The canary in the coal mine: the growth of patient-derived tumorgrafts in mice predicts clinical recurrence after surgical resection of pancreatic ductal adenocarcinoma.
The canary in the coal mine: the growth of patient-derived tumorgrafts in mice predicts clinical recurrence after surgical resection of pancreatic ductal adenocarcinoma.
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煤矿中的金丝雀：小鼠中患者衍生的肿瘤的生长预测胰腺导管腺癌手术切除后的临床复发。
DOI：
10.1245/s10434-014-4241-1
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发表时间：
2015
影响因子：
3.7
通讯作者：
Fleming JB
中科院分区：
文献类型：
--
作者：
Thomas RM;Truty MJ;Kim M;Kang Y;Zhang R;Chatterjee D;Katz MH;Fleming JB
胰腺导管腺癌（PDAC）切除术后复发是常见的，因此术后监测对于发现和治疗复发性疾病至关重要。基于生物学的早期复发检测技术的发展可能使这种复发性疾病的治疗更加及时和有效。将来自接受PDAC潜在治愈性切除的患者的肿瘤碎片异位植入NOD/SCID小鼠中。植入成功率和生长参数与临床病理学数据、术前治疗状态和肿瘤学结局相匹配，以关联无病生存期（DFS）和总生存期。70例患者同意参与，其中56例（80%）发生小鼠PDAC肿瘤移植物。与肿瘤移植物未能植入的患者相比，成功植入的患者的中位DFS较短（分别为9.8 vs. 40.9个月; p <0.01）。50例患者接受了术前治疗，其中36例（72%）肿瘤移植成功。在多变量分析中，淋巴结转移（风险比[HR] 3，95% CI 1.4-6.7，p \ 0.01）和成功植入（HR 5.8，95% CI 2-16.9，p \ 0.01）可预测术前治疗队列的DFS较短。在复发的患者中，在标准放射学复发检测方法之前的中位数134.5天确定了肿瘤移植物形成（p <0.01）。患者来源的PDAC切除肿瘤移植物可能在目前可用的监测模式之前几个月预测复发。这种提前期优势可能允许更早实施或改变治疗，因为成功的植入，特别是在那些经历了术前治疗的患者中，可能表明更具生物学侵袭性的疾病。
Recurrence after resection of pancreatic ductal adenocarcinoma (PDAC) is common, thus postoperative surveillance is critical for detection and treatment of recurrent disease. The development of biologically based techniques for early recurrence detection may enable more timely and effective treatment of such recurrences. Tumor fragments derived from patients who underwent potentially curative resection of PDAC were heterotopically implanted into NOD/SCID mice. Engraftment success rates and growth parameters were matched to clinicopathologic data, preoperative treatment status, and oncologic outcomes to correlate disease-free survival (DFS) and overall survival. Seventy patients consented to participate with 56 (80 %) developing a mouse PDAC tumorgraft. Patients with successful engraftment had a shorter median DFS compared with patients whose tumorgrafts failed to engraft (9.8 vs. 40.9 mo, respectively; p \ 0.01). Fifty patients received preoperative therapy with 36 (72 %) successful tumorgrafts from this cohort. On multivariate analysis, lymph node metastasis (hazard ratio [HR] 3, 95 % CI 1.4–6.7, p \ 0.01) and successful engraftment (HR 5.8, 95 % CI 2–16.9, p \ 0.01) were predictive of a shorter DFS in the preoperative therapy cohort. In patients who recurred, tumorgraft formation was identified at a median of 134.5 days before standard methods of radiographic recurrence detection (p \ 0.01). Patient-derived tumorgrafts from resected PDAC may potentially predict recurrence months before currently available surveillance modalities. This lead-time advantage may allow for earlier implementation or changes in therapy as successful engraftment, particularly in those having undergone preoperative therapy, may indicate a more biologically aggressive disease.