[ASCO2016]潜在可切除结直肠癌患者的多学科治疗

作者:肿瘤瞭望   日期:2016/7/1 17:23:42  浏览量:22222

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编者按:病灶能否切除对于转移性结直肠患者的预后十分重要,2016年ASCO年会结直肠癌领域“潜在可切除结直肠癌患者的多学科讨论”这一教育专场上,众位专家围绕如何制定最合理的转移性直肠癌患者的治疗策略慷慨陈词,各抒己见。会后,我们邀请该会场的主席,来自德国University Hospital Carl Gustav Carus的Gunnar Folprecht教授对这一话题发表自己的见解。

  《肿瘤瞭望》:本次大会上有一个比较有意思的环节是关于潜在可切除结直肠癌患者的多学科讨论。作为该会场的主席,您可以为我们具体介绍一下该案例的具体情况吗?为什么您选择这个案例进行讨论?
 
  Gunnar Folprecht教授:当面对转移性结直肠癌患者时,我们应该首先考虑该患者是否能够给予手术切除,这对于提高患者的预后非常关键。本会场,我们报告了2例转移性结直肠患者的病例:一例是潜在可切除的患者,这种情况下内科医生经常无法识别,因此此时多学科讨论显得尤为重要。手术切除肿瘤病灶虽然无法达到完全治愈,但能够极大地改善患者的生存。第二个病例是伴无法切除的肝转移患者,这类患者我们通常先给予化疗,可选择的方案有很多,如FOLFOX或XELOX,针对KRAS野生型患者,还可以联用EGFR单克隆抗体。今天的口头报告中指出,左半结肠癌患者使用EGFR为基础的联合化疗方案能提高疾病缓解率,缩小肿瘤病灶,部分患者也许能够转变为病灶可切除,因此患者化疗3-4个月和外科医生一起讨论,评估患者此时病灶能否切除十分重要。
 
  我们选择这两例患者一例是在开始化疗前评估病灶是否可切除,另一例是在治疗过程中评估病灶是否可切除,这是今天会议上最重要的内容。此外,我们还讨论了一些可以提高患者生存的除化疗以外的其他治疗手段,如联合射频消融术,或其他更为先进的手术技术以扩大可保留的肝脏范围,我们还可以联合一些动脉内治疗,如动脉内放疗等。
 
  《肿瘤瞭望》:在这次多学科讨论中,您印象最深刻的观点是什么?该案例给予临床怎样的提示和指导?
 
  Gunnar Folprecht教授:今天会议给我们的重要指导是,晚期结直肠癌患者可选择的治疗绝非只有化疗而已,其他的治疗手段占据越来越重要的地位,如肝切除术的发展十分迅速,我们不仅要在治疗开始前考虑使用,而且在治疗一段时间后同样可以考虑是否选择肝切除。事实上,就诊时肝转移灶可切除的患者并不常见,而有些患者经过一段时间的治疗病灶转变为可切除。
 
  本会场的主题是目前如何制定转移性结肠癌患者的最佳治疗策略,临床虽然有些非常晚期的患者只能选择高强度的化疗,然而也有许多患者是由于没有经过多学科讨论,内科医生不能够正确地评估患者的可切除性,从而失去了手术的机会。在大会上,我们还关注了一些预后很差的直肠癌患者,这类患者即使技术上能够达到病灶切除,很多医生仍然怀疑手术的价值。而去年ASCO会议上的一项研究中,不可切除的直肠癌患者随机分到单纯化疗组和化疗联合多学科治疗组,大多数是联合射频消融术。事实上,大部分患者都接受了病灶切除手术,并且术中对转移灶进行了消融,这部分患者的预后明显更佳,HR小于0.7,两者的长期生存差异明显。因此,评估患者的可切除性是我们讨论的重点,也是临床治疗的关键。
 
  《肿瘤瞭望》:目前肿瘤治疗的多学科治疗模式正在逐渐推广开来,您所在的医院关于这方面有什么成功经验要分享吗?
 
