PO.CL01.04 · 临床研究
QVT亚评分：一个可解释的肿瘤血管性放射组学面板揭示NSCLC中治疗特异性作用机制（MoA）
QVT Subscore: An interpretable radiomic panel of tumor vascularity reveals treatment-specific mechanisms-of-action (MoA) in NSCLC
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
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表1：从基线到首次治疗中CT的QVT评分及亚评分变化方向 治疗组 S0819 arm1：单药化疗（chemo） S0819 arm2：化疗+cetuximab（cet） S0819 arm3：化疗+bevacizumab（bev） S0819 arm4：化疗+cet+bev 单药ICI N 170 157 116 114 147 QVT评分 — — 下降 下降 上升 亚评分1：分支 — — 下降 下降 上升 亚评分2：曲率 — — 下降 下降 上升 亚评分3：扭转 — — 下降 下降 上升 亚评分4：半径 — — 下降 — — 亚评分5：血管体积 — — — — 上升 亚评分6：拐点 — — 下降 下降 上升 注：黑色箭头 p<=0.05，白色箭头 0.05<p<0.1，— 无趋势
背景：肿瘤血管生成通过营造免疫抑制性微环境驱动治疗耐药。VEGF抑制剂（VEGFi）靶向血管系统，而免疫检查点抑制剂（ICI）不直接作用于该机制。定量血管迂曲度（QVT）评分是一种血管性放射组学生物标志物，先前已显示其与ICI反应相关。在此，我们引入QVT亚评分，这是一个可解释的面板，能够分离出不同的血管属性（如分支、曲率、半径），从而对血管性MoA和血管正常化提供治疗特异性的洞察。
方法：QVT亚评分通过将构成QVT评分的910个QVT特征归为六个生物学类别、并以主成分分析加以汇总而得出。该面板在来自3期SWOG S0819试验的557例患者及一个真实世界ICI单药治疗队列（n=147）中进行了评估。通过配对t检验评估QVT评分/亚评分从基线到首次治疗中CT的变化，并按客观缓解（OR）进行再分层。
结果：单药化疗未显示血管性变化，而VEGFi方案降低了QVT评分，其中分支和曲率亚评分显著下降，但血管体积无变化。相比之下，ICI接受者的QVT评分及6项亚评分中的5项显著升高，在四项亚评分上与VEGFi呈相反变化，且在血管半径和体积上作用不同。VEGFi在达到OR的患者中产生了最大的血管性下降，而在非OR患者中下降较温和。对于ICI，OR患者的QVT变化可忽略，而在非OR患者中除半径外的所有亚评分血管性均显著升高。
结论：QVT亚评分面板捕捉了不同治疗所致的细粒度肿瘤血管重塑，为临床试验各治疗组的表现提供了具有机制基础的洞察。未来工作将评估该面板在识别可从加用VEGFi中获益的方案方面的潜力。
查看英文原文 English abstract
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Table1: Directionality of QVT Score and Subscore change from baseline to first on-treatment CT Treatment Group S0819 arm1: mono chemotherapy (chemo) S0819 arm2: chemo+cetuximab (cet) S0819 arm3: chemo+bevacizumab(bev) S0819 arm4: chemo+cet + bev mono ICI N 170 157 116 114 147 QVT Score — — ⬇︎ ⬇︎ ⬆︎ Subscore 1: Branching — — ⬇︎ ⬇︎ ⬆︎ Subscore 2: Curvature — — ⬇︎ ⬇︎ ⬆︎ Subscore 3: Torsion — — ⬇︎ ⇩ ⬆︎ Subscore 4: Radius — — ⬇︎ — — Subscore 5: Vessel Volume — — — — ⬆︎ Subscore 6: Inflection Points — — ⬇︎ ⇩ ⬆︎ Note: Black Arrow p<=0.05, White Arrow 0.05<p<0.1, — no trend
Background: Tumor angiogenesis drives treatment resistance by fostering an immunosuppressive microenvironment. VEGF inhibitors (VEGFi) target the vasculature, while immune checkpoint inhibitors (ICI) do not address this mechanism directly. Quantitative Vessel Tortuosity (QVT) Score is a radiomic biomarker of vascularity previously shown to be associated with ICI response. Here, we introduce QVT Subscore, an interpretable panel that isolates distinct vascular attributes (e.g., branching, curvature, radius), enabling treatment-specific insight into vascularity MoA and vascular normalization.
