Author: Miriam E. Tucker
Pretreatment CD4 levels predicted response to induction chemotherapy among 97 patients with advanced laryngeal cancer, but not for 66 patients with advanced oropharyngeal cancer, according to a retrospective analysis of data from two clinical trials.
The two groups of head and neck cancer patients were enrolled in two identical prospective, phase II trials of induction chemotherapy and organ preservation, in which tumor response after one cycle of cisplatin and 5-fluorouracil was used to select those who would undergo surgery or definitive chemoradiation (J. Clin. Oncol. 2006;24:593-8 in laryngeal cancer; J. Clin. Oncol. 2008;26:3138-46 in oropharyngeal cancer).
Several lymphocyte subsets were measured before treatment via routine flow cytometry in peripheral blood in the laryngeal cancer patients, but only CD4 (helper cell) levels were significantly associated with chemotherapy response. Both absolute CD4 counts and CD4 percentages were higher among induction chemotherapy responders than nonresponders (P = .006 and P = .04, respectively).
Investigators also saw a trend for responders to have an increased percentage of CD3 cells (P = .13), decreased percentage of CD8 cells (P = .11), and higher CD4/CD8 ratios.
“Host immune parameters are important factors in treatment outcome, and may be useful in identifying subsets of patients with cancers that are responsive to organ-preserving therapy,” said Dr. Gregory T. Wolf, who presented the data at a head and neck cancer symposium sponsored by the American Society for Radiation Oncology.
“It is likely that immunobiology of head and neck cancers differ significantly by tumor site and predisposing factors,” added Dr. Wolf, a professor in the department of otolaryngology at the University of Michigan, Ann Arbor.
The median length of follow-up in the two studies was 7.9 years for the patients with laryngeal cancer and 6.6 years for those with cancer of the oropharynx. Disease-free survival was 86% at 3 years and 82% at 5 years for laryngeal cancer, and 78% at 3 years and 76% at 4 years for oropharyngeal cancer. The proportions responding to induction chemotherapy were 75% in the laryngeal cancer trial and 82% in the oropharyngeal cancer study.
In an interview, Dr. Wolf said that having two identical treatment trials provided an opportunity to determine whether correlations of pretreatment CD4 levels with chemoresponse differed by tumor site. When the laryngeal and oropharyngeal cancer patient groups were combined, higher CD4 levels were still associated with response, but this was primarily because of the strong correlation among the larynx cancer patients.
Statistical regression testing determined that for patients with oropharyngeal cancer, CD8 cells were more closely associated with chemotherapy response, but the relationship was not as strong as the strong correlation of CD4 levels among laryngeal cancer patients.
There was a trend toward improved survival by both CD4 percentage (P = .36) and absolute CD4 count (P = .15) in the laryngeal cohort, but not in the oropharyngeal cohort. None of the other lymphocyte subsets predicted survival in either group, Dr. Wolf said.
Results for the oropharyngeal cancer patients were further stratified by human papillomavirus status, and were combined with the laryngeal cancer group. Both lower CD4/CD8 ratio and higher CD8 levels were consistent with better prognosis among patients who were HPV positive (P = .02 and P = .06, respectively).
“We combined the results to get the largest sample size and [to see] if the relationship was independent of tumor site, since the biology of these cancers is so different. It was remarkable that the prediction differed by tumor site, with CD4 cells being predictive for larynx and CD8 cells predictive for oropharynx,” Dr. Wolf explained in an interview. This finding likely reflects the major biological differences between these cancers, and is why it was important to also include HPV status, he added.
Note: Dr. Wolf is a consultant for IRX Therapeutics, Inc.