Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand; Excellent Center for Drug Discovery (ECDD), Mahidol University, Bangkok, Thailand.
Oral Oncol. 2023 Oct;145:106520. doi: 10.1016/j.oraloncology.2023.106520. Epub 2023 Jul 17.
Chemoradiotherapy (CRT) remains the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), based on numerous randomized controlled trials and meta-analyses demonstrating that CRT improved locoregional control and overall survival. Achieving locoregional control is a crucial outcome for the treatment of HNSCC, as it directly affects patient quality of life and survival. Cisplatin is the recommended standard-of-care radiosensitizing agent for LA-HNSCC patients undergoing CRT, whereas cetuximab-radiotherapy is reserved for cisplatin-ineligible patients. Immune checkpoint inhibitors (ICIs) have shown promise in the treatment of recurrent or metastatic HNSCC. However, the combination of ICIs with standard-of-care radiotherapy or chemoradiotherapy in LA-HNSCC has not demonstrated significant improvement in survivals. Over the past few decades, significant advancements in radiotherapy techniques have allowed for more precise and effective radiation delivery while minimizing toxicity to surrounding normal tissues. These advances have led to improved treatment outcomes and quality of life for patients with LA-HNSCC. Despite these advancements, the development of novel radiosensitizing agents remains an unmet need. This review discusses the mechanism of radiotherapy and its impact on the immune system. We summarize the latest clinical development of novel radiosensitizing agents, such as SMAC mimetics, DDR pathway inhibitors, and CDK4/6 inhibitor. We also elucidate the emerging evidence of combining ICIs with radiotherapy or chemoradiotherapy in curative settings for LA-HNSCC, using both concurrent and sequential approaches. Lastly, we discuss the future direction of systemic therapy in combination with radiotherapy in treatment for LA-HNSCC.
放化疗（CRT）仍然是局部晚期头颈部鳞状细胞癌（LA-HNSCC）的标准治疗方法，这基于许多随机对照试验和荟萃分析表明 CRT 改善了局部区域控制和总生存率。实现局部区域控制是治疗 HNSCC 的关键结果，因为它直接影响患者的生活质量和生存率。顺铂是接受 CRT 的 LA-HNSCC 患者推荐的标准放疗增敏剂，而西妥昔单抗-放疗则保留给不适合顺铂的患者。免疫检查点抑制剂（ICIs）在治疗复发性或转移性 HNSCC 方面显示出了希望。然而，ICI 与 LA-HNSCC 标准放疗或放化疗的联合并未显示出在生存率方面的显著改善。在过去几十年中，放疗技术的重大进展使得能够更精确和有效地传递辐射，同时将周围正常组织的毒性降到最低。这些进展为 LA-HNSCC 患者带来了更好的治疗结果和生活质量。尽管取得了这些进展，但新型放疗增敏剂的开发仍然是一个未满足的需求。这篇综述讨论了放疗的机制及其对免疫系统的影响。我们总结了新型放疗增敏剂的最新临床进展，例如 SMAC 模拟物、DDR 通路抑制剂和 CDK4/6 抑制剂。我们还阐明了在 LA-HNSCC 的根治性治疗中，使用同时和序贯方法，将 ICI 与放疗或放化疗联合使用的新出现的证据。最后，我们讨论了在 LA-HNSCC 的治疗中，联合放疗的系统治疗的未来方向。
