Are larynx cancer tumor genetic biomarkers predictive of outcome?
Background: More than 10,000 people are diagnosed with larynx cancer, and nearly 4,000 die in the United States each year. Most patients have advanced disease at the time of diagnosis. Conventional treatments combining radical resection and radiation therapy are associated with profound functional morbidity that affects quality of life. Identifying biomarkers that predict treatment response and prognosis will lead to targeted treatment options for patients and limit unnecessary patient morbidity.
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January 2014Study design: Prospectively collected biopsy specimens from 58 patients entered into a phase II trial of organ preservation in advanced laryngeal cancer.
Setting: University of Michigan, Ann Arbor.
Synopsis: Biomarkers of interest included p53, antiapoptotic proteins B-cell lymphoma-2 and B-cell lymphoma-extra large (Bcl-xL), epidermal growth factor receptor (EGFR), murine double minute 2, Bak, nuclear factor-kappaB (NFκB), proliferating cell nuclear antigen, RhoC, and survivin protein. Specimens were taken from pretreatment biopsies and during salvage surgery. All biomarkers were tested for correlations with chemotherapy response, chemoradiation response, overall survival, disease-specific survival, time to indication for surgery, and clinical covariates of interest such as age, gender, T stage, N stage, and smoking status. There was a statistically significant increase in Bcl-xL expression between pre-treatment and salvage specimens. Higher levels of mean Bak intensity and nuclear NFκB proportion were each significantly associated with poorer induction chemotherapy response. Expression of cyclin D1 (intensity) was associated with increased risk of death, while elevated cytoplasmic CD24 expression was associated with lowered risk of death. EGFR expression was associated with an increased risk of death from disease. NFκB, a key cancer cell survival regulator, may mediate resistance to induction chemotherapy in larynx cancer. A possible limitation is that the analysis regarding associations between biomarkers and induction chemotherapy response may be biased due to missing data.
Bottom line: Biomarker expression evaluation in pretreatment biopsy specimens can provide important predictive and prognostic information for patients with advanced larynx cancer, although a single biomarker with tremendous power to predict certain outcomes has not yet been identified.
Citation: Bradford CR, Kumar B, Bellile E, et al. Biomarkers in advanced larynx cancer. Laryngoscope. 2014;124:179-187.