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 Neck Pathol. 2017 Sep;11(3):338-345. doi: 10.1007/s12105-016-0775-9. Epub 2016 Dec 26.

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.

Keywords: Chemotherapy sensitivity; HNSCC; Ki-67 expression.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / drug therapy*
  • Cetuximab / administration & dosage
  • Cisplatin / administration & dosage
  • Docetaxel
  • Female
  • Fluorouracil / administration & dosage
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Induction Chemotherapy / methods*
  • Ki-67 Antigen / biosynthesis*
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Taxoids
  • Docetaxel
  • Paclitaxel
  • Cetuximab
  • Cisplatin
  • Fluorouracil