Liu Alex J, Ueberroth Benjamin E, McGarrah Patrick W, Buckner Petty Skye A, Kendi Ayse Tuba, Starr Jason, Hobday Timothy J, Halfdanarson Thorvardur R, Sonbol Mohamad Bassam
Mayo Clinic Internal Medicine Residency, Phoenix, Arizona, USA.
Mayo Clinic Cancer Center, Rochester, Minnesota, USA.
Oncologist. 2021 May;26(5):383-388. doi: 10.1002/onco.13686. Epub 2021 Feb 8.
Recent classification of neuroendocrine neoplasms has defined well-differentiated high-grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well-described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens.
This was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients' demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression-free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR).
Treatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki-67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum-etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96-16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months.
Among patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short-lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy.
High-grade well-differentiated neuroendocrine tumors (NET G3) are considered a different entity from low-grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well-differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors.
神经内分泌肿瘤的最新分类已将高分化高级别神经内分泌肿瘤（NET G3）定义为与低分化神经内分泌癌不同的实体。NET G3的最佳治疗方法尚未得到充分描述。本研究旨在评估转移性NET G3对不同治疗方案的反应。
这是一项对梅奥诊所数据库中NET G3患者的回顾性研究。评估了患者的人口统计学特征以及治疗特点、反应和生存情况。主要终点是无进展生存期（PFS）和总生存期。次要终点是客观缓解率（ORR）和疾病控制率（DCR）。
30例患者有治疗数据，诊断时中位年龄为59.5岁。原发肿瘤大多位于胰腺（73.3%）。26.7%的病例中Ki-67指数≥55%。治疗方法包括卡培他滨+替莫唑胺（CAPTEM）（n = 20）、镥177 DOTATATE（肽受体放射性核素治疗；PRRT；n = 10）、铂-依托泊苷（EP；n = 8）、FOLFOX（n = 7）和依维莫司（n = 2）。CAPTEM的ORR为35%，DCR为65%，中位PFS为9.4个月（95%置信区间，2.96 - 16.07）。EP和FOLFOX的影像学反应率相似，ORR分别为25.0%和28.6%；然而，中位PFS持续时间差异很大，分别为2.94个月和13.04个月。PRRT的ORR为20%，DCR为70%，中位PFS为9.13个月。
在NET G3患者中，CAPTEM是最常用的治疗方法，具有临床意义的疗效和疾病控制效果。FOLFOX或PRRT是其他潜在有效的治疗选择。EP在NET G3中有一定活性，但反应似乎是短暂的。需要进行前瞻性研究来评估不同治疗方法对NET G3患者的效果，以确定最佳治疗策略。
高分化高级别神经内分泌肿瘤（NET G3）在预后和管理方面被认为与低级别NET和神经内分泌癌不同。卡培他滨和替莫唑胺的口服联合被认为是转移性NET G3管理中的一个好选择，可能更受青睐。FOLFOX是另一种具有合理疗效的全身治疗选择。与其他高分化神经内分泌肿瘤类似，肽受体放射性核素治疗似乎对这些肿瘤有一定疗效。
