The Paradoxical Influence of Hyperthermia on Progression-Free Survival in Recurrent/Metastatic Oral Cancer Treated With Immune Checkpoint Inhibitors.

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Oral diseases Pub Date : 2025-08-04 DOI:10.1111/odi.70051

Shogo Kikuta, Chikayuki Hattori, Yushi Abe, Kiyosato Hino, Katsuhisa Matsuo, Jingo Kusukawa

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引用次数: 0

Abstract

Background: Clinical evidence for combining hyperthermia (HT) with immune checkpoint inhibitors (ICIs) in recurrent/metastatic oral cancer (RM-OC) is lacking. To our knowledge, this is the first study to investigate the clinical impact of this combination therapy in this specific cohort.

Methods: We retrospectively analyzed 35 patients with RM-OC treated with ICIs. Patients receiving concurrent HT (n = 8) were compared to those without HT (n = 27). Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier and Cox proportional hazards models.

Results: A significant discordance between endpoints emerged. Multivariate analysis revealed that concurrent HT was paradoxically associated with significantly worse PFS (hazard ratio, 3.06; 95% confidence interval, 1.08-8.64; p = 0.035). In stark contrast, HT had no corresponding negative impact on OS (median OS: 26.2 vs. 30.2 months; p = 0.53).

Conclusion: Concurrent HT with ICI therapy was paradoxically associated with diminished PFS without impacting OS. This critical discordance suggests that the observed radiographic progression may reflect intense, HT-induced immune-related inflammation (pseudoprogression) rather than true tumor progression. These findings underscore the complexity of interpreting efficacy endpoints for this novel combination therapy and highlight the need to reconsider standard response evaluation criteria.

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热疗对免疫检查点抑制剂治疗复发/转移口腔癌患者无进展生存的矛盾影响

背景：临床缺乏热疗（HT）联合免疫检查点抑制剂（ICIs）治疗复发/转移性口腔癌（RM-OC）的证据。据我们所知，这是第一个研究这种联合治疗在这一特定人群中的临床影响的研究。方法：回顾性分析35例经ICIs治疗的RM-OC患者。同时接受HT治疗的患者（n = 8）与未接受HT治疗的患者（n = 27）进行比较。采用Kaplan-Meier和Cox比例风险模型评估无进展生存期（PFS）和总生存期（OS）。结果：终点之间出现了显著的不一致。多变量分析显示，并发HT与PFS显著恶化相关(风险比，3.06；95%置信区间为1.08-8.64；p = 0.035)。与此形成鲜明对比的是，HT对OS没有相应的负面影响(中位OS: 26.2 vs 30.2个月；p = 0.53)。结论：同时HT与ICI治疗与PFS的降低相矛盾，而不影响OS。这一关键的不一致提示，观察到的影像学进展可能反映了强烈的、ht诱导的免疫相关炎症（假进展），而不是真正的肿瘤进展。这些发现强调了解释这种新型联合治疗的疗效终点的复杂性，并强调了重新考虑标准反应评估标准的必要性。

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

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

期刊介绍： Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.