Correlation of p16 status, hypoxic imaging using [18F]-misonidazole positron emission tomography and outcome in patients with loco-regionally advanced head and neck cancer.

Abstract

INTRODUCTION:

We investigated the relationship between hypoxia, human papillomavirus (HPV) status and outcome in head and neck squamous cell carcinoma.

METHODS:

Patients with stage III and IV head and neck squamous cell carcinoma treated on phase I and II chemoradiation trials with 70-Gy radiation combined with tirapazamine/cisplatin or cisplatin/fluorouracil (5FU), hypoxic imaging using [18F]-misonidazole positron emission tomography and known HPV status (by p16 immunohistochemistry) were included in this sub-study. Separate analyses were conducted to consider the impact of tirapazamine on HPV-negative tumours in the phase II trial.

RESULTS:

Both p16-positive oropharyngeal tumours and p16-negative head and neck squamous cell carcinoma tumours had a high prevalence of tumour hypoxia; 14/19 (74%) and 35/44 (80%), respectively. The distribution of hypoxia (primary, nodal) was similar. On phase II, trial patients with p16-negative hypoxic tumours had worse loco-regional control with cisplatin and 5FU compared with tirapazamine and cisplatin (P < 0.001) and worse failure-free survival (hazard ratio = 5.18; 95% confidence interval, 1.98-13.55; P = 0.001). Only 1 out of 14 p16-positive patients on the phase II trial experienced loco-regional failure.

CONCLUSION:

Hypoxia, as assessed by [18F]-misonidazole positron emission tomography, is frequently present in both p16-positive and negative head and neck cancer. Further research is required to determine whether hypoxic imaging can be used to predict benefit from hypoxia-targeting therapies in patients with p16-negative tumours.

• Authors: Mateya E Trinkaus, Rodney J Hicks, Richard J Young, Lester J Peters, Ben Solomon, Mathias Bressel, June Corry, Richard Fisher, David Binns, Grant A McArthur, Danny Rischin
• Journal: Journal of medical imaging and radiation oncology (J Med Imaging Radiat Oncol) Vol. 58 Issue 1 Pg. 89-97 (Feb 2014) ISSN: 1754-9485 [Electronic] Australia
• PMID: 24529061 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Royal Australian and New Zealand College of Radiologists.

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• CDKN2A protein, human
• Cyclin-Dependent Kinase Inhibitor p16
• Fluorine Radioisotopes
• Neoplasm Proteins
• Radiopharmaceuticals
• Misonidazole

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Biomarkers, Tumor
• Cell Hypoxia
• Cyclin-Dependent Kinase Inhibitor p16
• Fluorine Radioisotopes
• Head and Neck Neoplasms (diagnosis, drug therapy, metabolism)
• Humans
• Male
• Middle Aged
• Misonidazole
• Neoplasm Proteins (metabolism)
• Papillomavirus Infections (diagnosis, drug therapy, metabolism)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals
• Reproducibility of Results
• Sensitivity and Specificity
• Statistics as Topic
• Treatment Outcome