案例丨BRAF基因突变的肠癌预后差？结肠癌伴多发转移亦能达到没病状态
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">肠癌肝转移是少有的晚期依然有根治机会的癌症，但BRAF突变的晚期肠癌比较少见，预后相对较差，不少外科<span style="color: black;">大夫</span>认为，BRAF突变预后很差不必再积极的手术<span style="color: black;">干涉</span>而<span style="color: black;">选取</span>转向内科保守治疗，但事实果真如此吗？复旦大学<span style="color: black;">附庸</span>的权威医院<a style="color: black;"></a>介绍了一则案例，并分享了BRAF基因突变肠癌治疗的心得。</p>
<h2 style="color: black; text-align: left; margin-bottom: 10px;"><span style="color: black;">1、</span>结肠癌原发灶的切除</h2>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">这是一名39岁的女性<span style="color: black;">病人</span>，初诊为左半结肠肿瘤伴肝脏多发转移灶、卵巢可疑转移。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">针对</span>结肠癌肝转移的手术，同期手术还是分期手术、肝脏优先还是原发灶优先都<span style="color: black;">必须</span><span style="color: black;">按照</span><span style="color: black;">病人</span>的<span style="color: black;">详细</span><span style="color: black;">状况</span>来判断。<span style="color: black;">因为</span>这名<span style="color: black;">病人</span>CT<span style="color: black;">表示</span>肠管<span style="color: black;">显著</span>扩展，提示即将会<span style="color: black;">出现</span><span style="color: black;">显著</span>梗阻的症状，<span style="color: black;">因此</span>专家立即进行了原发灶的切除手术。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">术中除了原发灶切除外还探查了盆腔病灶，并尽最大可能进行了手术切除，以求达到R0切除，术后病理证实卵巢为转移灶，<span style="color: black;">同期</span>还检出BRAF基因突变。</p>
<h2 style="color: black; text-align: left; margin-bottom: 10px;"><span style="color: black;">2、</span>确定BRAF突变，三药联合贝伐珠单抗治疗</h2>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">都数</span>BRAF突变的肠癌<span style="color: black;">病人</span>为BRAF V600E突变，原发部位多<span style="color: black;">位置于</span>右半结肠，部分还会合并有微卫星不稳定性高MSI-H（<span style="color: black;">能够</span><span style="color: black;">思虑</span>免疫<span style="color: black;">检测</span>点<span style="color: black;">控制</span>剂），预后远远差于野生型。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">因为</span>这位<span style="color: black;">病人</span>术后肝脏病灶短期内<span style="color: black;">增加</span>增大，决定先进行积极的全身治疗，又<span style="color: black;">思虑</span>到预后问题，专家经讨论后<span style="color: black;">选取</span>了FOLFOXIRI三药联合贝伐珠单抗进行治疗。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">国际上有一项多中心的3期临床<span style="color: black;">科研</span>，对比了FOLFOXIRI三药联合贝伐珠单抗与FOLFIRI二药联合贝伐珠单抗治疗转移性结直肠癌的效果，结果<span style="color: black;">表示</span>不论是<span style="color: black;">所有</span>受试人员还是BRAF阳性亚组，三药联合治疗都<span style="color: black;">表示</span>出了更长的<span style="color: black;">存活</span>期<a style="color: black;"></a> 。<span style="color: black;">因此</span><span style="color: black;">针对</span><span style="color: black;">青年</span>体力耐受能力较好的<span style="color: black;">病人</span>，都<span style="color: black;">能够</span><span style="color: black;">思虑</span>三药联合用药。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">这名<span style="color: black;">病人</span>三药联合贝伐珠单抗的治疗后效果非常好，8个周期后，肿瘤得到了很好的<span style="color: black;">掌控</span>，肝脏肿瘤退缩非常<span style="color: black;">显著</span>，后腹膜肿大淋巴结缩小至正常，<span style="color: black;">况且</span>术后盆腔影像学<span style="color: black;">检测</span><span style="color: black;">亦</span>未提示残留病灶。</p>
