Combination of p16 Levels and Pre-Radiotherapy Factors Predicts Outcome in Patients Treated for Oropharyngeal Carcinoma

J BUON. Oct-Dec 2013;18(4):982-8.

Abstract

Purpose: To explore whether tumor biomarkers and pre-treatment factors correlate with treatment outcome in patients with oropharyngeal squamous cell carcinoma (SCC).

Methods: Fifty-seven consecutive patients diagnosed with oropharyngeal SCC were treated using intensity modulated radiotherapy (IMRT). Thirty-four (60%) patients were treated with definitive chemoradiotherapy to a median total dose of 70 Gy and 23 (40%) were treated with postoperative RT to a median total dose of 66 Gy. Concurrent platinum- based chemotherapy was used in 51 patients (90%) and cetuximab in 3 (5%) patients.

Results: Forty-four (77%) cases were positive and 13 (23%) were negative for p16 expression. Eighty-eight percent of non-smokers, 87% of smokers in their remote past and 56% of active smokers were diagnosed with p16-positive cancer. After 22 months median follow up, 51 (89%) patients were alive. Forty-five (77%) patients were without evidence of disease at their last follow up, 82% of the patients with p16-positive tumors vs 58% of those with p16-negative cancer, respectively (p= 0.04). Locoregional disease-free survival was 82% for the entire cohort, 91% for patients treated postoperatively and 76% for patients treated with definitive chemoradiotherapy. Five (9%) patients developed distant metastases, and 3 (5%) developed new malignancies. One third of the patients with pre-RT hemoglobin level of ≤ 11 g/dL experienced persistent/recurrent disease; 80% of patients with hemoglobin ≤ 11 g/dL were smokers and 42% had p16-negative tumors.

Conclusions: Smoking, p16 expression and pre-RT anemia are interrelated and influence outcome in oropharyngeal cancer patients and should be evaluated as stratifying variables in further clinical trials.

MeSH terms

  • Adult
  • Aged
  • Anemia / complications
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / chemistry*
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / radiotherapy*
  • Carcinoma, Squamous Cell / secondary
  • Chemoradiotherapy* / adverse effects
  • Chemoradiotherapy* / mortality
  • Chi-Square Distribution
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • Disease-Free Survival
  • Female
  • Head and Neck Neoplasms / chemistry*
  • Head and Neck Neoplasms / etiology
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / radiotherapy*
  • Head and Neck Neoplasms / secondary
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Oropharyngeal Neoplasms / chemistry*
  • Oropharyngeal Neoplasms / etiology
  • Oropharyngeal Neoplasms / mortality
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / radiotherapy*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Radiotherapy, Intensity-Modulated* / mortality
  • Risk Factors
  • Smoking / adverse effects
  • Squamous Cell Carcinoma of Head and Neck
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16