Abstract：
OBJECTIVE: To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.
RESULTS: Eight randomized controlled trials met the inclusion criteria for the systematic review.
CONCLUSIONS: Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)-positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.
RESULTS: Eight randomized controlled trials met the inclusion criteria for the systematic review.
CONCLUSIONS: Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)-positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
摘要：
目的：为高分化1级（G1）至3级（G3）转移性胃肠胰腺神经内分泌肿瘤（GEP-NETs）的全身治疗提供建议。
方法：ASCO召集了一个专家小组，对相关研究进行系统评价，并为临床实践提供建议。
结果：8项随机对照试验符合系统评价的纳入标准。
结论：促生长素抑制素类似物（SSAs）被推荐作为大多数G1级2级（G2）转移性高分化GI-NETs患者的一线全身治疗。对于没有症状的低容量或生长缓慢的疾病患者，观察是一种选择。在SSA上进展后，肽受体放射性核素治疗（PRRT）被推荐作为生长抑素受体（SSTR）阳性肿瘤患者的系统治疗。依维莫司是另一种二线治疗,特别是在无功能的NETs和SSTR阴性肿瘤患者中。SSA是SSTR阳性胰腺（泛）NETs的标准一线治疗。很少,观察可能适合无症状患者直至病情进展.panNETs的二线系统选择包括PRRT（用于SSTR阳性肿瘤），细胞毒性化疗，依维莫司,或者舒尼替尼.对于SSTR阴性肿瘤，一线治疗选择是化疗，依维莫司,或者舒尼替尼.没有足够的数据来推荐特定的疗法排序。G1-G2高容量疾病患者，相对较高的Ki-67指数，和/或与肿瘤生长相关的症状可能受益于早期细胞毒性化疗。对于G3GEP-NET，可以考虑G1-G2的系统选择，尽管对于有肿瘤相关症状的患者，细胞毒性化疗可能是最有效的选择，和SSA相对无效。提供合格陈述以帮助选择治疗。建议多学科团队管理，以及与患者共同决策，结合他们的价值观和偏好，潜在的好处和危害，以及其他特征和情况，如合并症，性能状态，地理位置,和获得护理的机会。其他信息可在www上获得。asco.org/胃肠道癌症指南。
方法：ASCO召集了一个专家小组，对相关研究进行系统评价，并为临床实践提供建议。
结果：8项随机对照试验符合系统评价的纳入标准。
结论：促生长素抑制素类似物（SSAs）被推荐作为大多数G1级2级（G2）转移性高分化GI-NETs患者的一线全身治疗。对于没有症状的低容量或生长缓慢的疾病患者，观察是一种选择。在SSA上进展后，肽受体放射性核素治疗（PRRT）被推荐作为生长抑素受体（SSTR）阳性肿瘤患者的系统治疗。依维莫司是另一种二线治疗,特别是在无功能的NETs和SSTR阴性肿瘤患者中。SSA是SSTR阳性胰腺（泛）NETs的标准一线治疗。很少,观察可能适合无症状患者直至病情进展.panNETs的二线系统选择包括PRRT（用于SSTR阳性肿瘤），细胞毒性化疗，依维莫司,或者舒尼替尼.对于SSTR阴性肿瘤，一线治疗选择是化疗，依维莫司,或者舒尼替尼.没有足够的数据来推荐特定的疗法排序。G1-G2高容量疾病患者，相对较高的Ki-67指数，和/或与肿瘤生长相关的症状可能受益于早期细胞毒性化疗。对于G3GEP-NET，可以考虑G1-G2的系统选择，尽管对于有肿瘤相关症状的患者，细胞毒性化疗可能是最有效的选择，和SSA相对无效。提供合格陈述以帮助选择治疗。建议多学科团队管理，以及与患者共同决策，结合他们的价值观和偏好，潜在的好处和危害，以及其他特征和情况，如合并症，性能状态，地理位置,和获得护理的机会。其他信息可在www上获得。asco.org/胃肠道癌症指南。
