Serre Raphaël, Gabro Alexandra, Andraud Mickael, Simon Jean-Marc, Spano Jean-Philippe, Maingon Philippe, Chargari Cyrus
Radiation Oncology Department, La Pitié Salpêtrière University Hospital, Assistance Publique des Hôpitaux de Paris.Sorbonne University, France.
Medical Oncology Department, La Pitié Salpêtrière University Hospital, Assistance Publique des Hôpitaux de Paris.Sorbonne University, France.
Clin Transl Radiat Oncol. 2025 Jan 19;52:100924. doi: 10.1016/j.ctro.2025.100924. eCollection 2025 May.
Combining brachytherapy with immunotherapies, particularly immune checkpoint inhibitors (ICIs), is a promising approach for potentiating both local control of the tumor and fully exploiting the synergies between pharmaceutic immunomodulation and radiotherapy. Compared to other radiotherapy techniques, BT has a potential to better spare lymphatic drainage areas and gut microbiota, thus reducing the immunosuppressive effects of radiation therapy. In addition, it delivers a broad range of doses due to inherent dose inhomogeneity within the implanted volume. This variability increases the probability that immune infiltrates would be activated, particularly since the optimal dose for immune activation is not yet firmly established. Even if preclinical models show that radiotherapy can stimulate immune responses, it can also induce toxic effects on immune effectors and combination trials show conflicting outcomes. There is a need for refining radiation modalities to enhance immune potentiation. The dosimetric specificities of BT may offer various advantages and should be explored further. Scarce clinical data on combining brachytherapy with ICIs in advanced cancer suggest potential benefits, with case reports of complete local responses and abscopal effects. However, validation requires a large number of patients in randomized clinical trials for which ideal design is discussed. In parallel with ongoing clinical developments, there is a need to refine preclinical models in order to better analyze the specific biological effects involved in BT, in light of immunomodulatory systemic treatments.
将近距离放射治疗与免疫疗法，尤其是免疫检查点抑制剂（ICI）相结合，是一种有前景的方法，可增强肿瘤的局部控制，并充分利用药物免疫调节与放射治疗之间的协同作用。与其他放射治疗技术相比，近距离放射治疗有潜力更好地保护淋巴引流区域和肠道微生物群，从而降低放射治疗的免疫抑制作用。此外，由于植入体积内固有的剂量不均匀性，它可提供广泛的剂量范围。这种变异性增加了免疫浸润被激活的可能性，特别是因为免疫激活的最佳剂量尚未完全确定。即使临床前模型表明放射治疗可刺激免疫反应，但它也可能对免疫效应器产生毒性作用，并且联合试验显示出相互矛盾的结果。因此需要改进放射治疗方式以增强免疫增强作用。近距离放射治疗的剂量学特异性可能具有多种优势，应进一步探索。关于晚期癌症中近距离放射治疗与ICI联合应用的临床数据稀缺，提示可能存在益处，有局部完全缓解和远隔效应的病例报告。然而，验证需要大量患者参与随机临床试验，本文对此进行了理想设计的讨论。在进行临床研究的同时，鉴于免疫调节全身治疗，有必要完善临床前模型，以便更好地分析近距离放射治疗所涉及的特定生物学效应。
