This thesis focused on risk factors and outcomes based on colorectal cancer auditing and aimed to provide new insights into outcome indicators, treatment modalities, and outcomes in high-risk... Show moreThis thesis focused on risk factors and outcomes based on colorectal cancer auditing and aimed to provide new insights into outcome indicators, treatment modalities, and outcomes in high-risk patients, and to monitor outcomes after implementation of minimally invasive surgery. Nationwide population-based studies with data of the Dutch ColoRectal Audit (DCRA) were used to provide information regarding colorectal cancer care on different levels (hospital, national, and international level) and in specific high-risk subpopulations. Show less
Although clinical aspects of melanoma have been extensively studied, the literature largely concerns relatively healthy 20-70 years old patients. Special populations, such as the elderly, children,... Show moreAlthough clinical aspects of melanoma have been extensively studied, the literature largely concerns relatively healthy 20-70 years old patients. Special populations, such as the elderly, children, patients with multiple primary melanoma and those with familial melanoma, are frequently excluded from clinical studies. The studies presented in this thesis were aimed to assess prognostic factors and management of patients with clinically localized melanoma, in particular among the aforementioned special populations. Show less
Survival of patients with colorectal cancer improved markedly over the past decades, as a result of advances in screening, staging procedures, treatment, and surveillance. However, still about 20%... Show moreSurvival of patients with colorectal cancer improved markedly over the past decades, as a result of advances in screening, staging procedures, treatment, and surveillance. However, still about 20% of patients with colorectal cancer develop metachronous metastases and 20% of all patients with colorectal cancer have metastatic disease at diagnosis. Several treatment modalities, such as total mesorectal excision (TME) and preoperative (chemo)radiotherapy for rectal cancer, as well as adjuvant chemotherapy for stage III colon cancer, have been studied extensively and showed to improve cancer-related outcomes. On the contrary, the effectiveness of other treatment modalities including adjuvant chemotherapy for rectal cancer and for stage II colon cancer, and surgery of the primary tumour in incurable metastatic colorectal cancer are still subject of debate. Moreover, there is considerable short-term and long-term morbidity after (chemo)radiotherapy or surgery which should be taken into account. Further defining optimal treatment strategies is therefore of great importance. This thesis focused on improving evidence for treatment modalities that are currently subject of debate for patients with colorectal cancer. This was done using data from randomised controlled trials as well as cancer registry data. Show less
The aim of this thesis was to answer currently unanswered questions regarding health-related quality of life (HRQoL) in glioma patients by undertaking powerful detailed secondary analyses of... Show moreThe aim of this thesis was to answer currently unanswered questions regarding health-related quality of life (HRQoL) in glioma patients by undertaking powerful detailed secondary analyses of existing pooled individual HRQoL patient data, which was previously collected in 15 RCTs in glioma patients.In total, data of 6048 glioma patients was included in the CODAGLIO database and 5 manuscripts were written that provide relevant information both for clinical practice as well as for clinical trials. Results of these studies entailed information on the added prognostic value of HRQoL at baseline in predicting survival. Furthermore, symptom clusters were identified and their association with functioning was investigated, and the impact of both (progression of) the disease and treatment on HRQoL deterioration was studied. Moreover, the ‘net clinical benefit’, weighing HRQoL and survival was calculated and different analytical methods to calculate change in HRQoL were compared.The CODAGLIO project, the largest individual patient data (IPD) project in neuro-oncology research so far, showed to represent an unique opportunity for secondary hypothesis testing, to answer clinically relevant questions with respect to HRQoL. Show less
The main objective of this thesis was to determine the value of dialysis and conservative care for older patients with advanced chronic kidney disease. To do so, we compared a combination of... Show moreThe main objective of this thesis was to determine the value of dialysis and conservative care for older patients with advanced chronic kidney disease. To do so, we compared a combination of patient-relevant outcomes and treatment costs in a cohort of older patients (≥70 years old) who chose either dialysis or conservative care after a shared decision-making process. Overall, we observed that older patients who chose dialysis lived longer compared with older patients who chose conservative care. There was, however, little or no significant survival advantage in patients aged ≥80 years old and patients aged ≥70 years old with severe comorbidity who chose dialysis over conservative care, while similar outcomes on quality of life and symptoms were observed between both patient groups, and lower treatment burden and treatment costs were observed in patients who chose conservative care. Therefore, we conclude that conservative care is a viable treatment alternative to dialysis in selected older patients. In clinical practice, conservative care needs to become available and openly discussed as one of the possible treatment pathways for advanced chronic kidney disease in older patients. Moreover, a shift towards a person-centered process of shared decision-making is needed that aims to focus on all that matters to the patient as person, in order to come to a treatment plan that fits best with the patient. Show less
