【Lancet子刊】复旦赵快乐团队联合江苏省肿瘤医院叶劲军团队发帖
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q1.itc.cn/q_70/images03/20240220/1eb3ff1b06614c8583a5c6b10cb16b07.jpeg" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">作者：Sophia</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;">导读：</strong>同步放化疗是局部晚期食管鳞状细胞癌的标准非手术治疗。然而，局部复发仍是<span style="color: black;">重点</span>的失败模式，占所有治疗失败的一半以上，<span style="color: black;">显示</span>放疗的<span style="color: black;">敏锐</span>性仍有待<span style="color: black;">加强</span>。该<span style="color: black;">实验</span>旨在证明 PD-1 <span style="color: black;">控制</span>剂后放化疗<span style="color: black;">可否</span><span style="color: black;">能够</span>促<span style="color: black;">摄食</span>管肿瘤血管正常化、缓解缺氧，从而<span style="color: black;">加强</span>放射<span style="color: black;">敏锐</span>性并改善局部<span style="color: black;">掌控</span>。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">近期</span>，复旦大学赵快乐团队联合江苏省肿瘤医院叶劲军团队在Lancet子刊《EClinicalMedicine》上<span style="color: black;">发布</span>“Induction sintilimab and chemotherapy followed by concurrent chemoradiotherapy for locally advanced esophageal cancer: a proof-of-concept, single-arm, multicenter, phase 2 trial”一文，<span style="color: black;">科研</span>结果以及<span style="color: black;">基本</span><span style="color: black;">科研</span>的现有证据<span style="color: black;">显示</span>，<strong style="color: blue;">诱导免疫治疗后进行同步放化疗可能是<span style="color: black;">将来</span>局部晚期食管鳞状细胞癌<span style="color: black;">病人</span>治疗的潜在<span style="color: black;">选取</span>。<span style="color: black;">必须</span> 3 期随机<span style="color: black;">实验</span>来确认这种治疗模式的临床益处。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="//q1.itc.cn/q_70/images03/20240220/59ee6384b19149d88be90998533a7fe4.jpeg" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00050-6/fulltext#%20</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span>背景</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">01 </span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">食管癌是最<span style="color: black;">平常</span>的癌症之一，2020年估计有604 100例新发病例和544,076例死亡。同步放化疗是局部晚期食管鳞状细胞癌的标准非手术治疗。然而，自20<span style="color: black;">数年</span>前RTOG-8501<span style="color: black;">科研</span><span style="color: black;">创立</span><span style="color: black;">败兴</span>，<span style="color: black;">存活</span>率并未有实质性<span style="color: black;">加强</span>。<span style="color: black;">科研</span>人员从不同的<span style="color: black;">方向</span>进行了<span style="color: black;">各样</span><span style="color: black;">科研</span>，<span style="color: black;">包含</span>不同的化疗<span style="color: black;">方法</span>、不同的放疗剂量和分割，或在放化疗<span style="color: black;">时期</span>加入靶向治疗，很少有尝试<span style="color: black;">表示</span>出<span style="color: black;">存活</span>率的<span style="color: black;">加强</span>。<strong style="color: blue;">局部复发仍是<span style="color: black;">重点</span>的失败模式，占所有治疗失败的一半以上，<span style="color: black;">显示</span>放疗的<span style="color: black;">敏锐</span>性仍有待<span style="color: black;">加强</span>。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">在以前的<span style="color: black;">科研</span>中，缺氧与放射<span style="color: black;">敏锐</span>性直接<span style="color: black;">关联</span>。肿瘤的快速生长和病理性血管生成<span style="color: black;">引起</span>缺氧，为放射抗性和肿瘤生长<span style="color: black;">供给</span>了有利的微环境。<strong style="color: blue;">缺氧和病理性血管生成形成恶性循环，使缺氧<span style="color: black;">作为</span>抗肿瘤治疗中的<span style="color: black;">困难</span>。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">抗血管生成<span style="color: black;">药品</span><span style="color: black;">经过</span>VEGF通路<span style="color: black;">控制</span>血管生成信号的转导，修剪<span style="color: black;">反常</span>血管并重塑剩余血管，使血管正常化，从而克服缺氧。然而，这种<span style="color: black;">功效</span>是暂时的，高剂量的抗血管生成<span style="color: black;">药品</span><span style="color: black;">经过</span>过度的血管修剪<span style="color: black;">引起</span>肿瘤血液灌注<span style="color: black;">快速</span>减少，从而加重缺氧，从而<span style="color: black;">引起</span>预后较差。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">免疫<span style="color: black;">检测</span>点<span style="color: black;">控制</span>剂在肿瘤治疗中起着里程碑式的<span style="color: black;">功效</span>。