Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; National Taiwan University Cancer Center, Taipei, Taiwan.
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Int J Radiat Oncol Biol Phys. 2020 Jul 1;107(3):449-454. doi: 10.1016/j.ijrobp.2020.03.012. Epub 2020 Mar 30.
A prospective trial of proton therapy for breast cancer revealed an increased rib fracture rate of 7%, which is higher than the expected rate based on the literature on photon therapies. We aim to evaluate the hypothesis that the increased relative biological effectiveness (RBE) at the distal edge of proton beams is the cause.
We combined the cohort from the prospective clinical trial and a retrospective cohort from a database. Monte Carlo simulations were performed to recalculate the physical dose and dose-averaged linear energy transfer (LETd). The first 10 ribs and fracture areas in patients with fractures were contoured and deformably registered. The LETd-weighted dose was used as a surrogate for biological effectiveness and compared with the conventional fixed RBE of 1.1. Dose to 0.5 cm of the ribs (D0.5) was selected to analyze the dose-response relationship using logistic regression. We chose an alpha/beta ratio of 3 to calculate the biological effective dose in Gy(RBE).
Thirteen of 203 patients in the cohorts exhibited a total of 25 fractures. The LETd in fractured areas is increased (6.1 ± 2.0 keV/μm, mean ± standard deviation), suggesting possible end-of-range radiobiological effects with increased RBE. The D0.5 of the fractured ribs is 80.3 ± 9.4 Gy(RBE) with a generic factor of 1.1 and is relatively low compared with historical photon results. On the other hand, the D0.5 of the fractured ribs is 100.0 ± 12.5 Gy(RBE) using the LETd-based model with a dose-response curve that is more consistent with historical photon data.
The increased rib fracture rate seen in our trial is probably associated with the increased LETd and RBE at the distal edge of proton beams. This phenomenon warrants further investigation and possible integration of LETd into treatment planning and optimization in proton therapy.
一项质子治疗乳腺癌的前瞻性试验显示肋骨骨折率增加了 7%，高于基于光子治疗文献的预期率。我们旨在评估以下假设，即质子束远场的相对生物效应（RBE）增加是导致这种情况的原因。
我们将前瞻性临床试验的队列与数据库中的回顾性队列相结合。进行蒙特卡罗模拟以重新计算物理剂量和剂量平均线性能量传递（LETd）。对骨折患者的前 10 根肋骨和骨折区域进行轮廓勾画和变形配准。LETd 加权剂量用作生物效应的替代物，并与传统的固定 RBE 为 1.1 进行比较。选择肋骨 0.5cm 处的剂量（D0.5），使用逻辑回归分析剂量-反应关系。我们选择了α/β比为 3，以 Gy（RBE）计算生物有效剂量。
两个队列的 203 名患者中有 13 名共发生了 25 处骨折。骨折区域的 LETd 增加（6.1±2.0keV/μm，平均值±标准差），提示可能存在末端区放射生物学效应和 RBE 增加。骨折肋骨的 D0.5 为 80.3±9.4Gy（RBE），通用因子为 1.1，与历史光子结果相比相对较低。另一方面，使用基于 LETd 的模型，骨折肋骨的 D0.5 为 100.0±12.5Gy（RBE），剂量-反应曲线更符合历史光子数据。
我们试验中肋骨骨折率的增加可能与质子束远场 LETd 和 RBE 的增加有关。这种现象值得进一步研究，并可能将 LETd 纳入质子治疗的计划和优化中。
