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Dissertation/Thesis Abstract

Feline oral squamous cell carcinoma: A comprehensive approach to improve treatment outcome
by Yoshikawa, Hiroto, Ph.D., Colorado State University, 2013, 175; 3593468
Abstract (Summary)

Feline oral squamous cell carcinoma (SCC) is a devastating disease that responds poorly to traditional treatment modalities. The tumor location directly impacts the patient's ability to eat and drink, and immediate intervention to alleviate clinical signs is important. To design better treatment strategies it is paramount to understand the underlying biological behavior of this poorly defined tumor. This research takes a comprehensive approach in attempt to understand this disease. A number of assays have been developed and applied to elucidate underlying biology. New imaging modalities have been used to better stage the disease and define tumor location. Finally, patients were treated with a new radiation therapy modality, stereotactic radiation therapy (SRT), and outcome was correlated with the biological assays for potential predictive value.

The goal of the prospective study described in Chapter 2 was to compare gross tumor volume measurements using 18F-FDG PET vs. those using computed tomography (CT) for SRT planning in cats with oral SCC. Twelve cats with confirmed oral SCC underwent pretreatment 18F-FDG PET/CT. Gross tumor volumes based on contrast-enhanced CT and 18F-FDG PET were measured and compared between cats. Mean PET gross tumor volume was significantly smaller than mean CT gross tumor volume in the mandibular/maxillary SCC group (n=8, P=0.002) and for all cats (n=12, P=0.006), but not for cats with lingual/laryngeal SCC (n=4, P=0.57). Mismatch fraction analysis revealed that most of the lingual/laryngeal patients had a large region of high-18F-FDG activity outside of the CT gross tumor volume. This mismatch fraction was significantly greater in the lingual/laryngeal group than the mandibular/maxillary group ( P=0.028). The effect of poor spatial resolution of PET imaging was greater when the absolute tumor volume was small. Findings from this study indicated that 18F-FDG PET warrants further investigation as a supplemental imaging modality in cats with oral SCC because it detected presumed regions of primary tumor that were not detected on CT images.

For canine and feline patients with tumors in the head region, simultaneous irradiation of the primary tumor and mandibular and retropharyngeal lymph nodes (LNs) is often indicated. The purpose of this study described in Chapter 3 was to assess the reliability of a planning target volume (PTV) expansion protocol for secondary targets (LNs).

Information about the molecular biology of feline oral SCC is still limited. In Chapter 4, 22 archived tumor samples of feline oral SCC were evaluated to develop immunohistochemical assays and to determine if there was correlation to clinical parameters. Immunohistochemistry for Ki67, MVD, and EGFR was performed and scored. Patient survival information was obtained from the medical records. These molecular markers as well as MI were correlated with tumor locations and patient survival time. The 22 tumors showed wide variation in Ki67, MI, MVD, and EGFR. Tongue SCC expressed higher MVD than mandibular/maxillary SCC (P=0.088).

Cancer stem cell or tumor initiating cell (TIC) theory and telomere biology are actively studied fields in human head and neck (H&N) cancer. In feline oral SCC, which has been advocated as a feline model for human H&N cancer, our knowledge about the TIC and telomere/telomerase biology is limited. Protein expression levels of putative TIC markers of human H&N cancer, CD44 and Bmi-1, were immunohistochemically evaluated for their possible role as prognostic markers in 20 patients with feline oral SCC who underwent SRT. This patient population was part of a clinical trial and information relevant to PFI and ST was available. A combined technique of fluorescent in-situ hybridization and immunofluorescent staining was used to determine telomere length ratio (fractions of very short telomere/average length telomere in the putative cancer stem cells) in the putative TICs that were positive for CD44 and Bmi-1. This was also correlated with treatment outcome. (Abstract shortened by UMI.)

Indexing (document details)
Advisor: LaRue, Susan M.
Commitee: Ehrhart, E. J., Randall, Elissa, Thamm, Douglas
School: Colorado State University
Department: Cell and Molecular Biology (Graduate Degree Program)
School Location: United States -- Colorado
Source: DAI-B 74/12(E), Dissertation Abstracts International
Subjects: Molecular biology, Cellular biology, Veterinary services
Keywords: Cancer biology, Fdg-pet, Feline oral squamous cell carcinoma, Patient immobilization, Stereotactic radiation therapy
Publication Number: 3593468
ISBN: 978-1-303-36313-9
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