ONCOLOGY FRONTIER: The theme of this CSCO-JSMO-KACO forum is the Standardizing GI Cancer Care in East Asia. What is the difference between the clinical guidelines of gastric cancer in your countries?

 

　　Prof. Zhang: You mean the difference between these three countries? So our neighbors first.

 

　　Prof. Woo: For gastric cancer the attitude of the new technology is a little bit different from each country. So， for Japanese surgeons， in my impression and my opinion， is that Japanese surgeons are a little bit more conservative， and Chinese surgeons are a little bit more brave， and we are in-between. It is like a geographical positioning. And the different thing between China， Korea and Japan is that we have a screening program in Korea and Japan. So， a very high number of early lesion is detected by the screening program， but in China they do not have any screening program so the proportion of the early gastric cancer is relatively low compared to Western countries. Still it is increasing in China， but still is quite low because they do not have any screening program here.

 

　　Prof. Yamazaki: The Japanese surgeons are little bit conservative， so I agree. But many treatment options for gastric cancer have been developed from Japanese surgeons. One of the difference from the other countries is that Japanese guideline is based on the drug approval status of the Japanese government. For example， FOLFOX as the optional approach for gastric cancer could not been used in Japan until last year. But we gradually improve and change these situations in Japan， and the next step is to collaborate with US， EU， and ASIA in the gastric cancer field，

 

　　Prof. Zhang: Yes， I am also a medical oncologist and I agree with my two colleagues. In China we do not have a national screening systems， but I think more people can do it by themselves， by population education we can accept that. But for the guidelines if you talk something like standardization of the treatment of gastric cancer， I think for the guidelines there is not so great difference for surgery recommendation， for the chemotherapy and even for the agents. There is some little difference for example oxaliplatin it has been approved in China， but nivolumab hasn’t been approved in China. So we don’t have in the list nivolumab as third line therapy. I do think we learned from our neighbors， for example the Japanese guidelines， I understand you have 30 to 40 clinical questions for guidelines. And in the fourth edition in the 7 clinical trials questions right. So these clinical questions， the answer to these questions differ from different countries just as the case we discussed this morning about the palliative surgery， how to give or reduce surgery or something， especially with facing challenges for the metastatic gastric cancer with the solitary non-curable metastases this is a very difficult case and we would like to base on the MDT discussion. But for the guidelines as in a way to based on the same trial and we are all from Asia so I don’t think there is much difference. But for clinical practice we are very happy we can have this symposium and we have a chance to communicate with our colleagues.

 

　　《肿瘤瞭望》：本次CSCO-JSMO-KACO论坛的主题是亚洲胃肠道肿瘤的标准治疗，请问从本次论坛现场讨论的情况来看，目前中日韩三国在胃癌的临床指南方面有何异同？

 

　　Woo Jin Hyung教授：对于胃癌而言，每个国家整体的新技术发展程度存在一定差别。另外，从我作为一名外科医生的角度来看，三个国家的手术态度存在地区差异，日本的外科医生比较保守一些，而中国外科医生要更积极，韩国则位于两者之间。另外三个国家的疾病分期构成明显不同，韩国和日本都建立了明确的筛查计划，通过有效筛查方案可以检测到很多早期胃癌患者，然而目前在中国还没有制定和实施胃癌筛查方案，早期胃癌诊断比例相对较低。尽管近年来有所改善，但中国早期胃癌比例仍较日韩为低，开展合理的筛查计划很关键。

 

　　Kentaro Yamazaki教授：日本的外科医生相对保守，这一点我同意。就治疗方案而言，日本和美国等其他国家之间的区别在于我们的指南是基于日本政府批准的情况而制定的，例如FOLFOX方案既往未能获批在日本使用。相信日后我们的治疗方案会逐渐有所改善，下一步也将在胃癌领域加强与美国等各国肿瘤学专家的合作。

 

　　张小田教授：同意前两位专家的观点，我国目前尚未建立国家的胃癌筛查制度，但通过宣传教育，已经有更多人群明了筛查的重要性，主动筛查。谈到胃癌的标准化诊疗的临床指南，三国都是基于同样的临床研究制定指南，人种相同，因此并没有太大的区别。我认为三国在手术指征和术式、化疗方案、甚至一线药物的选择等基本方面并没有太大的差异。当然也还存在一些差异，例如奥沙利铂已经在中国获得批准，而nivolumab还尚未获批，因此我们的三线治疗方案中并没有nivolumab，而是我国自主研发的一类新药阿帕替尼。

 

