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　　英國(guó)的一項(xiàng)研究確定了關(guān)于循環(huán)腫瘤細(xì)胞(CTC)對(duì)神經(jīng)內(nèi)分泌腫瘤患者的預(yù)后意義。研究結(jié)果在線發(fā)表于2012年12月17日的Journal of Clinical Oncology上[全文下載]。

　　這項(xiàng)單中心、前瞻性研究的研究，共納入了176例存在可測(cè)量病灶的轉(zhuǎn)移性神經(jīng)內(nèi)分泌腫瘤(NET)患者。循環(huán)腫瘤細(xì)胞通過(guò)使用一項(xiàng)半自動(dòng)技術(shù)進(jìn)行測(cè)定：利用免疫磁性分離方法對(duì)上皮細(xì)胞粘附的分子表達(dá)細(xì)胞進(jìn)行分離。

　　研究結(jié)果顯示，整體而言，49%的患者在每7.5mL血樣中存在≥1個(gè)循環(huán)腫瘤細(xì)胞，42%的患者存在≥2個(gè)循環(huán)腫瘤細(xì)胞，30%的患者存在≥5個(gè)循環(huán)腫瘤細(xì)胞。循環(huán)腫瘤細(xì)胞的存在與腫瘤負(fù)擔(dān)增加、腫瘤分級(jí)提高以及嗜鉻粒蛋白A(CgA)水平提高之間存在關(guān)聯(lián)。通過(guò)包含90例患者的訓(xùn)練集以及85例患者的驗(yàn)證集，研究者定義了<1個(gè)循環(huán)腫瘤細(xì)胞或≥1個(gè)循環(huán)腫瘤細(xì)胞為無(wú)進(jìn)展存活期(PFS)相關(guān)最佳預(yù)后閾值點(diǎn)。通過(guò)該閾值發(fā)現(xiàn)，存在≥1個(gè)循環(huán)腫瘤細(xì)胞與較差的PFS以及較差總生存期(OS)之間存在關(guān)聯(lián)(風(fēng)險(xiǎn)比分別為6.6與8.0；二者P<0.001)。

　　是否檢出CTC兩組患者的PFS曲線

　　對(duì)包括分級(jí)、腫瘤負(fù)擔(dān)以及等CgA在內(nèi)的其他預(yù)后指標(biāo)進(jìn)行的多變量分析結(jié)果顯示，循環(huán)腫瘤細(xì)胞仍為一個(gè)顯著預(yù)后因素。對(duì)于各等級(jí)腫瘤，根據(jù)存在的循環(huán)腫瘤細(xì)胞可對(duì)不良預(yù)后的患者亞群進(jìn)行界定。對(duì)于1級(jí)腫瘤，PFS風(fēng)險(xiǎn)比為5.0(P =0.017)，OS風(fēng)險(xiǎn)比為7.2(P =0.023)。而對(duì)于2級(jí)腫瘤，PFS風(fēng)險(xiǎn)比為3.5(P =0.018)，OS風(fēng)險(xiǎn)比為5.2(P =0.036)。

　　由此得出結(jié)論，對(duì)于轉(zhuǎn)移性神經(jīng)內(nèi)分泌癌患者，循環(huán)腫瘤細(xì)胞是一種有前途的預(yù)后指標(biāo)，應(yīng)在針對(duì)明確腫瘤亞型以及治療方法的臨床試驗(yàn)環(huán)境下，進(jìn)一步對(duì)其進(jìn)行評(píng)估。

　　Purpose

　　To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrinecancer.

　　Patients and Methods

　　In this single-center prospective study, 176 patients with measurable metastatic neuroendocrinetumors (NETs) were recruited. CTCs were measured using a semiautomated techniquebased on immunomagnetic separation of epithelial cell adhesion molecule-expressing cells.

　　Results

　　Overall, 49% patients had ≥ one CTC, 42% had ≥ two CTCs, and 30% had ≥ five CTCs in 7.5mL blood. Presence of CTCs was associated with increased burden, increased tumor grade,and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patientvalidation set, we defined a cutoff of < one or ≥ one as the optimal prognostic threshold withrespect to progression-free survival (PFS). Applying this threshold, the presence of one CTCwas associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0,respectively; both P<0.001). In multivariate analysis, CTCs remained significant when otherprognostic markers, grade, tumor burden, and CgA were included. Within grades, presence ofCTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 forPFS (P=0.017) and 7.2 for OS (P=0.023); for grade 2, HRs were 3.5 for PFS (P=0.018) and5.2 for OS (P=0.036).

　　Conclusion

　　CTCs are a promising prognostic marker for patients with NETs and should be assessed in thecontext of clinical trials with defined tumor subtypes and therapy.
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