VoiceS: Voice Quality After Transoral CO2-Laser Surgery Versus Single Vocal Cord Irradiation for Unilateral Stage 0 & I Glottic Larynx Cancer - A Randomized Phase III Trial

Background and Rationale

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common type of cancer worldwide. Of all head and neck cancers, approximately 30% originates from the larynx. In Europe, annually 52.000 patients are diagnosed with cancer of the larynx. About 50-60% of laryngeal squamous cell carcinomas arise from the glottic region and over 80% of these patients present in an early stage. The larynx has important roles in production of voice, coordination of deglutition, and respiration. Therefore, the treatment aim of laryngeal cancer is not only achievement of maximum disease control, but also maintenance of function. Transoral CO2-Laser Microsurgical Cordectomy (TLM) and radiotherapy are well-established standard treatment modalities for unilateral stage 0-I carcinoma in situ and squamous cell carcinoma of glottic larynx (for convenience, both will be mentioned as SCCGL throughout this protocol). Based on various clinical studies and meta-analyses, functional and oncological outcome (overall survival and local control) after both treatment modalities are comparable. However, no properly conducted randomized trials comparing these treatments exist. The only such trial with the endpoint of voice quality had to be prematurely closed due to low accrual.

The treatment option varies remarkably in different countries and among institutions. Especially in the case of unilateral SCCGL, other factors such as voice quality, cultural and socioeconomic factors, and patients' preference should be considered. Hoarseness is one of the main and early signs of SCCGL, whereas both radiotherapy and TLM influence voice quality by altering the vocal cord motion and anatomy. Another issue worth to consider is the treatment time. Surgery is performed in one day followed by a few days of hospital stay. In contrast, radiotherapy is applied in daily fractions. Although each fraction only takes few minutes, the patients have to visit the radiation oncology department over a course of 4 to 7 weeks, depending on the institutional preference of dose and fractionation. The post-treatment follow-up schedules are identical for both strategies.

The differences between both treatment modalities have been extensively reported. However, either due to no meaningful difference or due to the heterogeneity in the voice analysis techniques, several studies revealed no significant differences while better voice quality was reported after radiotherapy as compared with TLM in other studies.

The traditional radiotherapy involves the treatment of the whole larynx over a period of 4 to 7 weeks. Recently, a new radiotherapy technique was introduced by a team of researchers from Netherlands, where the treated target volume consists of involved vocal cord and therefore 8 to 10 fold smaller than the target volumes used for traditional whole larynx irradiation. The treatment is reduced to 16 fractions with higher dose per fraction which corresponds to 3 weeks and a day. The results of a prospective cohort (n=30) with single vocal cord irradiation (SVCI) were compared with the results of a historical prospective cohort (n=131) previously treated with whole larynx radiotherapy in the same institute. The median follow-up was 30 months. The voice handicap index (VHI) at all time points beginning from the 6th week after SVCI was significantly superior to the same time points with conventional radiotherapy. Moreover, a comparable local control with SVCI (100%) vs. conventional radiotherapy (92%) was reported at two years, p=0.2412.