Mitsuru Sasako 日本兵库医学院上消化道系
<Oncology Frontier>:What’s the position of neo-adjuvant chemotherapy in the treatment of advanced gastric cancer? How to pick up the appropriate patients, and which regimens are suggested?
Prof. Sasako: At the moment, the neoadjuvant chemotherapy is attractive, but we do not apply that neoadjuvant chemotherapy for all gastric cancer patients. In Korea and Japan, stage one patients is so many, so obviously, neoadjuvant treatment is over treatment for stage one patients. But still, we don’t have any diagnostic criteria to exclude the stage one patient. So we are now prospectively evaluating how much of the stage one patient can be mixed or included, if we apply some kind of clinical diagnosis criteria in staging. And if it can be less than 5 %, it is OK for us to start next neoadjuvant chemotherapy trial. But for them it’s needed to have such diagnostic criteria. And at the moment we apply the neoadjuvant chemotherapy for borderline resectable locally advanced patient without peritoneal seeding. It’s actual indication in Japan.
《肿瘤瞭望》:新辅助治疗在进展期胃癌治疗中的地位如何?适宜人群是哪些?推荐什么方案?
Sasako教授:在目前胃癌的治疗当中,新辅助化疗受到关注,但是我们并不是对所有的胃癌患者都使用新辅助化疗。在韩国和日本有许多Ⅰ期胃癌患者,对于Ⅰ期患者而言,新辅助化疗是过度治疗。但是目前没有明确诊断标准来排除Ⅰ期患者。如果我们应用某些临床诊断标准来对患者进行分期时,我们可以预估患者为Ⅰ期胃癌的可能性。当这种可能性小于5%时,我们可以对患者开始新辅助化疗。有一个明确的临床诊断标准是十分必要的。目前在日本,胃癌新辅助化疗的适应证是具有可切除的局部病灶且没有腹膜种植转移的晚期胃癌患者。
<Oncology Frontier>:Would you please give us a brief introduction on epidermal growth factor receptor family (EGFR) in gastric cancer, such as Her-1 and Her-2: there expressions and clinical significances?
Prof Sasako: At the moment the HER-2 is the only biomarker, established in gastric cancer clinical work, so according to the results of ToGA study, we know now that for all those patients with tumors show HER-2 positivity,Trastuzumab is effective,so we should add Trustuzumab in all chemotherapy when we treat these kinds of patients. But, unfortunately, we haven’t yet any results regarding the use of Trastuzumab in esophageal above seeding. But otherwise for, if you had advanced gastric cancer, and unresectable or metastatic disease or recurrent patient had to examination is essential before studying to select chemotherapy regiment.
B: At the moment trastuzumab is HER-2 on to body. So we have only that. But other drugs is coming. But still we haven’t yet results. So TDM-1 is another agent that several drugs are under investigation.
《肿瘤瞭望》:请您介绍一下表皮生长因子受体家族,尤其是HER-1和HER-2,在胃癌的表达情况和临床意义。
Sasako教授:目前在有关胃癌的临床研究当中,HER-2是唯一的生物标记物。根据ToGA试验的结果,曲妥珠单抗在治疗所有HER-2表达阳性的胃癌患者时是有效的,因此我们应该在治疗这类患者时将曲妥珠单抗与化疗联合。但是目前我们还并没有取得确切数据显示曲妥珠单抗在食管段或以上部位转移患者当中的有效性。对晚期胃癌不能手术切除,或者有远处转移的,以及肿瘤复发的患者,在选择合适的化疗方案前需要做充分的检查。
目前曲妥珠单抗是在临床当中应用的唯一一个针对HER-2阳性胃癌的治疗药物,其他的一些药物也将陆续出现,但是目前仍没有确切的临床数据。TDM-1等药物仍在不断研究当中。
<Oncology Frontier>:Is it necessary to repeat gastric endoscopy during treatment of unresectable metastatic gastric cancer, and what are the indications?
Prof Sasako: For most of patients undergoing, definitive chemotherapy I mean the postoperative chemotherapy, is not so much important to undergo endoscopy. Maybe for some patient who has some clinical, borderline clinical symptoms, like the stenosis of the pylorus, or the cardia, indication of stent for these patients, is a little bit delicate. So for such patients, repeated endoscopy might be helpful. Otherwise it’s not really important. But most of patients undergoing chemotherapy has other target to evaluate if they get the treatment.
《肿瘤瞭望》:重复进行胃镜检查在晚期胃癌患者评价疗效时是否必要,什么情况下需要重复进行?
Sasako教授:对于大多数接受术后辅助化疗的患者而言,没有必要进行重复的胃镜检查。或许对于某些具有临床症状的,如贲门及幽门狭窄,具有放支架指征的患者,重复胃镜检查可能有帮助。否则,重复胃镜检查的意义不大。对大多数接受化疗的患者来说,在治疗过程中仍有其他项目需要进行评估。
<Oncology Frontier>:TNM stage III gastric cancer has greater odds of post-operative recurrence. Which adjuvant regimen would you recommend for these patients to lower the risk of recurrence?
Prof Sasako: In both clinical trials, RCT and plastic study. The hazard ratio in stage 3 patient, is larger than stage 2 patient. That means effect of treatment is less in stage 3 than in stage 2. So everybody thinks that it is important, it is necessary to develop further more effective treatment for stage 3 patient.
《肿瘤瞭望》:Ⅲ期胃癌术后复发几率高,您建议这些患者采用什么方案进行术后辅助化疗来降低复发风险?
Sasako教授:在临床研究以及某些经典研究当中,Ⅲ期胃癌患者的复发风险高于Ⅱ期患者,这意味着Ⅲ期患者的治疗效果差于Ⅱ期患者。因此所有人都认为寻找对Ⅲ期患者更为有效的治疗方法是十分必要且十分重要的。
<Oncology Frontier>:Gastric cancer has different clinical manifestations across the world. What are the characteristics of gastric cancer in Asia, and how it influences treatment strategy?
Prof Sasako: Compared with western countries, still in Asia, we have more classic type gastric cancer. I mean the more distal tumor, mainly in distal type. But in the west, more edge junctional tumor of distal type, or more gastric cancer of the up body, which has undifferentiated type, defused type, have been increasing. So majority of gastric cancer patient in the west, the moment is up body tumor or edge junctional tumor, so their behavior, biological behaviors is a little different from the classic type gastric cancer.
so edge junctional tumor may have more wide spread possibility of the lymphnode metastasis to the up on side and to the lower side to the peritoneal area. And the body tumor of defused type has strong tendency to develop peritoneal metastasis. So to improve the treatment results we have the care of this point.
《肿瘤瞭望》:各个国家地区的胃癌临床表现存在差异,亚洲地区的胃癌有什么特点,对胃癌治疗模式的选择有什么影响?
Sasako教授:相比于西方国家,亚洲的胃癌多数为经典类型的胃癌,即发生在胃体远端的普通型胃癌。但是在一些西方国家,发生在胃体远端的边缘性交界型肿瘤,或发生在胃体上部的未分化胃癌以及复杂类型胃癌的数量正在增加。因此在西方国家,大部分的胃癌是发生在胃体上部或者是边缘性交界型肿瘤,它们的生物学行为与其他经典类型胃癌不同。
比如边缘性交界型胃癌有着更高的扩散性,可以通过淋巴结转移扩散至胃体的上部、下部或者腹膜区域。复杂类型肿瘤有着更强的腹膜转移性以及转移潜能。因此为了更好地治疗胃癌,我们需要注意到这些特殊肿瘤的生物学行为。