Towards an adequate description of the dose-response relationship in BNCT of glioblastoma multiforme

IF 3.2 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Medical physics Pub Date : 2025-02-22 DOI:10.1002/mp.17693

Barbara Marcaccio, Marco Crepaldi, Ian Postuma, Erica Simeone, Claretta Guidi, Setareh Fatemi, Ricardo Luis Ramos, Valerio Vercesi, Cinzia Ferrari, Laura Cansolino, Elena Delgrosso, Riccardo Di Liberto, Daniele Dondi, Dhanalakshmi Vadivel, Yi-Wei Chen, Fong-In Chou, Jinn-Jer Peir, Chuan-Jen Wu, Hui-Yu Tsai, Jia-Cheng Lee, Agustina Mariana Portu, Ana Mailén Dattoli Viegas, Sara Josefina González, Silva Bortolussi

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引用次数: 0

Abstract

Background

Boron Neutron Capture Therapy (BNCT) is a binary radiotherapy based on the intravenous administration of a borated drug to the patient and the subsequent irradiation with a low-energy neutron beam. The borated formulation accumulates in the tumor cells, and when neutrons interact with boron, a nuclear capture reaction occurs, releasing high-linear energy transfer, short-range particles that cause lethal damage to the cancer cells. Due to its selectivity, BNCT has the potential to treat aggressive brain tumors such as glioblastoma multiforme (GBM), minimizing the side effects. GBM is a brain neoplasia that poses significant treatment challenges due to its invasiveness and resistance to conventional treatments.

Purpose

This work aims to find a suitable model for calculating the photon isoeffective dose for GBM, producing ad hoc radiobiological data to feed the model.

Methods

To describe adequately the dose-effect relation of BNCT for GBM, the following strategy has been applied

1. We studied the impact of choosing two different photon radiation types (x- or gamma- rays)
2. We assumed that the correct description of the photon-equivalent dose is obtained with the photon isoeffective dose model. This model calculates the photon dose that equals the cell survival obtained with BNCT, taking into account synergism and sub-lethal damage (SLD).
3. Survival curves as a function of the dose for the human GBM U87 cell line were constructed using the clonogenic assays for irradiation with photons (reference), neutron beam, and BNCT.
4. Survival curves were fitted with the modified linear quadratic model, using SLD repair times derived for U87. The radiobiological parameters were determined for the photon isoeffective dose model.
5. The model was applied to a clinical case that received BNCT in Taiwan. Treatment planning has been simulated using an accelerator-based designed neutron beam following the real treatment process and parameters. The results were discussed and compared to the current method, which employs relative biological effectiveness (RBE) factors to obtain BNCT dosimetry in photon-equivalent units.

Results

The dose-survival curves have been obtained with two different photon radiation sources as the reference with a thermal neutron beam and neutrons in the presence of boron. The fitted parameters have been obtained as the input for the photon isoeffective dose and the traditional RBE model. For the first time, the radiobiological parameters of a photon isoeffective dose model were produced for BNCT of GBM. Photon isoeffective dose value can differ up to 32% using gamma photons and low-energy x-rays. Photon isoeffective dose values are lower (17%) than the RBE model currently employed in clinical trials.

Conclusion

The results highlight the impact of the reference radiation chosen for the isoeffective dose calculation and the importance of feeding the model with the appropriate radiobiological parameters.The dosimetry obtained with the new radiobiological data is consistent with the dose delivered in modern stereotactic radiotherapy, enabling tumor control predictions.

Abstract Image

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对多形性胶质母细胞瘤BNCT中剂量-反应关系的充分描述。

背景：硼中子俘获疗法（BNCT）是一种二元放疗，其基础是患者静脉注射含硼药物，随后用低能中子束照射。含硼的配方在肿瘤细胞中积累，当中子与硼相互作用时，就会发生核捕获反应，释放出高线性能量转移的短程粒子，对癌细胞造成致命伤害。由于其选择性，BNCT有可能治疗侵袭性脑肿瘤，如多形性胶质母细胞瘤（GBM），最大限度地减少副作用。GBM是一种脑瘤，由于其侵袭性和对常规治疗的抵抗，对治疗提出了重大挑战。目的：本工作旨在寻找一个合适的模型来计算GBM的光子等有效剂量，并为模型提供特定的放射生物学数据。方法：为了充分描述BNCT治疗GBM的量效关系，采用了以下策略1。我们研究了选择两种不同的光子辐射类型（x射线或伽马射线）的影响。我们假设用光子等有效剂量模型可以得到光子等效剂量的正确描述。该模型在考虑协同作用和亚致死损伤（SLD）的情况下，计算出与BNCT获得的细胞存活率相等的光子剂量。3.利用光子（参考）、中子束和BNCT辐照的克隆实验，构建了人GBM U87细胞系随剂量的生存曲线。4.生存曲线用改良的线性二次模型拟合，使用U87的SLD修复时间。确定了光子等有效剂量模型的放射生物学参数。5.并将该模型应用于台湾一名接受BNCT的临床病例。根据实际治疗过程和参数，利用基于加速器的设计中子束模拟了治疗计划。讨论并比较了目前采用相对生物效应（RBE）因子获得以光子当量为单位的BNCT剂量测定的方法。结果：在硼存在的情况下，以热中子束和中子为参考，得到了两种不同光子辐射源的剂量生存曲线。将拟合参数作为光子等有效剂量和传统RBE模型的输入。首次建立了GBM BNCT的光子等有效剂量模型的放射生物学参数。使用伽马光子和低能x射线时，光子等有效剂量值可相差32%。光子等有效剂量值比目前临床试验中使用的RBE模型低（17%）。结论：研究结果突出了计算等有效剂量时参考辐射选择的影响，以及给模型提供适当的放射生物学参数的重要性。利用新的放射生物学数据获得的剂量学与现代立体定向放疗中的剂量一致，从而能够预测肿瘤控制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medical physics 医学-核医学

CiteScore

6.80

自引率

15.80%

发文量

660

审稿时长

1.7 months

期刊介绍： Medical Physics publishes original, high impact physics, imaging science, and engineering research that advances patient diagnosis and therapy through contributions in 1) Basic science developments with high potential for clinical translation 2) Clinical applications of cutting edge engineering and physics innovations 3) Broadly applicable and innovative clinical physics developments Medical Physics is a journal of global scope and reach. By publishing in Medical Physics your research will reach an international, multidisciplinary audience including practicing medical physicists as well as physics- and engineering based translational scientists. We work closely with authors of promising articles to improve their quality.