我们旨在调查局部区域放疗（LRRT）对首次治疗的伴随原发转移性鼻咽癌（dmNPC）患者进行化疗联合抗程序化细胞死亡受体-1单克隆抗体（anti-PD-1 mAbs）的疗效，并确定最合适接受LRRT 的候选患者。我们招募了接受铂类为基础的姑息化疗和anti-PD-1 mAbs后是否接受LRRT的dmNPC患者，共四个中心。终点指标为无进展生存期（PFS）、客观缓解率（ORR）和总生存期（OS）。我们使用反向治疗概率加权（IPTW）来平衡LRRT组和非-LRRT组的基线特征，以减少选择偏倚。多变量分析采用Cox比例风险模型进行。我们纳入了163例dmNPC患者（中位随访时间：22个月）。中位PFS为20个月，ORR为92.0%；中位OS尚未达到。经过IPTW调整，接受LRRT的患者与未接受LRRT的患者相比，具有显著的生存益处（中位PFS：28 vs 15个月，P < 0.001）。经过抗PD-1 mAbs 4-6个疗程后的Epstein-Barr病毒DNA（EBV DNA）水平（加权风险比（HR）：2.19，95%置信区间（CI）1.22-3.92，P = 0.008）和LRRT（加权HR：0.58，95% CI 0.34-0.99，P = 0.04）是独立的预后因素。抗PD-1 mAbs 4-6个疗程后EBV DNA水平不可检测（早期EBV DNA消除）的患者从LRRT中受益（HR：0.41，95% CI 0.22-0.79，P = 0.008），而检测到EBV DNA水平的患者则不受益（HR：1.30，95% CI 0.59-2.87，P = 0.51）。姑息化疗联合抗PD-1 mAbs后接受LRRT与dmNPC患者的PFS改善相关，尤其对于早期EBV DNA消除的患者。版权所有©2023 The Authors。由Elsevier Ltd.出版。版权所有。

We aimed to investigate the efficacy of locoregional radiotherapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combined with anti-programmed cell death receptor-1 monoclonal antibodies (anti-PD-1 mAbs) as first-line treatment and identify optimal candidates for LRRT.We enrolled patients with dmNPC receiving platinum-based palliative chemotherapy and anti-PD-1 mAbs followed or not followed by LRRT from four centers. The endpoints were progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). We used the inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of the LRRT and non-LRRT groups to minimize selection bias before comparative analyses. Multivariate analyses were carried out using the Cox proportional hazards model.We included 163 patients with dmNPC (median follow-up: 22 months). The median PFS was 20 months, and the ORR was 92.0%; the median OS was not achieved. After IPTW adjustments, patients who received LRRT had a significant survival benefit over those not receiving LRRT (median PFS: 28 versus 15 months, P < 0.001). The Epstein-Barr virus DNA (EBV DNA) level after four to six cycles of anti-PD-1 mAbs [weighted hazard ratio (HR): 2.19, 95% confidence interval (CI) 1.22-3.92, P = 0.008] and LRRT (weighted HR: 0.58, 95% CI 0.34-0.99, P = 0.04) were independent prognostic factors. Patients with undetectable EBV DNA levels after four to six cycles of anti-PD-1 mAbs (early EBV DNA clearance) benefitted from LRRT (HR: 0.41, 95% CI 0.22-0.79, P = 0.008), whereas those with detectable levels did not (HR: 1.30, 95% CI 0.59-2.87, P = 0.51).Palliative chemotherapy combined with anti-PD-1 mAbs followed by LRRT was associated with improved PFS in patients with dmNPC, especially for patients with early EBV DNA clearance.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.