<h2 style="color: black; text-align: left; margin-bottom: 10px;"><span style="color: black;">3、</span>肝转移灶手术能进行吗</h2>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">8个周期治疗之后面临的<span style="color: black;">重要</span>问题是，应该积极地进行手术切除还是继续维持治疗？</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">非常多</span>外科<span style="color: black;">大夫</span>认为，鉴于BRAF突变肠癌预后很差不必再进行积极的手术<span style="color: black;">干涉</span>。事实果真如此吗？</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">在2019年的ESMO会议上一项法国<span style="color: black;">科研</span><span style="color: black;">报告</span>分析了114例BRAF基因突变的肠癌肝转移<span style="color: black;">病人</span>，BRAF V600E突变占93%，90%是<span style="color: black;">同期</span>性肝转移，肝脏转移灶＞4个的<span style="color: black;">病人</span>超过一半，<span style="color: black;">而后</span>经<span style="color: black;">太多</span><span style="color: black;">原因</span>分析<span style="color: black;">发掘</span>手术切除是影响<span style="color: black;">存活</span>的预后指标，肝转移灶手术切除<span style="color: black;">病人</span>的总<span style="color: black;">存活</span>期远远高于未手术切除的<span style="color: black;">病人</span><a style="color: black;"></a>。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">再结合<span style="color: black;">另一</span>几项临床<span style="color: black;">科研</span>，<span style="color: black;">针对</span><span style="color: black;">通常</span><span style="color: black;">情况</span>较好，接受了有效治疗后只剩肝转移灶的BRAF突变肠癌<span style="color: black;">病人</span>，是值得积极<span style="color: black;">思虑</span>手术治疗的。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">这名<span style="color: black;">病人</span>虽然肝外<span style="color: black;">亦</span>有受累，但经过复旦大学<span style="color: black;">附庸</span>肿瘤医院的MDT多学科会诊讨论分析后，依然决定予以积极地手术治疗，非常幸运在<span style="color: black;">大夫</span>和<span style="color: black;">病人</span>的<span style="color: black;">一起</span><span style="color: black;">奋斗</span>下手术成功R0切除达到了<span style="color: black;">没</span>病状态。<span style="color: black;">日前</span>这位<span style="color: black;">病人</span>已结束了术后化疗进入了<span style="color: black;">长时间</span>随访<span style="color: black;">周期</span>。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">肠癌肝转移<span style="color: black;">病人</span>的<span style="color: black;">状况</span><span style="color: black;">一般</span>都会比较<span style="color: black;">繁杂</span>，能<span style="color: black;">不可</span>手术、何时手术、<span style="color: black;">怎么样</span><span style="color: black;">选取</span><span style="color: black;">药品</span><span style="color: black;">方法</span>都会影响治疗效果，<span style="color: black;">必须</span><span style="color: black;">大夫</span><span style="color: black;">按照</span><span style="color: black;">病人</span><span style="color: black;">详细</span><span style="color: black;">状况</span>综合<span style="color: black;">评定</span>后决定，<span style="color: black;">因此</span><span style="color: black;">意见</span>找正规三甲医院的权威专家进行诊治。想<span style="color: black;">认识</span><span style="color: black;">更加多</span><span style="color: black;">能够</span>在评论区留言，<span style="color: black;">咱们</span><span style="color: black;">能够</span>对接北京、上海一线资源专家。</p>
<h2 style="color: black; text-align: left; margin-bottom: 10px;">参考</h2><a style="color: black;">^</a><span style="color: black;">复旦大学<span style="color: black;">附庸</span>肿瘤医院</span><a style="color: black;">^</a><span style="color: black;">Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. The Lancet Oncology, 2015, 16(13): 1306-1315.</span><a style="color: black;">^</a><span style="color: black;">Schirripa, Marta, et al. "Class 1, 2, and 3 BRAF-mutated metastatic colorectal cancer: a detailed clinical, pathologic, and molecular characterization." Clinical Cancer Research 25.13 (2019): 3954-3961</span>
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