  Gunnar Folprecht教授:是的,我们中心通过多学科治疗,部分患者几乎达到了肿瘤根治,且许多转移性直肠癌患者的生存超过了十年。有些时候我们给予患者多次手术切除和消融手术,患者的生存明显提高,有些甚至达到肿瘤治愈,有几例患者至今仍然生存,我们没有再进行随访,因为他们已没有随访的必要,手后6~8年内肿瘤都没有复发,相信许多中心都有同样成功的经验。
 
  Yesterday you chaired a multidisciplinary discussion on potentially resectable metastatic colorectal cancer. Could you explain the specific circumstances of the cases presented?
 
  I think what we should consider if we see a patient with metastatic colorectal cancer is a little bit more complex than just whether the patient might be resectable or not. I think this is one of the resources where we can most improve the outcome for some of our patients. What we presented yesterday were two patients. One was upfront resectable. This is a situation that is often not recognized by the treating physicians and therefore multidisciplinary cooperation is extremely important. This is ordinarily a situation where you can improve the outcome of the patient at very low cost just by resecting them. Of course we don’t cure all patients but we improve the outcome a lot and in these patients we can even cure many. There was a second situation, which was a patient who had a non-resectable liver metastasis. This patient we have given chemotherapy. There are different options. One of them, for example, would be FOLFOXFIRI or a combination of Cetuximab. There would also be options for antibodies. For example, for EGF receptor antibodies in patients who are KRAS wild type. After the oral presentation we should also consider treating left colorectal cancer patients with this EGF-receptor-antibody-based combination because these two options provide relatively high response rates. And then we can try to shrink the tumor, and the patient might be resected later on. The important point is to re-discuss that for the patient, after 3 to 4 months, with the surgical colleagues, and to re-discuss whether the patient might become, or might have become, resectable later on.
 
  (Why did you choose these two particular cases and these two patients?)
 
  First because we wanted to remind [physicians], “Think of resection before you start chemotherapy” and secondly, “Think of resection when the patient is on chemo”. Then we discussed the patients. I think this was an important message within this meeting and we discussed a little bit more about the options, about how we can improve the outcome with other methods. There are more methods than just chemo. We can combine resection with ablation. There are more advanced surgical techniques to combine it with portal vein embolization to enlarge the potentially remaining liver lope, and also to combine it with some intra-arterial therapy, for example intra-arterial radiotherapy.
 
  (What kind of guidance do you think that discussion and these cases represent for clinical physicians?)
 
  As I said, the most important thing is to think that there are more options than chemo alone. Perhaps also to become educated and more experienced, because liver surgery has developed a lot, as much as chemotherapy. And not only to think before but also to think after. Even in my region and situation, it’s not very uncommon that patients are presented who might be resectable and who we actually resect.
 
  (During the discussion, in your opinion, where there any impressive or interesting views that were proposed either by speakers or by people from the audience?)
 
  We tried to discuss beforehand, and had given an overview of treatment for metastatic colorectal cancer. I think it might have been very interesting for the audience to learn what the options are to treat patients nowadays. There are some very advanced options where we need very intensive chemotherapy, but there are also many patients who will not be presented by medical oncologists to the surgeons. This is even in the newest research, we can observe that many patients are not presented, are not discussed, are not recognized to be resectable. Of course, there are also limits for resection. Sometimes we focus a little bit too much on the patients who have very poor prognoses. There are some patients who might be technically resectable but who have very poor prognostic factors. These patients’ resectable or even multimodal treatment might be debatable. At the same meeting last year, we learned from the EORTC CLOCC trial about randomized, so-called non-resectable patients’ [response] to chemotherapy alone or to chemotherapy + multimodal treatments. So it was often radiofrequency ablation but it could be combined with resection and in fact most of the patients were operated on and received an intra-operative ablation of their metastasis. The outcome was much better. The hazard ratio was less than 0.7, so it was a huge difference in long-term survival. Just by thinking of resectability, I think it’s as important as all the fancy drugs we have discussed over the last days.
 
  (The multidisciplinary treatment model in oncology is gradually spreading throughout the world. At your hospital, have you had any successful cases that you could share with us?)
 
  Yes, of course we have. So there are several patients who are actually cured. There are other patients who live with their metastatic disease for more than 10 years, sometimes with re-resections or re-re-resections and ablations but it has improved the survival a lot, and it has even cured patients. We have several patients who are still alive, who are not doing follow ups anymore because they don’t need it anymore, because they are cured. They have had no relapse 6 or 8 years after the resection and I think you can get the same experience from many centers.

 

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