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胰腺癌:综述。

Pancreatic Cancer: A Review.

机构信息

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York.

出版信息

JAMA. 2021 Sep 7;326(9):851-862. doi: 10.1001/jama.2021.13027.

Abstract

IMPORTANCE

Pancreatic ductal adenocarcinoma (PDAC) is a relatively uncommon cancer, with approximately 60 430 new diagnoses expected in 2021 in the US. The incidence of PDAC is increasing by 0.5% to 1.0% per year, and it is projected to become the second-leading cause of cancer-related mortality by 2030.

OBSERVATIONS

Effective screening is not available for PDAC, and most patients present with locally advanced (30%-35%) or metastatic (50%-55%) disease at diagnosis. A multidisciplinary management approach is recommended. Localized pancreas cancer includes resectable, borderline resectable (localized and involving major vascular structures), and locally advanced (unresectable) disease based on the degree of arterial and venous involvement by tumor, typically of the superior mesenteric vessels. For patients with resectable disease at presentation (10%-15%), surgery followed by adjuvant chemotherapy with FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) represents a standard therapeutic approach with an anticipated median overall survival of 54.4 months, compared with 35 months for single-agent gemcitabine (stratified hazard ratio for death, 0.64 [95% CI, 0.48-0.86]; P = .003). Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach for resectable and borderline resectable disease. For patients with locally advanced and unresectable disease due to extensive vascular involvement, systemic therapy followed by radiation is an option for definitive locoregional disease control. For patients with advanced (locally advanced and metastatic) PDAC, multiagent chemotherapy regimens, including FOLFIRINOX, gemcitabine/nab-paclitaxel, and nanoliposomal irinotecan/fluorouracil, all have a survival benefit of 2 to 6 months compared with a single-agent gemcitabine. For the 5% to 7% of patients with a BRCA pathogenic germline variant and metastatic PDAC, olaparib, a poly (adenosine diphosphate [ADB]-ribose) polymerase inhibitor, is a maintenance option that improves progression-free survival following initial platinum-based therapy.

CONCLUSIONS AND RELEVANCE

Approximately 60 000 new cases of PDAC are diagnosed per year, and approximately 50% of patients have advanced disease at diagnosis. The incidence of PDAC is increasing. Currently available cytotoxic therapies for advanced disease are modestly effective. For all patients, multidisciplinary management, comprehensive germline testing, and integrated supportive care are recommended.

摘要

重要性

胰腺导管腺癌 (PDAC) 是一种相对罕见的癌症,预计 2021 年在美国将有 60430 例新诊断病例。PDAC 的发病率每年以 0.5% 至 1.0%的速度增长,预计到 2030 年将成为癌症相关死亡的第二大原因。

观察结果

目前尚无有效的 PDAC 筛查方法,大多数患者在诊断时已处于局部晚期(30%-35%)或转移性(50%-55%)疾病。建议采用多学科管理方法。局限性胰腺癌包括可切除、交界可切除(局部且累及主要血管结构)和局部晚期(不可切除)疾病,这取决于肿瘤对肠系膜上动脉的侵犯程度,通常涉及肠系膜上血管。对于初诊时可切除疾病的患者(10%-15%),手术联合氟尿嘧啶、伊立替康、亚叶酸钙、奥沙利铂(FOLFIRINOX)辅助化疗是一种标准治疗方法,预计中位总生存期为 54.4 个月,而单独使用吉西他滨为 35 个月(死亡分层风险比,0.64[95%CI,0.48-0.86];P=0.003)。新辅助全身治疗联合或不联合放疗,然后评估手术,是可切除和交界可切除疾病的一种可接受的治疗方法。对于由于广泛血管受累而导致局部晚期和不可切除疾病的患者,全身治疗联合放疗是一种明确的局部区域疾病控制方法。对于局部晚期和转移性 PDAC 患者,多药化疗方案,包括 FOLFIRINOX、吉西他滨/白蛋白结合型紫杉醇和伊立替康/氟尿嘧啶纳米脂质体,与单药吉西他滨相比,均有 2 至 6 个月的生存获益。对于 5%至 7%的具有 BRCA 种系致病性变异和转移性 PDAC 的患者,聚(二磷酸腺苷[ADP]-核糖)聚合酶抑制剂奥拉帕利是一种维持治疗选择,可改善初始基于铂的治疗后的无进展生存期。

结论和相关性

每年约有 60000 例新诊断的 PDAC 病例,约有 50%的患者在诊断时已处于晚期疾病。PDAC 的发病率正在上升。目前用于晚期疾病的细胞毒性疗法疗效有限。建议所有患者采用多学科管理、全面的种系检测和综合支持性护理。

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