678 results on '"Spector, Matthew E."'
Search Results
2. Utility of bioselection with neoadjuvant chemotherapy for organ preservation in patients with T4 laryngeal cancer
- Author
-
Benjamin, William J., Feng, Allen L., Heft Neal, Molly, Bellile, Emily, Casper, Keith A., Malloy, Kelly M., Rosko, Andrew J., Stucken, Chaz L., Prince, Mark E., Mierzwa, Michelle L., Taylor, Jeremy M.G., Eisbruch, Avraham, Spector, Matthew E., Wolf, Gregory T., Swiecicki, Paul L., Worden, Francis P., and Chinn, Steven B.
- Published
- 2024
- Full Text
- View/download PDF
3. Color Match following Free Flap Surgery in Head and Neck Reconstruction: A Colorimetric and Aesthetic Analysis
- Author
-
Dermody, Sarah M., Kahng, Peter W., Rao, Vishwanatha M., Casper, Keith A., Malloy, Kelly M., Rosko, Andrew J., Stucken, Chaz L., Chinn, Steven B., Spector, Matthew E., and Feng, Allen L.
- Published
- 2024
- Full Text
- View/download PDF
4. Association of prealbumin with complications after total laryngectomy with free flap reconstruction
- Author
-
Tang, Anthony, Dang, Sophia, Lao, Isabella, Pandya, Sumaarg, Solari, Mario G., Maxwell, Jessica, Contrera, Kevin J., Zevallos, Jose P., Ferris, Robert, Kim, Seungwon, Sridharan, Shaum, and Spector, Matthew E.
- Published
- 2024
- Full Text
- View/download PDF
5. 3D modeling of anterior 2/3rds glossectomy reconstruction: A volume based donor site evaluation
- Author
-
Smith, Brandon, Rosko, Andrew, VanKoevering, Kyle K., Heft Neal, Molly, Ellsperman, Susan, Fenberg, Rachel B., Cho, Joshua, Vita, Alex, Feng, Allen L., Contrera, Kevin J., Sridharan, Shaum S., and Spector, Matthew E.
- Published
- 2024
- Full Text
- View/download PDF
6. Association of preoperative thyroid hormone replacement with perioperative complications after major abdominal surgery
- Author
-
Haring, Catherine T., Heft Neal, Molly E., Jaffe, Craig A., Shuman, Andrew G., Rosko, Andrew J., and Spector, Matthew E.
- Published
- 2024
- Full Text
- View/download PDF
7. Use of the spider limb positioner for fibular free flap reconstruction of head and neck bony defects
- Author
-
Smith, Joshua D., Sridharan, Shaum S., Contrera, Kevin J., Richmon, Jeremy D., Feng, Allen L., Chinn, Steven B., Heft-Neal, Molly E., and Spector, Matthew E.
- Published
- 2024
- Full Text
- View/download PDF
8. Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury
- Author
-
Smith, Joshua D., Mentz, Graciela, Leis, Aleda M., Yuan, Yuan, Stucken, Chaz L., Chinn, Steven B., Casper, Keith A., Malloy, Kelly M., Shuman, Andrew G., McLean, Scott A., Rosko, Andrew J., Prince, Mark E. P., Tremper, Kevin K., Spector, Matthew E., and Schechtman, Samuel A.
- Published
- 2023
- Full Text
- View/download PDF
9. Tumor-Infiltrating Lymphocytes in Patients With Advanced Laryngeal Cancer Undergoing Bioselection
- Author
-
Neal, Molly E Heft, Smith, Joshua D, Birkeland, Andrew C, Haring, Catherine T, Chinn, Steven B, Shuman, Andrew G, Casper, Keith A, Malloy, Kelly M, Stucken, Chaz L, Mclean, Scott A, Rosko, Andrew J, Mierzwa, Michelle L, Shah, Jennifer, Schonewolf, Caitlin, Swiecicki, Paul L, Worden, Francis P, Wolf, Gregory T, Bradford, Carol R, Prince, Mark EP, Brenner, J Chad, and Spector, Matthew E
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Rare Diseases ,Clinical Research ,Good Health and Well Being ,Head and Neck Neoplasms ,Humans ,Laryngeal Neoplasms ,Larynx ,Lymphocytes ,Tumor-Infiltrating ,Prognosis ,Retrospective Studies ,Squamous Cell Carcinoma of Head and Neck ,larynx cancer ,tumor-infiltrating lymphocytes ,induction selection ,Clinical Sciences ,Otorhinolaryngology ,Clinical sciences - Abstract
ObjectiveBioselection to assess tumor response after induction chemotherapy has been introduced as an alternative treatment strategy to total laryngectomy for patients with advanced larynx squamous cell carcinoma (LSCC). Tumor-infiltrating lymphocytes (TILs) have proven to serve as prognostic biomarkers in head and neck cancer but have not been evaluated as a way to select patients for treatment paradigms. The aim of this study is to evaluate the role of pretreatment TILs in patients with advanced LSCC undergoing the bioselection paradigm.Study designRetrospective study.SettingTertiary care hospital.MethodsPatients with advanced LSCC treated with bioselection and available tissue were included (N = 76). Patients were stratified into CD8-low and CD8-high cohorts by using the median TIL count. Kaplan-Meier survival analysis and multivariate cox regression were performed with SPSS version 26 (IBM).ResultsAfter controlling for tobacco use, tumor site, and stage, a high CD8 TIL count was an independent predictor of improved 5-year disease-specific survival (hazard ratio, 0.17 [95% CI, 0.03-0.84]; P = .03). CD8 TIL counts did not predict response to induction chemotherapy; however, subgroup analysis of patients treated with chemoradiation therapy revealed that CD8 TIL count was significantly associated with degree of response (P = .012).ConclusionThese findings support prior data published by our group showing that TILs are predictive of disease-specific survival in patients with head and neck cancer. CD8 TIL counts were significantly associated with degree of clinical response after induction chemotherapy. These results suggest that pretreatment assessment of tumor-infiltrating CD8 cells could be useful in selecting patients.
- Published
- 2022
10. Initial Feasibility and Acute Toxicity Outcomes From a Phase 2 Trial of 18F-Fluorodeoxyglucose Positron Emission Tomography Response-Based De-escalated Definitive Chemoradiotherapy for p16+ Oropharynx Cancer: A Planned Interim Analysis
- Author
-
Allen, Steven G., Rosen, Benjamin S., Aryal, Madhava, Cao, Yue, Schipper, Matthew J., Wong, Ka Kit, Casper, Keith A., Chinn, Steven B., Malloy, Kelly M., Prince, Mark E., Rosko, Andrew J., Shuman, Andrew G., Spector, Matthew E., Stucken, Chaz L., Swiecicki, Paul L., Worden, Francis P., Brenner, J. Chad, Schonewolf, Caitlin A., Elliott, David A., Mierzwa, Michelle L., and Shah, Jennifer L.
- Published
- 2023
- Full Text
- View/download PDF
11. Development of a high-performance multi-probe droplet digital PCR assay for high-sensitivity detection of human papillomavirus circulating tumor DNA from plasma
- Author
-
Bhambhani, Chandan, Sandford, Erin, Haring, Catherine T., Brummel, Collin, Tuck, Kirsten L., Olesnavich, Mary, Bhangale, Apurva D., Walline, Heather M., Dermody, Sarah M., Spector, Matthew E., Chinn, Steven B., Casper, Keith, Mierzwa, Michelle, Swiecicki, Paul L., Chad Brenner, J., and Tewari, Muneesh
- Published
- 2023
- Full Text
- View/download PDF
12. Prognostic Significance of Oxidation Pathway Mutations in Recurrent Laryngeal Squamous Cell Carcinoma.
- Author
-
Heft Neal, Molly E, Bhangale, Apurva D, Birkeland, Andrew C, McHugh, Jonathan B, Shuman, Andrew G, Rosko, Andrew J, Swiecicki, Paul L, Spector, Matthew E, and Brenner, J Chad
- Subjects
HNSCC ,Nrf2/Keap1 ,larynx ,oxidation ,Nrf2 ,Keap1 ,Cancer ,Genetic Testing ,Genetics ,Clinical Research ,Rare Diseases ,Human Genome ,2.1 Biological and endogenous factors ,Oncology and Carcinogenesis - Abstract
Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer. Recurrence thereafter is associated with poor survival. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. 62%, p = 0.02). Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1-9.2, p = 0.03). Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort.
