肿瘤粒子治疗的现状及进展

Particle therapy is an advanced form of radiotherapy characterized by high precision and minimal side effects. It primarily includes two modalities: external and internal irradiation. External irradiation, such as proton and carbon ion therapy, utilizes the Bragg peak effect to deliver a high radiation dose concentrated at the tumor site, significantly reducing exposure to surrounding healthy tissues. This is particularly beneficial for tumors located near critical organs or in pediatric patients. Internal irradiation, represented by boron neutron capture therapy (BNCT) and radiopharmaceutical therapy (RPT), relies on nuclear reactions induced by neutrons or the decay of radionuclides to release short-range high-LET (linear energy transfer) particles, to achieve precise and selective tumor cell killing. These approaches are particularly effective against deep-seated, hypoxic, or radioresistant tumors. The physical advantages of particle therapy include concentrated depth-dose distribution, minimal range straggling, and low lateral scattering, enabling superior conformality in complex target regions. Biologically, high-LET particles induce clustered DNA double-strand breaks (DSBs) that are difficult to repair, while also triggering autophagy and immune responses, which enhance tumor control. Furthermore, high-LET radiation is less dependent on oxygen presence and exhibits lower oxygen enhancement ratios (OER), making it an ideal choice for treating hypoxic tumors. As of April 2025, 145 particle therapy centers have been established worldwide, with rapid expansion observed in China. Proton and heavy ion therapy have now been implemented clinically, supported by core equipment such as synchrotrons, cyclotrons, and active scanning systems. These systems integrate with respiratory gating and image-guided techniques to improve targeting accuracy. Several Chinese centers have successfully treated cancers including nasopharyngeal carcinoma, lung cancer, liver cancer, and prostate cancer. Notably, some have extended applications to rare indications such as breast and bladder cancers, achieving promising treatment outcomes in both efficacy and safety. The radiobiological effects of particle therapy have become a major research focus. Relative biological effectiveness (RBE), a key parameter, is influenced by LET, dose distribution, and cell type. Various models—Such as LQ, LEM, MKM, and LNDM—Are employed in clinical planning. For hypoxia modeling, the Alper–Howard-Flanders, Wenzl-Wilkens, and Bopp models provide theoretical foundations for OER evaluation. Additionally, the immunomodulatory effects of particle therapy are attracting attention. High-LET radiation can enhance antigen release and preserve lymphocyte function, showing potential for synergy with immunotherapy. Emerging technologies are further enriching the particle therapy landscape. FLASH radiotherapy delivers ultrahigh dose rates while sparing normal tissues, spot-scanning arc therapy (SPArc) improves dose conformity in complex tumors, and stereotactic body radiation therapy (SBRT) enables high-precision treatment of small lesions. BNCT uses nuclear reactions, while RPT relies on molecular delivery, both providing targeted internal irradiation strategies. Future advancements will focus on three areas: (1) integrating AI-driven adaptive planning and multimodal imaging for precision, (2) developing combined external/internal irradiation modalities, and (3) exploring synergies with immunotherapy. These efforts aim to improve efficacy and expand particle therapy’s applicability to complex, treatment-resistant tumors.