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肽受体放射性核素治疗可改善胃肠胰神经内分泌肿瘤切除术后进展患者的生存率。

Peptide Receptor Radionuclide Therapy Improves Survival in Patients Who Progress After Resection of Gastroenteropancreatic Neuroendocrine Tumors.

作者信息

Borbon Luis C, Sherman Scott K, Breheny Patrick J, Chandrasekharan Chandrikha, Menda Yusuf, Bushnell David, Bellizzi Andrew M, Ear P H, O'Dorisio M Sue, O'Dorisio Thomas M, Dillon Joseph S, Howe James R

机构信息

Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA.

Department of Public Health, University of Iowa Carver College of Medicine, Iowa City, IA, USA.

出版信息

Ann Surg Oncol. 2025 Feb;32(2):1136-1148. doi: 10.1245/s10434-024-16463-7. Epub 2024 Nov 6.

DOI:10.1245/s10434-024-16463-7
PMID:39505730
Abstract

BACKGROUND

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). We investigated a 2-decade experience with PRRT to determine whether PRRT confers a survival advantage to patients who progress after surgery versus other therapies.

METHODS

We identified patients from our clinic who had resection/cytoreduction of GEP-NETs, then disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Kaplan-Meier method assessed progression-free survival (PFS) and overall survival (OS), calculated from progression after surgery (no-PRRT group) or the start of PRRT. Cox regression with time-dependent covariates controlled for immortal time bias and other confounders.

RESULTS

Overall, 237 patients progressed after surgery; 95 received PRRT and 142 did not. No differences existed in sex, T or N stage, tumor grade/differentiation, primary site, or time to progression; 94% of PRRT patients had metastases at diagnosis versus 77% in the no-PRRT group. Median PFS was longer in the PRRT group versus the no-PRRT group (32.4 vs. 11.0 months, p < 0.001), as was median OS (49.8 vs. 38.4 months; p = 0.009). In subgroup analysis, the PRRT group had improved PFS in small bowel NETs and pancreatic NETs. Time-dependent covariate analysis revealed a lower risk of death associated with PRRT (hazard ratio 0.61, p = 0.028) after adjusting for sex, age, M stage, tumor grade, and primary site.

CONCLUSION

Surgical resection and cytoreduction is an effective treatment for patients with GEP-NETs, but most patients with metastatic disease develop recurrent disease. Surgery followed by PRRT after progression conferred superior PFS and OS over no PRRT/other therapies, and is an effective strategy for managing patients with GEP-NETs.

摘要

背景

肽受体放射性核素治疗(PRRT)是晚期胃肠胰(GEP)神经内分泌肿瘤(NETs)的一种有效治疗方法。我们调查了20年的PRRT治疗经验,以确定与其他疗法相比,PRRT是否能为术后病情进展的患者带来生存优势。

方法

我们从诊所中识别出接受过GEP-NETs切除/减瘤治疗、然后根据实体瘤疗效评价标准(RECIST)1.1出现疾病进展的患者。采用Kaplan-Meier方法评估无进展生存期(PFS)和总生存期(OS),从术后进展(非PRRT组)或PRRT开始计算。使用时间依赖性协变量的Cox回归控制了不朽时间偏倚和其他混杂因素。

结果

总体而言,237例患者术后病情进展;95例接受了PRRT,142例未接受。在性别、T或N分期、肿瘤分级/分化、原发部位或进展时间方面无差异;94%接受PRRT的患者在诊断时有转移,而非PRRT组为77%。PRRT组的中位PFS长于非PRRT组(32.4个月对11.0个月,p<0.001),中位OS也是如此(49.8个月对38.4个月;p=0.009)。在亚组分析中,PRRT组在小肠NETs和胰腺NETs中的PFS有所改善。时间依赖性协变量分析显示,在调整性别、年龄、M分期、肿瘤分级和原发部位后,PRRT相关的死亡风险较低(风险比0.61,p=0.028)。

结论

手术切除和减瘤是GEP-NETs患者的有效治疗方法,但大多数转移性疾病患者会出现复发性疾病。进展后接受PRRT的手术患者的PFS和OS优于未接受PRRT/其他疗法的患者,是管理GEP-NETs患者的有效策略。

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Ann Surg Oncol. 2022 Oct;29(11):6501-6503. doi: 10.1245/s10434-022-12149-0. Epub 2022 Jul 11.
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Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors. upfront 肽受体放射性核素治疗与肠胰神经内分泌肿瘤患者无进展生存的关系。
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Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial.
Lu-Dotatate 联合长效奥曲肽与高剂量长效奥曲肽治疗肠神经内分泌肿瘤患者(NETTER-1):一项开放标签、随机、对照、III 期临床试验的最终总生存和长期安全性结果。
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Prior Resection of the Primary Tumor Prolongs Survival After Peptide Receptor Radionuclide Therapy of Advanced Neuroendocrine Neoplasms.原发性肿瘤的先前切除可延长晚期神经内分泌肿瘤肽受体放射性核素治疗后的生存期。
Ann Surg. 2021 Jul 1;274(1):e45-e53. doi: 10.1097/SLA.0000000000003237.
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Effective cytoreduction can be achieved in patients with numerous neuroendocrine tumor liver metastases (NETLMs).对于存在大量神经内分泌肿瘤肝脏转移(NETLMs)的患者,可实现有效的细胞减灭术。
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Clusterin in Neuroendocrine Epithelial Neoplasms: Absence of Expression in a Well-differentiated Tumor Suggests a Jejunoileal Origin.神经内分泌上皮肿瘤中的簇集蛋白:在高分化肿瘤中无表达提示空肠回肠起源。
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