Novel perspectives in treatment and follow-up of sarcomas, with a focus on gastrointestinal stromal tumors

Sarcomas are rare and account for only 1% of all adult cancer types. There are more than 50 histologic subtypes of soft tissue sarcomas (STS), which are all subsumed in the World Health Organization (WHO) classification of Tumors of Soft Tissue and Bone. Within the STS group, both gastrointestinal stromal tumors (GIST) and undifferentiated pleomorphic soft tissue sarcomas (UPS) contribute to the most common subtypes of this rare cancer type. This thesis of Roos Bleckman aims to give an insight in new treatments and less invasive follow-up strategies in these common STS subtypes. The first part of this thesis focusses on different aspects of systemic and surgical treatment in patients with GIST, with an emphasis on identifying optimal follow-up strategies by highlighting the use of circulating tumor DNA (ctDNA) as promising follow-up tool. The second part of this thesis concentrates on treatment with radiotherapy in surgically treated older patients with UPS of the extremities.

Several conclusions can be drawn:

• Since higher imatinib concentrations measured in the blood of older patients with GIST were more frequently associated with side effects, leading to an initial treatment adjustment and subsequent dose reduction, a lower starting dose could be considered in this group.
• In patients with a localized gastrointestinal stromal tumor (GIST) of the stomach, minimally invasive (laparoscopic) surgery (MIS) can be safely performed. MIS is associated with fewer complications and a shorter hospital stay, without an increased risk of tumor rupture during surgery.
• Among patients with primary localized and surgically treated GIST, only fifteen percent developed a recurrence, with only a quarter of them experiencing a local recurrence. As a result, the follow-up interval for CT scans could be extended.
• For the implementation of ctDNA as an alternative follow-up tool in GIST, it is essential to detect ctDNA in baseline samples.
• The ctDNA concentration in plasma correlates with tumor stage and tumor volume.