Keywords: Pancreatic cancer, personalized medicine, body composition, cachexia, sarcopenia, tumor organoids

"Shifting Perspectives From Tumor To Patient: Combining patient and tumor phenotyping to predict response and personalize treatment in pancreatic cancer"

Pancreatic cancer is one of the deadliest types of cancer. The prognosis of this disease is dismal; after 5 years, only 9% of the patients are still alive. Treatment options for pancreatic cancer should be improved. One of the ways to improve treatment is by personalizing the treatment options (“personalized medicine”). This thesis describes factors that influence the effectiveness of treatment for pancreatic cancer and specifically focuses on patient characteristics rather than tumor characteristics. The first part of this thesis describes the impact of body composition on cancer survival. It is known that patients with cachexia, a syndrome of weight- and muscle loss, have a shorter survival. This thesis shows that patients with muscle loss also develop more chemotherapy toxicity. By adapting the dose of chemotherapy to muscle mass rather than weight, chemotherapy toxicity could be reduced. Furthermore, there are indications that chemotherapy treatment works less well in patients with cachexia. In order to investigate this, tumor cells from patients with pancreatic cancer were cultured as so-called “organoids”. The second part of this thesis describes how organoids can be used to investigate tumor characteristics, such as by analyzing them with mass spectrometry, by investigating how well immune cells can target and kill the tumor cells, or by testing how well chemotherapy works on the cells. Finally, all this is combined to investigate whether pancreatic cancer organoids from cachectic patients respond worse to chemotherapy. This thesis shows that patients with low-fat mass respond worse to chemotherapy. This lays the basis for personalized treatment options for pancreatic cancer that take into account both tumor and patient factors.

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