Lysyl Oxidase a Marker for Metastasis and Survival

It is now possible to identify head and neck cancer patients who have a higher risk of developing distant metastases or suffering a relapse, according to new research by Radiation Therapy Oncology Group (RTOG) investigators published in the Journal of Clinical Oncology. RTOG is a National Cancer Institute-funded national cooperative clinical trials group. Using tumor biopsies and data from 306 patients entered in RTOG 9003, a phase 3 multicenter randomized trial of four radiation therapy schedules for locally advanced head and neck squamous cell carcinoma, investigators found that an increase in lysyl oxidase (LOX) expression is a predictor for the development of distant metastases, disease progression, and overall survival.  LOX is an enzyme associated with hypoxia, or a reduction in tissue oxygen, which is thought to increase the likelihood of metastases.
 
“We have validated LOX as a marker for metastasis, and thereby the significance of hypoxia, in head and neck cancer patients treated with radiation therapy,” says Quynh-Thu Le, MD, the lead author on the study and a professor in the department of radiation oncology at Stanford University.
 
Le and her team initially performed traditional immunohistochemistry and automated quantitative analysis (AQUA) staining on 66 tumor samples and found that LOX expression was predictive of a decrease in the time to metastasis. They subsequently used AQUA on 306 patients entered on the multicenter RTOG study and found that an increase in LOX expression was an independent predictor of time to metastasis (hazard ratio [HR], 1.21 for every 10 unit increment of LOX protein expression; 95% CI, 1.10 to 1.33; P = .0001), time to disease progression (HR, 1.06; 95% CI, 1.02 to 1.10; P = .0069), and overall survival (HR, 1.04; 95% CI, 1.00 to 1.07; P = .0311). This translates into a 259% increase in metastatic risk for a patient at the 75th percentile of LOX compared with one at the 25th percentile.
 
“We plan to continue our investigations of the prognostic abilities of LOX through future studies with patients treated with concurrent chemoradiotherapy and determine the impact of LOX in relation to HPV (human papillomavirus) status, another known prognostic marker in these cancers,” Le says.
 
— Source: Radiation Therapy Oncology Group