定义胰腺腺癌生物学边界情况的新生物标记物--PANACHE01-PRODIGE48 试验的辅助研究结果

IF 7.5 1区 医学 Q1 SURGERY Annals of surgery Pub Date : 2024-11-01 Epub Date: 2024-08-05 DOI:10.1097/SLA.0000000000006468
Jean Pinson, Julie Henriques, Ludivine Beaussire, Nasrin Sarafan-Vasseur, Antonio Sa Cunha, Jean-Baptiste Bachet, Dewi Vernerey, Frederic Di Fiore, Lilian Schwarz
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引用次数: 0

摘要

目的基于PANACHE01-PRODIGE 48试验的一项计划辅助研究,研究基线CA19-9和循环肿瘤DNA(ctDNA)对可切除胰腺导管腺癌(PA)患者总生存期(OS)的预后价值,以改善死亡风险分层:在 2016 年国际共识会议之后,MD Anderson 首次使用的生物边界情况成为管理 PA 的标准做法。考虑到全身性疾病的风险,尤其是在 CA19-9 "明显升高 "的情况下,建议进行新辅助治疗,以避免不必要的手术和早期复发的风险。为了更好地界定生物学边界情况,需要新的生物标志物:方法:比较有或没有ctDNA状态的患者的诊断特征和OS。OS 采用 Kaplan Meier 法估算,并用对数秩检验进行比较。采用限制立方样条法确定用于死亡风险分层的生物参数的最佳阈值。估算了单变量和多变量考克斯比例危险模型,以评估ctDNA状态和其他参数与OS的关系:在PANACHE01 -PRODIGE 48试验的主要分析人群132名患者中,有92人(71%)在诊断时可获得ctDNA状态。有无ctDNA状态的患者之间未发现选择偏差。14名患者(15%)为ctDNA+,死亡风险较高(P=0,0188;HR95% CI:2.28(1.12-4.63))。在 92 例可获得 ctDNA 状态的患者中,在分析的其他参数中,只有 CA19-9 在单变量分析中与 OS 有统计学相关性。CA19-9对数等于或大于4.4(相当于CA19-9为80 UI/mL)的患者死亡风险较高(P=0,0143;HR95% CI:2.2(1.15-4.19))。在多变量分析中,CA19-19 仍与 OS 独立相关(P 值=0.0323)。如果将两种生物标志物结合起来,"CA19-9高和ctDNA+组"、"CA19-9高或ctDNA+组 "和 "CA19-9低和ctDNA-组 "的中位OS分别为19.4个月(IC 95% 3.8-未达到)、30.2个月(IC 95% 17.1-NR)和未达到(IC 95% 39.3-NR)(logrank P=0,0069):讨论:潜在可手术 PA 的治疗进展仍然有限,仅依赖于基于现代多药化疗(FOLFIRINOX、GemNabPaclitaxel)和手术切除的完全治疗顺序优化策略。确定风险标准(如存在全身性疾病)是一个重要问题,目前被称为 "生物学边界疾病"。很少有数据,尤其是来自前瞻性研究的数据,能让我们确定 CA19-9 以外的生物标志物:结论:将ctDNA与CA19-9结合起来可能有助于更好地界定PA的生物学边界情况。
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New Biomarkers to Define a Biological Borderline Situation for Pancreatic Adenocarcinoma: Results of an Ancillary Study of the PANACHE01-PRODIGE48 Trial.

Objective: To investigate in patients treated for a resectable pancreatic ductal adenocarcinoma [pancreatic adenocarcinoma (PA)], the prognostic value of baseline carbohydrate antigen 19.9 (CA19-9) and circulating tumor DNA (ctDNA) for overall survival (OS), to improve death risk stratification, based on a planned ancillary study from PANACHE01-PRODIGE 48 trial.

Background: Biological borderline situation that was first used by the MD Anderson, became a standard practice following the international consensus conference in 2016 to manage PA. Regarding the risk of systemic disease, especially in the setting of "markedly elevated" CA19-9, neoadjuvant therapy is advised to avoid unnecessary surgery, with a risk of early recurrence. To best define biological borderline situations, new biomarkers are needed.

Methods: Characteristics at diagnosis and OS were compared between patients with or without ctDNA status available. OS was estimated with the Kaplan-Meier method and compared with a log-rank test. The restricted cubic spline approach was used to identify the optimal threshold for biological parameters for death risk stratification. Univariate and multivariate Cox proportional hazard models were estimated to assess the association of ctDNA status and other parameters with OS.

Results: Among the 132 patients from the primary population for analysis in the PANACHE01 -PRODIGE 48 trial, 92(71%) were available for ctDNA status at diagnosis. No selection bias was identified between patients with or without ctDNA status. Fourteen patients (15%) were ctDNA+ and exhibited a higher risk for death [ P = 0.0188; hazard ratio (95% CI): 2.28 (1.12-4.63)]. In the 92 patients with ctDNA status available among the other parameters analyzed, only CA19-9 was statically associated with OS in univariate analysis. Patients with a log of CA19-9 equal or superior to 4.4 that corresponds to a CA19-9 of 80 UI/mL were identified at higher risk for death [ P = 0.0143; hazard ratio (95% CI): 2.2 (1.15-4.19)]. In multivariate analysis, CA19-19 remained independently associated with OS ( P = 0.0323). When combining the 2 biomarkers, the median OS was 19.4 [IC 95%: 3.8-not reached (NR)] months, 30.2 (IC 95%: 17.1-NR) months and NR (IC 95%: 39.3-NR) for "CA19-9 high and ctDNA+ group," "CA19-9 high or ctDNA+ group," and "CA19-9 low and ctDNA- group," respectively (log-rank P = 0.0069).

Conclusions: Progress in the management of potentially operable PA remains limited, relying solely on strategies to optimize the sequence of complete treatment, based on modern multidrug chemotherapy (FOLFIRINOX, GemNabPaclitaxel) and surgical resection. The identification of risk criteria, such as the existence of systemic disease, is an important issue, currently referred to as "biological borderline disease." Few data, particularly from prospective studies, allow us to identify biomarkers other than CA19-9. Combining ctDNA with CA19-9 could be of interest to best define biological borderline situations in PA.

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来源期刊
Annals of surgery
Annals of surgery 医学-外科
CiteScore
14.40
自引率
4.40%
发文量
687
审稿时长
4 months
期刊介绍: The Annals of Surgery is a renowned surgery journal, recognized globally for its extensive scholarly references. It serves as a valuable resource for the international medical community by disseminating knowledge regarding important developments in surgical science and practice. Surgeons regularly turn to the Annals of Surgery to stay updated on innovative practices and techniques. The journal also offers special editorial features such as "Advances in Surgical Technique," offering timely coverage of ongoing clinical issues. Additionally, the journal publishes monthly review articles that address the latest concerns in surgical practice.
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