Risk factors which predict persistent cancer in the abnormal larynx following definitive irradiation

Laryngeal abnormalities following definitive irradiation for carcinoma of the larynx are common. The objective of this study was to identify risk factors for persistent cancer in such patients who were found to have abnormal larynges following definitive irradiation. A retrospective evaluation of 185 consecutive patients undergoing primary irradiation for a glottic or supraglottic laryngeal squamous carcinoma treated between 1976 and 1990 at the Affiliated Hospitals of the Medical College of Wisconsin was performed. From chart review, data concerning site, stage, intent of treatment, smoking history, treatment dose, fraction size, failure patterns, and outcome were obtained. In addition, worrisome signs and symptoms including ulceration, dysphasia, odynophagia, airway distress, aphonia, blood, pain, oedema, aspiration, and pneumonia were recorded. Univariate association with failure and a persistently abnormal laryngeal examination was assessed using the Mantel-Haenszel test. The odds ratio was used to estimate relative risk associated with dichotomous risk factors. Disease-free and overall survival were estimated using Kaplan-Meier methodology. The log rank test was used to compare survival as defined by the levels of various risk factors. Two-year disease-free survival was 83% (T1 = 93%, T2 = 72%, T3/T4 = 66%). Primary failure was associated with the presence of an abnormal examination (P = 0.001), tracheotomy (P = 0.001), symptom index (P = 0.002), aphonia (P = 0.003), advanced T stage (P = 0.03), and lower total dose (P = 0.03). Of 151 patients who survived 6 months disease-free with an intact larynx, an abnormal examination was seen in those with advanced T stage (P = 0.002), supraglottic primary (P = 0.003), symptom index (P = 0.008), eventual failure at the primary site (P = 0.008), continued smoking (P = 0.01), and higher total dose (P = 0.01). The symptom index (total signs and symptoms of airway distress, aphonia, ulceration, pain, oedema, dysphagia, blood production, aspiration, pneumonia, and odynophagia) was correlated with primary failure and continued smoking. Of 37 patients with continually normal examinations, only 1 (3%) failed at the primary site. Of 102 who survived 6 months but with an abnormal examination, 22 (22%) eventually developed a primary failure. Persistently abnormal larynges are common after radiation therapy, yet not all harbour cancer. Risk factors for persistent cancer include stage, airway, total dose, and symptom index. Patients whose larynges return to normal after radiation rarely fail at the primary site.