Improved local control in p16 negative oropharyngeal cancers with hypermethylated MGMT.

Abstract

INTRODUCTION:

Patients with oropharyngeal cancers that are p16 negative (p16-) have worse outcomes than those who are p16 positive (p16+) and there is an unmet need for prognostic markers in this population. O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated with response to chemoradiotherapy (CRT) in glioblastoma. We sought to find if MGMT promoter methylation was associated with outcomes of locally advanced oropharyngeal and oral cavity squamous cell carcinoma (OOSCC) in patients treated with definitive concurrent CRT.

METHODS:

Patients were identified with primary OOSCC, known p16 status, retrievable pre-treatment biopsies, and at least 6 months of follow-up who received definitive concurrent CRT from 2004 to 2015. Biopsies were tested for MGMT hypermethylation (MGMT+) using a Qiagen pyrosequencing kit (Catalog number 970061). Outcomes were subsequently recorded and analyzed.

RESULTS:

Fifty-eight patients were included with a median follow up of 78 (range 6-196) months. Fourteen patients (24.1%) had oral cavity cancer and 44 (75.9%) had oropharyngeal cancer. A significant difference was found for local recurrence free survival (LRFS) by combined MGMT and p16 status (p = 0.0004). Frequency of LR in MGMT+/p16+, MGMT+/p16-, MGMT-/p16+, and MGMT-p16- patients was 14.3%, 14.3%, 13.0%, and 69.2%, respectively (p = 0.0019). A significant difference was not found for distant recurrence free survival (p = 0.6165) or overall survival (p = 0.1615). LRFS remained significant on analysis restricted to oropharyngeal cancer patients (p-value = 0.0038).

CONCLUSION:

Patients who are p16- and MGMT+ with oropharyngeal and oral cavity squamous cell carcinoma have significantly better LC with definitive CRT than those who are p16- and MGMT-. Prospective studies are needed to verify these findings.

• Authors: Garrett L Jensen, Gabriel Axelrud, David Fink, Kendall Hammonds, Kimberly Walker, Marcus Volz, Alan Gowan, Arundhati Rao, Niloyjyoti Deb, Sameer G Jhavar
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 157 Pg. 234-240 (04 2021) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 33577867 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Tumor Suppressor Proteins
• DNA Modification Methylases
• MGMT protein, human
• O(6)-Methylguanine-DNA Methyltransferase
• DNA Repair Enzymes

Topics

• Carcinoma, Squamous Cell (genetics, therapy)
• DNA Methylation
• DNA Modification Methylases (genetics)
• DNA Repair Enzymes (genetics)
• Humans
• Mouth Neoplasms
• O(6)-Methylguanine-DNA Methyltransferase (genetics, metabolism)
• Oropharyngeal Neoplasms (genetics, therapy)
• Prognosis
• Prospective Studies
• Tumor Suppressor Proteins (genetics)