Pancreatic surgery today involves a wide variety of surgical and non-surgical medical disciplines. Several aspects to improve the multidisciplinary management of patients undergoing pancreatic... Show morePancreatic surgery today involves a wide variety of surgical and non-surgical medical disciplines. Several aspects to improve the multidisciplinary management of patients undergoing pancreatic surgery were identified, implemented and used to design future studies. More than 15 medical disciplines were involved during the studies involved in this thesis. Highly needed further improvement of outcome of pancreatic patients can be made by multidisciplinary collaborations on a hospital, regional, national and international level. Show less
For part I population-based data from the national cancer registries of Belgium, the Netherlands, Norway, and Sweden was used. In all countries, the use of chemotherapy increased with stage and... Show moreFor part I population-based data from the national cancer registries of Belgium, the Netherlands, Norway, and Sweden was used. In all countries, the use of chemotherapy increased with stage and decreased with age. Also, 30-day and one-year excess mortality decreased over the years for colon and rectal cancer. After surviving the first postoperative year, the survival of surgically treated older patients aligned with their younger counterparts, except for patients with stage III disease. Part II describes the results of the analyses of the RAPIDO trial. DRTF decreased from 30% in the standard-care group to 24% in the experimental group at 3 years after randomisation, mainly due to a decrease in DM, which is probably due to better compliance preoperatively and perhaps due the earlier treatment of micrometastases in the treatment process. Although patients with DM in the experimental group had worse survival compared to patients in the standard-care group, the cumulative probability of overall survival remained comparable for both treatment groups. If the patients with a complete response can be identified during reassessment after neoadjuvant therapy, surgery may be omitted, a W&W after a cCR with an appropriate follow-up has no additional oncological risk in young patients compared to older patients (part III). This opens the door for potential organ preservation. Show less
Gemcitabine was examined as switch maintenance therapy after standard first line chemotherapy in the NVALT19 trial, which provided the first conformation of gemcitabine activity in malignant... Show moreGemcitabine was examined as switch maintenance therapy after standard first line chemotherapy in the NVALT19 trial, which provided the first conformation of gemcitabine activity in malignant mesothelioma (MM). We describe additional analyses to confirm the prognostic value of CYFRA 21-1 and examine the prognostic value of CYFRA 21-1 in MM patients treated with gemcitabine. We also searched how gemcitabine could improve antitumor immune responses by positively modulating the immune system.In this thesis we describe a cohort of 107 malignant mesothelioma patients treated with nivolumab in the Netherlands. The real- world data of single agent PD-1 blocking were disappointing compared to previous reported single arm phase II trials. To examine clinical and peripheral blood biomarkers univariable and multivariable analyses were performed.As malignant peritoneal mesothelioma is even rarer then pleural mesothelioma, we hypothesized that centralization of care for peritoneal mesothelioma could benefit patients as they would likely receive treatment more often.Prognosis has a significant influence on the treatment preferences of patients, but prognosis of individual MM patients is variable and is hard to predict. We presented the MESOPRO score for patient with MM which are about the start with any systemic treatment. Show less
This thesis describes the effects of shortterm fasting on chemotherapy outcome in patients with breast cancer and the IGF-1 and insulin pathway as a target for cancer therapy and as a biomarker for... Show moreThis thesis describes the effects of shortterm fasting on chemotherapy outcome in patients with breast cancer and the IGF-1 and insulin pathway as a target for cancer therapy and as a biomarker for chemotherapy outcome.Preclinical research is evaluated, which shows that short-term fasting during chemotherapy is effective. The effects of short-term fasting in humans is not evident yet. Although the first small clinical studies of short-term fasting as adjunct to chemotherapy are promising in terms of decreased toxicity and enhanced efficacy, the exact mechanism and effects are not established yet. More studies and a longer follow-up are needed to prove this.Insulin-like growth factor 1 (IGF-1) and insulin are members of the IGF-1 pathway, which is involved in cell growth and proliferation. The effects of the IGF-1 pathway on chemotherapy outcome and the pathway itself as target for cancer therapy are described. The disappointing results of clinical studies of IGF-1R inhibitors may be caused by the complexity of the IGF-1R pathway. Lowering both insulin and IGF-1, perhaps with a short-term fasting intervention, serves as a possible target in cancer therapy. Show less
In this thesis, the effects of a new form of immunotherapy was investigated and studied how it can be used against different types of cancers. The investigated immunotherapy is based on injecting... Show moreIn this thesis, the effects of a new form of immunotherapy was investigated and studied how it can be used against different types of cancers. The investigated immunotherapy is based on injecting nanoparticles loaded with various immunologically active molecules (immunomodulatory nanoparticles) that can modulate the immune system to attack cancer cells more efficiently. The effectiveness of this immunomodulatory nanoparticles have been studied on different mouse cancer models and investigated as a single treatment or in combination with other known therapies, such as chemotherapy, therapeutic cancer vaccination, or photodynamic therapy. Show less
Door de toepassing van hoofdhuidkoeling kan haaruitval worden verminderd of voorkomen. Hoofdhuidkoeling heeft, afhankelijk van de soort chemotherapie, bij ongeveer 50% van de patiënten een positief... Show moreDoor de toepassing van hoofdhuidkoeling kan haaruitval worden verminderd of voorkomen. Hoofdhuidkoeling heeft, afhankelijk van de soort chemotherapie, bij ongeveer 50% van de patiënten een positief effect. Farmacologische interventies om haaruitval te voorkomen zijn niet toereikend. De incidentie van haaruitval kan verminderd worden door de methode van hoofdhuidkoeling te optimaliseren.De afgelopen jaren is door het Leids Universitair Medisch Centrum, Noordwest Ziekenhuisgoep en Integraal Kankercentrum Nederland in samenwerking met verschillende ziekenhuizen in Nederland onderzoek verricht naar factoren die van invloed kunnen zijn op het effect van hoofdhuidkoeling. Show less
My PhD studies focused on understanding the role of macrophages, a type of immune cells which are abundantly present in several tumor types, in breast cancer progression and therapy response.In the... Show moreMy PhD studies focused on understanding the role of macrophages, a type of immune cells which are abundantly present in several tumor types, in breast cancer progression and therapy response.In the first part of my thesis, I describe how macrophages can acquire different functional characteristics in different types of breast cancer. Next, I focused on understanding the interplay between macrophages and cancer therapies. In particular, I revealed that macrophages counteract the efficacy of conventional chemotherapy drugs. I showed that eliminating macrophages with an antibody that targets CSF-1 receptor (CSF-1R) enhances the anti-cancer efficacy of platinum-based chemotherapeutic agents in breast cancer. I mechanistically discovered that CSF-1R inhibition stimulates intratumoral type I interferon signaling which is essential for the therapeutic synergy between cisplatin and CSF-1R blockade. I also uncovered that further elimination of immunosuppressive neutrophils, another type of immune cells, was required to engage an efficacious anti-tumor immunity. Show less
