignancy due to the physical characteristics of photon irradiation which deliver moderately higher doses to normal tissues. On the other hand, proton beam therapy delivers substantially lesser dose to normal tissues due to the sharp dose fall off beyond Bragg peak compared to photon therapy. The aim of this work is to quantify the relative decrease in the risk with proton therapy compared to other photon treatments for CSI. Ten anonymized patient DICOM datasets treated previously were selected for this study. 3DCRT, IMRT, VMAT, tomotherapy and proton therapy with pencil beam scanning (PBS) plans were generated. The prescription dose was 36 Gy in 20 fractions. PBS was chosen due to substantially lesser neutron dose compared to passive scattering. The age of the patients ranged from 3 to 12 with a median age of eight with six male and four female patients. Commonly used linear and a mechanistic doseresponse models (DRM) were used for the analyses. Dose-volume histograms (DVH) were calculated for critical structures to calculate organ equivalent doses (OED) to obtain excess absolute risk (EAR), life-time attributable risk (LAR) and other risk relevant parameters. A α' value of 0.018 Gy and a repopulation factor R of 0.93 was used in the mechanistic model for carcinoma induction. Gender specific correction factor of 0.17 and - 0.17 for females and males were used for the EAR calculation. The relative integral dose of all critical structures averaged were 6.3, 4.8, 4.5 and 4.7 times higher in 3DCRT, IMRT, VMAT and tomotherapy respectively compared to proton therapy. The mean relative LAR calculated from the mean EAR of all organs with linear DRM were 4.0, 2.9, 2.9, 2.7 higher for male and 4.0, 2.9, 2.8 and 2.7 times higher for female patients compared to proton therapy. The same values with the mechanistic model were 2.2, 3.6, 3.2, 3.8 and 2.2, 3.5, 3.2, 3.8 times higher compared to proton therapy for male and female patients respectively. All critical structures except lungs and kidneys considered in this study had a substantially lower OED in proton plans. Risk of radiation-induced second malignancy in Proton PBS compared to conventional photon treatments were up to three and four times lesser for male and female patients respectively with the linear DRM. Using the mechanistic DRM these were up to two and three times lesser in proton plans for male and female patients respectively.
颅脊髓照射（CSI）广泛应用于儿童髓母细胞瘤的治疗。辐射诱发的第二原发恶性肿瘤备受关注；尤其是儿童，因为他们预期寿命长且幼年组织对辐射更敏感。可用于CSI的技术有多种，包括三维适形放疗（3DCRT）、调强放疗（IMRT）、容积旋转调强放疗（VMAT）和断层放疗。然而，由于光子照射的物理特性会给正常组织带来相对较高剂量，这些技术与第二原发恶性肿瘤的较高风险相关。另一方面，与光子治疗相比，质子束治疗由于在布拉格峰之外剂量急剧下降，给正常组织的剂量要少得多。本研究的目的是量化与其他光子治疗相比，质子治疗用于CSI时风险的相对降低情况。本研究选择了之前治疗过的10个匿名患者的DICOM数据集。生成了3DCRT、IMRT、VMAT、断层放疗和笔形束扫描质子治疗（PBS）计划。处方剂量为36 Gy，分20次给予。选择PBS是因为与被动散射相比，其产生的中子剂量要少得多。患者年龄在3至12岁之间，中位年龄为8岁，男性6例，女性4例。分析采用常用的线性和机制剂量反应模型（DRM）。计算关键结构的剂量体积直方图（DVH）以计算器官等效剂量（OED），从而获得超额绝对风险（EAR）、终生归因风险（LAR）和其他风险相关参数。在癌诱发机制模型中使用α'值0.018 Gy和再增殖因子R 0.93。EAR计算中，女性和男性的性别特异性校正因子分别为0.17和 -0.17。所有关键结构的相对积分剂量，3DCRT、IMRT、VMAT和断层放疗分别比质子治疗平均高6.3、4.8、4.5和4.7倍。对于男性患者，由所有器官的平均EAR通过线性DRM计算得出的平均相对LAR比质子治疗高4.0、2.9、2.9、2.7倍；对于女性患者，比质子治疗高4.0、2.9、2.8和2.7倍。机制模型的相同值，男性和女性患者分别比质子治疗高2.2、3.6、3.2、3.8倍和2.2、3.5、3.2、3.8倍。本研究中考虑的除肺和肾之外的所有关键结构在质子计划中的OED均显著更低。对于男性和女性患者，与传统光子治疗相比，质子PBS辐射诱发第二原发恶性肿瘤的风险分别低至三倍和四倍（线性DRM）。使用机制DRM时，质子计划中男性和女性患者的风险分别低至两倍和三倍。
