Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, associated with a high tendency for metastasis to the liver. Proton beam therapy (PBT) is the preferred external radiotherapy treatment for primary UM of certain sizes and locations in the eye, due to its efficacy and good local tumour control, as well as its precision to spare surrounding ocular structures. PBT is an effective alternative to surgical enucleation and other non-precision-targeted radiotherapies. Despite this, the radiobiology of UM in response to PBT is still not fully understood. This enhanced knowledge would help to further optimise UM treatment and improve patient outcomes through reducing radiation dosage to ocular structures, treating larger tumours that would otherwise require enucleation, or even offering a treatment strategy for the otherwise fatal liver metastases. In this review, we explore current knowledge of the treatment of UM with PBT, evaluating the biological responses to the therapy. Molecular factors, such as tumour size, oxygen tension levels, DNA damage proficiency, and autophagy, are known to influence the cellular response to radiotherapy, and these will be discussed. Furthermore, we examine innovative strategies to enhance radiotherapy outcomes, such as combination therapies with DNA damage repair and autophagy modulators, as well as advancements in PBT planning and delivery. By integrating current research and emerging technologies, we aim to provide opportunities to improve the therapeutic effectiveness of PBT in UM management.
葡萄膜黑色素瘤（UM）是成人最常见的原发性眼内恶性肿瘤，具有较高的肝脏转移倾向。质子束治疗（PBT）因其疗效显著、局部肿瘤控制良好，且能精准保护眼周结构，已成为特定大小和位置的原发性UM首选外放射治疗方案。作为手术摘除及其他非精准靶向放疗的有效替代方案，PBT的应用日益广泛。然而，UM对PBT的放射生物学反应机制尚未完全阐明。深化该领域认知将有助于进一步优化UM治疗：通过降低眼周结构辐射剂量、治疗原本需摘除眼球的较大肿瘤，甚至为致命的肝转移提供治疗策略，从而改善患者预后。本文综述了PBT治疗UM的现有认知，评估了该疗法引发的生物学反应。肿瘤大小、氧张力水平、DNA损伤修复能力及自噬等分子因素已知会影响细胞对放疗的反应机制，本文将对此展开探讨。此外，我们研究了提升放疗效果的创新策略，包括与DNA损伤修复调节剂及自噬调节剂的联合疗法，以及PBT计划与实施技术的进展。通过整合现有研究与新兴技术，我们旨在为提升PBT在UM治疗中的疗效提供新的可能性。
Understanding and Exacerbating the Biological Response of Uveal Melanoma to Proton Beam Therapy
肿瘤(癌症)患者之家