Milea Timbergen

336 treatment most commonly surgery and systemic treatment. The reported median follow-up time ranged between 8 and 73 months, and the reported median time to progression and/or initiation of the subgroup shifting from active surveillance to ‘active’ therapy ranged from 6.5 months to 19.7 months. Selecting patients who will benefit from this active surveillance approach upfront should be the priority of future studies. Chapter 7 describes a meta-analysis of seven retrospective studies with individual patient data of 329 patients to analyse differences in risk of recurrent according to the CTNNB1 mutation status. From the total group of patients, 154 had a tumour with a T41A mutation, 66 patients presented tumours with a S45F mutation, 24 tumours displayed a S45P mutation and 85 contained WT CTNNB1 tumours. Eighty-three patients (25.2%) experienced a tumour recurrence after surgery. Multivariable analysis, adjusting for sex, age and tumour site yielded a p-value of 0.011 for CTNNB1 mutation and risk of recurrence after surgery. Additional adjustment for tumour size yielded a p-value of 0.082 with hazard ratio’s (HR) of 0.83 (95% confidence interval [CI] 0.48-1.42), 0.37 (95% CI 0.12-1.14) and 0.44 (95% CI 0.21-0.92) for T41A, S45P and WT DTF tumours compared to S45F DTF tumours. From this study we concluded that primary, sporadic DTFs harbouring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P and WT DTF, but this association appears to be mediated by tumour size. Part III - Health-Related Quality of Life Chapter 8 investigated the impact of DTF on HRQoL. A mixed methods methodology was used consisting of a systematic literature review to provide an overview of measures previously used to evaluate HRQoL among DTF patients and focus groups, to gain insight into HRQOL-issues experienced by DTF patients. Thirteen articles reporting HRQoL- measures using a wide variety of cancer-specific HRQoL tools, functional scores, symptom scales, and single-item outcomes (e.g., pain and functional impairment) were identified but no DTF specific HRQoL-tool was found. Qualitative analysis of three focus groups (6 males, 9 females) showed that participants emphasised the negative impact of DTF and/or its treatment on several HRQoL-domains. Six themes were identified including diagnosis, treatment, follow-up and recurrence, the physical domain, the psychological and emotional domain and the social domain. This study indicates that HRQoL of DTF patients was negatively affected in several domains. A DTF-specific HRQoL-measure could improve our understanding of short- and long-term effects and, ideally, can be used in both clinic and for research purposes. 13