- Published
- 2020
13. Prognostic Significance of Oxidation Pathway Mutations in Recurrent Laryngeal Squamous Cell Carcinoma
- Author
-
Neal, Molly E Heft, Bhangale, Apurva D, Birkeland, Andrew C, McHugh, Jonathan B, Shuman, Andrew G, Rosko, Andrew J, Swiecicki, Paul L, Spector, Matthew E, and Brenner, J Chad
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Genetics ,Genetic Testing ,Rare Diseases ,Cancer ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,HNSCC ,larynx ,Nrf2 ,Keap1 ,oxidation ,Nrf2/Keap1 ,Oncology and carcinogenesis - Abstract
Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer. Recurrence thereafter is associated with poor survival. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. 62%, p = 0.02). Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1-9.2, p = 0.03). Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort.
- Published
- 2020
14. Color Match Following Free Flap Surgery in Head and Neck Reconstruction: A Colorimetric and Aesthetic Analysis
- Author
-
Dermody, Sarah M., Kahng, Peter W., Rao, Vishwanatha M., Casper, Keith A., Malloy, Kelly M., Rosko, Andrew J., Stucken, Chaz L., Chinn, Steven B., Spector, Matthew E., and Feng, Allen L.
- Published
- 2023
- Full Text
- View/download PDF
15. Phase II Clinical Trial of Intravenous Levothyroxine to Mitigate Pharyngocutaneous Fistula in Euthyroid Patients Undergoing Salvage Laryngectomy
- Author
-
Heft Neal, Molly E., primary, Haring, Catherine T., additional, Bellile, Emily, additional, Jaffe, Craig C., additional, Shuman, Andrew G., additional, Chinn, Steven B., additional, Stucken, Chaz L., additional, Malloy, Kelly M., additional, Casper, Keith A., additional, Prince, Mark E.P., additional, Chepeha, Douglas B., additional, Rosko, Andrew J., additional, and Spector, Matthew E., additional
- Published
- 2024
- Full Text
- View/download PDF
16. Upfront neck dissection to guide single-modality therapy for early stage supraglottic squamous cell carcinoma
- Author
-
Smith, Joshua D., primary, Heft-Neal, Molly E., additional, Rosko, Andrew J., additional, Chepeha, Douglas B., additional, and Spector, Matthew E., additional
- Published
- 2024
- Full Text
- View/download PDF
17. Telemedicine‐enabled biofeedback electropalatography rehabilitation (TEBER): A pilot study for patients treated with surgery for oral cavity carcinoma
- Author
-
Chepeha, Douglas B., primary, Barbon, Carly E. A., additional, Esemezie, Alex O., additional, Al Mardini, Majd, additional, Philteos, Justine, additional, Spector, Matthew E., additional, Bressmann, Tim, additional, Martino, Rosemary, additional, Bratman, Scott V., additional, Cho, John B. C., additional, Hope, Andrew J., additional, Hosni, Ali Abdalati, additional, Kim, John J. H., additional, Ringash, Jolie G., additional, Waldron, John N., additional, Brown, Dale H., additional, de Almeida, John R., additional, Gilbert, Ralph W., additional, Goldstein, David P., additional, Gullane, Patrick J., additional, Irish, Jonathan C., additional, Monteiro, Eric A., additional, and Yao, Christopher M. K. L., additional
- Published
- 2024
- Full Text
- View/download PDF
18. Prognostic value of CD103+ tumor-infiltrating lymphocytes and programmed death ligand-1 (PD-L1) combined positive score in recurrent laryngeal squamous cell carcinoma
- Author
-
Smith, Joshua D., Bellile, Emily L., Ellsperman, Susan E., Heft-Neal, Molly E., Mann, Jacqueline E., Birkeland, Andrew C., Hoesli, Rebecca C., Swiecicki, Paul L., Worden, Francis P., Schonewolf, Caitlin, Shah, Jennifer L., Mierzwa, Michelle L., Rosko, Andrew J., Stucken, Chaz L., Chinn, Steven B., Shuman, Andrew G., Casper, Keith A., Malloy, Kelly M., Prince, Mark E.P., Wolf, Gregory T., Thomas, Dafydd G., McHugh, Jonathan B., Chad Brenner, J., and Spector, Matthew E.
- Published
- 2022
- Full Text
- View/download PDF
19. The molecular landscape of the University of Michigan laryngeal squamous cell carcinoma cell line panel
- Author
-
Mann, Jacqueline E, Kulkarni, Aditi, Birkeland, Andrew C, Kafelghazal, Judy, Eisenberg, Julia, Jewell, Brittany M, Ludwig, Megan L, Spector, Matthew E, Jiang, Hui, Carey, Thomas E, and Brenner, J Chad
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Dental/Oral and Craniofacial Disease ,Genetics ,Digestive Diseases ,Biotechnology ,Cancer ,Human Genome ,Rare Diseases ,Good Health and Well Being ,Aged ,Carcinoma ,Squamous Cell ,Cell Line ,Tumor ,Female ,Humans ,Laryngeal Neoplasms ,Male ,Middle Aged ,Mutation ,Transcriptome ,Exome Sequencing ,HNSCC ,UM-SCC ,cell lines ,exome sequencing ,laryngeal cancer ,precision medicine ,Clinical Sciences ,Dentistry ,Otorhinolaryngology ,Clinical sciences - Abstract
BackgroundLaryngeal squamous cell carcinomas (LSCCs) have a high risk of recurrence and poor prognosis. Patient-derived cancer cell lines remain important preclinical models for advancement of new therapeutic strategies, and comprehensive characterization of these models is vital in the precision medicine era.MethodsWe performed exome and transcriptome sequencing as well as copy number analysis of a panel of LSCC-derived cell lines that were established at the University of Michigan and are used in laboratories worldwide.ResultsWe observed a complex array of alterations consistent with those reported in The Cancer Genome Atlas head and neck squamous cell carcinoma project, including aberrations in PIK3CA, EGFR, CDKN2A, TP53, and NOTCH family and FAT1 genes. A detailed analysis of FAT family genes and associated pathways showed disruptions to these genes in most cell lines.ConclusionsThe molecular profiles we have generated indicate that as a whole, this panel recapitulates the molecular diversity observed in patients and will serve as useful guides in selecting cell lines for preclinical modeling.
- Published
- 2019
20. Elective Paratracheal Lymph Node Dissection in Salvage Laryngectomy
- Author
-
Farlow, Janice L, Birkeland, Andrew C, Rosko, Andrew J, VanKoevering, Kyle, Haring, Catherine T, Smith, Joshua D, Brenner, J Chad, Shuman, Andrew G, Chinn, Steven B, Stucken, Chaz L, Malloy, Kelly M, Moyer, Jeffrey S, Casper, Keith A, McLean, Scott A, Prince, Mark EP, Bradford, Carol R, Wolf, Gregory T, Chepeha, Douglas B, and Spector, Matthew E
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Clinical Trials and Supportive Activities ,Clinical Research ,Rare Diseases ,Carcinoma ,Squamous Cell ,Elective Surgical Procedures ,Female ,Follow-Up Studies ,Humans ,Laryngeal Neoplasms ,Laryngectomy ,Lymph Node Excision ,Lymph Nodes ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Prognosis ,Retrospective Studies ,Salvage Therapy ,Survival Rate ,Tracheal Neoplasms ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BACKGROUND:Indications for and efficacy of paratracheal nodal dissection (PTND) in patients undergoing laryngectomy (salvage) for persistent or recurrent laryngeal squamous cell carcinoma are not well-defined. METHODS:A retrospective cohort study was performed for patients undergoing salvage laryngectomy with clinically and radiographically negative neck disease between 1998 and 2015 (n = 210). Univariate and multivariate Cox regression analyses were performed. RESULTS:PTND was performed on 77/210 patients (36%). The PTND cohort had a greater proportion of advanced T classification (rT3/rT4) tumors (78%) than subjects without PTND (55%; p = 0.001). There was a 14% rate of occult nodal metastases in the paratracheal basin; of these, 55% did not have pathologic lateral neck disease. Multivariate analysis controlling for tumor site, tumor stage, and pathologic lateral neck disease demonstrated that PTND was associated with improved overall survival [OS] (p = 0.03; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.38-0.96), disease-free survival [DFS] (p = 0.03; HR 0.55, 95% CI 0.31-0.96), and distant DFS survival (p = 0.01; HR 0.29, 95% CI 0.11-0.77). The rate of hypocalcemia did not differ between subjects who underwent bilateral PTND, unilateral PTND, or no PTND (p = 0.19 at discharge, p = 0.17 at last follow-up). CONCLUSIONS:PTND at the time of salvage laryngectomy was more common in patients with rT3/rT4 tumors and was associated with improved OS and DFS, with no effect on hypocalcemia. In patients undergoing PTND, the finding of occult paratracheal metastases was often independent of lateral neck metastases.
