Clinical impact of UV mutational signatures in Veterans with cancer.

IF 4.8 2区医学 Q1 ONCOLOGY Oncologist Pub Date : 2024-12-15 DOI:10.1093/oncolo/oyae335

Ni-Chi Wu, Richard S P Huang, Chin-Lin Tseng, Ethan S Sokol, Christine N Serway, Gregory Chadwick, Jerry Mitchell, Michael J Kelley

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Abstract

Background: UV-related DNA damage signature (UVsig) is highly specific for cutaneous cancers. The prevalence of UVsig among tumors without a primary site and tumors of extracutaneous origin were previously reported, suggesting potential misclassification of cancers. Our study aims to assess if the knowledge of UVsig at diagnosis would change first-line treatment recommendation.

Methods: The main outcome was the potential clinical impact (PCI) of UVsig. High PCI was defined as UVsig leading to change in diagnosis and first-line therapy. Medium PCI was a change in diagnosis, but appropriate therapy was offered. Low PCI group had diagnosis modified by clinicians and treated as cutaneous cancer independently of UVsig.

Results: Among 5565 cases, 650 (12%) were positive for a UVsig. In the cancer of unknown primary group: 20 (49%), 9 (22%), and 12 (29%) cases were categorized in the high, medium, and low PCI group, respectively. In the cancer of extracutaneous origin cohort: 22 (54%), 15 (36%), and 4 (10%) cases were high, medium, and low PCI, respectively. The diagnosis would have changed in 14% of Veterans with UVsig positive tumor. Among all high PCI cases, 37 (88%) received chemotherapy that was not indicated based on a UVsig-informed diagnosis of cutaneous malignancy.

Conclusion: Our study suggested that UVsig would lead to revision of the working clinical diagnosis and significantly alter the first-line treatment in at least half of cancers of unknown primary or extracutaneous origin with UVsig. Knowledge of UVsig could lead to more effective and less toxic therapy for patients with cancer.

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紫外线突变特征对退伍军人癌症患者的临床影响。

背景：紫外线相关DNA损伤特征（UVsig）对皮肤癌具有高度特异性。UVsig在无原发部位的肿瘤和皮肤外起源肿瘤中的患病率此前有报道，提示可能存在癌症的错误分类。我们的研究旨在评估在诊断时了解UVsig是否会改变一线治疗建议。方法：以UVsig的潜在临床影响（PCI）为主要观察指标。高PCI被定义为导致诊断和一线治疗改变的UVsig。中PCI改变了诊断，但给予了适当的治疗。低PCI组经临床医师修改诊断，作为独立于UVsig的皮肤癌治疗。结果：5565例患者中，有650例（12%）UVsig阳性。原发癌未知组：高PCI组20例（49%），中PCI组9例（22%），低PCI组12例（29%）。在皮外起源癌队列中：分别有22例（54%）、15例（36%）和4例（10%）为高、中、低PCI。在患有UVsig阳性肿瘤的退伍军人中，14%的诊断会发生变化。在所有高PCI病例中，37例（88%）接受的化疗不是基于uvsig告知的皮肤恶性肿瘤诊断。结论：我们的研究表明，UVsig将导致至少一半的未知原发或皮肤外起源的UVsig癌症的临床诊断的修订，并显着改变一线治疗。了解UVsig可以为癌症患者带来更有效、毒性更小的治疗方法。

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

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.