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Abstract：
Altered fractionation concepts and especially moderate hypo-fractionation are evaluated as alternatives to standard treatment for head and neck squamous cell carcinoma (HNSCC), associated with or not concurrent with or sequential to chemotherapy. The calculation of the iso-equivalent dose regimens has as its starting point the linear quadratic (LQ) formalism traditionally based on the \"4Rs\" of radiobiology. The higher rates of therapeutic failure after radiotherapy of HNSCC are associated with the heterogeneity of radio-sensibility. The identification of genetic signatures and radio-resistance scores aims to improve the therapeutic ratio of radiotherapy and to conceptualize personalized fractionation schemes. The new data regarding the involvement of the sixth \"R\" of radiobiology in HNSCC, especially for the HPV-driven subtype, but also for the \"immune active\" minority of HPV-negative HNSCCs, bring to the fore a multifactorial variation of the α/β ratio. The involvement of the antitumor immune response and the dose/fractionation/volume factors as well as the therapeutic sequence in the case of new multimodal treatments including immune checkpoint inhibitors (ICIs) could be included as an additional term in the quadratic linear formalism especially for hypo-fractionation regimens. This term should take into account the dual immunomodulatory effect (immunosuppressant and stimulator of antitumor immunity) of radiotherapy, which varies from case to case and can bring benefit or a detrimental effect.
摘要：
改变的分级概念，尤其是中度的低分级被评估为头颈部鳞状细胞癌（HNSCC）标准治疗的替代方案。与化疗相关或不与化疗同时或序贯。等当量剂量方案的计算以传统上基于放射生物学的“4Rs”的线性二次（LQ）形式主义为起点。HNSCC放疗后较高的治疗失败率与放射敏感性的异质性有关。遗传特征和放射抗性评分的鉴定旨在提高放射治疗的治疗比例并概念化个性化分割方案。关于HNSCC放射生物学第六个“R”的新数据，特别是对于HPV驱动的亚型，而且对于“免疫活性”少数HPV阴性HNSCCs，突出α/β比的多因素变化。在包括免疫检查点抑制剂（ICI）的新的多模式治疗的情况下，抗肿瘤免疫反应和剂量/分级/体积因子以及治疗顺序的参与可以作为二次线性形式中的附加术语包括特别是对于低分级方案。该术语应考虑放疗的双重免疫调节作用（免疫抑制剂和抗肿瘤免疫刺激剂），这在不同的情况下有所不同，可能会带来好处或不利的影响。
