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Metabolic Imaging of Head and Neck Cancer Organoids.

ABSTRACT: Head and neck cancer patients suffer from toxicities, morbidities, and mortalities, and these ailments could be minimized through improved therapies. Drug discovery is a long, expensive, and complex process, so optimized assays can improve the success rate of drug candidates. This study applies optical imaging of cell metabolism to three-dimensional in vitro cultures of head and neck cancer grown from primary tumor tissue (organoids). This technique is advantageous because it measures cell metabolism using intrinsic fluorescence from NAD(P)H and FAD on a single cell level for a three-dimensional in vitro model. Head and neck cancer organoids are characterized alone and after treatment with standard therapies, including an antibody therapy, a chemotherapy, and combination therapy. Additionally, organoid cellular heterogeneity is analyzed quantitatively and qualitatively. Gold standard measures of treatment response, including cell proliferation, cell death, and in vivo tumor volume, validate therapeutic efficacy for each treatment group in a parallel study. Results indicate that optical metabolic imaging is sensitive to therapeutic response in organoids after 1 day of treatment (p<0.05) and resolves cell subpopulations with distinct metabolic phenotypes. Ultimately, this platform could provide a sensitive high-throughput assay to streamline the drug discovery process for head and neck cancer.

SUBMITTER: Shah AT

PROVIDER: S-EPMC5242529 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Metabolic Imaging of Head and Neck Cancer Organoids.

Shah Amy T AT Heaster Tiffany M TM Skala Melissa C MC

PloS one 20170118 1

Head and neck cancer patients suffer from toxicities, morbidities, and mortalities, and these ailments could be minimized through improved therapies. Drug discovery is a long, expensive, and complex process, so optimized assays can improve the success rate of drug candidates. This study applies optical imaging of cell metabolism to three-dimensional in vitro cultures of head and neck cancer grown from primary tumor tissue (organoids). This technique is advantageous because it measures cell metab ...[more]

PMID: 28099487

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Project description:ImportanceThe role of surveillance imaging after treatment for head and neck cancer is controversial and evidence to support decision-making is limited.ObjectiveTo determine the use of surveillance imaging in asymptomatic patients with head and neck cancer in remission after completion of chemoradiation.Design, setting, and participantsThis was a retrospective, comparative effectiveness research review of adult patients who had achieved a complete metabolic response to initial treatment for head and neck cancer as defined by having an unequivocally negative positron emission tomography (PET) scan using the PET response criteria in solid tumors (PERCIST) scale within the first 6 months of completing therapy. The medical records of 501 consecutive patients who completed definitive radiation therapy (with or without chemotherapy) for newly diagnosed squamous cell carcinoma of the head and neck between January 2014 and June 2022 were reviewed.ExposureSurveillance imaging was defined as the acquisition of a PET with computed tomography (CT), magnetic resonance imaging (MRI), or CT of the head and neck region in the absence of any clinically suspicious symptoms and/or examination findings. For remaining patients, subsequent surveillance after the achievement of a complete metabolic response to initial therapy was performed on an observational basis in the setting of routine follow-up using history-taking and physical examination, including endoscopy. This expectant approach led to imaging only in the presence of clinically suspicious symptoms and/or physical examination findings.Main outcome and measuresLocal-regional control, overall survival, and progression-free survival based on assignment to either the surveillance imaging or expectant management cohort.ResultsThis study included 340 patients (mean [SD] age, 59 [10] years; 201 males [59%]; 88 Latino patients [26%]; 145 White patients [43%]) who achieved a complete metabolic response during this period. There was no difference in 3-year local-regional control, overall survival, progression-free survival, or freedom from distant metastasis between patients treated with surveillance imaging vs those treated expectantly.Conclusions and relevanceIn this comparative effectiveness research, imaging-based surveillance failed to improve outcomes compared with expectant management for patients who were seemingly in remission after completion of primary radiation therapy for head and neck cancer.

Dataset Information

Metabolic Imaging of Head and Neck Cancer Organoids.

Publications

Metabolic Imaging of Head and Neck Cancer Organoids.

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