Milea Timbergen

175 Discussion This systematic literature review evaluated the outcomes of the AS approach in sporadic DTF. Twenty-five articles, describing the outcomes of the AS in DTF, were identified. The majority of the reported patients experienced SD, and about one-third of the patients needed to shift to “active” treatment. The median time of follow-up was reported by twelve studies and ranged between 8 months and 73 months, and the median time to shift from AS to active treatment or to progression ranged from 6.5 months to 19.7 months. AS has increasingly been advocated in for sporadic DTF 39 . This is underlined by the number of publications about this subject since the year of 2006. In the most recent European consensus paper, published by the Desmoid Tumor Work Group in 2020, AS is advocated as a first line treatment in symptomatic patients, independently of the tumour site or size. In case of progression, other treatments such as surgery or systemic therapies, and treatments (including AS), should preferably take place in an expert clinic with an experienced multidisciplinary sarcoma team 7 . A study by Eastly et al. showed that almost half of the clinicians prefer AS an initial management strategy for primary DTF for which function- sparing surgery is possible. In case of recurrent DTF after a previous complete resection without adjuvant treatment, this rate dropped to 20% 40 . This is illustrated by the current study as the majority of included patients have primary tumours. The definition of AS varies widely between studies. Some studies also allowed the usage of non-narcotic analgesics, NSAIDs or hormonal treatment in the AS group 6, 8, 38 . Especially for NSAIDs, which are non-prescription drugs in many countries and mainly used for relieving pain symptoms, the usage of these drugs can be severely under-reported by patients, clinicians and researchers. Inclusion of these patients in studies evaluating the AS approach can distort the true outcomes because NSAIDs and hormonal treatment (e.g., tamoxifen) can be beneficial for DTF with a reported response rate of 85% 41 . The current study did not include the results of the phase 3 trial comparing sorafenib to placebo 42 . Whilst placebo treatment can be considered a form of AS, as patients do not receive an active form of treatment, we decided not to include this trial in the current study. This was because only patients with progressive, recurrent or primary disease which were deemed inoperable or required extensive surgical resection or were symptomatic were included in this clinical trial. In daily clinical practice, AS will not be offered as a front-line approach to these patients, and therefor3 this study was not included in the current review. 6