Wu Ni-Chi, Huang Richard S P, Tseng Chin-Lin, Sokol Ethan S, Serway Christine N, Chadwick Gregory, Mitchell Jerry, Kelley Michael J
Department of Veterans Affairs, VA National Oncology Program. Durham, NC, United States.
Foundation Medicine Inc., Boston, MA, United States.
Oncologist. 2024 Dec 15. doi: 10.1093/oncolo/oyae335.
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.
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.
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.
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.
紫外线相关的DNA损伤特征（UVsig）对皮肤癌具有高度特异性。先前已报道了UVsig在无原发部位肿瘤和皮肤外起源肿瘤中的患病率，提示癌症可能存在错误分类。我们的研究旨在评估诊断时UVsig的知识是否会改变一线治疗建议。
主要结局是UVsig的潜在临床影响（PCI）。高PCI定义为UVsig导致诊断和一线治疗发生改变。中PCI是诊断发生改变，但提供了适当的治疗。低PCI组由临床医生修改诊断，并独立于UVsig作为皮肤癌进行治疗。
在5565例病例中，650例（12%）UVsig呈阳性。在原发不明癌症组中：分别有20例（49%）、9例（22%）和12例（29%）病例被归类为高、中、低PCI组。在皮肤外起源癌症队列中：分别有22例（54%）、15例（36%）和4例（10%）病例为高、中、低PCI。UVsig阳性肿瘤的退伍军人中，14%的诊断会发生改变。在所有高PCI病例中，37例（88%）接受了基于UVsig告知的皮肤恶性肿瘤诊断不适用的化疗。
我们的研究表明，UVsig将导致工作临床诊断的修订，并显著改变至少一半具有UVsig的原发不明或皮肤外起源癌症的一线治疗。UVsig的知识可为癌症患者带来更有效且毒性更小的治疗。
