title: 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.
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 SUVmaxof measured lesions was 71.6% (range: 8.3-100%). The Pearson correlation coefficient between Ki-67 expression and the percent decrease in summed SUVmaxwas 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.
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chatzkel
authors.affiliation: Department of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO, 63110, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Ley
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO, 63110, USA.|Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Wildes
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Wade
authors.initials: W
authors.lastname: Thorstad
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Hiram
authors.initials: H
authors.lastname: Gay
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Daly
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Department of Otolaryngology, Division of Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Jackson
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Department of Otolaryngology, Division of Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Rich
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Department of Otolaryngology, Division of Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Randal
authors.initials: R
authors.lastname: Paniello
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Department of Otolaryngology, Division of Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Nussenbaum
authors.affiliation: Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Mallinckrodt Institute of Radiology, Division of Nuclear Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Siegel
authors.affiliation: Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.|Mallinckrodt Institute of Radiology, Division of Nuclear Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Farrokh
authors.initials: F
authors.lastname: Dehdashti
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, Washington University School of Medicine, 660 South Euclid, Campus Box 8056, St. Louis, MO, 63110, USA. dadkins@wustl.edu.|Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA. dadkins@wustl.edu.
authors.forename: Douglas
authors.initials: D
authors.lastname: Adkins
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000068818:Cetuximab / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil
keywords: Chemotherapy sensitivity; HNSCC; Ki-67 expression