Browsing by Subject "Squamous Cell Carcinoma of Head and Neck"

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    Factors for Differential Outcome Across Cancers in Clinical Molecule-Targeted Fluorescence Imaging.
    (Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2022-11) Zhou, Quan; van den Berg, Nynke S; Kang, Wenying; Pei, Jacqueline; Nishio, Naoki; van Keulen, Stan; Engelen, Myrthe A; Lee, Yu-Jin; Hom, Marisa; Vega Leonel, Johana CM; Hart, Zachary; Vogel, Hannes; Cayrol, Romain; Martin, Brock A; Roesner, Mark; Shields, Glenn; Lui, Natalie; Gephart, Melanie Hayden; Raymundo, Roan C; Yi, Grace; Granucci, Monica; Grant, Gerald A; Li, Gordon; Rosenthal, Eben L
    Clinical imaging performance using a fluorescent antibody was compared across 3 cancers to elucidate physical and biologic factors contributing to differential translation of epidermal growth factor receptor (EGFR) expression to macroscopic fluorescence in tumors. Methods: Thirty-one patients with high-grade glioma (HGG, n = 5), head-and-neck squamous cell carcinoma (HNSCC, n = 23), or lung adenocarcinoma (LAC, n = 3) were systemically infused with 50 mg of panitumumab-IRDye800 1-3 d before surgery. Intraoperative open-field fluorescent images of the surgical field were acquired, with imaging device settings and operating room lighting conditions being tested on tissue-mimicking phantoms. Fluorescence contrast and margin size were measured on resected specimen surfaces. Antibody distribution and EGFR immunoreactivity were characterized in macroscopic and microscopic histologic structures. The integrity of the blood-brain barrier was examined via tight junction protein (Claudin-5) expression with immunohistochemistry. Stepwise multivariate linear regression of biologic variables was performed to identify independent predictors of panitumumab-IRDye800 concentration in tissue. Results: Optimally acquired at the lowest gain for tumor detection with ambient light, intraoperative fluorescence imaging enhanced tissue-size dependent tumor contrast by 5.2-fold, 3.4-fold, and 1.4-fold in HGG, HNSCC, and LAC, respectively. Tissue surface fluorescence target-to-background ratio correlated with margin size and identified 78%-97% of at-risk resection margins ex vivo. In 4-μm-thick tissue sections, fluorescence detected tumor with 0.85-0.89 areas under the receiver-operating-characteristic curves. Preferential breakdown of blood-brain barrier in HGG improved tumor specificity of intratumoral antibody distribution relative to that of EGFR (96% vs. 80%) despite its reduced concentration (3.9 ng/mg of tissue) compared with HNSCC (8.1 ng/mg) and LAC (6.3 ng/mg). Cellular EGFR expression, tumor cell density, plasma antibody concentration, and delivery barrier were independently associated with local intratumoral panitumumab-IRDye800 concentration, with 0.62 goodness of fit of prediction. Conclusion: In multicancer clinical imaging of a receptor-ligand-based molecular probe, plasma antibody concentration, delivery barrier, and intratumoral EGFR expression driven by cellular biomarker expression and tumor cell density led to heterogeneous intratumoral antibody accumulation and spatial distribution whereas tumor size, resection margin, and intraoperative imaging settings substantially influenced macroscopic tumor contrast.
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    ItemOpen Access
    Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx.
    (Scientific reports, 2017-01-03) Zhang, Yang; Sturgis, Erich M; Li, Yuncheng; Wei, Qingyi; Huang, Zhigang; Li, Guojun
    Functional mouse double minute-2 (MDM2) promoter variants may alter MDM2 expression and thus affect radiotherapy response and prognosis of squamous cell carcinoma of oropharynx (SCCOP). Thus we assessed association of 2 functional MDM2 promoter variants with recurrence risk of SCCOP. The disease-free survival (DFS) of patients with MDM2rs2279744 TT or MDM2rs937283 AA genotypes was significantly reduced compared with that of patients with corresponding GT/GG or AG/GG genotypes. Multivariable analysis showed patients with TT or AA genotypes had a significantly higher risk of SCCOP recurrence than those with corresponding GT/GG or AG/GG genotypes did. Furthermore, patients with combined risk genotypes of the 2 polymorphisms had significantly worse DFS and a higher recurrence risk than patients with fewer combined risk genotypes did (Ptrend < 0.001). Compared with patients with 0 risk genotypes, patients with 1 or 2 risk genotypes had an approximately 3- or 11-fold increased risk of SCCOP recurrence, respectively. Notably, for both individual and combined polymorphisms, the above similar recurrence risks were particularly higher among patients with human papilloma virus (HPV)-positive tumors. Taken together, our findings suggest that MDM2 promoter variants individually, or more likely jointly, play a role in determining the risk of recurrence of SCCOP, particularly HPV-positive SCCOP.