Digital Public Defence: Toto Hølmebakk
Cand.med. Toto Hølmebakk at Institute of Clinical Medicine will be defending the thesis "Re-appraisal of prognostic factors in primary gastrointestinal stromal tumour. Refining definitions" for the degree of dr.philos. (Doctor Philosophiae).
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture over a chosen topic
Digital Trial Lecture over a given topic
- First opponent: Professor Carol Swallow, University of Toronto, Canada
- Second opponent: Professor Robin L. Jones, The Institute of Cancer Research, London, United Kingdom
- Third member and chair of the evaluation committee: Professor II Tom Mala, Institute of Clinical Medicine, University of Oslo
Chair of defence
Professor Emeritus Arild Nesbakken, Institute of Clinical Medicine, University of Oslo
Gastrointestinal stromal tumour (GIST) is the most common type of sarcoma and occurs exclusively in the alimentary tract. For patients at presumed high risk of recurrence after surgical resection 3 years of adjuvant treatment is recommended. However, the specificity of risk criteria is low. With the aim of improving prognostication we investigated established and potential risk factors in a population-based cohort, and additional molecular analyses were performed.
Tumour rupture is considered a negative prognostic factor but its definition has been at the discretion of the surgeon and its significance varies across studies. We proposed an exact definition, making a distinction between major and minor defects of tumour integrity. Major defects were strongly and independently associated with recurrence whereas minor defects were not.
Positive resection margins and peritoneal tumour penetration are both associated with recurrence in gastrointestinal carcinomas, and their negative significance in these tumours has been transferred to the assessment of GIST. In our studies, excluding patients with tumour rupture, these variables were without prognostic importance.
Most GISTs are situated in the stomach, and here, they exhibit specific growth patterns: luminal, exophytic or transmural. We demonstrated that these patterns were related to clinical and molecular risk factors as well as prognosis. Furthermore, mutations (tumour genotype) had a characteristic anatomical distribution in the stomach, adding evidence for a link between molecular and anatomical features and clinical course.
Our studies have identified patients at particularly high risk of recurrence of GIST; likewise, they singled out patients at low risk despite their having high-risk features according to established criteria. Adjuvant therapy, follow-up and counselling could thereby be made more specific.
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