编者按：2024年10月21-27日，江城武汉迎来一场学术氛围热烈、国际交流深入的会议——国际肝胆胰协会中国分会第九届学术研讨会。《肿瘤瞭望》联合《国际肝病》采访了国际肝胆胰协会（IHPBA）现任主席、法国巴黎AP-HP Paul Brousse医院的René Adam教授，分享了肝移植联合化疗用于结直肠癌肝转移治疗的研究探索。
Editor's Note: October 21-27, 2024, Wuhan, at the 9th Academic Symposium of the Chinese Chapter of the International Hepato-Pancreato-Biliary Association (IHPBA), we interviewed Professor René Adam, the current President of the IHPBA and a famous surgeon at AP-HP Paul Brousse Hospital in Paris, France, to share his research explorations on the use of liver transplantation combined with chemotherapy for the treatment of colorectal cancer with liver metastases (CRLM).
01
问：您在本次论坛上还以“肝移植在结直肠癌肝转移治疗中的作用”为主题进行了专门报告，能否为读者们介绍一下报告的核心要点？
At this forum, you also delivered a specialized report on the topic of 'The Role of Liver Transplantation in the Treatment of Colorectal Cancer with Liver Metastases'. Could you please introduce the core points of your report to our readers?
Prof. René Adam
国际肝胆胰协会（IHPBA）现任主席
这项研究无疑具有里程碑式的意义，其核心价值在于它是一项在外科领域较为罕见的随机临床试验。就结直肠癌肝转移（CRLM）的治疗而言，当前的临床实践表明，对于可切除的转移灶，肝部分切除术依然是患者的首选治疗方案，能够为患者提供最佳的生存机会。然而，现实情况是，仅有约20%的患者在初次诊断时，其结直肠癌肝转移病灶处于可切除的状态。
对于那些面临不可切除肿瘤的患者，化疗常作为一线治疗手段，旨在缩小转移灶，为后续的手术切除创造条件。这一策略确实能够使部分患者获得手术机会，进而实现5年生存率在30%-40%之间的提升。但遗憾的是，50%-60%患者的转移灶被判定为绝对不可切除。对于这些患者，化疗长期以来一直是标准的治疗方案。尽管过去15-20年间，化疗方案取得了显著的进步，这些进步主要体现在短期和中期生存率的提升上，但长期生存率仍然有限，患者面临着持续的治疗挑战。
在我们的研究中，我们创新性地对比了单独化疗与化疗联合肝移植两种治疗策略的效果。研究结果显示，对于经过严格筛选的不可切除转移灶患者，化疗联合肝移植显著提高了患者的总生存期和无进展生存期。这一显著疗效的取得，得益于严格的患者选择标准、科学的器官分配优先级管理，以及由独立委员会进行的严格监督。
具体而言，接受肝移植的患者五年生存率高达73%，而仅接受化疗的患者五年生存率则仅为9%。这一生存率数据与因其他明确指征接受肝移植的患者相当，甚至在某些情况下更为优异。更为引人注目的是，肝移植为那些原本长期预后不佳的患者提供了潜在的治愈机会。在移植组中，有42%的患者在长达50个月的随访期间内，显示出无疾病证据（NED）的状态，而化疗组这一比例仅为3%。这些发现不仅令人振奋，更提示我们，肝移植有望成为不可切除结直肠癌肝转移患者的新标准治疗方案，为他们带来新的希望和生命曙光。
（滑动查看英文完整版）
Prof. René Adam：This is indeed a pivotal study, primarily because it is randomized, which is rare in surgical research. What we currently know about treating colorectal liver metastases is that partial hepatic resection is the optimal therapy for patients deemed resectable. However, only 20% of patients with colorectal liver metastases present with resectable disease.
For those initially deemed unresectable, chemotherapy can sometimes downsize the tumor, allowing for secondary resection of the liver metastases and offering a significant survival benefit, with a five-year overall survival rate of approximately 30% to 40%. Yet, 50% to 60% of patients present with definitively unresectable colorectal liver metastases.
In such cases, the standard of care has been chemotherapy, which has shown remarkable advancements over the past 15 to 20 years. However, these improvements have primarily impacted short- and medium-term survival; long-term survival remains poor, with almost no chance of five-year survival.
Therefore, in this study, we compared chemotherapy combined with liver transplantation to chemotherapy alone —the previous standard of care—. The results revealed that liver transplantation plus chemotherapy significantly improves both overall survival and progression-free survival in selected patients with unresectable colorectal liver metastases compared to chemotherapy alone.