免疫<span style="color: black;">检测</span>点<span style="color: black;">控制</span>剂除了<span style="color: black;">经过</span>恢复细胞毒性T细胞的功能来<span style="color: black;">加强</span>抗肿瘤免疫力外，还<span style="color: black;">能够</span><span style="color: black;">经过</span>免疫<span style="color: black;">关联</span>途径重塑肿瘤微环境。Tian等人在《自然》杂志上提出，PD-1<span style="color: black;">控制</span>剂<span style="color: black;">能够</span><span style="color: black;">经过</span>激活CD4 T淋巴细胞来促进血管正常化，从而克服缺氧。然而，<span style="color: black;">以上</span>机制<span style="color: black;">可否</span><span style="color: black;">能够</span>改善放射<span style="color: black;">敏锐</span>性和局部<span style="color: black;">掌控</span>，从而改善<span style="color: black;">病人</span>的<span style="color: black;">存活</span>率仍不得而知。<span style="color: black;">因此呢</span>，<strong style="color: blue;"><span style="color: black;">咱们</span>设计了一项单臂、多中心、II 期临床概念验证<span style="color: black;">科研</span>，以证明 PD-1 <span style="color: black;">控制</span>剂后进行放化疗<span style="color: black;">可否</span><span style="color: black;">能够</span>促<span style="color: black;">摄食</span>管肿瘤血管正常化、克服缺氧，从而<span style="color: black;">加强</span>放射<span style="color: black;">敏锐</span>性。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span>结果</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">02 </span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">本<span style="color: black;">科研</span>纳入了局部晚期食管癌<span style="color: black;">病人</span>。在诱导<span style="color: black;">周期</span>，<span style="color: black;">病人</span>每 21 天接受两个周期的信迪利单抗、紫杉醇和卡铂治疗。在同步<span style="color: black;">周期</span>，<span style="color: black;">病人</span>每周接受一次 5 个周期的卡铂和紫杉醇治疗，<span style="color: black;">同期</span>进行 50.4Gy 的放疗，分 28 次给药。<span style="color: black;">重点</span>终点是2年局部<span style="color: black;">掌控</span>率。<span style="color: black;">运用</span>免疫荧光和灌注 CT 在诱导期前后<span style="color: black;">评定</span>缺氧和血管正常化。该<span style="color: black;">实验</span>已在 ClinicalTrials.gov （NCT03985046） 注册。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">2019 年 10 月至 2021 年 4 月<span style="color: black;">时期</span>，有 75 名食管癌<span style="color: black;">病人</span>参加了这项<span style="color: black;">科研</span>。<strong style="color: blue;">存活<span style="color: black;">病人</span>的中位随访时间为 33.6 个月 （IQR 29.3–35.7）。2年局部<span style="color: black;">掌控</span>率为81.7%（95%置信区间，72.7%–90.7%），远高于既往<span style="color: black;">科研</span>中仅同步放化疗的71.3%。在活检标本和灌注 CT 中均观察到血管正常化和缺氧缓解。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">科研</span><span style="color: black;">道理</span></strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">03 </span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">据<span style="color: black;">咱们</span>所知，这项<span style="color: black;">科研</span>是<span style="color: black;">第1</span>个<span style="color: black;">发布</span>的在标准同步放化疗中加入诱导免疫疗法的<span style="color: black;">实验</span>，以改善局部晚期食管癌<span style="color: black;">做为</span>非手术治疗的放射<span style="color: black;">敏锐</span>性。本<span style="color: black;">科研</span><span style="color: black;">显示</span>，<strong style="color: blue;">在标准同步放化疗的<span style="color: black;">基本</span>上加入诱导免疫治疗<span style="color: black;">能够</span>改善局部晚期食管癌的放射<span style="color: black;">敏锐</span>性，<span style="color: black;">做为</span>非手术治疗。新的治疗组合<span style="color: black;">经过</span>促进血管正常化和缓解缺氧，<span style="color: black;">加强</span>了局部<span style="color: black;">掌控</span>率。</strong></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">参考资料：</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00050-6/fulltext#%20</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">注：本文旨在介绍医学<span style="color: black;">科研</span><span style="color: black;">发展</span>，<span style="color: black;">不可</span><span style="color: black;">做为</span>治疗<span style="color: black;">方法</span>参考。如需<span style="color: black;">得到</span>健康<span style="color: black;">指点</span>，请至正规医院就诊。</p>
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