CHARM 2: Chemotherapy for ablation and resolution of mucinous pancreatic cysts: a prospective, randomized, double-blind, multi-center clinical trial

难以定性和治疗的癌前胰腺囊肿日益增多 由于成像技术的进步和老龄化，在过去的20年里在美国发现了 人口。随着美国高致命性胰腺癌发病率的上升，干预 具有恶性潜在性的胰腺囊肿是一种安全有效的公共卫生方法 担忧。虽然患者历史上一直局限于放射检查或潜在地 作为处理这些囊肿的不良方法的危险手术，内窥镜超声 引导细针注射(EUS-FNI)是一种创伤小、安全有效的方法 早期干预方法。对于目前EUS引导下的胰腺囊肿治疗，通常情况下 包括用乙醇灌洗。然而，专家们一致认为，观察到的不良事件 在治疗过程中是由于乙醇的使用。最近，基于对周围安全的担忧 乙醇的使用，以及与紫杉醇输注有关的有希望的治疗结果，我们的 该团队创造了一种无乙醇(EF)的联合化疗疗法，由 混合物-紫杉醇和吉西他滨-专门针对胰腺囊性病变而设计 超声引导下注射肿瘤。我们的团队完成了对这种新型治疗策略的测试 2017年作为初步随机试验，显示EF灌洗(即生理盐水)与 与相同的化疗方法相比，化疗同样有效，而且要安全得多 包括乙醇灌洗(EL)。在这项建议中，我们的目的是扩大我们的试点研究的规模， 进行一项大型、明确的多中心试验，这将是第一个资助的随机对照试验 EL转无酒精(EF)联合化疗的治疗 探员们。所有受试者都将接受抽吸和疏散符合条件的囊性病变，并接受 术后3个月复查，12个月复查。我们将随机分配100 成人胰腺囊肿患者分为两个研究组：(1)无水乙醇灌洗(EL)：EL，然后 输注紫杉醇-吉西他滨混合液，或(2)无乙醇(EF)：生理盐水灌洗 通过输注相同的紫杉醇-吉西他滨混合物。我们假设EF治疗将 显著减少不良事件，并将有完全的囊性消融率 并不逊色于EL治疗。如果外汇储备干预被证明不逊于 比EL治疗安全得多，它将验证EUS-FNI作为一种可行的治疗方式 介入癌前囊肿，将改变胰腺囊肿的护理标准 管理层。关键是，如果EF治疗成功，它可能会改变治疗决定， 患者做出并改变卓越中心提供的治疗选择。

Pre-malignant pancreatic cysts that are difficult to characterize and treat are increasingly discovered in the US over the last two decades due to advances in imaging and an aging population. With the incidence of highly lethal pancreatic cancer rising in the US, intervening on pancreatic cysts with malignant potential in a safe and effective way is a major public health concern. While patients have been historically limited to radiographic surveillance or potentially hazardous surgery as undesirable methods of managing these cysts, endoscopic ultrasound guided fine needle injection (EUS-FNI) has emerged as a less-invasive, safe and effective method of early intervention. For EUS-guided treatment of pancreatic cysts today, care typically includes lavage with ethanol. However, experts agree that adverse events (AEs) observed during treatment are due to ethanol use. Recently, based on the safety concerns surrounding ethanol use, as well as the promising treatment findings linked to the infusion of paclitaxel, our team created an ethanol-free (EF), combination chemotherapy treatment consisting of an admixture—paclitaxel and gemcitabine—specifically designed to target pancreatic cystic neoplasia by EUS-guided injection. Our team completed testing of this novel treatment strategy in 2017 as a preliminary randomized trial, showing that EF lavage (i.e., saline) with combination chemotherapy was as effective, and far safer, than the same chemotherapy treatment with the inclusion of ethanol lavage (EL). In this proposal, our aim is increase the scale of our pilot study, conducting a large and definitive multi-center trial that will be the first funded RCT to compare treatment with EL to ethanol-free (EF) treatment with combination infusion of chemotherapeutic agents. All subjects will have qualifying cystic lesions aspirated and evacuated, and undergo a follow-up procedure at 3 months and final imaging at 12 months. We will randomly assign 100 adult patients with pancreatic cysts to two study arms: (1) Ethanol lavage (EL): EL, followed by infusion of a paclitaxel-gemcitabine admixture, or (2) Ethanol Free (EF): saline lavage, followed by infusion of the same paclitaxel-gemcitabine admixture. We hypothesize that EF treatment will result in significantly fewer adverse events and will have complete cyst ablation resolution rates that are not inferior to EL treatment. If the EF intervention proves to be non-inferior to, and significantly safer than, treatment with EL, it will validate EUS-FNI as a viable treatment modality for intervening on pre-malignant cysts and will change the standard of care for pancreatic cyst management. Critically, if EF treatment is successful, it may alter the treatment decisions that patients make and change the treatment options that centers of excellence offer.