RTOG Validates Lysyl Oxidase as a Prognostic Marker for Metastasis and Survival for Patients with Head and Neck Squamous Cell Carcinoma
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 an early release of new research by Radiation Therapy Oncology Group (RTOG) investigators published online this week and in an upcoming issue of 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 on RTOG 9003, a phase III 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 disease spread (metastases).
“This important study from the RTOG Translational Research Program is the first to validate a hypoxia marker, LOX, that identifies patients who have a higher probability of developing spread of disease in a prospective, phase III RTOG head and neck trial,” said Adam Dicker, M.D., Ph.D., chair of the RTOG Translational Research Program and Professor and Interim Chairman, Department of Radiation Oncology Director-Christine Baxter Research Laboratory for Experimental Cancer Therapeutics, Thomas Jefferson University. “This was performed using both traditional immunohistochemistry as well as a cutting edge image analysis tool-AQUA (automated quantitative analysis). We plan to incorporate the LOX biomarker in our upcoming clinical trials.”
According to Quynh-Thu Le, M.D., the lead author on the study and professor in the Department of Radiation Oncology at Stanford University, “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. 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.”
Dr. Le and her team initially performed traditional immunohistochemical (IHC) and AQUA staining on 66 tumor samples from Stanford University 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.
“This exciting new research highlights the group’s commitment to developing novel therapies to prevent and treat cancer by defining treatment strategies based on each patient’s personalized tumor characteristics,” said Walter J. Curran, Jr., M.D., the RTOG Group Chair, and the Lawrence W. Davis Professor and Chair of the Department of Radiation Oncology in the Emory School of Medicine and Chief Medical Officer of the Emory Winship Cancer Institute.