- Published
- 2019
21. Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma
- Author
-
Mann, Jacqueline E, Smith, Joshua D, Birkeland, Andrew C, Bellile, Emily, Swiecicki, Paul, Mierzwa, Michelle, Chinn, Steven B, Shuman, Andrew G, Malloy, Kelly M, Casper, Keith A, McLean, Scott A, Moyer, Jeffery S, Wolf, Gregory T, Bradford, Carol R, Prince, Mark E, Carey, Thomas E, McHugh, Jonathan B, Spector, Matthew E, and Brenner, J Chad
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Antigens ,CD ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,Carcinoma ,Squamous Cell ,Disease-Free Survival ,Female ,Head and Neck Neoplasms ,Humans ,Immunologic Memory ,Integrin alpha Chains ,Lymphocytes ,Tumor-Infiltrating ,Male ,Middle Aged ,Multivariate Analysis ,Neoplasm Recurrence ,Local ,Prognosis ,CD103 ,HNSCC ,Larynx ,Resident memory ,T-cell ,Oncology and carcinogenesis - Abstract
BackgroundRecurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+, CD8+ and/or CD103+ TIL status in patients with advanced LSCC.MethodsTissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+, CD8+, and CD103+ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4+, CD8+, and CD103+ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC.ResultsHigh tumor CD103+ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8+ or CD4+ TIL content. On multivariate analysis, an "immune-rich" phenotype, in which tumors were enriched for both CD103+ and CD4+ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC.ConclusionsAn immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.
- Published
- 2019
22. Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma.
- Author
-
Smith, Joshua D, Birkeland, Andrew C, Rosko, Andrew J, Hoesli, Rebecca C, Foltin, Susan K, Swiecicki, Paul, Mierzwa, Michelle, Chinn, Steven B, Shuman, Andrew G, Malloy, Kelly M, Casper, Keith A, McLean, Scott A, Wolf, Gregory T, Bradford, Carol R, Prince, Mark E, Brenner, John Chad, and Spector, Matthew E
- Subjects
Humans ,Carcinoma ,Squamous Cell ,Laryngeal Neoplasms ,Neoplasm Recurrence ,Local ,Survival Rate ,Cohort Studies ,DNA Mutational Analysis ,Mutation ,Adult ,Aged ,Middle Aged ,Male ,TCGA ,laryngeal squamous cell carcinoma ,larynx ,persistent ,recurrent ,Clinical Research ,Human Genome ,Rare Diseases ,Cancer ,Genetics ,Good Health and Well Being ,Clinical Sciences ,Dentistry ,Otorhinolaryngology - Abstract
BACKGROUND:We sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene-specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA). METHODS:The tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene-specific alteration frequencies were compared (Chi-Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform. RESULTS:Persistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53. CONCLUSIONS:Our results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.
- Published
- 2019
23. Window of opportunity trials in head and neck cancer
- Author
-
Farlow, Janice L, Birkeland, Andrew C, Swiecicki, Paul L, Brenner, J Chad, and Spector, Matthew E
- Subjects
Clinical Research ,Rare Diseases ,Dental/Oral and Craniofacial Disease ,Clinical Trials and Supportive Activities ,Biotechnology ,Cancer ,Orphan Drug ,Window of opportunity trial ,biomarker ,head and neck cancer ,oncology ,preoperative ,translational research ,trials - Abstract
Head and neck squamous cell carcinoma (HNSCC) has a large global burden of disease and poor survival outcomes. Recent targeted therapies and immunotherapies have been explored in HNSCC, but there has been limited translation to clinical practice outside of recurrent or metastatic cases. Window of opportunity settings, where novel agents are administered between cancer diagnosis and planned definitive therapy, have begun to be employed in HNSCC. Tumor tissue biopsies are obtained at diagnosis and after the investigation treatment, along with other biospecimens and radiographic exams. Thus, this study design can characterize the safety profiles, pharmacodynamics, and initial tumor responses to novel therapies in a treatment-naïve subject. Early window studies have also identified potential biomarkers to predict sensitivity or resistance to treatments. However, these early investigations have revealed multiple challenges associated with this trial design. In this review, we discuss recent window of opportunity trials in HNSCC and how they inform design considerations for future studies.
- Published
- 2019
24. The genomic landscape of UM-SCC oral cavity squamous cell carcinoma cell lines
- Author
-
Ludwig, Megan L, Kulkarni, Aditi, Birkeland, Andrew C, Michmerhuizen, Nicole L, Foltin, Susan K, Mann, Jacqueline E, Hoesli, Rebecca C, Devenport, Samantha N, Jewell, Brittany M, Shuman, Andrew G, Spector, Matthew E, Carey, Thomas E, Jiang, Hui, and Brenner, J Chad
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Human Genome ,Genetics ,Dental/Oral and Craniofacial Disease ,Clinical Research ,Biotechnology ,Genetic Testing ,Cancer ,Good Health and Well Being ,Caspase 8 ,Cell Line ,Tumor ,Class I Phosphatidylinositol 3-Kinases ,Cyclin-Dependent Kinase Inhibitor p16 ,DNA Copy Number Variations ,Humans ,Karyotyping ,Mouth Neoplasms ,Mutation ,Squamous Cell Carcinoma of Head and Neck ,Tumor Suppressor Protein p53 ,Exome Sequencing ,Cell Lines ,Exome ,HNSCC ,Oral cancer ,UM-SCC ,Dentistry ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
ObjectivesWe sought to describe the genetic complexity of 14 UM-SCC oral cavity cancer cell lines that have remained uncharacterized despite being used as model systems for decades.Materials and methodsWe performed exome sequencing on 14 oral cavity UM-SCC cell lines and denote the mutational profile of each line. We used a SNP array to profile the multiple copy number variations of each cell line and use immunoblotting to compare alterations to protein expression of commonly amplified genes (EGFR, PIK3CA, etc.). RNA sequencing was performed to characterize the expression of genes with copy number alterations.ResultsThe cell lines displayed a highly complex network of genetic aberrations that was consistent with alterations identified in the HNSCC TCGA project including PIK3CA amplification, CDKN2A deletion, as well as TP53 and CASP8 mutations, enabling genetic stratification of each cell line in the panel. Copy number FISH and spectral karyotyping analysis demonstrate that cell lines retain chromosomal heterogeneity.ConclusionsCollectively, we developed an important resource for future oral cavity HNSCC cell line studies and highlight the complexity of genomic aberrations in cell lines.
