OBJECTIVE We integrate a new approach to chemosensitivity data for clinically-relevant regimen matching, and demonstrate the relationship with clinical outcomes in a large PDO biobank. SUMMARY BACKGROUND DATA Pancreatic ductal adenocarcinoma (PDAC) usually recurs following potentially curative resection. Prior studies related patient-derived organoid (PDO) chemosensitivity with clinical responses. METHODS PDOs were established from pre-treatment biopsies in a multi-institution clinical trial (n=21) and clinical specimens at a high-volume pancreatectomy center (n=74, of which 48 were pre-treated). PDO in vitro chemosensitivities to standard-of-care chemotherapeutics (pharmacotypes) were matched to potential clinically-relevant regimens by a weighted nearest-neighbors analysis. Clinical outcomes were then compared for patients who had well-matched versus poorly-matched treatment according to this metric. RESULTS Our function matched 91% of PDOs to a standard-of-care regimen (9% pan-resistant). PDOs poorly-matched to the neoadjuvant regimen received would have matched to an alternative in 34% of cases. Patients receiving neoadjuvant chemotherapy well-matched to their pharmacotype experienced improved CA 19-9 response (60% decreased to normal when well-matched, 29% when poorly-matched, P<0.05) and lymph node down-staging (33% N0 after poorly-matched, 69% after well-matched, P<0.05). Patients receiving both well-matched neoadjuvant and adjuvant chemotherapy experienced improved recurrence-free- and overall survival (median RFS 8.5 mo poorly-matched, 15.9 mo well-matched, P<0.05; median OS 19.5 vs. 30.3 mo, P<0.05). CONCLUSION In vitro PDO pharmacotyping can inform PDAC therapy selection. We demonstrate improved outcomes including survival for patients treated with regimens well-matched to their PDO chemosensitivities. A subsequent prospective study using PDO pharmacotype matching could improve oncologic outcomes and improve quality of life by avoiding therapies not expected to be effective.

中文翻译：

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患者来源的类器官药分型作为胰腺导管腺癌治疗选择的预测工具。


目的 我们整合了一种新的化疗敏感性数据方法，用于临床相关的方案匹配，并在大型 PDO 生物库中证明了与临床结果的关系。摘要 背景数据 胰腺导管腺癌 （PDAC） 通常在可能治愈性的切除后复发。先前的研究将患者来源的类器官 （PDO） 化疗敏感性与临床反应相关联。方法 根据多机构临床试验中的治疗前活检 （n=21） 和大容量胰腺切除术中心的临床标本 （n=74，其中 48 例进行了预处理） 建立 PDO。通过加权最近邻分析，将 PDO 体外化疗对标准护理化疗药物（药型）的敏感性与潜在的临床相关方案相匹配。然后根据该指标，比较治疗匹配良好与匹配不佳的患者的临床结局。结果： 我们的功能将 91% 的 PDO 与标准护理方案相匹配 （9% 泛耐药）。在 34% 的病例中，与接受的新辅助方案不匹配的 PDO 将与替代方案匹配。接受与其药型完全匹配的新辅助化疗的患者的 CA 19-9 反应有所改善 （匹配良好时降低 60% 至正常，匹配不佳时降低 29%，P<0.05） 和淋巴结降级 （匹配不良后 N0 为 33%，匹配后为 69%，P<0.05）。接受匹配良好的新辅助和辅助化疗的患者无复发生存期和总生存期均有所改善 （中位 RFS 8.5 mo 匹配不佳，15.9 mo 匹配良好，P<0.05;中位 OS 19.5 vs. 30.3 mo，P<0.05）。结论 体外 PDO 药分可以为 PDAC 治疗的选择提供信息。 我们证明了接受与其 PDO 化学敏感性完全匹配的方案治疗的患者的结局有所改善，包括生存率。随后一项使用 PDO 药型匹配的前瞻性研究可以通过避免预期无效的治疗来改善肿瘤学结局并改善生活质量。