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During recent decades, many studies have been performed in patients with early glottic cancer, which provide new insight into the two main treatment modalities, TOLMS and radiotherapy, and their outcomes. The aim of this thesis was: (i) What is the role of TOLMS in T2 glottic carcinoma in the Netherlands? (ii) Should more patients with T2 glottic carcinoma be treated with TOLMS? Within this thesis, we found that (i) the laryngeal preservation rate for T2 glottic carcinoma is higher after primary treatment with TOLMS than after primary treatment with radiotherapy; (ii) that the binary use (yes/no) for the involvement of the anterior commissure (AC) as a prognostic factor leads to inconsistent results, whereas studies with a more detailed classification of the AC show that there is a significant impact on oncological outcomes; (iii) that vertical involvement of the AC on imaging has a significant impact on local control not only in patients treated with TOLMS but also in patients receiving primary radiotherapy; and (iv) that patient with T2 glottic carcinoma treated with radiotherapy reported good long-term functional outcomes, although patients with tumors infiltrating the vocal fold muscle show a trend toward a higher degree of voice handicap than patients with tumor with only superficial spread.

During recent decades, many studies have been performed in patients with early glottic cancer, which provide new insight into the two main treatment modalities, TOLMS and radiotherapy, and their outcomes. The aim of this thesis was: (i) What is the role of TOLMS in T2 glottic carcinoma in the Netherlands? (ii) Should more patients with T2 glottic carcinoma be treated with TOLMS? Within this thesis, we found that (i) the laryngeal preservation rate for T2 glottic carcinoma is higher after primary treatment with TOLMS than after primary treatment with radiotherapy; (ii) that the binary use (yes/no) for the involvement of the anterior commissure (AC) as a prognostic factor leads to inconsistent results, whereas studies with a more detailed classification of the AC show that there is a significant impact on oncological outcomes; (iii) that vertical involvement of the AC on imaging has a significant impact on local control not only in patients treated with TOLMS but also in patients receiving primary radiotherapy; and (iv) that patient with T2 glottic carcinoma treated with radiotherapy reported good long-term functional outcomes, although patients with tumors infiltrating the vocal fold muscle show a trend toward a higher degree of voice handicap than patients with tumor with only superficial spread.

Because of the disappointing progress that has been made in the last decades in survival in patients with head and neck cancer, existing therapy needs to be improved and/or new treatment needs to be introduced. This thesis describes a new promising treatment, apoptin gene therapy. The scope of this study was to investigate the applicability of apoptin in head and neck squamous cell carcinoma (HNSCC). First, we assessed its potential in-vitro. Next, a suitable animal model was established, which was used for in-vivo experiments with apoptin. In chapter 2 we describe the results of apoptin treatment in a HNSCC cell line with a mutated p53 and the effect of over-expression of Bcl-xL on the outcome. Chapter 3 describes the synergistic effect of apoptin and irradiation in HNSCC both in radiation sensitive and in more radioresistant HNSCC cell lines. The applicability of an immune competent animal model for in-vivo research is described in chapter 4. The time needed to establish a useful oral squamous cell carcinoma in mice is assessed and immunological comparisons are made with human counterparts. In chapter 5 the tumorigenesis of the same carcinogenic immune competent model is investigated and characteristics are analyzed. The efficacy of the apoptin therapy in-vivo is described in chapter 6. This is done by looking into the effect of intratumoral injection of a constructed adenovirus expressing the apoptin protein. Finally, the data are critically discussed in chapter 7 in view of apoptin as a potential new anti-cancer therapy.

The general aim of this thesis is to determine and compare disease and voice outcome for T1 glottic carcinoma treated with radiotherapy or laser surgery. The findings show similar oncological and functional results for radiotherapy and laser surgery in __superficial midcord T1a glottic carcinoma__. This outcome supports the Dutch national guideline __Treatment of Laryngeal Carcinoma__ which was published during the life-time of this thesis. In this guideline laser surgery is labeled treatment of choice in these lesions because of the shorter treatment duration, lower costs and the possibility for repeated treatments and/or additional radiotherapy. For larger T1 lesions, our literature review concludes that more comparative data, especially on functional results, are needed before definite conclusions can be drawn as to the role of laser surgery in these lesions. These studies are now being perform ed in a collaboration between the Leiden University Medical Center and the Eramus Medical Center, Rotterdam.