- Published
- 2018
25. Head and Neck
- Author
-
Kovoor, Jerry M., Kademian, Jack, Moritani, Toshio, Neal, Molly Heft, Birkeland, Andrew C., Spector, Matthew E., Moritani, Toshio, editor, and Capizzano, Aristides A., editor
- Published
- 2021
- Full Text
- View/download PDF
26. Imaging response assessment for predicting outcomes after bioselection chemotherapy in larynx cancer: A secondary analysis of two prospective trials
- Author
-
Gharzai, Laila A., Pakela, Julia, Jaworski, Elizabeth M., El Naqa, Issam, Shah, Jennifer, Hawkins, Peter G., Spector, Matthew E., Bradford, Carol R., Chinn, Steven B., Malloy, Kelly, Kupfer, Robbi, Shuman, Andrew, Morrison, Robert, Stucken, Chaz L., Rosko, Andrew, Prince, Mark E., Casper, Keith, Eisbruch, Avraham, Wolf, Gregory, Swiecicki, Paul L., Worden, Francis, and Mierzwa, Michelle L.
- Published
- 2022
- Full Text
- View/download PDF
27. The future of circulating tumor DNA as a biomarker in HPV related oropharyngeal squamous cell carcinoma
- Author
-
Haring, Catherine T., Dermody, Sarah M., Yalamanchi, Pratyusha, Kang, Stephen Y., Old, Matthew O., Chad Brenner, J., Spector, Matthew E., and Rocco, James W.
- Published
- 2022
- Full Text
- View/download PDF
28. Pharyngeal Mucosal Margin Vessel Counts Predict Pharyngocutaneous Fistula in Salvage Laryngectomy.
- Author
-
Prince, Andrew D.P., Heft Neal, Molly E., Buchakjian, Marisa R., Chinn, Steven B., Stucken, Chaz L., Casper, Keith A., Malloy, Kelly M., Prince, Mark E.P., Rosko, Andrew J., McHugh, Jonathan B., and Spector, Matthew E.
- Abstract
Objective: We evaluated vessel counts in the pharyngeal mucosal margins of patients who underwent salvage laryngectomy to establish whether mucosal vascularity might predict fistula risk. Study Design: Retrospective cohort. Setting: Tertiary Medical Center. Methods: Patients who underwent salvage total laryngectomy at our institution between 1999 and 2015 were identified. Pharyngeal mucosal margins from laryngectomy specimens were evaluated histologically for each patient, and vessel counts were performed on 5 ×10 images. The primary outcome measure was fistula within 30 days of surgery and mean vessel counts were assessed as the principle explanatory variable. Results: Seventy patients were included and 40% developed a postoperative fistula. There was a large difference in the mean vessel count in patients who did develop fistula (48.6 vessels/×10 field) compared to those who did not (34.7 vessels/×10 field). A receiver operative characteristic curve found that a cutoff value of 33.9 vessels/×10 field provided a sensitivity of 75% and specificity of 62% to predict the likelihood of fistula occurrence (area under the curve = 0.71, 95% confidence interval [CI]: 0.59‐0.83). In a binary logistic regression, patients with vessel counts greater than 33.9 had a 5‐fold increased risk of developing fistula (95% CI: 1.8‐16.45). Histologically, vessels in the pharyngeal mucosa of patients who developed fistulas were more disorganized. Conclusion: After salvage laryngectomy, patients with higher mean mucosal margin vessel counts are at increased risk of fistula. The mechanism is unknown, but the disorganization of the vasculature may contribute to poor wound healing. Vessel counting may allow for fistula risk stratification and guide postoperative care. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
29. Application of Time‐Driven Activity‐Based Costing for Head and Neck Microvascular Free Flap Reconstruction.
- Author
-
Yalamanchi, Pratyusha, Marentette, Lawrence J., Fendrick, A. Mark, Chinn, Steven B., Prince, Mark E.P., Rosko, Andrew J., Shuman, Andrew G., Spector, Matthew E., Stucken, Chaz L., Malloy, Kelly M., and Casper, Keith A.
- Abstract
Objective: Traditional hospital accounting fails to provide an accurate cost of complex surgical care. Here we describe the application of time‐driven activity‐based costing (TDABC) to characterize costs of head and neck oncologic procedures involving free tissue transfer. Study Design: Retrospective cohort study. Setting: Single tertiary academic medical center. Methods: An analysis of head and neck oncologic procedures involving microvascular free flap reconstruction from 2018 to 2020 (n = 485) was performed using TDABC methodology to measure cost across operative case and postoperative admission, using quantity of time and cost per unit of each resource to characterize resource utilization. Univariate and generalized linear mixed models were used to examine associations between patient and hospital characteristics and cost of care delivery. Results: The total cost of care delivery was $41,905.77 ± 21,870.27 with operating room (OR) supplies accounting for only 10% of the total cost. Multivariable analyses identified significant cost drivers including operative time, postoperative length of stay, number of return trips to the OR, postoperative complication, number of free flaps performed, and patient transfer from another hospital or via emergency department admission (P <.05). Conclusion: Operative time and postoperative length of stay, but not operative supplies, were primary drivers of cost of care for head and neck oncology cases involving free tissue transfer. TDABC offers granular cost characterization to inform cost optimization through unused capacity identification and postoperative admission efficiencies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Hypothyroidism and Wound Healing After Salvage Laryngectomy
- Author
-
Rosko, Andrew J, Birkeland, Andrew C, Bellile, Emily, Kovatch, Kevin J, Miller, Ashley L, Jaffe, Craig C, Shuman, Andrew G, Chinn, Steven B, Stucken, Chaz L, Malloy, Kelly M, Moyer, Jeffrey S, Casper, Keith A, Prince, Mark EP, Bradford, Carol R, Wolf, Gregory T, Chepeha, Douglas B, and Spector, Matthew E
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Aged ,Carcinoma ,Squamous Cell ,Cutaneous Fistula ,Female ,Humans ,Hypothyroidism ,Laryngeal Neoplasms ,Laryngectomy ,Male ,Middle Aged ,Neck Dissection ,Neoplasm Recurrence ,Local ,Pharyngeal Diseases ,Postoperative Complications ,Postoperative Period ,Reoperation ,Respiratory Tract Fistula ,Retrospective Studies ,Risk Factors ,Salvage Therapy ,Thyrotropin ,Wound Healing ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BACKGROUND:Patients undergoing salvage laryngectomy are predisposed to radiation-induced hypothyroidism and impaired wound healing secondary to the tissue effects of prior treatment. The impact of hypothyroidism on postoperative wound healing is not established. METHODS:A single-institution retrospective case series was performed. The inclusion criteria specified preoperatively euthyroid adults who underwent salvage laryngectomy with concurrent neck dissection between 1997 and 2015 for persistent or recurrent laryngeal squamous cell carcinoma after radiation or chemoradiation therapy (n = 182). The principal explanatory variable was postoperative hypothyroidism, defined as thyroid-stimulating hormone (TSH) higher than 5.5 mIU/L. The primary end points of the study were pharyngocutaneous fistulas and wounds requiring reoperation. Multivariate analysis was performed. RESULTS:The fistula rate was 47% among hypothyroid patients versus 23% among euthyroid patients. In the multivariate analysis, the patients who experienced hypothyroidism in the postoperative period had a 3.6-fold greater risk of fistula [95% confidence interval (CI) 1.8-7.1; p = 0.0002]. The hypothyroid patients had an 11.4-fold greater risk for a required reoperation (24.4 vs 5.4%) than the euthyroid patients (95% CI 2.6-49.9; p = 0.001). The risk for fistula (p = 0.003) and reoperation (p = 0.001) increased with increasing TSH. This corresponds to an approximate 12.5% incremental increase in the absolute risk for fistula and a 10% increase in the absolute risk for reoperation with each doubling of the TSH. CONCLUSION:Postoperative hypothyroidism independently predicts postoperative wound-healing complications. The association of hypothyroidism with fistula formation may yield opportunities to modulate wound healing with thyroid supplementation or to provide a biomarker of wound progression.
