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使用可变相对生物效应(RBE)模型比较质子与光子立体定向体部放疗(SBRT)治疗脊柱转移瘤的疗效

Comparison of Proton Versus Photon SBRT for Treatment of Spinal Metastases Using Variable RBE Models.

作者信息

Shaaban Sherif G, LeCompte Michael, Chen Hao, Lubelski Daniel, Bydon Ali, Theodore Nicholas, Khan Majid, Lee Sang, Kebaish Khaled, Kleinberg Lawrence, Hooker Ted, Li Heng, Redmond Kristin J

机构信息

Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD, USA.

Neurosurgery, Johns Hopkins University, Baltimore, MD, USA.

出版信息

Int J Part Ther. 2025 Mar 5;16:100743. doi: 10.1016/j.ijpt.2025.100743. eCollection 2025 Jun.

Abstract

PURPOSE

Study of proton stereotactic body radiation therapy (SBRT) for spinal metastasis has been limited, largely due to concerns of increased risk of spinal cord injury given the challenges of end of range relative biological effectiveness (RBE). Although the 1.1 RBE constant for proton beam has been adopted for clinical use, data indicate that proton RBE is variable and dependent on technical-, tissue-, and patient factors. To better understand the safety of proton SBRT for spinal metastasis, this dosimetric analysis compares plans using photon robotic techniques and proton therapy accounting for RBE-weighted dose (D_{RBE}).

MATERIALS AND METHODS

Nine patients with spinal metastasis were selected to be representative of a broad range of complex clinical practice (3 cervical, 3 thoracic, 3 lumbar) that are uniquely challenging to treat with SBRT were identified. Each vertebral level contained a case with paraspinal extension, a reirradiation case, and a case with high-grade epidural disease (Bilsky grade ≥1c) given that such complex cases in current practice often require target volume under-coverage with photon SBRT (PH-SBRT) in order to meet organ at risk (OAR) dose constraints. All selected patients were treated with PH-SBRT using a robotic system to a prescription dose of 30 Gy in 5 fractions despite our institutional preference for further dose escalation, because further dose escalation was not feasible in the original planning process while keeping normal tissues below acceptable dose constraints. To see if superior target coverage could be achieved with proton treatment, comparative intensity modulated proton therapy (IMPT) plans were generated with the same prescription dose as what was clinically delivered using the 1.1 RBE constant. Dose escalated IMPT plans were then generated to 45 Gy(RBE) in 5 fractions. Variable RBE models (Carabe, McNamara, and Wedenberg) were then utilized to generate RBE-weighted dose D_{RBE} distribution for 30 Gy(RBE) and 45 Gy(RBE) plans using the α/β value (which was 3.76 in this study), physical dose, linear energy transfer (LET) value, and dose per fraction parameters. Proton plans used the robust optimization parameters of ±3.5% range and 2-mm setup uncertainties. Planning target volume (PTV) coverage and OARs sparing were compared using the Wilcoxon signed-rank test.

RESULTS

Planning target volume coverage was significantly improved when comparing PH-SBRT at 30 Gy in 5 fractions (median: 25 Gy) to IMPT at 30 Gy[RBE] in 5 fractions (median: 30.3 Gy[RBE],  = .02) and 45 Gy(RBE) in 5 fractions (median 35.6 Gy[RBE],  = .001). Maximum dose of the spinal cord (cord Dmax) was significantly lower with IMPT at 30 Gy(RBE) (median: 17.6 Gy[RBE],  = .04) and 45 Gy(RBE) (median: 16.1 Gy[RBE],  = .04) compared to conventional plan at 30 Gy (median: 18 Gy). Spinal cord expansion (cord + 2 mm) maximum dose did not change in both photon (median 21.5 Gy) and proton plans (median 22.5,  = .27). Other OARs were better spared with the same and dose-escalated proton plans. No difference was seen in cord Dmax when comparing the PH-SBRT at 30 Gy to D_{RBE} at 30 and 45 Gy(RBE) using Carabe-, McNamara-, or Wedenberg models. However, for spinal cord expansion (cord + 2 mm), there was significant difference between PH-SBRT and D_{RBE} at 30 Gy(RBE) and 45 Gy(RBE) in 5 fractions using Carabe- (median: 25.4 Gy[RBE],  = .002), McNamara- (median: 25.1 Gy[RBE],  = .003), or Wedenberg (median: 24.8 Gy[RBE],  = .0001) models. The average increase in the spinal cord expansion maximum dose using these models compared to the fixed RBE plans was 5.3%.