　　此外，中国学者非常乐意从日韩邻国的指南中学习借鉴，例如日本指南在第四版中提出7个临床问题，都是欠缺充分循证医学依据的临床实践难题，在第五版中更是增加到了30~40个。对这些治疗有争议的问题，不同国家的临床实践是存在差别的，例如我们今天上午讨论的转移性胃癌的姑息手术，特别是针对伴有单一不可治愈因素的转移性胃癌这种复杂的临床问题，目前的临床实践是基于MDT讨论得出有效的治疗方案。我非常高兴能够参加这次研讨会，有机会与各国肿瘤学者一起交流和探讨，相信对于推动胃癌临床诊疗水平的进步意义匪浅。

 

　　ONCOLOGY FRONTIER: With the progress of science and improvement in clinicians’ level of diagnosis and treatment， the survival of patients with gastric cancer also had a significant improvement compared with that of a dozen years ago. Can you tell us about the main research progress and discovery in various areas of gastric cancer respectively? 

 

　　Prof. Zhang: You mean what improvements we have made in gastric cancer? So， here we have one surgeon and two medical oncologists. Since surgery is still the only one to cure the disease so Dr. Woo should go first. 

 

　　Prof. Woo: We think that in clinical trials developed previously some surgeons were really brave to treat the patient with distant metastases and then finally we have some clue regarding surgeons have to keep the surgery in some patient. So selecting the proper candidate for surgery is really， really important. And the second one is that quite difference， a very big study from the United States was the DCG analysis. That improved a lot in the clinical practice and also in Asian research for gastric cancer. Because previously actually many doctors were interested in molecular biology and the biology is original nature of the gastric cancer. But there is a little bit not determined， but we have some kind of strong backbones now and then all the researchers are trying to find out based on some very big fundamentals. Now， compared to the colorectal or breast cancer， the gastric cancer was not a big interest in Western and the only Asian surgeons and doctors were interested in gastric cancer， but now if you think of the population size of three countries， and not only these three countries actually only in China the huge population and then they are quite susceptible to gastric cancer. So it’s a real big issue， so the scientific way that has been done for colorectal and breast cancer should be repeated again in the near future to improve the survival. So actually we have learned from other cancers， but there are many good things because gastric cancer itself is quite different， has a very different biology behavior compared to the colorectal or breast cancer. So， it is a very long way to go but we have to. 

 

　　Prof. Yamazaki: In the last decade there was little change in gastric cancer treatment. Only 3 cytotoxic drugs such as fluoropyrimidines， irinotecan， and taxanes were the active agents for gastric cancer， and trastuzumab improved clinical outcome only for HER2 positive gastric cancer. However， recently new active agents such as VEGF receptor inhibitor， ramucirumab and check point inhibitors are coming to clinical practice. Now a lot of combination chemotherapies with new active agents are developed in the metastatic stage and/or perioperative stage and these developments will dramatically change gastric cancer treatment in the near future. 

 

　　Prof. Zhang:I think in addition， gastric cancer it is a really very difficult disease. I think especially for the locally advanced gastric cancer for this population we can do much better than before because now we have the idea with that we should discuss a patient with surgeons， radiologist and chemotherapy medical oncologists based on the precise staging by CT scan， by endoscopy， by laparoscopy. And for these kind of population whether to give the chemo or the radiation pre-operatively or post-operatively and how to arrange or manage all the treatment during the course of the disease and since we made great progress and we try to collaborate with our pathologists and now the different countries. So I think from this point of view I do think we have made great progresses， yes.

 

　　《肿瘤瞭望》：随着科学技术的进步和临床医生诊疗水平的提高，胃癌患者的生存较十几年前也有了显著的改善。您可以从各自的研究领域为我们介绍一下胃癌各领域的主要研究进展和发现吗？

 

　　Woo Jin Hyung教授：在临床研究广泛开展之前，一些外科医生在治疗远处转移等患者方面是很激进的。然而现在有研究表明外科医生必须选择合适的患者进行手术，筛选可切除患者这一点非常关键。另外一点比较重要的是，美国开展的大型研究TCGA分析在亚洲胃癌的临床实践以及基础研究方面取得了很大的进步。实际上，目前很多临床医生都对胃癌的分子生物学感兴趣，因为它涉及到胃癌的根本特性。以前人们对这方面的了解非常有限，但现在我们已经发现了一些非常重要的信号通路，所有的研究人员也正在努力寻找一些有效的靶点。

 

　　与结直肠癌或乳腺癌相比，西方国家对于胃癌的研究兴趣似乎并不浓厚，而亚洲的外科和内科肿瘤学家对胃癌则进行了很多探索。中日韩等亚洲国家胃癌的发病人群数量较多，尤其是在中国，胃癌发病率很高。因此，这是一个非常严峻的问题，在不久的将来应该在胃癌中重复结直肠癌和乳腺癌中应用的科学方法以提高生存率。由于胃癌本身的异质性很强，与结直肠癌和乳腺癌的生物学行为存在很大的差异，因此还有很多未知的领域有待于我们去探索，这也是我们必须肩负起的重大使命！