Methods: QVT Subscores are derived by grouping the 910 QVT features comprising QVT Score into six biological categories, summarized by principal component analysis. The panel was evaluated in 557 patients from the phase 3 SWOG S0819 trial and a real-world ICI monotherapy cohort (n=147). QVT score/subscore changes from baseline to first on-treatment CTs were assessed by paired t-test and substratified by objective response (OR).
Results:While the mono-chemotherapy showed no vascularity changes, VEGFi regimens reduced QVT Score, with Branch and Curvature Subscores decreasing significantly but Vessel Volume unchanged. In contrast, ICI recipients exhibited significant increases in QVT Score and 5/6 Subscores, showing opposite changes to VEGFi in four subscores and differing effects on vessel Radius and Volume. VEGFi produced the greatest vascularity decrease in patients achieving OR, with milder decreases in non-OR. For ICI, OR showed negligible QVT change, while vascularity significantly increased in non-OR across all subscores except Radius.
Conclusions: The QVT Subscore panel captures granular tumor vascular remodeling from different treatments, providing mechanistically grounded insights into clinical trial arm performance. Future work will assess the panel's potential for identifying regimens that benefit from adding VEGFi.
利益披露 Disclosure
H. Li,
Picture Health Employment, Stock Option.
P. Mutha, None.
Y. Chae,
Roche/Genentech advisory board.
AstraZeneca advisory board.
Foundation Medicine advisory board.
Counsyl advisory board.
Neogenomics advisory board.
Guardant Health advisory board.
Boehringer Ingelheim advisory board.
Biodesix advisory board.
Immuneoncia advisory board.
Lilly Oncology advisory board.
Merck advisory board.
Takeda advisory board.
Pfizer advisory board.
Tempus advisory board.
AbbVie ).
BMS ).
Biodesix ).
Lexent Bio ).
Freenome ).
K. Zhang,
Picture Health Employment, Stock, Stock Option, Patent, Other Intellectual Property, Royalties.
Sirona Medical Stock.
L. Chung, None.
A. Hiremath,
Picture Health Employment, Stock.
R. Chitalia,
Picture Health Employment, Stock.
Invicro Employment.
J. Yau, None.
O. Haji-Maghsoudi,
Picture Health Employment, Stock.
T. Arul,
Picture Health Employment, Stock, Leadership.
Path Presenter Consulting or Advisory Role.
V. Velcheti,
Galvanize Therapeutics Honoraria.
Amgen Consulting or Advisory Role.
AstraZeneca/MedImmune Consulting or Advisory Role.
Bristol-Myers Squibb ), Consulting or Advisory Role.
GlaxoSmithKline ), Consulting or Advisory Role.
Janssen Oncology Consulting or Advisory Role.
Merck ), Consulting or Advisory Role.
Novocure Consulting or Advisory Role.
Picture Health Consulting or Advisory Role.
Regeneron Consulting or Advisory Role.
Taiho Oncology Consulting or Advisory Role.
Takeda Consulting or Advisory Role.
Alkermes ).
Altor BioScience ).
Atreca ).
Eisai ).
Genentech ).
Genoptix ).
Heat Biologics ).
Leap Therapeutics ; NantWorks ; OncoPlex Diagnostics ; RSIP Vision ; Trovagene ).
A. Madabhushi,
Picture Health Employment, Stock, Leadership ,IP Licensed.
Inspirata Stock, Leadership, Honoraria, IP licensed ,2 different R01 grants.
Elucid Bioimaging Stock, IP Licensed.
AstraZeneca Honoraria.
Aiforia Consulting or Advisory Role.
Caris Life Sciences Consulting or Advisory Role.
Castle Biosciences Consulting or Advisory Role.
Cernostics Consulting or Advisory Role.
Merck Consulting or Advisory Role.
Roche Consulting or Advisory Role.
SimBioSys Consulting or Advisory Role.
Boehringer Ingelheim ).
Bristol Myers-Squibb ).
Philips Healthcare ).
Frederick National Laboratory Advisory Committee member.
N. Braman,
Picture Health Employment, Stock, Patent, Other Intellectual Property.
Tempus Stock, Patent, Other Intellectual Property.
IBM Research Patent, Other Intellectual Property.