- Published
- 2018
31. The potential for liquid biopsies in head and neck cancer.
- Author
-
Spector, Matthew E, Farlow, Janice L, Haring, Catherine T, Brenner, J Chad, and Birkeland, Andrew C
- Subjects
Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Oncology and Carcinogenesis ,Cancer ,Rare Diseases ,Clinical Research ,Health Services ,Prevention ,Dental/Oral and Craniofacial Disease ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Good Health and Well Being ,Biopsy ,Head and Neck Neoplasms ,Humans - Abstract
Head and neck cancers consist of a heterogeneous group of cancers that are difficult to treat successfully. Limited screening options result in patients being diagnosed at advanced stages at presentation, and difficulty with treatment options and post-treatment surveillance can lead to poor outcomes. In this setting, tools for early and precise detection of disease will be highly valuable. Liquid biopsies, or use of analytes in blood, saliva, and other body fluid samples, provide new avenues for cancer screening with the potential for early detection, treatment modification, and surveillance of head and neck cancers. Early studies of liquid biopsies in specific head and neck cancers have had encouraging results. Nevertheless, various challenges remain before its routine adoption into clinical use is feasible. With continued advancement in the field of liquid biopsies, there is great promise for clinical implementation and significant improvement in head and neck cancer care.
- Published
- 2018
32. Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in persistent/recurrent laryngeal squamous cell carcinoma
- Author
-
Hoesli, Rebecca, Birkeland, Andrew C, Rosko, Andrew J, Issa, Mohamad, Chow, Kelsey L, Michmerhuizen, Nicole L, Mann, Jacqueline E, Chinn, Steven B, Shuman, Andrew G, Prince, Mark E, Wolf, Gregory T, Bradford, Carol R, McHugh, Jonathan B, Brenner, J Chad, and Spector, Matthew E
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Clinical Research ,Biomarkers ,Tumor ,CD4-CD8 Ratio ,Carcinoma ,Squamous Cell ,Female ,Humans ,Kaplan-Meier Estimate ,Laryngeal Neoplasms ,Lymphocytes ,Tumor-Infiltrating ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Prognosis ,CD4 ,CD8 ,Head and neck cancer ,Laryngectomy ,Recurrence ,Salvage ,Survival ,Tumor infiltrating lymphocytes ,Dentistry ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Tumor infiltrating lymphocytes (TILs) have been shown to be an important prognostic factor in patients with previously untreated head and neck cancer. After organ preservation therapy for laryngeal cancer and subsequent persistence/recurrence, the prognostic value of TILs is unknown. Our goal was to determine if TILs have value as a prognostic biomarker in patients with surgically salvageable persistent/recurrent laryngeal squamous cell carcinoma. Levels of TILs were quantified on tissue microarrays from 183 patients undergoing salvage total laryngectomy for persistent/recurrent laryngeal cancer after radiation or chemoradiation between 1997 and 2014. Demographic and clinical data were abstracted. Immunohistology evaluation included CD4, CD8, PDL-1, p16, CD31, Vimentin, EGFR, and p53. Elevated levels of either CD8 or CD4 positive TILs were associated with improved disease specific survival (CD8: HR 0.46, 95% CI 0.24-0.88, CD4: HR 0.43; 95% CI 0.21-0.89) and disease free survival (CD8: HR 0.53, 95% CI 0.29-0.94, CD4: HR 0.52; 95% CI 0.27-0.99). Levels of CD8 (HR 0.74; 95% CI 0.47-1.17) or CD4 (HR 0.66; 95% CI 0.40-1.08) TILs were not significantly associated with overall survival. In bivariate analysis, patients with elevated CD4 and/or CD8 TILs had significantly improved disease specific survival (HR 0.42; 95% CI 0.21-0.83) and disease free survival (HR 0.45; 95% CI 0.24-0.84) compared to patients with low levels of CD4 and CD8. PDL-1, p16, CD31, Vimentin, EGFR, and p53 were not significant prognostic factors. On multivariate analysis, elevated CD8 TILs were associated with improved disease specific survival (HR 0.35; 95% CI 0.14-0.88, p = .02) and disease free survival (HR 0.41; 95% CI 0.17-0.96, p = .04). CD8, and possibly CD4, positive TILs are associated with favorable disease free and disease specific survival for recurrent/persistent laryngeal cancer.
- Published
- 2018
33. Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma
- Author
-
Birkeland, Andrew C, Beesley, Lauren, Bellile, Emily, Rosko, Andrew J, Hoesli, Rebecca, Chinn, Steven B, Shuman, Andrew G, Prince, Mark E, Wolf, Gregory T, Bradford, Carol R, Brenner, J Chad, and Spector, Matthew E
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Cancer ,Digestive Diseases ,Adult ,Aged ,Carcinoma ,Squamous Cell ,Chemoradiotherapy ,Cohort Studies ,Databases ,Factual ,Disease-Free Survival ,Female ,Follow-Up Studies ,Head and Neck Neoplasms ,Humans ,Kaplan-Meier Estimate ,Laryngeal Neoplasms ,Laryngectomy ,Male ,Middle Aged ,Neoplasm Invasiveness ,Neoplasm Recurrence ,Local ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,Risk Assessment ,Squamous Cell Carcinoma of Head and Neck ,Survival Analysis ,Time Factors ,Treatment Outcome ,Adult Comorbidity Evaluation-27 ,disease-specific survival ,overall survival ,recurrent laryngeal cancer ,salvage laryngectomy ,Dentistry ,Otorhinolaryngology ,Clinical sciences - Abstract
BackgroundTotal laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.MethodsA prospectively maintained single-institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan-Meier survival curves and hazard ratios (HRs) were calculated.ResultsFive-year overall survival (OS) was 49%. Five-year disease-free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation-27 [ACE-27] scale; HR 3.76; 95% confidence interval [CI] 1.56-9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74-4.88).ConclusionSevere comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies.
- Published
- 2017
34. Evaluation of the safety and effectiveness of robot‐assisted neck dissections
- Author
-
Snyder, Vusala, primary, Smith, Brandon, additional, Kim, Seungwon, additional, Spector, Matthew E., additional, and Duvvuri, Umamaheswar, additional
- Published
- 2024
- Full Text
- View/download PDF
35. Consideration of liquid biomarkers for surveillance of HPV-related oropharyngeal cancer in veteran populations
- Author
-
Smith, Joshua D., primary, Spector, Matthew E., additional, Brenner, J. Chad, additional, and Maxwell, Jessica H., additional
- Published
- 2024
- Full Text
- View/download PDF
36. Preoperative Tracheostomy Is Associated with Poor Disease‐Free Survival in Recurrent Laryngeal Cancer
- Author
-
Birkeland, Andrew C, Rosko, Andrew J, Beesley, Lauren, Bellile, Emily, Chinn, Steven B, Shuman, Andrew G, Prince, Mark E, Wolf, Gregory T, Bradford, Carol R, Brenner, J Chad, and Spector, Matthew E
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Cancer ,Carcinoma ,Squamous Cell ,Disease-Free Survival ,Female ,Humans ,Laryngeal Neoplasms ,Laryngectomy ,Male ,Neoplasm Recurrence ,Local ,Preoperative Care ,Retrospective Studies ,Tracheostomy ,laryngeal squamous cell carcinoma ,laryngectomy ,salvage surgery ,survival ,tracheostomy ,Otorhinolaryngology ,Clinical sciences - Abstract
Objectives It is unknown if preoperative tracheostomy for persistent/recurrent laryngeal squamous cell carcinoma (LSCC) plays a role in unrecognized local disease spread and disease recurrence after salvage laryngectomy. The goals of this study were to determine the effect of preoperative tracheostomy on disease-free survival (DFS) in patients with recurrent/persistent LSCC undergoing salvage laryngectomy. Study Design Retrospective case series derived from prospectively maintained database. Setting Tertiary care academic center. Subjects Patients with recurrent/persistent LSCC after radiation/chemoradiation (RT/CRT) who underwent salvage laryngectomy at the University of Michigan from 1997 to 2015. Methods Demographic, clinical, pathologic, and survival data were collected. Kaplan-Meier survival estimates were performed. Results DFS was worse for patients with tracheostomy prior to laryngectomy than patients without a tracheostomy (5 year: 39% vs 67%; P < .001). Patients with tracheostomy prior to RT/CRT compared to patients with tracheostomy after RT/CRT or patients without a tracheostomy had worse DFS (5-year: 25%, 49%, and 67%, respectively; P < .001). In bivariable analyses controlling for T classification, N classification, or overall stage, preoperative tracheostomy was associated with worse DFS. In multivariable analysis, presence of a preoperative tracheostomy had a worse DFS (hazard ratio, 1.63; 95% confidence interval, 1.00-2.67; P = .048). Conclusion Preoperative tracheostomy is associated with disease recurrence in patients with persistent/recurrent LSCC undergoing salvage laryngectomy, particularly in patients who had tracheostomy prior to completion of initial RT/CRT. Notably, preoperative tracheostomy as a causal factor vs marker for disease recurrence is difficult to ascertain. Nevertheless, clinicians should be aware of the increased risk of locoregional recurrence in patients with preoperative tracheostomy when counseling on surgical salvage and when considering the role of additional therapy.
