Abstract：
BACKGROUND: Recurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective.
METHODS: We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias.
RESULTS: We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved.
CONCLUSIONS: CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.
METHODS: We systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias.
RESULTS: We screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %-29 %), median PFS of 2.37 months (95 %CI = 1.23-3.51) and median OS of 10.16 months (95 %CI = 0.67-19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %-93 %), SD rate was 22 % (95 %CI = 2 %-75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %-98 %), SD rate of 11 % (95 % CI = 0 %-82 %) and incidence rate of any grade adverse events of 29 % was achieved.
CONCLUSIONS: CBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.
摘要：
背景：复发性/转移性鼻咽癌（RM-NPC）仍然难以治疗，并导致相当大的死亡率。RM-NPC的一线治疗是吉西他滨和顺铂，二线治疗方案不同。NPC的地方性变异与EB病毒(EBV)有关。因此,靶向EBV特异性RM-NPC的基于细胞的免疫治疗（CBI）可能是有效的。
方法：我们系统地搜索了PubMed，Embase和Cochrane图书馆进行随机或观察性研究，研究CBI治疗RM-NPC的疗效和安全性。我们使用随机效应模型进行了所有荟萃分析。研究进一步按地方性分层，我们采用疾病性质和药物类型来调查研究间的潜在异质性,并采用额外的预先指定测试来评估发表偏倚.
结果：我们筛选了1,671项研究，包括13项研究，包括403名参与者，其中9项研究符合荟萃分析的条件.使用CBI单一疗法作为EBV阳性RM-NPC的第二或后续线治疗显示ORR为10％（95CI=3％-29％），中位PFS为2.37个月(95CI=1.23~3.51),中位OS为10.16个月(95CI=0.67~19.65).对于EBV特异性细胞毒性T淋巴细胞单一疗法，合并PD率为54%(95CI=9%-93%)，SD率为22％（95CI=2％-75％），任何级别不良事件的发生率为45％。对于树突状细胞单一疗法，PD率为80%(95%CI=29%-98%)，SD率为11％（95％CI=0％-82％），任何级别的不良事件发生率为29％。
结论：CBI单一疗法在预处理的RM-NPC中显示出一定的活性。需要更多的试验来更好地了解如何将CBI整合到RM-NPC护理中。
方法：我们系统地搜索了PubMed，Embase和Cochrane图书馆进行随机或观察性研究，研究CBI治疗RM-NPC的疗效和安全性。我们使用随机效应模型进行了所有荟萃分析。研究进一步按地方性分层，我们采用疾病性质和药物类型来调查研究间的潜在异质性,并采用额外的预先指定测试来评估发表偏倚.
结果：我们筛选了1,671项研究，包括13项研究，包括403名参与者，其中9项研究符合荟萃分析的条件.使用CBI单一疗法作为EBV阳性RM-NPC的第二或后续线治疗显示ORR为10％（95CI=3％-29％），中位PFS为2.37个月(95CI=1.23~3.51),中位OS为10.16个月(95CI=0.67~19.65).对于EBV特异性细胞毒性T淋巴细胞单一疗法，合并PD率为54%(95CI=9%-93%)，SD率为22％（95CI=2％-75％），任何级别不良事件的发生率为45％。对于树突状细胞单一疗法，PD率为80%(95%CI=29%-98%)，SD率为11％（95％CI=0％-82％），任何级别的不良事件发生率为29％。
结论：CBI单一疗法在预处理的RM-NPC中显示出一定的活性。需要更多的试验来更好地了解如何将CBI整合到RM-NPC护理中。
