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Lancet oncol:类癌综合征与预后

2017-04-08 月下荷花 肿瘤资讯

神经内分泌肿瘤(NETs)分泌生物活性胺类,产生类癌综合征,症状包括潮热、腹泻。目前为止NET患者发生类癌综合征的频度并不清楚,与临床病理特征的关联也不明确。美国Halperin教授就上述问题进行了研究,结果发表在The Lancet Oncology杂志。法国的Ducreux教授在同期杂志中发表评说,强调类癌综合征的认识虽已超过75年,但也仅限于诊断NETs,与临床再无其它任何关联。

神经内分泌肿瘤(NETs)分泌生物活性胺类,产生类癌综合征,症状包括潮热、腹泻。目前为止NET患者发生类癌综合征的频度并不清楚,与临床病理特征的关联也不明确。美国Halperin教授就上述问题进行了研究,结果发表在The Lancet Oncology杂志。

法国的Ducreux教授在同期杂志中发表评说,强调类癌综合征的认识虽已超过75年,但也仅限于诊断NETs,与临床再无其它任何关联。Halperin教授通过近万例数据,力争无偏倚评估类癌综合征,因此这项研究具有开创性意义。

这项研究数据来自SEER数据库,共纳入9512例NETs患者,统计诊断NET前后3个月期间出现潮热和腹泻表现患者的比率,比较伴或不伴类癌综合征患者的人口统计学特征和临床特征,评估类癌综合征与生存是否存在关联。

1786(19%)例伴有类癌综合征,伴或不伴类癌综合征患者的年龄、区域分布无差别,女性伴类癌综合征者更多,种族、肿瘤分级、分期和原发肿瘤位置与类癌综合征的发生有明显关联,类癌综合征患者总生存更短(5和5.6年),使用奥曲肽和化疗更多,不伴类癌综合征患者手术治疗更多,放疗使用无差别。

根据研究每5例NETs就有1例出现类癌综合征,改善症状是治疗的重要方面,类癌综合征患者的生存较差,提示控制激素分泌的治疗作用可能超过以往认识,女性和非西班牙裔白人患者类癌综合征发生率更高,可能与对疾病认识和诊断的提高有关。

Halperin研究显示类癌综合征与进展期疾病相关,但某些区域性疾病也有极高的类癌综合征发生率,如小肠,超过了以往报告,研究还报告结直肠NETs的类癌综合征发生率也很高;肺的NETs发生类癌综合征的频率很低,可能是其分泌的激素经肝脏清除,综合征表现不典型,Ducreux教授指出这些不典型表现可能只是轻度皮肤潮热、每天2-3次腹泻、腹痛等,医师必需警惕,注意识别,发现后尽早治疗。

Halperin研究结论还包括类癌综合征在起源中肠、分化良好(I-II)肿瘤和肿瘤高负荷者中更多见,伴类癌综合征者诊断3个月内接受奥曲肽或化疗者更多,不伴类癌综合征者更多机会接受手术切除,放疗应用无差别(外照射推荐治疗高级别神经内分泌癌,内照射常用于分化良好肿瘤的减症治疗)。意外的是类癌综合征多发生于化疗不敏感的小肠NETs。

Ducreux教授指出类癌综合征一旦诊断就应立即治疗,特别是有症状的类癌综合征。生长激素抑制素类似物作为一线药物,经动脉化疗栓塞用作一线失败后。药物治疗剂量应充足以良好控制症状,一旦疗效不佳就应快速转为二线治疗。几乎所有共识和指南都不推荐化疗作为治疗选择。

最重要的是Halperin研究首次显示类癌综合征与生存差有关,譬如转移性分化良好小肠NETs伴或不伴类癌综合征总生存的差别可达2年以上,类癌综合征可能反应了肿瘤负荷的差别,也反应了肿瘤侵袭性的差别,控制类癌综合征对生存是否有影响目前尚不明确,因此未来应设计更合理的研究,精确评估NETs,明确改善NETs治疗能否延长患者生存。

Ducreux教授指出临床工作中可考虑将类癌综合征作为不良预后指标,生长激素抑制素类似物有抗肿瘤作用,诊断后应尽早治疗。类癌综合征的预后作用机制不清,不能排除类癌心脏病在其中的作用,但Halperin的研究受数据来源影响未能更好的阐述类癌心脏病对生存影响。看起来类癌综合征是大肿瘤的体现,大肿瘤本身就是不良预后表现。

Ducreux教授进一步指出,30年来只有几种药物可用于治疗类癌综合征如奥曲肽和兰曲肽,经动脉化疗栓塞是另一种控制肿瘤分泌活性激素的方法,依维莫司也可能控制胰腺NETs分泌,另有研究显示代谢性放疗能延长PFS,telotristat etiprate可能对难治性类癌综合征有治疗作用,与其它药物联合有可能成为标准治疗。

总之肿瘤医生应当知道类癌综合征提示预后不良,一旦诊断应尽早进行有效治疗,随访中应有多学科医师参与,如心内科医师,以阻止类癌心脏病的发生。

原始出处:

Halperin D M, Shen C, Dasari A, et al. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncology, 2017.

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    2017-10-09 howi
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    2018-02-12 minlingfeng
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