These findings were achieved through rigorous patient selection and prioritization for organ allocation. An independent selection committee was established to ensure optimal patient selection. Notably, patients who underwent transplantation for colorectal liver metastases had a five-year survival rate of 73%, compared to only 9% in the chemotherapy-alone group—a notable difference.
Furthermore, this 73% five-year survival rate is comparable to that of patients transplanted for other established transplantation indications. Importantly, liver transplantation plus chemotherapy not only adds a survival benefit but also offers a potential cure for cancer patients who otherwise have a poor long-term prognosis: in the transplantation group, 42% of patients were free of disease at 50 months of follow-up, compared to only 3% in the chemotherapy-alone group. These results are highly significant and could potentially revolutionize the treatment of patients with colorectal liver metastases.
In conclusion, these findings support the idea that liver transplantation could become a new standard option, changing our approach to treating patients with definitively unresectable colorectal liver metastases.
02
问：从您的临床诊治经验来看，肝移植主要适用于哪些结直肠癌肝转移患者？您在进行治疗方案的决策时，一般会考量哪些要素？
Based on your clinical experience, which patients with colorectal cancer and liver metastases are primarily suitable for liver transplantation? What factors do you typically consider when making treatment decisions?
Prof. René Adam
国际肝胆胰协会（IHPBA）现任主席
您提出的问题确实非常关键。在我们的治疗方案中，患者的选择过程对于取得积极疗效起到了至关重要的作用。为了确保治疗效果和患者的安全，我们设定了一系列严格的筛选标准。
首先，适合的患者年龄需在65岁以下，且肿瘤仅局限于肝脏，即仅存在肝转移。这是因为在这个年龄段内，患者的身体状况通常较好，更能耐受手术和后续的康复过程。同时，无肝外疾病是患者入选的必要条件，因为肝外疾病的存在会增加手术的风险，也是肝移植的禁忌证之一。
其次，患者对化疗的客观反应是我们选择的关键因素之一。化疗作为术前治疗的重要手段，能够有效地缩小肿瘤体积，降低手术难度，并为后续的肝移植创造有利条件。
此外，我们还特别排除了携带BRAF突变的患者。BRAF突变与肿瘤的恶性程度和不良预后密切相关，因此，携带这种突变的患者可能不适合进行肝移植手术。
为了确保患者选择的准确性和科学性，我们要求候选患者必须已接受至少三个月的化疗，并根据病情需要，可接受最多三线的化疗方案。在选择过程中，我们还特别注重多学科团队的协作。由肿瘤学家、外科医生和放射学家等专家组成的独立专家委员会会对每一位候选患者进行严格的评估和验证，以确保只有最符合标准的患者才能接受肝移植手术。
正是这种严谨的选择方法和多学科团队的协作，使我们能够实现高达73%的五年生存率。未来，我们相信，对于每一位年龄相对较轻、仅存在肝转移且对化疗反应良好的患者，肝移植都将成为他们潜在的治疗选择，为他们带来新的希望和生命曙光。
（滑动查看英文完整版）
Prof. René Adam：Thank you very much for your question. It is incredibly significant and crucial. The selection process is arguably one of the primary factors in achieving favorable outcomes. In our protocol, patients were required to be under the age of 65 and have liver-only metastases. It was essential that the patient's disease was confined solely to the liver; any extrahepatic disease was a contraindication. Therefore, we focused on younger patients with liver-only disease. Another pivotal aspect was that they must respond objectively to chemotherapy.
This is a vital consideration. Patients needed to demonstrate a response to chemotherapy. Additionally, they should not have the BRAF mutation. BRAF is a gene associated with a poor prognosis, so we excluded patients with this mutation. Furthermore, patients had to have undergone chemotherapy for at least three months and up to three lines of treatment. This was a highly stringent selection process.
Moreover, the selection was conducted by a university hospital and validated by an independent expert committee including oncologists, surgeons, and radiologists. Through this rigorous process, we excluded 40% of candidates who were submitted to the validation committee. It was a very strict selection process, but it allowed us to achieve a 73% five-year survival rate.
Looking to the future, I believe that any patient with liver-only metastases who responds well to chemotherapy and is relatively young should be considered for liver transplantation.
（来源：《肿瘤瞭望》编辑部）
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