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Correlation of Ki-67 Proliferative Antigen Expression and Tumor Response to Induction Chemotherapy Containing Cell Cycle-Specific Agents in Head and Neck Squamous Cell Carcinoma

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Abstract

Determine if highly proliferative head and neck squamous cell carcinomas, assessed by pretreatment Ki-67 expression, respond more robustly to induction chemotherapy (IC) that is selectively toxic to cycling cells. Retrospective analysis of 59 patients treated with IC and chemoradiation. IC included either nab-paclitaxel, cisplatin, 5-FU and cetuximab (APF-C, n = 27) or docetaxel, cisplatin, 5-FU +/− cetuximab (TPF+/−C, n = 32). Ki-67 expression was assessed by immunohistochemistry. Tumor response (complete/partial/stable/progressive) at the primary site after two IC cycles was evaluated by visual examination in all patients. In the APF-C sub-group, tumor response (primary site and neck nodes) after two IC cycles was evaluated by computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT. Ki-67 expression (median 66%, range: 16–97) did not differ across the tumor response categories assessed by visual examination (p = 0.95), CT (p = 0.30), or FDG-PET/CT (p = 0.65). Median decrease in summed SUVmax of measured lesions was 71.6% (range: 8.3–100%). The Pearson correlation coefficient between Ki-67 expression and the percent decrease in summed SUVmax was 0.48 (p = 0.02). Ki-67 expression was not different between those with or without a relapse (median: 60 and 71%, p = 0.10). In multivariate regression analysis (MVA) controlling for p16 positive oropharyngeal SCC status and smoking status, Ki-67 expression was not significantly associated with tumor response by visual examination (coefficient estimate −0.002, standard error 0.010, p = 0.84), CT (coefficient estimate −0.007, standard error 0.011, p = 0.54), FDG-PET/CT (coefficient estimate 0.006, standard error 0.008, p = 0.51), the percent decrease in summed SUVmax (coefficient estimate 0.389, standard error 0.222, p = 0.09), or relapse events (OR = 1.02(95%CI:0.99–1.05), p = 0.28). No significant relationships were found in MVA between pretreatment Ki-67 expression and tumor response to IC or to relapse.

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Funding

We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri for the use of the Clinical Trials Core, which provided protocol development and clinical trial support and for use of the Imaging and Response Assessment Core. The Siteman Cancer Center is supported in part by NCI Cancer Center Support Grant #P30 CA91842, (Eberlein, PI).

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO, 63110, USA

    Jonathan Chatzkel, Jessica C. Ley, Tanya M. Wildes & Douglas Adkins

  2. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Tanya M. Wildes, Wade Thorstad, Hiram Gay, Mackenzie Daly, Ryan Jackson, Jason Rich, Randal Paniello, Brian Nussenbaum, Barry A. Siegel, Farrokh Dehdashti & Douglas Adkins

  3. Department of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine, Nashville, TN, USA

    James S. Lewis Jr.

  4. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Wade Thorstad, Hiram Gay & Mackenzie Daly

  5. Department of Otolaryngology, Division of Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Ryan Jackson, Jason Rich, Randal Paniello & Brian Nussenbaum

  6. Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA

    Jingxia Liu

  7. Mallinckrodt Institute of Radiology, Division of Nuclear Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Barry A. Siegel & Farrokh Dehdashti

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  1. Jonathan Chatzkel
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  2. James S. Lewis Jr.
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  15. Douglas Adkins
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Correspondence to Douglas Adkins.

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Conflict of interest

Dr. Adkins has received Research Funding from Celgene. All other authors have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study, as part of a registry protocol.

Additional information

Presented in abstract form at the 2015 Annual Meeting of the American Society of Clinical Oncology.

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Chatzkel, J., Lewis, J.S., Ley, J.C. et al. Correlation of Ki-67 Proliferative Antigen Expression and Tumor Response to Induction Chemotherapy Containing Cell Cycle-Specific Agents in Head and Neck Squamous Cell Carcinoma. Head and Neck Pathol 11, 338–345 (2017). https://doi.org/10.1007/s12105-016-0775-9

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  • DOI: https://doi.org/10.1007/s12105-016-0775-9

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