The Impact of Total Laryngectomy on Non-oncologic Causes of Death in Patients Treated with Radiation Therapy for Advanced Larynx and Hypopharynx Cancer

Abstract

There was an unexplained increase in deaths unrelated to cancer for patients treated with primary concomitant cisplatin and radiotherapy (CRT) in RTOG 91-11 for laryngeal preservation. We have previously demonstrated that patients who undergo primary CRT for larynx or hypopharynx cancer may have increased risk of non-oncologic pulmonary deaths likely secondary to aspiration. We hypothesized that patients treated with adjuvant radiation therapy (RT) after total laryngectomy would have a lower rate of pulmonary death because they are anatomically protected from aspiration. Between August 2004 and December 2014, 96 patients were treated with primary CRT (Group 1) and 22 patients were treated with total laryngectomy and neck dissection followed by adjuvant RT or CRT (Group 2) for advanced stage larynx and hypopharynx cancer. Seventy-nine percent and 73% of each group had baseline swallowing evaluations using modified barium swallow. Patients in Group 1 received a median dose of 7000 cGy in 35 fractions while patients in Group 2 received 6000 cGy in 30 fractions. Ninety-two percent of Group 1 were treated with concomitant cisplatin or cetuximab compared to 54.5% of Group 2. Nineteen of 22 patients in Group 2 had bilateral neck dissections, while 3 of 22 had a unilateral neck dissection. Median age at diagnosis for both cohorts was 63 years (range, 41-94 years and 42-84 years). Median follow-up was 38 (Group 1) and 47 (Group 2) months. Group 1 had median overall (OS) and progression-free survival (PFS) of 40.2 and 30.8 months, while Group 2 had a median OS and PFS of 45.6 and 34.8 months. For patients with recurrences, 50% of first recurrences were local in Group 1 while 1 patient in Group 2 had a recurrence in the hypopharynx. Cause of death was able to be determined for 93% and 70% of Group 1 and 2 patients, respectively. 48.1% vs 40% were due to index cancer, 11.5% vs 10% due to secondary malignancy, 21.2% vs 0% due to non-oncologic pulmonary failure. 49% and 31% had abnormal swallows at baseline. For those who died of pulmonary failure in Group 1, 7/8 had evidence of aspiration on their last post-CRT examination. Four percent of patients in Group 1 without evidence of larynx cancer required laryngectomy for laryngeal dysfunction, 18% were PEG-tube dependent for 6 months or more after CRT, and 16% developed esophageal strictures requiring intervention. In Group 2, 23% were PEG-tube dependent for 6 months or more after treatment, and 14% developed esophageal strictures requiring intervention. While rates of progression and overall survival were similar, patients who underwent definitive CRT for advanced larynx and hypopharynx cancer had a higher rate of pulmonary death than those treated with a total laryngectomy followed by adjuvant RT or CRT likely secondary to aspiration. This finding emphasizes the importance of post-treatment surveillance for aspiration and early intervention if detected.