- Published
- 2017
37. E6 and E7 Antibody Levels Are Potential Biomarkers of Recurrence in Patients with Advanced-Stage Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma
- Author
-
Spector, Matthew E, Sacco, Assuntina G, Bellile, Emily, Taylor, Jeremy MG, Jones, Tamara, Sun, Kan, Brown, William C, Birkeland, Andrew C, Bradford, Carol R, Wolf, Gregory T, Prince, Mark E, Moyer, Jeffrey S, Malloy, Kelly, Swiecicki, Paul, Eisbruch, Avraham, McHugh, Jonathan B, Chepeha, Douglas B, Rozek, Laura, and Worden, Francis P
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Infectious Diseases ,Dental/Oral and Craniofacial Disease ,Clinical Research ,Digestive Diseases ,Prevention ,Cervical Cancer ,Cancer ,Sexually Transmitted Infections ,Adult ,Aged ,Antibodies ,Viral ,Biomarkers ,Tumor ,Carcinoma ,Squamous Cell ,Enzyme-Linked Immunosorbent Assay ,Female ,Humans ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Oncogene Proteins ,Viral ,Oropharyngeal Neoplasms ,Papillomaviridae ,Papillomavirus E7 Proteins ,Papillomavirus Infections ,Repressor Proteins ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
Purpose: There is a paucity of biomarkers to predict failure in human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) following curative therapy. E6/E7 viral oncoproteins are constitutively expressed in HPV+ tumors and highly immunogenic, resulting in readily detected serum antibodies. The purpose of this study is to determine whether serum E6 and E7 antibody levels can potentially serve as a biomarker of recurrence in patients with HPV+OPSCC.Experimental Design: We evaluated E6/E7 antibody levels in patients with previously untreated, advanced stage (III, IVa-b), HPV+OPSCC receiving definitive chemoradiation under a uniform protocol from 2003 to 2010. Baseline and longitudinal serum samples were obtained from our archived repository. E6/E7 serum levels were measured using a glutathione-S-transferase capture ELISA and quantified by approximating the area under the dilution curve, and were analyzed using ANOVA and linear mixed model for longitudinal analysis.Results: We compared 22 HPV+OPSCC patients who developed recurrence with 30 patients who remained disease-free. There were no differences in T classification, N classification, disease subsite, or smoking status between the groups. In a longitudinal analysis, recurrent patients had significantly higher E6 and E7 serum antibody levels than the nonrecurrent patients over the follow-up period (P = 0.02 and P = 0.002, respectively). Patients who recurred had a lower clearance of E7 antibody than patients who remained disease-free (P = 0.0016).Conclusions: Patients with HPV+OPSCC whose disease recurs have a lower clearance of E6 and E7 antibodies than patients who do not have recurrence. The ratio of E7 antibody at disease recurrence compared with baseline is potentially a clinically significant measurement of disease status in HPV+OPSCC. Clin Cancer Res; 23(11); 2723-9. ©2016 AACR.
- Published
- 2017
38. Positron emission tomography–CT prediction of occult nodal metastasis in recurrent laryngeal cancer
- Author
-
Rosko, Andrew, Birkeland, Andrew, Shuman, Andrew, Prince, Mark, Bradford, Carol, Wolf, Gregory, Worden, Francis, Eisbruch, Avraham, Srinivasan, Ashok, Wong, Ka Kit, and Spector, Matthew E
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Clinical Research ,Biomedical Imaging ,Clinical Trials and Supportive Activities ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Aged ,Carcinoma ,Squamous Cell ,Female ,Humans ,Laryngeal Neoplasms ,Laryngectomy ,Male ,Middle Aged ,Neck Dissection ,Neoplasm Recurrence ,Local ,Positron Emission Tomography Computed Tomography ,Predictive Value of Tests ,Retrospective Studies ,Salvage Therapy ,laryngeal squamous cell carcinoma ,occult nodal metastasis ,positron emission tomography (PET)-CT ,recurrent laryngeal cancer ,salvage laryngectomy ,Dentistry ,Otorhinolaryngology ,Clinical sciences - Abstract
BackgroundThe purpose of this study was to evaluate the predictive value of positron emission tomography (PET)-CT in identifying occult nodal metastasis in clinically and radiographically N0 patients with recurrent laryngeal cancer undergoing salvage laryngectomy.MethodsRetrospective review of 46 clinically and radiographically N0 patients with recurrent laryngeal cancer who underwent a PET-CT examination before salvage laryngectomy with neck dissection from January 1, 2002, to December 31, 2014, was performed.ResultsTwo patients (16.7%) had true-positive PET-CT results, whereas 10 patients (83.3%) had false-negative scans, 1 patient (2.9%) had a false-positive result and 33 patients (97.1%) had a true-negative PET-CT. The sensitivity of PET-CT was 16.7% (95% confidence interval [CI], 3.5% to 46.0%) with a specificity of 97.1% (95% CI, 83.8% to 99.9%), positive predictive value (PPV) of 66.7% (95% CI, 20.2% to 94.4%), and negative predictive value (NPV) of 76.7% (95% CI, 62.1% to 87.0%).ConclusionPET-CT has poor sensitivity and NPV making PET-CT an imperfect predictor of nodal disease in recurrent laryngeal cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 980-987, 2017.
- Published
- 2017
39. Correlation of Crtc1/3-Maml2 fusion status, grade and survival in mucoepidermoid carcinoma
- Author
-
Birkeland, Andrew C, Foltin, Susan K, Michmerhuizen, Nicole L, Hoesli, Rebecca C, Rosko, Andrew J, Byrd, Serena, Yanik, Megan, Nor, Jacques E, Bradford, Carol R, Prince, Mark E, Carey, Thomas E, McHugh, Jonathan B, Spector, Matthew E, and Brenner, J Chad
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Digestive Diseases ,Genetics ,Cancer ,Carcinoma ,Mucoepidermoid ,Cohort Studies ,DNA-Binding Proteins ,Female ,Gene Fusion ,Humans ,Male ,Mutation ,Nuclear Proteins ,Retrospective Studies ,Survival Analysis ,Trans-Activators ,Transcription Factors ,CRTC1-MAML2 ,CRTC1/3-MAML2 ,CRTC3-MAML2 ,Gene fusion ,Head and neck cancer ,Mucoepidermoid carcinoma ,Dentistry ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
ObjectiveMucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary glands. Tumor stage and grade have historically been important predictors of survival. An oncogenic CRTC1- or CRTC3-MAML2 gene fusion has been identified in a number of MECs. Historically, these gene fusions have been associated with lower grade tumors and better survival. However, reported gene fusion rates and prognosis varies widely across studies, and have not controlled for tumor grade. We sought to identify gene fusion rates and outcomes in our cohort of MEC patients.Materials and methodsAn IRB-approved retrospective cohort of patients with MEC was identified at the University of Michigan. Clinical, histologic, and outcome data was collected from medical records. RNA was isolated from formalin fixed paraffin-embedded tumor sections, and qRT-PCR was performed to identify CRTC1/3-MAML2 gene fusions. Sanger sequencing of qRT-PCR products was used to confirm gene fusions.ResultsOverall, 90 patient MEC tumors were collected (58 low-grade, 25 intermediate-grade, and 7 high-grade). Gene fusions were identified in 59% (53/90) of tumors. On univariate and bivariate analysis, fusion status did not significantly associate with grade or survival.ConclusionWe have identified a high rate of CRTC1/3-MAML2 gene fusions in a large cohort of MEC. We do not identify any correlation between fusion status with tumor grade or survival. These findings suggest further characterization of MECs is needed before considering the CRTC1/3-MAML2 gene fusion as a prognostic biomarker. Additional genetic drivers may account for survival and grade in MECs.
