Complete response of somatic POLE-ultramutated recurrent undifferentiated uterine sarcoma to pembrolizumab and concurrent radiotherapy

IF 1.3 Q3 OBSTETRICS & GYNECOLOGY

Gynecologic Oncology Reports Pub Date : 2025-07-21 DOI:10.1016/j.gore.2025.101814

Natasha E. Charewycz , I-Chow Joe Hsu , Kevin Lu , Katherine Fuh , Lee-may Chen , Varun Monga , Stephanie Cham

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引用次数: 0

Abstract

Objectives

To discuss the role of immunotherapy and concurrent radiotherapy in the treatment of POLE-ultramutated undifferentiated uterine sarcoma (UUS).

Methods

We present the case of a woman with rapidly recurrent POLE-ultramutated UUS who exhibited a complete response to treatment with pembrolizumab and concurrent radiotherapy.

Results

A 67-year-old woman diagnosed with stage IB UUS underwent surgical resection with negative margins and experienced rapid locoregional recurrence within six weeks. Next-generation sequencing (NGS) identified a somatic POLE mutation (p.V411L) and high tumor mutational burden (171 mutations/Mb), classifying the tumor as POLE-ultramutated. The patient was subsequently treated with concurrent radiation and pembrolizumab and demonstrated complete disease resolution after cycle 3 of pembrolizumab and one month post-radiation completion. She has since remained disease-free for 17 months on pembrolizumab maintenance therapy.

Conclusions

To our knowledge, this is the first reported case of a POLE-ultramutated uterine sarcoma, and it highlights a striking and durable response to immunotherapy in combination with radiation. This case underscores the potential value of comprehensive molecular profiling in uterine sarcomas to guide personalized treatment approaches. POLE-ultramutated status, previously characterized in endometrial carcinoma as a favorable prognostic biomarker, may have therapeutic implications in other gynecologic and soft tissue sarcomas. Further investigation into the prevalence and significance of POLE mutations in sarcomas is warranted, along with continued exploration of immunotherapy and radiation synergy in this context.

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体细胞极-超突变复发性未分化子宫肉瘤对派姆单抗和同步放疗的完全缓解

目的探讨免疫治疗与同步放疗在pole -超突变未分化子宫肉瘤（UUS）治疗中的作用。方法：我们报告了一名快速复发的极-超突变UUS的女性病例，她对派姆单抗和同步放疗治疗表现出完全反应。结果一名67岁的女性诊断为IB期UUS，手术切除切缘阴性，6周内迅速局部复发。下一代测序（NGS）鉴定出体细胞POLE突变（p.V411L）和高肿瘤突变负担（171个突变/Mb），将肿瘤归类为POLE超突变。患者随后接受同步放疗和派姆单抗治疗，并在派姆单抗治疗第3周期和放疗结束后1个月后显示疾病完全消退。此后，她在派姆单抗维持治疗中保持无病17个月。结论：据我们所知，这是首例极点超突变子宫肉瘤的报道，它突出了免疫治疗联合放射治疗的显著和持久的反应。本病例强调了综合分子谱分析在子宫肉瘤中指导个性化治疗方法的潜在价值。pole -超突变状态，以前在子宫内膜癌中被认为是一个有利的预后生物标志物，可能在其他妇科和软组织肉瘤中具有治疗意义。进一步研究POLE突变在肉瘤中的患病率和意义是有必要的，同时在此背景下继续探索免疫治疗和放射协同作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gynecologic Oncology Reports OBSTETRICS & GYNECOLOGY-

CiteScore

2.00

自引率

0.00%

发文量

183

审稿时长

41 days

期刊介绍： Gynecologic Oncology Reports is an online-only, open access journal devoted to the rapid publication of narrative review articles, survey articles, case reports, case series, letters to the editor regarding previously published manuscripts and other short communications in the field of gynecologic oncology. The journal will consider papers that concern tumors of the female reproductive tract, with originality, quality, and clarity the chief criteria of acceptance.