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辅助性吉西他滨治疗的完整性、复发模式及后续治疗对切除的胰腺导管腺癌患者预后的影响——CONKO-001、CONKO-005和CONKO-006试验的汇总分析

Impact of completeness of adjuvant gemcitabine, relapse pattern, and subsequent therapy on outcome of patients with resected pancreatic ductal adenocarcinoma - A pooled analysis of CONKO-001, CONKO-005, and CONKO-006 trials.

作者信息

Kurreck Annika, Weckwerth Johanna, Modest Dominik P, Striefler Jana K, Bahra Marcus, Bischoff Sven, Pelzer Uwe, Oettle Helmut, Kruger Stephan, Riess Hanno, Sinn Marianne

机构信息

Charité University Medicine Berlin, Department of Hematology, Oncology, and Tumorimmunology, CVK, Berlin, Germany.

Charité University Medicine Berlin, Department of General, Visceral, and Transplantation Surgery, Berlin, Germany.

出版信息

Eur J Cancer. 2021 Jun;150:250-259. doi: 10.1016/j.ejca.2021.03.036. Epub 2021 Apr 30.

DOI:10.1016/j.ejca.2021.03.036
PMID:33940349
Abstract

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most fatal malignancies worldwide. It is suggested that survival in PDAC depends, among other things, on pattern of disease recurrence.

PATIENTS AND METHODS

We performed a pooled analysis of the adjuvant therapy studies CONKO-001, CONKO-005, and CONKO-006, including a total of 912 patients with regard to prognostic factors in patients with recurrent disease. Overall survival from disease recurrence (OS 2) and disease-free survival (DFS) from the day of surgery were expressed by Kaplan-Meier method and compared using log-rank testing and Cox regression.

RESULTS

Of 912 patients treated within the previously mentioned CONKO trials, we identified 689 patients with disease recurrence and defined site of relapse. In multivariable analysis, the presence of isolated pulmonary metastasis, low tumour grading, and low postoperative level of CA 19-9 remained significant factors for improved OS 2 and DFS. Furthermore, completeness of adjuvant gemcitabine-based treatment (OS 2: P = 0.006), number of relapse sites (OS 2: P = 0.015), and type of palliative first-line treatment (OS 2: P < 0.001) significantly affected overall survival after disease recurrence in PDAC.

CONCLUSIONS

Determining tumour subgroups using prognostic factors may be helpful to stratify PDAC patients for future clinical trials. In case of disease recurrence, the site of relapse may have a prognostic impact on subsequent survival. Further investigations are needed to identify differences in tumour biology, reflecting relapse patterns and the differing survival of PDAC patients.

摘要

背景

胰腺导管腺癌(PDAC)是全球最致命的恶性肿瘤之一。有研究表明,PDAC患者的生存情况在很大程度上取决于疾病复发模式。

患者与方法

我们对辅助治疗研究CONKO - 001、CONKO - 005和CONKO - 006进行了汇总分析,纳入了总共912例复发疾病患者的预后因素。采用Kaplan - Meier法计算疾病复发后的总生存期(OS 2)和术后无病生存期(DFS),并使用对数秩检验和Cox回归进行比较。

结果

在上述CONKO试验中接受治疗的912例患者中,我们确定了689例疾病复发患者并明确了复发部位。多变量分析显示,孤立性肺转移的存在、低肿瘤分级以及术后低水平的CA 19 - 9仍然是改善OS 2和DFS的显著因素。此外,基于吉西他滨的辅助治疗的完成情况(OS 2:P = 0.006)、复发部位数量(OS 2:P = 0.015)以及一线姑息治疗类型(OS 2:P < 0.001)对PDAC疾病复发后的总生存期有显著影响。

结论

利用预后因素确定肿瘤亚组可能有助于对PDAC患者进行分层,以便未来开展临床试验。在疾病复发的情况下,复发部位可能对后续生存有预后影响。需要进一步研究以确定肿瘤生物学差异,这些差异反映了复发模式以及PDAC患者不同的生存情况。

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