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基于放化疗序贯免疫治疗的初治转移性鼻咽癌局部区域放疗后递归分区分析模型。

Recursive partitioning analysis model for de novo metastatic nasopharyngeal carcinoma treated with locoregional radiotherapy following chemoimmunotherapy.

机构信息

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, Guangdong Province, People's Republic of China; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, Guangdong Province, People's Republic of China.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, Guangdong Province, People's Republic of China; Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China.

出版信息

ESMO Open. 2024 Nov;9(11):103960. doi: 10.1016/j.esmoop.2024.103960. Epub 2024 Oct 18.

Abstract

BACKGROUND

Chemoimmunotherapy is the first-line treatment of de novo metastatic nasopharyngeal carcinoma (dmNPC), with additional locoregional radiotherapy (LRRT) significantly prolonging patient survival. De novo metastatic nasopharyngeal carcinoma, however, demonstrates considerable heterogeneity, resulting in significant variability in patient outcomes. We developed and validated a prognostic tool for patients undergoing first-line chemoimmunotherapy plus LRRT and to evaluate the benefit of local therapy (LT) for distant metastases across different risk levels.

PATIENTS AND METHODS

We studied 364 dmNPC patients receiving initial platinum-based chemotherapy and anti-programmed cell death protein 1 immunotherapy followed by LRRT. Patients were randomly divided into training and validation cohorts (7 : 3 ratio). The primary endpoint was progression-free survival (PFS). A prognostic model for PFS was developed using recursive partitioning analysis (RPA).

RESULTS

An RPA model categorized patients into five prognostic groups based on number of metastatic lesions, liver metastasis status, and post-treatment Epstein-Barr virus DNA levels. Survival analysis identified three distinct risk groups. High-risk patients had significantly poorer PFS compared with medium- and low-risk groups (2-year PFS rate: training cohort: 13.7% versus 69.4% versus 94.4%, P < 0.001; validation cohort: 7.8% versus 65.1% versus 87.3%, P < 0.001). We investigated the impact of LT for distant metastases across these risk groups and found that only patients in the medium-risk group derived benefit from LT (2-year PFS rate: 77.5% versus 64.0%; hazard ratio = 0.535, 95% confidence interval 0.297-0.966, P = 0.035). Conversely, no survival benefit from LT for distant metastases was observed in the low-risk (P = 0.218) and high-risk subgroups (P = 0.793).

CONCLUSIONS

Our RPA-based prognostic model integrates number of metastatic lesions, liver metastasis status, and post-treatment Epstein-Barr virus DNA levels to predict PFS in dmNPC patients undergoing chemoimmunotherapy plus LRRT. This model offers personalized treatment guidance, suggesting that patients in the medium-risk group may benefit from LT for distant metastases, while those in high- and low-risk groups may not.

摘要

背景

化疗免疫治疗是新诊断转移性鼻咽癌(dmNPC)的一线治疗方法,额外的局部区域放疗(LRRT)显著延长了患者的生存时间。然而,新诊断的转移性鼻咽癌表现出相当大的异质性,导致患者结局存在显著差异。我们开发并验证了一种用于接受一线化疗免疫治疗加 LRRT 的患者的预后工具,并评估了局部治疗(LT)对不同风险水平的远处转移的获益。

患者和方法

我们研究了 364 名接受初始铂类化疗和抗程序性细胞死亡蛋白 1 免疫治疗后接受 LRRT 的 dmNPC 患者。患者被随机分为训练和验证队列(比例为 7:3)。主要终点是无进展生存期(PFS)。使用递归分区分析(RPA)建立了用于 PFS 的预后模型。

结果

RPA 模型根据转移性病变数量、肝转移状态和治疗后 EBV DNA 水平将患者分为五个预后组。生存分析确定了三个不同的风险组。高风险患者的 PFS 明显差于中低风险组(训练队列:2 年 PFS 率:13.7%对 69.4%对 94.4%,P<0.001;验证队列:7.8%对 65.1%对 87.3%,P<0.001)。我们研究了 LT 对这些风险组中远处转移的影响,发现只有中风险组的患者从 LT 中获益(2 年 PFS 率:77.5%对 64.0%;风险比=0.535,95%置信区间 0.297-0.966,P=0.035)。相反,在低风险(P=0.218)和高风险亚组(P=0.793)中,LT 对远处转移没有生存获益。

结论

我们基于 RPA 的预后模型将转移性病变数量、肝转移状态和治疗后 EBV DNA 水平整合在一起,预测接受化疗免疫治疗加 LRRT 的 dmNPC 患者的 PFS。该模型提供了个性化的治疗指导,提示中风险组患者可能从远处转移的 LT 中获益,而高风险和低风险组患者可能不会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/968a/11533042/c6c7a8cae246/gr1.jpg

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