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肽受体放射性核素治疗(PRRT)转移性直肠神经内分泌肿瘤(NEN)的效果非常好。

Highly favourable outcomes with peptide receptor radionuclide therapy (PRRT) for metastatic rectal neuroendocrine neoplasia (NEN).

机构信息

Centre for Cancer Imaging, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.

Neuroendocrine Service, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

出版信息

Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):718-727. doi: 10.1007/s00259-018-4196-8. Epub 2018 Oct 20.

Abstract

PURPOSE

Rectal neuroendocrine neoplasia (NEN) is more common than other NEN origins, but is less commonly metastatic. However, when present, distant disease carries a particularly poor prognosis. Evidence guiding optimal treatment of such patients is lacking. We assessed PRRT outcomes in patients with somatostatin receptor (SSTR) positive metastatic rectal NEN from two referral centres.

METHODS

Patients treated with PRRT were retrospectively reviewed. Morphologic (RECIST 1.1), SSTR imaging responses and toxicity were assessed 3 months post-PRRT. Kaplan-Meier estimate was used to determine progression-free survival (PFS) and overall survival (OS) from start of PRRT.

RESULTS

Twenty-seven consecutive patients (M = 20, age 31-81 years) were reviewed. The majority (70%) had ENETs grade 2 disease (19 patients), three had Grade 3, one Grade 1, and four not documented. Overall, 63% (10/16 patients with available FDG PET/CT) had FDG avid disease. Twenty-six patients were treated for disease progression. Most had Lu-DOTA-octreotate with median cumulative activity of 30 GBq, median four cycles. 14 patients had radiosensitising chemotherapy (5FU or capecitabine). At 3 months post-PRRT, CT disease control rate (DCR) was 96%: partial response was observed in 70% (19/27) and stable disease in 26%. All but one had partial SSTR imaging response. The median PFS was 29 months. Ten patients died, with median overall survival 81 months with a median follow-up of 67 months. Seventeen patients had further treatments after initial PRRT (10 had further cycles of PRRT). Three patients had grade 3 lymphopenia, without significant renal toxicity, MDS or leukaemia.

CONCLUSION

Our results indicate high efficacy and morphologic responses with minimal toxicity and very encouraging survival from PRRT in patients with metastatic rectal NEN despite the adverse prognostic features of this cohort. Further prospective PRRT trials are warranted in this subgroup.

摘要

目的

直肠神经内分泌肿瘤(NEN)比其他 NEN 起源更为常见,但转移的情况较少见。然而,当转移发生时,远处疾病的预后尤其差。目前缺乏指导此类患者最佳治疗的证据。我们评估了来自两个转诊中心的 SSTR 阳性转移性直肠 NEN 患者的 PRRT 治疗结果。

方法

回顾性分析接受 PRRT 治疗的患者。在 PRRT 治疗后 3 个月,评估形态学(RECIST 1.1)、SSTR 成像反应和毒性。使用 Kaplan-Meier 估计从 PRRT 开始确定无进展生存期(PFS)和总生存期(OS)。

结果

共回顾了 27 例连续患者(M=20,年龄 31-81 岁)。大多数(70%)患者患有 2 级神经内分泌肿瘤(NETs)(19 例),3 例为 3 级,1 例为 1 级,4 例未记录。总体而言,63%(16 例可提供 FDG PET/CT 的患者中有 10 例)有 FDG 活性疾病。26 例患者因疾病进展接受治疗。大多数患者接受了 Lu-DOTA-奥曲肽治疗,累积活性中位数为 30GBq,中位数为 4 个周期。14 例患者接受了增敏化疗(5-FU 或卡培他滨)。在 PRRT 治疗后 3 个月,CT 疾病控制率(DCR)为 96%:27 例中有 70%(19 例)观察到部分缓解,26%为稳定疾病。除 1 例外,所有患者均有部分 SSTR 成像反应。中位 PFS 为 29 个月。10 例患者死亡,中位总生存期为 81 个月,中位随访时间为 67 个月。17 例患者在初始 PRRT 后接受了进一步治疗(10 例患者接受了进一步的 PRRT 周期)。3 例患者出现 3 级淋巴细胞减少症,但无明显肾毒性、骨髓增生异常或白血病。

结论

尽管该队列具有不利的预后特征,但我们的结果表明,转移性直肠 NEN 患者接受 PRRT 治疗后具有较高的疗效和形态学反应,毒性最小,且生存情况非常令人鼓舞。在这一分组中,需要进一步进行前瞻性 PRRT 试验。

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