《肿瘤瞭望》：针对结直肠癌术后化疗方案颇有争议，譬如一项名为JCOG0910的随机对照研究旨在比较替吉奥和卡培他滨对III期结肠癌的化疗疗效。您觉得这项临床研究结果能给结直肠癌的治疗带来什么样的变化？

　　Takayuki Yoshino教授：JCOGO910是一项日本全国性的III期临床试验，主要针对III期结肠癌患者以及中上部直肠癌患者。这个试验没有证实S-1的疗效优于卡培他滨，根据我个人经验，这并不奇怪。试验的结论是不推荐S-1用于R0切除的III期结直肠癌患者的辅助治疗，卡培他滨仍是结直肠癌患者标准的辅助治疗方案，所以这项试验没有改变现有的临床治疗方案。

　　JCOG091012 is a national phase III clinical trial inJapan， which targets stage III colon cancer patients including upper and middle level rectal cancer.Explanatorily，this trial doesn’t show any inferiority to Capecitabine. The conclusion of this trial shows S-1 should not be conducted in surgery resected stage III colon patients in adjuvant setting，soCapecitabine is still the standard care in adjuvant setting of colorectal cancer. This trial brings no change of clinical practice.

　　《肿瘤瞭望》：近年来，抗HER-2靶向药物在晚期胃肠癌和乳腺癌中已经取得了比较明显的生存获益，那同为消化道肿瘤，您认为抗HER-2靶向药物在结直肠癌中的应用空间有多大？

 　　At this year’s ASCO meeting， Italian group Dr. Salvatore Siena presented promising efficacy and safety f o trastuzumab and lapatinib in HER-2 amplified colorectal cancer patients. In this trial， only 5 % patients have HER-2 amplification of all KRAS wild type colorectal cancer patients. However， great response was observed in the cohort， so I believe the combination of HER-2 targeted therapy will be one of the new choices expected for HER2 amplified colorectal cancer patients.

　　Takayuki Yoshino教授：在今年的ASCO会议上，意大利的Salvatore Siena报告了曲妥珠单抗联合拉帕替尼在HER-2扩增的结直肠癌患者中的有效性和安全性。在这项试验中，虽然只有5%的患者存在HER-2基因过表达，但疗效显著。我认为未来将抗HER-2靶向治疗与标准治疗联合或许能够成为一种适用于HER-２阳性结直肠癌患者的值得期待的新治疗方案。

　　《肿瘤瞭望》：近年来，肿瘤免疫治疗得到越来越多研究者的关注，它或许能成为继手术和放化疗之后的又一治疗肿瘤的有力手段。不知道在结直肠癌中这方面的研究有没有取得突破性的成就？

 　　Standard care globally for colorectal cancer is chemo-radiotherapy followed by 2-3 months rest and then surgery. At this time no standardchemotherapy suggested for adjuvant therapy ofcolorectal cancer patients， so adopting the immunotherapy will bring a new breakthrough. Immunotherapy would enhance function of effector T cell and also the “Abscopal effect”was observed inimmunotherapy trials. I believe after chemo-radiation， adopting PD-1 immune checkpoint inhibitor is aninnovation in adjuvant setting.

　　Takayuki Yoshino教授：III期结直肠癌的标准治疗方案是放化疗后休息2～3个月继以手术治疗。目前尚无标准的辅助化疗方案。所以我相信采纳入免疫治疗将具有突破意义。在黑色素瘤试验中，我们观察到免疫治疗能够增强效应T细胞的作用及“Abscopal"效应。如前所述，放化疗后给予抗PD-1免疫检查点抑制剂将是一种突破。

　　《肿瘤瞭望》：有研究表明，免疫治疗在特定人群中疗效突出，这是不是说明基因组学可以指导这个肿瘤免疫治疗？

 　　At this ASCO， John Hopkins group have showed the promising effect of immune checkpoint inhibitors in the MicrosatellitesInstability (MSI) high metastatic colorectal cancer. SO maybe in the very near future， MSI testing or MMR IHC is mandatory for colorectal cancer. In my question， whether all MSI colorectal cancer shows response to immunotherapy is a very important question.Based on preclinical research， inhibition of the beta-catenin or that pathway shows the recovery of immune T cell response，so I believe the combination of the new agent plus anti PD-1 therapy will resolve the question. Related trials targeting the MSI metastatic colorectal cancer are under investigation， in the near future， suchdate will offer excellent options to resolve this question.

　　Takayuki Yoshino教授：这是肯定的。今年ASCO年会上，John Hopkins研究小组汇报了免疫检查点抑制剂在微卫星高度不稳定（MSI）的转移性结直肠癌患者中的有效性。所以，不久之后，结直肠癌患者MSI和错配修复缺损（dMMR）基因检测将成为临床上不可或缺的检测。但是是否所有MSI 结直肠癌患者都对免疫治疗有效呢? 这是个很重要的问题。临床前研究研究，抑制β-catenin通路免疫可恢复T细胞效应。我认为联合PD-1拮抗剂和新的靶向β-catenin的药物将给出回答，目前相关的临床试验正在进行当中，我们可以期待它们的结果。

　　Takayuki Yoshino教授

　　日本千叶国家癌症中心医院

　　主要研究领域：胃肠肿瘤的规范化治疗，特别是针对结直肠癌潜在预测性生物标志物的研究。在同行评议期刊发表大量学术文章，在2014年巴塞罗那世界胃肠肿瘤大会上首次发布了RECOURSE研究的成果。