Department of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
Department of Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Canada.
Curr Oncol Rep. 2021 May 3;23(7):80. doi: 10.1007/s11912-021-01071-5.
Pancreatic neuroendocrine neoplasms (panNENs) often present as advanced disease and there is little data to guide treatment sequencing in the advance disease setting. Therefore, we aim to provide a comprehensive summary of the current evidence supporting the use of systemic treatment for patients with diagnosis of advanced and metastatic panNENs, as well as to provide strategies for treatment selection and address challenges for treatment selection and sequencing of therapy.
Substantial advances have been made and many clinical trials have been performed over the past two decades expanding therapeutic options available for patients with advanced panNETs. Available systemic treatments for patients with well-differentiated pancreatic neuroendocrine tumors include somatostatin receptors ligands (SRLs), traditional cytotoxic chemotherapy regimens, peptide receptor radiotherapy (PRRT), and biologically targeted therapies, whereas patients with poorly differentiated neurodocrine carcinomas have more limited treatment options. Despite these advances, no clear guidelines exist to support the best sequence of treatments, not only the first-line, but also subsequent lines of therapy in patients with panNENs. Advances in molecular research and discovery of biomarkers for response allowing a more personalized approach to the multimodality therapy of panNENs are still limited. Understanding the impact of previous therapies on subsequent treatment efficacy and toxicity is also an ongoing research question. In the absence of definite predictive markers and paucity of comparative randomized trials, along with the heterogeneity of this patient population, systemic therapy selection in advanced non-resectable disease should be patient centered and often require evaluation within a multidisciplinary setting. The specific clinical context of the patient, with assessment of individual patient clinical and pathological features, somatostatin receptors imaging, and goals of treatment must all be considered when deciding on systemic therapy in the patient. Additional research is needed to address the gap in knowledge regarding optimal sequencing and timing of therapies and to provide individual care.
胰腺神经内分泌肿瘤（panNENs）常表现为晚期疾病，在晚期疾病的治疗中，几乎没有数据可以指导治疗方案的选择。因此，我们旨在全面总结目前支持对诊断为晚期和转移性 panNENs 患者使用全身治疗的证据，同时提供治疗选择策略，并解决治疗选择和方案排序方面的挑战。
在过去的二十年中，已经取得了实质性的进展，并开展了许多临床试验，为晚期 panNETs 患者提供了更多的治疗选择。用于分化良好的胰腺神经内分泌肿瘤患者的全身治疗包括生长抑素受体配体（SRL）、传统细胞毒性化疗方案、肽受体放射性核素治疗（PRRT）和生物靶向治疗，而分化差的神经内分泌癌患者的治疗选择有限。尽管取得了这些进展，但目前尚无明确的指南来支持 panNENs 患者的最佳治疗方案，不仅是一线治疗，也包括二线治疗。用于 panNENs 的多模式治疗的分子研究和生物标志物的发现仍有局限性，这些生物标志物可以预测治疗反应。了解先前治疗对后续治疗效果和毒性的影响也是一个正在进行的研究问题。在缺乏明确的预测标志物和缺乏比较随机试验的情况下，加上该患者人群的异质性，晚期不可切除疾病的全身治疗选择应基于患者，并经常需要在多学科环境中进行评估。在决定患者的全身治疗时，必须考虑患者的具体临床情况，包括个体患者的临床和病理特征、生长抑素受体成像以及治疗目标。需要进一步的研究来解决关于治疗方案最佳排序和时机的知识差距，并为患者提供个体化的护理。
