编者按:2024年10月25-27日,国际肝胆胰协会中国大会第九届学术研讨会于在武汉举行。大会吸引来自美国、德国、法国俄罗斯、澳大利亚等20余个国家的50余位国际知名专家学者、21位两院院士、700余位国内肝胆胰领域专家学者参会。在本次大会上,欧洲-非洲肝胰胆协会主席(E-AHPBA)、南非开普敦大学Groote Schuur医院Eduard Jonas教授带来了题为“肝细胞癌治疗中从指南到个体化治疗的转变——全球视角(Transitioning from guidelines to personalized medicine in the treatment of hepatocellular carcinoma-a global perspective)”的精彩报告。《肿瘤瞭望》联合《国际肝病》特邀请Eduard Jonas教授进行了深度访谈,与广大同道分享了有关肝癌个体化治疗的精彩解读。
01
您在本次会议上带来了以“肝细胞癌治疗中从指南到个体化治疗的转化——全球视角”为主题的报告,能否为广大读者分享一下此次报告的要点?
Eduard Jonas教授:非常感谢您的提问。我们目前主要遵循的仍是1999年首度颁布的指南,这些指南在全球范围内以多种版本被广泛采纳。其核心原则依然围绕肿瘤特征,即依据肝细胞癌(HCC)患者的肿瘤尺寸与数量来制定治疗方案。自那以后,我们在探索其他预后因素方面取得了显著进步,尤其是全组学研究领域的蓬勃发展,已经揭示了一系列生物学标志物,它们能为我们提供超越传统肿瘤大小与数量评估的更深层次信息。
然而,遗憾的是,这些先进的检测技术往往复杂繁琐,其复杂程度可能阻碍了它们被纳入现行指南的进程。因此,在临床实践层面,相较于多组学研究领域所取得的丰硕成果,真正能够应用于临床决策的相关数据仍显得相对匮乏。这一现状凸显了将前沿科研发现转化为临床实践应用的迫切需求与挑战。
Q1:At this conference,you delivered a report on the topic"Transitioning from guidelines to personalized medicine in the treatment of hepatocellular carcinoma-a global perspective"Could you share the key points of this presentation with our readers?
Prof.Eduard Jonas:Thank you very much for the question.So,we basically still apply the same guideline that was first published in 1999,in many forms present in national or regional hepatocellular carcinoma(HCC)management guidelines in the world.Those are still based on tumor characteristics,in other words,the size of the tumor and the number of the tumors in patients with HCC.Since then,there’s been a lot of development in looking at other prognostic factors,which includes the whole spectrum of omics research,where they’ve even identified some markers that will tell us more,give us more information than just the size and the number of the tumors.Unfortunately,these tests are still very complex and probably too complex to include it in the guidelines.So,there’s really a paucity of data in the clinical field related to the amount of research that has been done in the field of multi-omics.
02
在您所在的非洲地区,肝细胞癌诊疗指南推荐与世界其他国家,特别是欧美和亚洲国家有怎样的差异?
Eduard Jonas教授:的确,有迹象表明,在撒哈拉以南非洲地区,肝细胞癌主要由慢性乙型肝炎感染驱动,其独特之处在于,我们在非常年轻的患者群体中观察到大量病例,且这些肿瘤往往发现时已是晚期,除此之外,还频繁出现在未患肝硬化的个体中。这一现状无疑极具挑战性,对传统的诊断和治疗策略提出了严峻考验。
更为遗憾的是,即便在全球范围内有多个指南作为指导,但在许多国家,特别是资源有限的地区,这些指南中推荐的治疗手段往往难以获取。这不仅限制了医生的有效治疗选择,也给这类疾病的管理带来了极大的困难。因此,我们需要针对这些特定地区的疾病特征,探索更加适应本地实际情况的治疗策略,并努力提升医疗资源的可及性,以更好地应对这一挑战。
Q2:In your region of Africa,how do the guidelines for the diagnosis and treatments of hepatocellular carcinoma differ from those in other parts of the world,particularly in Western and Asian countries?
Prof.Eduard Jonas:The problem is that there are some indications that we are dealing with a different disease in Africa,especially in sub-Saharan Africa,where the disease is driven by chronic hepatitis B infection.We see a lot of tumors in very young people,with very advanced tumors,and also in patients without cirrhosis of the liver.And that is the problem.Unfortunately,even if we follow the guidelines,in many countries,the treatments that are advised in the current guidelines are not available,and that really presents a major challenge for managing this disease.
03
您如何评价肝细胞癌个体化治疗的应用现状?临床上可能会基于哪些患者特征或检验检查指标,适当对治疗方案进行个体化调整?
Eduard Jonas教授:正如我之前所提及的,尽管多组学研究领域已经取得了丰硕的成果,成功识别出众多能够预测HCC预后的遗传及细胞层面的特异性标志,然而,这些研究成果中真正能够转化为临床实用信息的却屈指可数。即便我们以甲胎蛋白(AFP)这一历史悠久的标志物为例,它作为HCC的标志性指标已存在多年,且在生存预测方面展现出一定的价值,但令人遗憾的是,其在临床指南中的被采纳程度仍然较低,未能充分发挥其应有的指导作用。
Q3:How do you assess the current application of personalized treatment for hepatocellular carcinoma?In clinical practice,which patient characteristics or test results might be used to appropriately tailor treatment plans?
Prof.Eduard Jonas:As I’ve said,the wealth of research that has been done in the field of multi-omics,where different characteristics on a genetic or a cellular level have been identified that can predict prognosis,very few of these have actually resulted in any clinically usable information.And even if we look at alpha-fetoprotein,a very old marker that has been around for many,many years.We know it has got predictive characteristics in terms of survival but it is still for may reasons quite poorly integrated into the guidelines.
04
为了更进一步推动肝细胞癌的个体化诊疗,您最期待哪种创新疗法能够取得成功?
Eduard Jonas教授:个人认为,未来取得突破性进展的关键在于系统治疗的发展。在手术治疗方面,我们已接近其极限,最彻底的手段即是进行肝移植,以彻底移除含有肿瘤的整个肝脏。因此,要取得进一步的飞跃,必须聚焦于系统治疗领域,这一领域能够全面应对肝脏之外的疾病问题。只有当手术不再是首选治疗方式,而是转变为系统治疗的辅助手段或新辅助治疗方式时,我们才能真正在这场战斗中取得胜利。因此,系统治疗将成为成功救治这些患者的核心所在。
Q4:To further advance personalized treatment for hepatocellular carcinoma,which innovative therapy are you most hopeful will succeed?
Prof.Eduard Jonas:I think there’s no doubt in my mind that the key to advances in managing HCC is really in systemic therapies.I think in terms of surgery,we have basically come to the limit in terms of liver resection and liver transplantation where the whole diseased liver with a tumor is removed.I think further advances really are going to be or need to be in the field of systemic therapies,where disease outside the liver is addressed sufficiently.And I will go as far as to say I think this battle will only be won when surgery is not a primary treatment,but it becomes an adjuvant or a neoadjuvant treatment to effective systemic therapies that will be the key to treat these patients successfully.