李健教授:小众迷离,MSI-H肠癌肝转移如何精准治疗?

2019-09-02 佚名 ioncology

结直肠癌发病率和死亡率呈现逐年上升趋势,其防控面临的挑战日趋严峻。而且,肝脏是结直肠癌血行转移的最主要靶器官,结直肠肝转移也是结直肠癌质量的重点和难点,如何精准、规范,甚至创新治疗结直肠肝转移成为临床热点和研究焦点。

直肠癌发病率和死亡率呈现逐年上升趋势,其防控面临的挑战日趋严峻。而且,肝脏是直肠癌血行转移的最主要靶器官,结直肠肝转移也是结直肠癌质量的重点和难点,如何精准、规范,甚至创新治疗结直肠肝转移成为临床热点和研究焦点。

MSI-H肠癌肝转移发生率低,预后存在争议

MSI-H肠癌肝转移发生率尚无大样本数据,现有研究表明其发病率约2.0%~3.0%。有文献报道MSI-H的肠癌中BRAF突变率约50%,但在IV期肠癌MSI-H合并BRAF MT发生率并不高,II/III期肠癌中MSI-H/BRAF 野生型患者预后优于MSI-H/BRAF MT与MSS患者, 现有小样本研究表明MSI状态对肠癌肝转移预后未见影响。随着精准医疗的不断发展,以分子分型为指导的肿瘤药物治疗成为必然。患者临床特征如年龄、CEA、原发部位、转移部位、肿瘤负荷、临床症状帮助定位治疗目标,肿瘤分子特征有助于精准选择治疗方案如RAS、BRAF、HER-2、MSI、MGMT、ERCC1/TS等。2016年ASCO大会报道PD-1联合CTLA4单抗治疗MSI-H 结直肠癌较PD-1单抗更显着缩小病灶(81% vs. 56%)。2018年ESMO大会报道免疫治疗作为MSI直肠癌新辅助治疗可使得大部分患者获得pCR。

那么,结直肠癌原发灶与肝转移MSI是否具有较高一致性?免疫治疗能否用于MSI肠癌肝转移围手术期治疗?这些问题均值得探讨。

MSI肠癌肝转移的治疗仍在探索中

评价免疫治疗与标准化疗联合靶向治疗在MSI肠癌肝转移围手术期治疗的优劣,需要综合考虑两种治疗方案在MSI肠癌中的疗效与安全性因素,但现有的数据相对匮乏。依据北京大学肿瘤医院消化肿瘤内科研究数据与临床现象,目前有如下观点可进行参考:(1)IV期MSI-H肠癌患者接受一线化疗的疗效并不理想;(2)免疫治疗相对于标准化疗联合靶向治疗在MSI-H肠癌中可能具有疗效优势;(3)在MSI-H肠癌肝转移中,免疫治疗疗效似乎不及MSI-H非肝转移患者;(4)MSI-H肠癌术后辅助化疗获益不佳;(5)MSI-H肠癌术后免疫治疗对比化疗的研究正在进行中,目前尚无结论;(6)目前使用的CRS评分不一定适用于MSI-H肠癌肝转移术后复发风险的评估。

因此,综合现有有限的临床数据与临床现象,在MSI-H肠癌肝转移围手术期治疗中,初步做如下推荐:

不可切除的MSI-H肠癌肝转移转化治疗:首选推荐免疫治疗(PD-1+CTLA-4单抗),次选化疗联合靶向治疗。

可切除的MSI-H肠癌肝转移新辅助治疗:不推荐免疫治疗,也不推荐化疗,建议直接手术。

辅助治疗:推荐免疫治疗(PD-1单抗单药,治疗一年),不推荐辅助化疗。

MSI-H肠癌肝转移发病率低,预计未来也很难有针对该类人群的大样本研究与高级别循证医学证据,但MSI-H与MSS肠癌肝转移的生物学行为以及对不同药物的反应均存在较大差异,因此,该类人群的治疗需要在临床研究中case by case的去进行探索,特别是多学科的治疗模式在该类患者的治疗策略制定中可发挥重要作用。MSI-H 肠癌肝转移的治疗任重道远,仍在不停的探索中。

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    2019-09-04 小几洁

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肠癌肝转移并非不可治,“微波消融”能否根治肿瘤

一听到肿瘤复发转移,就让人心灰意冷。的确,从前只要肿瘤复发转移,基本上就被叛了“死刑”。如今,新技术可以帮助部分患者跨过这道坎。上海复旦大学附属肿瘤医院中西医结合科/肿瘤微创治疗中心副主任医师王鹏表示,对于结直肠癌肝转移的患者,转移病灶在3个以内,且大小小于3厘米的,可以用微波消融的方式消灭病灶,达到根治的效果。微波消融是通过超声、CT或磁共振引导,将一根能发射能量的针直接经皮肤刺入肿瘤中心,通过