Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST-Spedali Civili, Brescia, Italy.
Otorhinolaryngology - Head and Neck Surgery Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST-Spedali Civili, Brescia, Italy.
Cancer Treat Rev. 2023 Dec;121:102644. doi: 10.1016/j.ctrv.2023.102644. Epub 2023 Oct 12.
The treatment of locally advanced (LA) Head and Neck Squamous Cell Carcinoma (HNSCC) is based on surgery followed by (chemo)radiation or on curative (chemo)radiation, depending on site and stage. Despite optimal locoregional treatment, about 50% of patients recur, with a huge impact on prognosis and substantial morbidity. The advent of immunotherapy (IT) with immune checkpoint inhibitors (ICIs) changed the paradigm of systemic treatment for recurrent/metastatic (RM) disease, showing activity, efficacy, and safety in both platinum-resistant and platinum-naïve patients. Such data led clinicians to design clinical trials to investigate early administration of IT even in the neoadjuvant or window of opportunity setting. In this review, we examine the published and ongoing trials investigating IT in the neoadjuvant setting for LA HNSCC. We address the current challenges of this treatment modality: optimal patient selection for neoadjuvant IT; choosing the appropriate systemic approach to enhance response without compromising tolerability; determining the ideal study endpoint, with a focus on major pathological response as a potential surrogate for overall survival; evaluating treatment response through imaging, considering the discordance between radiological and pathological assessments; and the influence of neoadjuvant IT response on locoregional treatment de-escalation strategies.
局部晚期（LA）头颈部鳞状细胞癌（HNSCC）的治疗基于手术联合（放）化疗或根治性（放）化疗，具体取决于肿瘤部位和分期。尽管采用了最佳的局部区域治疗，仍有约 50%的患者复发，这对预后和发病率有很大影响。免疫检查点抑制剂（ICIs）的免疫疗法（IT）的出现改变了复发性/转移性（RM）疾病的系统治疗模式，在铂类耐药和铂类敏感患者中均显示出活性、疗效和安全性。这些数据促使临床医生设计临床试验，以研究甚至在新辅助或治疗窗口期内早期使用 IT。在这篇综述中，我们检查了已发表和正在进行的研究，这些研究调查了 LA HNSCC 新辅助治疗中的 IT。我们讨论了这种治疗方式的当前挑战：新辅助 IT 的最佳患者选择；选择合适的全身治疗方法以提高反应率而不影响耐受性；确定理想的研究终点，重点关注主要病理反应作为总生存的潜在替代指标；通过影像学评估治疗反应，考虑影像学和病理学评估之间的差异；以及新辅助 IT 反应对局部区域治疗降级策略的影响。
