Background Molecular analysis of KIT and PDGFRA is critical for tyrosine kinase inhibitor treatment selection of gastrointestinal stromal tumors (GISTs) and hence recommended by international... Show moreBackground Molecular analysis of KIT and PDGFRA is critical for tyrosine kinase inhibitor treatment selection of gastrointestinal stromal tumors (GISTs) and hence recommended by international guidelines. We performed a nationwide study into the application of predictive mutation testing in GIST patients and its impact on targeted treatment decisions in clinical practice. Methods Real-world clinical and pathology information was obtained from GIST patients with initial diagnosis in 2017-2018 through database linkage between the Netherlands Cancer Registry and the nationwide Dutch Pathology Registry. Results Predictive mutation analysis was performed in 89% of the patients with high risk or metastatic disease. Molecular testing rates were higher for patients treated in expertise centers (96%) compared to non-expertise centers (75%, P < 0.01). Imatinib therapy was applied in 81% of the patients with high risk or metastatic disease without patient's refusal or adverse characteristics, e.g., comorbidities or resistance mutations. Mutation analysis that was performed in 97% of these imatinib-treated cases, did not guarantee mutation-tailored treatment: 2% of these patients had the PDGFRA p.D842V resistance mutation and 7% initiated imatinib therapy at the normal instead of high dose despite of having a KIT exon 9 mutation. Conclusion In conclusion, nationwide real-world data show that over 81% of the eligible high risk or metastatic disease patients receive targeted therapy, which was tailored to the mutation status as recommended in guidelines in 88% of cases. Therefore, still 27% of these GIST patients misses out on mutation-tailored treatment. The reasons for suboptimal uptake of testing and treatment require further study. Show less
In this thesis, a perspective of attachment theory is used to investigate relationships between adverse childhood experiences, adult attachment style, emotion regulation strategies, and distress... Show moreIn this thesis, a perspective of attachment theory is used to investigate relationships between adverse childhood experiences, adult attachment style, emotion regulation strategies, and distress before and after predictive testing, in persons from families with a late onset hereditary disorder. The hereditary disorders at issue are Huntington__s disease (HD), Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), Hereditary Cerebral Hemorrhage With Amyloidosis __ Dutch type (HCHWA-D), or BRCA1 or BRCA2 Hereditary Breast and Ovarian Cancer (HBOC).The aim of the studies described in this thesis was to find out whether growing up with a parent who has one of these hereditary diseases is associated with adverse childhood experiences in offspring, whether there is a relationship between these experiences and adult psychological characteristics, especially attachment style and style of emotion regulation, and whether these characteristics are associated with the level of distress during and after predictive genetic testing. Show less
