Milea Timbergen

328 The Usefulness of RECIST in DTF Tumour size in DTF remains an ambiguous variable since DTF can display variable shapes with irregular margins and infiltrative growth 12, 13 . Currently, Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) 14, 15 is used for determining treatment success using the categories; complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) 15 . However, these criteria assumes spherical-shaped tumours and a uniform decrease in size 16 . To obtain a “partial response” status, a 30% tumour size reduction has to be achieved. This may not always be feasible in DTF; hence, the relatively high number of reported SD in retrospective trials evaluating systemic treatments and active surveillance. Furthermore, distinction of natural DTF tumour behaviour and the true efficacy of treatment can be challenging 17, 18 . This is illustrated in the phase 3 sorafenib versus placebo trial, in which 20% of patients on placebo display a partial response 19 . Therefore, we encourage to use a volumetric parameter, alongside RECIST, to evaluate treatment response and/or to observe the natural growth of DTF 16 . Our radiomics model might provide a platform to obtain such volume measurements as it uses semi- automatic segmentation of the entire tumour in multiple dimensions. Moreover, it can be used in various imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging (MRI). It can also provide insights into changes in histological activity, reflected by hyperintense signals on T2 weighted MRI, which can be diminished without changes in tumour size 20 . We encourage efforts to improve the radiomics platform, exploring automatic segmentation options to make the process less time consuming, and to include volumetric parameters when evaluating treatment response or natural growth of DTF. This radiomics platform could also be used in a longitudinal manner to map tumour growth, and to predict tumour behaviour. Health-Related Quality Of Life HRQoL is increasingly used as an endpoint in clinical trials for DTF (e.g., NCT04195399 21 , NCT01876082 22 , and NCT03966742 23 ). Measuring HRQoL in DTF is relevant as the mortality rate is low and traditional oncologic endpoints are less relevant. However, there are some factors to consider. First, appropriate time points for assessing HRQoL have to be identified so that treatment arms are evaluated in a fair and similar manner. The accurate choosing of time points to assess HRQoL can be challenging by the unpredictable response of DTF to certain treatments, for example delayed response or late recurrences 24-26 . Additionally, measurable response does not necessarily mean a decrease in symptoms 26-28 . Choosing accurate time points depends on the treatment type, the type and timing of 12