5-Aminolevulinic acid as an emerging radiosensitizer for radiodynamic therapy in solid tumors: a systematic review of available data and clinical potential.

IF 2.7 3区 医学 Q3 ONCOLOGY
Niklas B Pepper, Fabian M Troschel, Walter Stummer, Hans T Eich
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引用次数: 0

Abstract

Background: 5‑Aminolevulinic acid (5-ALA) is a keto-carbon amino acid frequently used in glioma surgery for fluorescence-guided resection. Additionally, cytotoxic properties of 5‑ALA can be induced via stimulation with laser light in photodynamic therapy (PDT). Preclinical in vitro and in vivo trials have also demonstrated this effect to be inducible by photon irradiation as used in radiation treatment. This makes 5‑ALA a potential sensitizer for radiation therapy whose capabilities and limitations have not yet been fully evaluated. In this article, we present results from a systematic literature review regarding the evidence of 5‑ALA's radiosensitizing properties and the context of its use. We discuss these findings in terms of the underlying mechanisms, their limitations, and the questions to be addressed in future clinical trials.

Methods: A systematic review in the PubMed database was performed via a specifically designed search term, including all search results that featured the combination of 5‑ALA with ionizing radiation. The last date of search was November 13, 2024. Risk of bias among study data was assessed individually according to the study setup after full-text analysis. The results were synthesized based on the underlying tumor entity.

Results: A total of 31 articles were included that examined the combination of 5‑ALA with radiotherapy (RT) in glioma (n = 12), melanoma (n = 6), breast (n = 3), lung (n = 2), prostate (n = 4), and colorectal (n = 1) cancer as well as in sarcoma (n = 2) and primary CNS lymphoma (n = 1). The radiosensitizing effect of 5‑ALA varies among these entities, with glioma and melanoma presenting the strongest body of evidence.

Conclusion: These results imply a basis for 5‑ALA as a possible radiosensitizer for RT, but several questions remain unanswered, as limitations arise from the fact that data are predominantly based on in vitro or rodent in vivo trials, with only two ongoing clinical trials and one case report involving human patients. Moreover, trial setups varied in terms of ALA dose and application timing.

5-氨基乙酰丙酸作为实体肿瘤放射动力学治疗的新兴放射增敏剂:对现有数据和临床潜力的系统回顾
背景:5-氨基乙酰丙酸(5- ala)是一种酮碳氨基酸,常用于胶质瘤手术中荧光引导切除。此外,5 - ALA的细胞毒性可以通过光动力疗法(PDT)中的激光刺激诱导。临床前的体外和体内试验也证明了这种效应可以通过用于放射治疗的光子照射诱导。这使得5 - ALA成为放射治疗的潜在致敏剂,其能力和局限性尚未得到充分评估。在这篇文章中,我们介绍了系统文献综述的结果,关于5 - ALA的辐射致敏特性及其使用背景的证据。我们讨论这些发现的潜在机制,其局限性,并在未来的临床试验中需要解决的问题。方法:通过一个特别设计的搜索词对PubMed数据库进行系统回顾,包括所有以5 - ALA与电离辐射结合为特征的搜索结果。最后一次搜索日期是2024年11月13日。在全文分析后,根据研究设置单独评估研究数据的偏倚风险。结果是根据潜在的肿瘤实体合成的。结果:共纳入31篇文章,研究了5 - ALA联合放疗(RT)在胶质瘤(n = 12)、黑色素瘤(n = 6)、乳腺癌(n = 3)、肺癌(n = 2)、前列腺癌(n = 4)、结直肠癌(n = 1)以及肉瘤(n = 2)和原发性中枢神经系统淋巴瘤(n = 1)中的应用。5 - ALA的放射增敏作用在这些实体中有所不同,胶质瘤和黑色素瘤提供了最有力的证据。结论:这些结果暗示了5 - ALA作为放疗可能的放射增敏剂的基础,但由于数据主要基于体外或啮齿动物体内试验,只有两个正在进行的临床试验和一个涉及人类患者的病例报告,因此一些问题仍未得到解答。此外,试验设置在ALA剂量和应用时间方面各不相同。
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来源期刊
CiteScore
5.70
自引率
12.90%
发文量
141
审稿时长
3-8 weeks
期刊介绍: Strahlentherapie und Onkologie, published monthly, is a scientific journal that covers all aspects of oncology with focus on radiooncology, radiation biology and radiation physics. The articles are not only of interest to radiooncologists but to all physicians interested in oncology, to radiation biologists and radiation physicists. The journal publishes original articles, review articles and case studies that are peer-reviewed. It includes scientific short communications as well as a literature review with annotated articles that inform the reader on new developments in the various disciplines concerned and hence allow for a sound overview on the latest results in radiooncology research. Founded in 1912, Strahlentherapie und Onkologie is the oldest oncological journal in the world. Today, contributions are published in English and German. All articles have English summaries and legends. The journal is the official publication of several scientific radiooncological societies and publishes the relevant communications of these societies.
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