Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease.
Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease.
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DOI：
10.1186/s12885-017-3186-8
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发表时间：
2017-03-29
期刊：
影响因子：
3.8
通讯作者：
Bruns CJ
中科院分区：
文献类型：
--
作者：
Popp FC;Popp MC;Zhao Y;Betzler C;Kropf S;Garlipp B;Benckert C;Kalinski T;Lippert H;Bruns CJ
胰腺导管腺癌（PDAC）是当今最致命的恶性肿瘤之一，迫切需要新的治疗策略。生物标志物分析有助于更好地了解肿瘤生物学，并可能成为开发个性化治疗的工具。该研究的目的是调查四种有希望的生物标志物，以预测临床过程，特别是手术切除后肿瘤复发的模式。接受PDAC手术的患者可入组PANCALYZE试验。将通过免疫组织化学前瞻性评估CXCR 4、SMAD 4、SOX 9和IFIT 3的生物标志物表达，并通过rt.来自手术标本的肿瘤和邻近健康胰腺组织的PCR。所有四种生物标志物的免疫组织化学表达模式将合并为单个评分。从住院开始，将收集并随访入组患者的临床数据。不同的辅助化疗方案将用于创建亚组。组合的生物标志物表达评分将与患者的进一步临床病程相关，以检验CXCR 4阳性、SMAD 4阴性、SOX 9阳性、IFIT 3阳性肿瘤是否将主要发展为转移性扩散的假设。胰腺癌与不同的进展模式相关，需要个性化的治疗策略。生物标志物表达分析可能是一种预测肿瘤复发模式的工具，并将发展全身转移性疾病的患者与那些随着时间的推移而发展局部复发的肿瘤患者区分开来。这些数据可能会导致个性化的辅助治疗决策，因为与全身复发的患者相比，局部肿瘤患者可能会受益于辅助局部治疗，如放射化疗。此外，传播模式可能是胰腺癌的预定义特征，由肿瘤的遗传特征决定。在未来，可以对肿瘤活检进行生物标志物表达分析，以在癌症诊断后立即开发个性化的治疗途径。德国临床试验注册中心，DRKS 00006179。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection. Patients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread. Pancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy. Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer. German Clinical Trials Register, DRKS00006179.