帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好,仅出现轻度胃肠道不良事件,并展现出有前景的活性,值得在随机试验中进一步研究。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Histological tumor necrosis predicts decreased survival after neoadjuvant chemotherapy in head and neck squamous cell carcinoma.
Histological tumor necrosis predicts decreased survival after neoadjuvant chemotherapy in head and neck squamous cell carcinoma.
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肿瘤坏死检测和 AI 驱动的深度学习有效预测 HNSCC 的新辅助 RT/CRT 反应。
尽管对新辅助治疗的兴趣日益增长,但目前尚无方法预测头颈部鳞状细胞癌(HNSCC)对放疗(RT)或放化疗(CRT)的反应。本研究的目的是探讨新辅助RT或CRT对HNSCC肿瘤免疫微环境及患者生存的影响。
从1033例患者的回顾性队列中识别出所有接受新辅助RT或CRT治疗的HNSCC患者(n = 53)。对同一患者新辅助治疗前后的癌症样本进行了与癌症免疫学相关的生物标志物分析:TIL(肿瘤浸润淋巴细胞)(CD8)、肿瘤相关巨噬细胞(CD68、CD206、Clever-1)、免疫反应调节因子(PD-L1)以及组织学肿瘤坏死。关注的结果是个体免疫景观分析及其对接受新辅助RT/CRT治疗的HNSCC患者5年总生存期(OS)的影响。
588 例全切片染色的结果显示,RT/CRT 后免疫景观出现多个具有统计学显著性的改变。治疗前肿瘤坏死是预测不良结局最有用的生物标志物,伴坏死者的 OS 为 14.3%,无坏死者为 48.5%(HR 2.87;95% CI:1.23 至 6.66,p=0.014)。此外,成功开发了一种基于人工智能(AI)的深度学习方法,用于从组织病理学标本中识别肿瘤坏死。组织学坏死在新辅助 RT/CRT 中的预测作用在另外 171 例未接受新辅助治疗的 HNSCC 患者样本中得到了验证。
Despite growing interest in neoadjuvant therapies, there are no methods to predict radio- (RT) or chemoradiotherapy (CRT) response in head and neck squamous cell carcinoma (HNSCC). The aim of this research was to study the effect of neoadjuvant RT or CRT on the tumor immune landscape and patient survival in HNSCC.
All HNSCC patients treated with neoadjuvant RT or CRT (n = 53) were identified from a retrospective cohort of 1033 patients. Pre- and post-neoadjuvant cancer samples from the same patient were analyzed with biomarkers related to cancer immunology: tumor-infiltrating lymphocytes (CD8), tumor-associated macrophages (CD68, CD206, Clever-1), immune response regulator (PD-L1) and histologic tumor necrosis. Outcomes of interest were individual immune landscape profiling and its impact on 5-year overall survival (OS) in HNSCC patients treated with neoadjuvant RT/CRT.
Results from 588 whole-section stainings revealed multiple statistically significant alterations in immune landscape in response to RT/CRT. Pretreatment tumor necrosis was the most useful biomarker in predicting poor outcome, as the OS was 14.3% with necrosis and 48.5% without necrosis (HR 2.87; 95% CI: 1.23 to 6.66, p=0.014). In addition, an artificial intelligence-based (AI) deep learning method for identifying tumor necrosis from histopathological specimens was successfully developed. The predictive role of histological necrosis in neoadjuvant RT/CRT was validated in additional samples from 171 HNSCC patients untreated with neoadjuvant therapy.
Detection of tumor necrosis and AI-driven deep learning effectively predict neoadjuvant RT/CRT responses in HNSCC.
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