Zhang Hualin, Donnelly Eric D, Strauss Jonathan B, Qi Yujin
Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, Illinois 60611.
Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522, Australia.
Med Phys. 2016 Jan;43(1):483. doi: 10.1118/1.4939064.
To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model.
A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model was used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution.
EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0)(4) to (13.4)(4) for the radiosensitive normal tissue depending on the cylinder size, treatment lengths, prescription depth, and dose as well. However, for a uniform cancer cell distribution, the EUDs were between 6.3 Gy × 4 and 7.1 Gy × 4, and the TRs were found to be between (1.4)(4) and (1.7)(4). For the uniformly interspersed cancer and radio-resistant normal cells, the TRs were less than 1. The two VCBT prescription regimens were found to be equivalent in terms of EUDs and TRs.
HDR VCBT strongly favors cylindrical target volume with the cancer cell distribution following its dosimetric trend. Assuming a half-Gaussian distribution of cancer cells, the HDR VCBT provides a considerable radiobiological advantage over the external beam radiotherapy (EBRT) in terms of sparing more normal tissues while maintaining the same level of cancer cell killing. But for the uniform cancer cell distribution and radio-resistant normal tissue, the radiobiology outcome of the HDR VCBT does not show an advantage over the EBRT. This study strongly suggests that radiation therapy design should consider the cancer cell distribution inside the target volume in addition to the shape of target.
使用线性二次(LQ)模型评估高剂量率(HDR)阴道残端近距离放射治疗(VCBT)在治疗圆柱形靶区内癌细胞分布各异或恒定的子宫内膜癌中的效果。
采用蒙特卡罗(MC)技术计算不同圆柱直径和治疗长度下HDR VCBT的三维剂量分布。使用治疗计划系统(TPS)根据临床方案为不同的圆柱直径、治疗长度和处方制定计划。将从TPS获得的驻留时间输入MC。LQ模型用于评估两种近距离放射治疗方案的治疗效果,这两种方案分别是在0.5 cm深度处方(5.5 Gy×4分次)或在阴道黏膜表面处方(8.8 Gy×4分次)以治疗子宫内膜癌。在放射生物学建模中使用了实验确定的子宫内膜癌细胞分布,该分布呈现各异且类似半高斯分布。计算每种治疗方案对癌细胞的等效均匀剂量(EUD)。治疗比(TR)通过在相同癌细胞杀伤水平下比较VCBT与均匀剂量放射治疗计划的正常细胞存活情况来定义。假设圆柱形靶区内有两种不同类型的癌细胞密度分布,对临床影响进行了两次计算:(1)半高斯分布或(2)均匀分布。
EUD对圆柱尺寸、治疗长度和处方深度的依赖性较弱,但对癌细胞分布的依赖性很强。TR强烈依赖于圆柱尺寸、治疗长度、癌细胞分布类型以及正常组织的敏感性。对于癌细胞在阴道黏膜处分布最多的半高斯分布,根据圆柱尺寸、治疗长度、处方深度和剂量的不同,EUD在6.9 Gy×4至7.8 Gy×4之间,对于放射敏感的正常组织,TR在(5.0)(4)至(13.4)(4)范围内。然而,对于均匀的癌细胞分布,EUD在6.3 Gy×4至7.1 Gy×4之间,TR在(1.4)(4)至(1.7)(4)之间。对于癌细胞均匀散布且正常细胞具有放射抗性的情况,TR小于1。发现两种VCBT处方方案在EUD和TR方面是等效的。
HDR VCBT强烈倾向于癌细胞分布遵循其剂量学趋势的圆柱形靶区。假设癌细胞呈半高斯分布,HDR VCBT在保留更多正常组织的同时保持相同水平的癌细胞杀伤,相对于外照射放疗(EBRT)具有相当大的放射生物学优势。但对于均匀的癌细胞分布和放射抗性正常组织,HDR VCBT的放射生物学结果相对于EBRT没有优势。本研究强烈表明,放射治疗设计除了考虑靶区形状外,还应考虑靶区内的癌细胞分布。