This thesis aims to improve the treatment of patients with stage III melanoma. The first part describes different aspects of treatment with Talimogene Laherparepvec (T-VEC), a genetically modified... Show moreThis thesis aims to improve the treatment of patients with stage III melanoma. The first part describes different aspects of treatment with Talimogene Laherparepvec (T-VEC), a genetically modified herpes virus, which is used as oncolytic immunotherapy for skin and lymph node metastases in melanoma patients. We show that patients with a low tumor burden have the best outcomes, suggesting T-VEC should be used earlier on in the course of the disease. We present a prediction model, allowing a more accurate selection of patients for T-VEC monotherapy. Two studies focused on the use of T-VEC in clinical practice and the results allowed us to make recommendations on the use of PET/CT and dermoscopy during T-VEC treatment. Part two focuses on the value of surveillance and screening imaging in high-risk melanoma patients. We show that FDG-PET/CT is a valuable imaging tool to detect recurrence after complete resection of stage III disease, even shortly after surgery (before starting adjuvant therapy). Finally, we conclude that nodal staging with US as adjunct to SLNB is useful in the work- up of stage IIB/C melanoma, as it can lead to alterations in treatment and prevent unnecessary surgery. Show less
Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first... Show moreBeing a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with a (p16-Leiden) mutation in the high penetrance melanoma susceptibility gene CDKN2A were compared with the general population. Significant differences with respect to several characteristics are reported. In the second part of the thesis the yield, effectiveness, and causes for failure of surveillance of melanoma families are discussed. We report that surveillance is associated with a more favorable tumor stage. Several aspects of surveillance, including interval melanomas, surveillance interval, noncompliance, and overdiagnosis are discussed. Based on analyses of melanoma detection rates in families with different family and genetic characteristics, we propose a risk stratification for members of melanoma families. In the third part of the thesis we investigate the impact of dermoscopy on management decisions. It is demonstrated that dermoscopy by dermoscopy experts in the setting of melanoma family surveillance resulted in a considerable reduction of unnecessary excisions. This effect was considerably less in the setting of dermoscopy non-experts examining patients in general dermatology clinics. Show less