- Published
- 2017
40. Impact of extrinsic tongue muscle invasion on stage migration in AJCC 8th edition staging of oral cavity carcinoma
- Author
-
Marchiano, Emily J., Mathis, Noah J., Bellile, Emily L., Lobo, Remy, Ibrahim, Mohannad, Smith, Joshua D., Birkeland, Andrew C., Casper, Keith A., Malloy, Kelly M., Swiecicki, Paul L., Worden, Francis P., Mierzwa, Michelle L., Chad Brenner, J., Bradford, Carol R., Stucken, Chaz L., Prince, Mark E., Rosko, Andrew J., Shuman, Andrew G., McHugh, Jonathan B., Spector, Matthew E., and Chinn, Steven B.
- Published
- 2020
- Full Text
- View/download PDF
41. Advances in Facial Nerve Paralysis: Surgical Innovation, Tissue Engineering, and Emerging Technology
- Author
-
Brennan, Julia R., Spector, Matthew E., Kim, Jennifer C., Brenner, Michael J., Duscher, Dominik, editor, and Shiffman, Melvin A., editor
- Published
- 2019
- Full Text
- View/download PDF
42. Three-dimensional modeling of the scapular tip for anterolateral and lateral mandibular defects
- Author
-
Marchiano, Emily, Stevens, Jayne R., Liao, Eric, Rosko, Andrew J., Powell, Allison R., Chinn, Steven B., Stucken, Chaz L., and Spector, Matthew E.
- Published
- 2020
- Full Text
- View/download PDF
43. Patient-reported financial toxicity and adverse medical consequences in head and neck cancer
- Author
-
Beeler, Whitney H., Bellile, Emily L., Casper, Keith A., Jaworski, Elizabeth, Burger, Nicholas J., Malloy, Kelly M., Spector, Matthew E., Shuman, Andrew G., Rosko, Andrew, Stucken, Chaz L., Chinn, Steven B., Dragovic, Aleksandar F., Chapman, Christina H., Owen, Dawn, Jolly, Shruti, Bradford, Carol R., Prince, Mark E.P., Worden, Francis P., Jagsi, Reshma, Mierzwa, Michelle L., and Swiecicki, Paul L.
- Published
- 2020
- Full Text
- View/download PDF
44. Tumor Biomarkers in Spindle Cell Variant Squamous Cell Carcinoma of the Head and Neck
- Author
-
Rosko, Andrew J, Birkeland, Andrew C, Wilson, Kevin F, Muenz, Daniel G, Bellile, Emily, Bradford, Carol R, McHugh, Jonathan B, and Spector, Matthew E
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Rare Diseases ,Dental/Oral and Craniofacial Disease ,Adult ,Aged ,Aged ,80 and over ,Biomarkers ,Tumor ,Carcinoma ,Squamous Cell ,Case-Control Studies ,Female ,Head and Neck Neoplasms ,Humans ,Male ,Microarray Analysis ,Middle Aged ,Neoplasm Recurrence ,Local ,Retrospective Studies ,Risk Factors ,Sarcoma ,Squamous Cell Carcinoma of Head and Neck ,Survival Rate ,EGFR ,biomarkers ,cMet ,cyclin D1 ,head and neck cancer ,p16 ,sarcomatoid ,spindle cell ,Clinical Sciences ,Otorhinolaryngology ,Clinical sciences - Abstract
ObjectiveTo determine biomarkers of recurrence and survival in patients with spindle cell variant squamous cell carcinoma (SpSCC) of the head and neck.Study designRetrospective case control study.SettingTertiary academic center.Subjects and methodsThirty-two SpSCC patients (mean age, 68.8) between 1987 and 2009 were identified and reviewed. A tissue microarray (TMA) was constructed from tumor specimens. Tumor biomarkers under study included p16, epidermal growth factor receptor (EGFR), p53, EZH2, cyclin D1, CD104, HGFa, p21, and cMET. An additional TMA was constructed from patients with non-SpSCC oral cavity squamous cell carcinoma for comparative purposes. The main outcomes were overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS).ResultsIn the SpSCC cohort, tumors positive for cMet had worse OS (P < .001). Patients positive for cMet (P = .007), cyclin D1 (P = .019), and p16 (P = .004) had worse DSS. Recurrence-free survival was also worse in patients with tumors positive for cMet (P = .037), cyclin D1 (P = .012), and p16 (P < .001). Compared with the oral cavity cohort, there was a significantly larger proportion of patients in the SpSCC group with tumors staining positive for cMet and a lower proportion of tumors positive for cyclin D1.ConclusioncMet, cyclin D1, and p16 are predictive tumor biomarkers for risk of recurrence and worse DSS in patients with SpSCC.
- Published
- 2016
45. Identification of Targetable ERBB2 Aberrations in Head and Neck Squamous Cell Carcinoma
- Author
-
Birkeland, Andrew C, Yanik, Megan, Tillman, Brittny N, Scott, Megan V, Foltin, Susan K, Mann, Jacqueline E, Michmerhuizen, Nicole L, Ludwig, Megan L, Sandelski, Morgan M, Komarck, Christine M, Carey, Thomas E, Prince, Mark EP, Bradford, Carol R, McHugh, Jonathan B, Spector, Matthew E, and Brenner, J Chad
- Subjects
Biotechnology ,Clinical Research ,Human Genome ,Dental/Oral and Craniofacial Disease ,Genetics ,Cancer ,Rare Diseases ,Blotting ,Western ,Bridged Bicyclo Compounds ,Heterocyclic ,Carbamates ,Carcinoma ,Squamous Cell ,Cell Line ,Tumor ,Cell Survival ,Enzyme Inhibitors ,ErbB Receptors ,Gene Expression Profiling ,Humans ,Hydroxybutyrates ,Immunohistochemistry ,Laryngeal Neoplasms ,Mouth Neoplasms ,Mutation ,Purines ,Quinazolines ,Receptor ,ErbB-2 ,Retrospective Studies ,Triazines ,Receptor ,erbB-2 - Abstract
ImportanceERBB2 (formerly HER2) is an important drug target in breast cancer, where anti-ERBB2 therapy has been shown to lead to improvements in disease recurrence and overall survival. ERBB2 status in head and neck squamous cell carcinoma (HNSCC) has not been well studied. Identification of ERBB2-positive tumors and characterization of response to ERBB2 therapy could lead to targeted treatment options in HNSCC.ObjectiveTo identify ERBB2 aberrations in HNSCCs and investigate the potential for ERBB2-targeted therapy in HNSCCs.Design, setting, and participantsA retrospective case series of patients with laryngeal (42 tumor specimens) and oral cavity (94 tumor specimens) SCC enrolled in the University of Michigan Head and Neck Specialized Program of Research Excellence was conducted. Publicly available sequencing data (The Cancer Genome Atlas), as well as data from other studies, were reviewed to identify additional mutations and overexpression in ERBB2 in HNSCC. Established HNSCC cell lines were used for follow-up in vitro analysis. The study was conducted from October 1, 2014, to August 30, 2015.InterventionsWith the use of targeted, amplicon-based sequencing with the Oncomine Cancer Panel, the copy number and mutation status of commonly altered genes in HNSCCs were assessed. Immunohistochemical staining was performed on tissue microarrays of HNSCCs to assess the expression of ERBB2. Western blotting for HNSCC cell line ERBB2 expression and cell survival assays after treatment with ERBB2 inhibitors were performed.Main outcomes and measuresThe prevalence of ERBB2 genetic aberrations and ERBB2 overexpression in laryngeal and oral cavity SCCs, prevalence of ERBB2 aberrations in HNSCC in The Cancer Genome Atlas, ERBB2 protein expression in HNSCC cell lines, and response of HNSCC cell lines to targeted ERBB2 inhibitors.ResultsOf the 42 laryngeal SCC samples screened by targeted sequencing, 4 (10%) were positive for ERBB2 amplification. Two of these samples showed ERBB2 overexpression on immunohistochemistry. Two of the 94 oral cavity SCC samples (2%) were positive for ERBB2 on immunohistochemistry. Analysis of 288 patients from publicly available HNSCC sequencing data revealed 9 amplifications (3%) in ERBB2. Protein expression was variable across HNSCC cell lines, and a subset of these cell lines showed responsiveness to anti-ERBB2 therapy.Conclusions and relevanceERBB2 aberrations were identified in a subset of HNSCCs. These tumors may be responsive to targeted therapy against ERBB2. Screening for ERBB2 aberrations and applying targeted therapy in ERBB2-positive patients may be useful in personalized therapy trials, particularly in patients who are refractory to current treatment paradigms.