CONCLUSION

We report the first dosimetric analysis of proton SBRT for spine metastasis using variable RBE dose models. Compared to photon SBRT, IMPT may provide improved target coverage and better spare adjacent OARs, though fixed RBE models can underestimate the maximum dose to adjacent OARs. Future prospective studies are needed to validate these results.

摘要

目的

质子立体定向体部放射治疗(SBRT)用于脊柱转移瘤的研究有限,主要是因为考虑到射程末端相对生物效应(RBE)的挑战,脊髓损伤风险增加。尽管质子束的1.1 RBE常数已被用于临床,但数据表明质子RBE是可变的,并且取决于技术、组织和患者因素。为了更好地理解质子SBRT治疗脊柱转移瘤的安全性,本剂量分析比较了使用光子机器人技术和考虑RBE加权剂量(D_RBE)的质子治疗的计划。

材料与方法

选择9例脊柱转移瘤患者,代表广泛的复杂临床实践(3例颈椎、3例胸椎、3例腰椎),这些病例对SBRT治疗具有独特的挑战性。每个椎体水平包含一个伴有椎旁扩展的病例、一个再照射病例和一个伴有高级别硬膜外疾病(Bilsky分级≥1c)的病例,因为在当前实践中,此类复杂病例通常需要光子SBRT(PH-SBRT)对靶体积进行欠量覆盖,以满足危及器官(OAR)的剂量限制。尽管我们机构倾向于进一步增加剂量,但所有选定患者均使用机器人系统接受PH-SBRT治疗,处方剂量为30 Gy,分5次给予,因为在原始计划过程中,在将正常组织保持在可接受剂量限制以下的同时进一步增加剂量是不可行的。为了观察质子治疗是否能实现更好的靶区覆盖,生成了与临床使用1.1 RBE常数给予的相同处方剂量的对比调强质子治疗(IMPT)计划。然后将剂量增加的IMPT计划增加到45 Gy(RBE),分5次给予。然后利用可变RBE模型(Carabe、McNamara和Wedenberg),使用α/β值(本研究中为3.76)、物理剂量、线能量转移(LET)值和分次剂量参数,生成30 Gy(RBE)和45 Gy(RBE)计划的RBE加权剂量D_RBE分布。质子计划使用±3.5%射程和2 mm摆位不确定性的稳健优化参数。使用Wilcoxon符号秩检验比较计划靶体积(PTV)覆盖情况和OARs的保护情况。

结果

将5次分割给予30 Gy的PH-SBRT(中位数:25 Gy)与5次分割给予30 Gy[RBE]的IMPT(中位数:30.3 Gy[RBE],P =.02)和5次分割给予45 Gy(RBE)的IMPT(中位数35.6 Gy[RBE],P =.001)进行比较时,计划靶体积覆盖情况有显著改善。与30 Gy的传统计划(中位数:18 Gy)相比,30 Gy(RBE)的IMPT(中位数:17.6 Gy[RBE],P =.04)和45 Gy(RBE)的IMPT(中位数:16.1 Gy[RBE],P =.04)的脊髓最大剂量(脊髓Dmax)显著更低。光子计划(中位数21.5 Gy)和质子计划(中位数22.5,P =.27)中脊髓扩展(脊髓 + 2 mm)的最大剂量均未改变。相同和剂量增加的质子计划对其他OARs的保护更好。使用Carabe、McNamara或Wedenberg模型将30 Gy的PH-SBRT与30和45 Gy(RBE)的D_RBE进行比较时,脊髓Dmax未见差异。然而,对于脊髓扩展(脊髓 + 2 mm),在5次分割给予30 Gy(RBE)和45 Gy(RBE)时,使用Carabe模型(中位数:25.4 Gy[RBE],P =.002)、McNamara模型(中位数:25.1 Gy[RBE],P =.003)或Wedenberg模型(中位数:24.8 Gy[RBE],P =.0001)时,PH-SBRT与D_RBE之间存在显著差异。与固定RBE计划相比,使用这些模型时脊髓扩展最大剂量的平均增加为5.3%。

结论

我们报告了首次使用可变RBE剂量模型对质子SBRT治疗脊柱转移瘤进行的剂量分析。与光子SBRT相比,IMPT可能提供更好的靶区覆盖并更好地保护相邻OARs,尽管固定RBE模型可能低估相邻OARs的最大剂量。未来需要进行前瞻性研究来验证这些结果。

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