 

　　Kentaro Yamazaki教授：从过去十年的临床实践看，氟尿嘧啶、伊立替康和紫杉醇等传统化疗药物并没有很大的改变。而基于分子生物学的靶向药物正在进入并改变胃癌治疗的临床实践，目前我们已经有了HER-2抑制剂曲妥珠单抗以及VEGF受体抑制剂等，目前nivolumab等免疫检查点抑制剂也正在进入临床。我相信在不久的将来，其他联合化疗方案在转移期或围手术期胃癌治疗中的应用也会有一定的进展。

 

　　张小田教授：除以上几点外，多学科综合治疗的理念也极大得推动了胃癌治疗的进步。胃癌是一种临床诊断和治疗都存在巨大挑战的疾病，例如针对局部晚期胃癌我们取得的进步中，一方面CT扫描、内窥镜、腹腔镜等影像学技术的进步使我们可以做到精准分期，另一方面得益于包括外科、放疗科和内科医生等的多学科综合治疗模式理念的提升。对于局部晚期患者，在术前还是手术后给予化疗或放疗以及整个疾病过程如何管理方面，我们已经取得了很大的进展，而且我们还在试图与病理学家以及不同国家的肿瘤学家开展交流和合作，相信未来一定会更加光明！

 

　　Professor Yamazaki: In our hospital， every week the MDT for gastric cancer is held in the Monday afternoon， and we discuss the treatment plan for each case with the surgeon， radiologist and pathologist. And we are making efforts day by day to provide the best treatment based on the evidence for patients. 

 

　　Prof. Woo: It is a quite comprehensive patient care. As a surgeon， I was not interested in chemo or radiotherapy because if I perform surgery that was all， actually. But nowadays after having the multidisciplinary principles we can understand more about chemotherapy and more about radiation and also not only for the diagnosis， we can understand more about our patient and the treatment modality can be decided not only by the surgeon’s idea of curative therapy， oncologist’s idea or radiation oncologist’s idea. By communicating with each other we can find out the most optimal treatment for our patient. Before that， everybody would think that they are the expert in their area so once they decided is the truth， but now we can realize that we are making many errors in the previous years and that maybe still now， but by having more closer conversation we can reach to more high score with the improving survival and quality of life and better patient treatment would be achieved. 

 

　　Prof. Zhang: Yes， it’s a great question. I think the MDT have two points， first in clinical practice just as our two colleagues have just mentioned， and another is for clinical trial. And for this comprehensive treatment we need chemoradiation and surgery especially for the locally advanced gastric cancer or metastatic gastric cancer with controversial therapy is rather more difficult than the surgery trial， than the chemotherapy therapeutic agent’s trials， it needs collaboration and it needs more efforts on the management on the critical design， and on the quality control. Finally， I think the patient can benefit from the MDT trial and before the trial we should accumulate experience from MDT clinical practice and what we can do best in the trails. 

 

　　Kentaro Yamazaki教授：在我们医院，每周一下午都会进行胃癌的MDT会议，组织外科、放疗科和内科医生一起进行病例讨论，虽然仍然很难决定哪种是患者的最佳治疗模式，但是通过多学科团队讨论我们每天都有所进步。

 

　　Woo Jin Hyung教授：胃癌是一个需要综合治疗的疾病。作为外科医生，以前我对化疗或放射治疗不感兴趣，只专注于胃癌的手术治疗。现在多学科治疗的理念开始普及，我对于化疗和放疗有了更深的了解。我们对于疾病的了解也日趋加深，不仅表现在对疾病的诊断，更体现在疾病的治疗和管理。通过外科、内科和放疗科医生的相互交流和讨论，我们可以一起寻找到患者的最佳治疗方式。在多学科模式出现之前，每个人都会比较偏颇地认为自己决定的就是正确的，但现在我们意识到过去这些年我们犯了很多错误，也许现在仍然是这样，但是通过更密切的交流和合作，我们可以改善患者的生存预后，提高其生活质量和健康评分状态。

 

　　张小田教授：我认为MDT模式的应用有两个方面。一个就是刚刚两位专家提到的临床实践，另一个就是临床研究。胃癌的综合治疗需要手术和放化疗，特别是针对局部晚期或治疗有争议的转移性胃癌患者开展的临床试验，研究设计复杂，设计学科繁多，质控需要多环节管理，其复杂性远远超过单纯手术或药物治疗的临床研究，但这些研究结果也必将最大程度的解决临床实践难题，为患者带来受益，当然我们设计这类的临床研究也首先需要在MDT临床实践中积累经验。