- Published
- 2016
46. Fibroblast growth factor family aberrations as a putative driver of head and neck squamous cell carcinoma in an epidemiologically low‐risk patient as defined by targeted sequencing
- Author
-
Tillman, Brittny N, Yanik, Megan, Birkeland, Andrew C, Liu, Chia-Jen, Hovelson, Daniel H, Cani, Andi K, Palanisamy, Nallasivam, Carskadon, Shannon, Carey, Thomas E, Bradford, Carol R, Tomlins, Scott A, McHugh, Jonathan B, Spector, Matthew E, and Brenner, J Chad
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Human Genome ,Genetics ,Rare Diseases ,Clinical Research ,Cancer ,Dental/Oral and Craniofacial Disease ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Carcinoma ,Squamous Cell ,Class I Phosphatidylinositol 3-Kinases ,DNA Copy Number Variations ,DNA Mutational Analysis ,Female ,Fibroblast Growth Factors ,Gene Expression Regulation ,Neoplastic ,Head and Neck Neoplasms ,High-Throughput Nucleotide Sequencing ,Humans ,Middle Aged ,Neoplasm Recurrence ,Local ,amplification ,fibroblast growth factor ,fibroblast growth factor receptor ,head and neck squamous cell carcinoma ,mutant ,Dentistry ,Otorhinolaryngology ,Clinical sciences - Abstract
BackgroundTargeted sequencing of patients with epidemiologically low-risk (ELR) head and neck squamous cell carcinoma (HNSCC) could help identify novel drivers or lost suppressors leading to precision medicine protocols and improved survival rates.MethodsA patient with ELR-HNSCC was selected for targeted sequencing. We then assessed next generation sequencing cohorts from the Oncomine Powertool Database, which contains pan-cancer data from The Cancer Genome Atlas (TCGA).ResultsTargeted sequencing revealed fibroblast growth factor receptor-1 (FGFR1) amplifications as a putative driver of the patient's tumor. Patients with HNSCC from TCGA data demonstrated fibroblast growth factor (FGF) family mutations, rearrangements, or amplifications in over 35% of HNSCC cases, with a statistically significant higher frequency in African American populations. FGF alterations were unique from activating phosphatidylinositol 3-kinase (PIK3CA) mutations.ConclusionTogether, these data suggest that FGF signaling may be critical for a subset of patients with HNSCC independent of other known pathways and provides rationale for leveraging patients with ELR-HNSCC to define molecular subsets of high-risk HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1646-E1652, 2016.
- Published
- 2016
47. Changing the paradigm: the potential for targeted therapy in laryngeal squamous cell carcinoma
- Author
-
Ludwig, Megan L, Birkeland, Andrew C, Hoesli, Rebecca, Swiecicki, Paul, Spector, Matthew E, and Brenner, J Chad
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Genetics ,Rare Diseases ,Good Health and Well Being ,Head and neck cancer ,genetics ,laryngeal squamous cell carcinoma ,personalized medicine ,targeted therapy ,Medical Biotechnology ,Oncology and carcinogenesis - Abstract
Laryngeal squamous cell carcinoma (LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21(st) century.
- Published
- 2016
48. The potential for tumor suppressor gene therapy in head and neck cancer.
- Author
-
Birkeland, Andrew C, Ludwig, Megan L, Spector, Matthew E, and Brenner, J Chad
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Cancer ,Gene Therapy ,Rare Diseases ,Dental/Oral and Craniofacial Disease ,Orphan Drug ,Biotechnology ,2.1 Biological and endogenous factors ,Aetiology ,Animals ,Carcinoma ,Squamous Cell ,Genes ,Tumor Suppressor ,Genetic Therapy ,Head and Neck Neoplasms ,Humans - Abstract
Head and neck squamous cell carcinoma remains a highly morbid and fatal disease. Importantly, genomic sequencing of head and neck cancers has identified frequent mutations in tumor suppressor genes. While targeted therapeutics increasingly are being investigated in head and neck cancer, the majority of these agents are against overactive/overexpressed oncogenes. Therapy to restore lost tumor suppressor gene function remains a key and under-addressed niche in trials for head and neck cancer. Recent advances in gene editing have captured the interest of both the scientific community and the public. As our technology for gene editing and gene expression modulation improves, addressing lost tumor suppressor gene function in head and neck cancers is becoming a reality. This review will summarize new techniques, challenges to implementation, future directions, and ethical ramifications of gene therapy in head and neck cancer.
- Published
- 2016
49. Prevalence and Outcomes of Head and Neck versus Non-Head and Neck Second Primary Malignancies in Head and Neck Squamous Cell Carcinoma: An Analysis of the Surveillance, Epidemiology, and End Results Database
- Author
-
Birkeland, Andrew C, Rosko, Andrew J, Chinn, Steven B, Prince, Mark E, Sun, Gordon H, and Spector, Matthew E
- Subjects
Clinical Research ,Cancer ,Rare Diseases ,Dental/Oral and Craniofacial Disease ,Aged ,Carcinoma ,Squamous Cell ,Female ,Follow-Up Studies ,Head and Neck Neoplasms ,Humans ,Male ,Middle Aged ,Neoplasm Staging ,Neoplasms ,Second Primary ,Prevalence ,Retrospective Studies ,Risk Assessment ,Risk Factors ,SEER Program ,Squamous Cell Carcinoma of Head and Neck ,Survival Rate ,United States ,Clinical Sciences ,Otorhinolaryngology - Abstract
Background/aimsPatients with head and neck squamous cell carcinoma (HNSCC) are at risk for second primary malignancies (SPMs). The prevalence, distribution, and patient survival in head and neck versus non-head and neck SPMs are not fully elucidated. The objective of this study was to quantify the rate of SPMs in patients with HNSCC.MethodsThis is a population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Prevalence and location of SPMs, and survival data were analyzed.ResultsThere were 58,363 HNSCC patients, and the prevalence of HNSCC and non-HNSCC SPMs was 3.0% (1,746) and 8.8% (5,109), respectively. Overall survival (OS) was higher in patients with HNSCC SPMs compared to non-HNSCC SPMs (p < 0.001), with no difference in disease-specific survival. Patients with SPMs in the lung and esophagus had a worse OS (p < 0.001), and patients with SPMs in the prostate and breast had a better OS (p < 0.001).ConclusionIn HNSCC patients who develop SPMs, nearly 75% are non-HNSCC SPMs. Patients with non-HNSCC SPMs have a lower OS. Future clinical practice guidelines should take the risks and locations of SPM development into consideration for screening.
- Published
- 2016
50. Team-Based Surgical Approach to Head and Neck Microvascular Free Flap Reconstruction
- Author
-
Yalamanchi, Pratyusha, primary, Peddireddy, Nithin S., additional, McMichael, Brennan, additional, Keilin, Charles, additional, Casper, Keith A., additional, Malloy, Kelly M., additional, Moyer, Jeffrey S., additional, Prince, Mark E. P., additional, Rosko, Andrew J., additional, Stucken, Chaz L., additional, Spector, Matthew E., additional, and Chinn, Steven B., additional
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.