Jacky Luiten

General discussion and future perspectives | 131 9 technique consists of the implantation of a titanium seed containing slightly radioactive iodine (I ‐ 125). A logistic advantage of this technique is the possibility to place the seed days to weeks in advance of the operation, reducing scheduling conflicts and give the possibility to be used in the neoadjuvant setting. ROLL and I ‐ 125 GL have been compared to the gold standard WGL in several studies. The ROLL study group, which compared ROLL to WGL, concluded that ROLL leads to the excision of larger tissue volumes and therefore cannot replace WGL as standard of care. 38 A randomized controlled trial published in 2017 comparing WGL and I ‐ 125 GL showed similar positive margin rates and no differences in complication rates, but major logistic advantages in favor of I ‐ 125 GL. 39 Moreover, in a systematic review and meta ‐ analysis [ which includes chapter 6 of this thesis ] published in 2019, it was concluded that I ‐ 125 GL is superior over WGL to gain negative margins and the reduction of re ‐ excisions needed. 40 Even though the radiation exposure of I ‐ 125 is almost negligible, the radiation safety precautions required to set up and support this technique limits its implementation. 41 An upcoming alternative localization method is magnetic seed localization, consisting of a steel and iron oxide seed detectable using a probe. However further studies are needed to ensure that a magnetic seed is detectable at all depths, which is currently still a limitation of this technique especially for posterior lesions in very large breasts. 42 Moreover, like any clip, a magnetic seed will cause void artefacts in MRI, which limits the possibilities of imaging follow ‐ up in patients who receive neoadjuvant chemotherapy. In the last thirty ‐ years, pattern of care in treatment of DCIS shifted toward less extensive treatment, with an increased use of BCS and a decrease in the use of adjuvant radiotherapy in more recent years, as was illustrated by data of the Netherlands Cancer Registry [ this thesis, chapter 7 ]. Analyses of these same data showed that the risk of invasive local recurrence was strongly dependent on the use adjuvant radiotherapy, especially for the patients diagnosed in the period 1989 ‐ 2010. The absolute difference in the risk of local recurrence between patients with and without adjuvant radiotherapy however was much smaller for the patients treated in more recent years (2011 ‐ 2018). This drives the discussion about further limiting the indication for radiotherapy after BCS in the context of reducing overtreatment of DCIS. Four large randomized controlled trials on adjuvant radiotherapy in DCIS patients have been published. 43 ‐ 46 An overview of these trials showed that additional radiotherapy halves the risk of an ipsilateral breast event (invasive and non ‐ invasive cancer). However, it has not been shown to improve breast cancer overall survival. 47 Over the years, research has focused on the identification of subgroups