In this thesis we showed the clinical impact of several methodological issues that should be taken into account when studying chronic kidney disease progression and in order to find an answer to... Show moreIn this thesis we showed the clinical impact of several methodological issues that should be taken into account when studying chronic kidney disease progression and in order to find an answer to the question when to start dialysis. From a methodological point of view, the observations from this thesis provide several recommendations for future research with regard to studying associations of risk factors with CKD progression: the use of an inception cohort of incident patients, and using linear mixed effects models for analyses. Ultimately, patients with kidney failure could be subjected to dialysis. The optimal timing for dialysis initiation is unclear. Ideally, a randomized trial with all possible starting moments would be performed. However, this seems to be unfeasible due to the high patient number needed in each treatment arm. We have to rely on observational data, where methodological issues such as lead-time and immortal time bias arise. In this thesis, we showed the clinical impact of lead-time bias and how both types of bias were avoided by emulating a randomized trial using observational data in a pilot study. The methodology and recommendations provided in the thesis will be highly useful to find a more definitive answer in future research. Show less
One of the main questions in Ewing sarcoma treatment is to identify low-risk patients that can be treated with less intensive treatment so that toxicity and the occurrence of long-term adverse... Show moreOne of the main questions in Ewing sarcoma treatment is to identify low-risk patients that can be treated with less intensive treatment so that toxicity and the occurrence of long-term adverse effects can be limited while still maintaining high cure rates or to identify those patients for whom treatment is expected to have limited benefit. Furthermore, to identify high-risk patients in which treatment needs to be intensified to improve outcome. Selection of risk groups and adjusted treatment allows for early decision making, will help to improve future outcomes and assists in clinical trial design. Additionally, treatment of Ewing sarcoma is multimodal and surgery, if feasible, is crucial for curative management. However, accurate detection and localization of tumor boundaries, especially in anatomical complex locations such as the pelvic is challenging. Inadequate surgical margins lead to a higher risk of local recurrence which has major impact on oncological outcome. Developments in intra-operative imaging, like CT-based navigation systems and near infrared (NIR)fluorescence guided surgery (FGS) make accurate defining and localization of surgical margins possible. They represent a whole new field of precision medicine and provide new treatment options for patients, thereby improving function outcome and healthcare quality. Show less
This thesis focus on the quality assurance in the surgical treatment of gastric cancer. This has been investigated using data of the CRITICS trial. In this randomized clinical patients underwent... Show moreThis thesis focus on the quality assurance in the surgical treatment of gastric cancer. This has been investigated using data of the CRITICS trial. In this randomized clinical patients underwent preoperative chemotherapy, followed by surgery, followed by adjuvant chemotherapy or chemoradiotherapy. Surgical quality in the CRITICS trial was investigated and was excellent (PART I). Furthermore, the influence of hospital volume on surgical quality and survival was analyzed using data of the CRITICS trial (PART II). Surgery performed in hospitals with high hospital volume was associated with better surgical quality and better survival. In part III of this thesis analyses were performed to analyze treatment strategy and survival in patients with resectable gastric cancer and in patients with metastatic gastric cancer. Show less
Bone metastases of the long bones can cause pain and pathologic fractures. Local treatment consists of radiotherapy or surgical stabilisation. The most appropriate treatment depends on many factors... Show moreBone metastases of the long bones can cause pain and pathologic fractures. Local treatment consists of radiotherapy or surgical stabilisation. The most appropriate treatment depends on many factors, including the symptoms, the location and extent of the lesion, the wishes and expectations of the patient, and the expected remaining survival. Survival estimation of patients with symptomatic long bone metastases is crucial to prevent over- and undertreatment. This thesis aimed to develop a prognostic model for estimating survival in patients with cancer and symptomatic metastases of the long bones, evaluate current (surgical) treatment modalities and trends, and provide rationale for future prospective randomized trials. As a result, the OPTIModel was developed: an easy-to-use prognostic model that categorises patients into four clinically relevant survival categories based on only three variables (tumour type, Karnofsky Performance Score, visceral/brain metastases). To enable easy use of the model, an app was created (OPTIModel). Futhermore, this thesis shows that almost all treatments of pathologic fractures are based on expert opinion and small, retrospective cohorts, as opposed to large, prospective (randomized) trials, which is interesting in an era of evidence based medicine. This confirms the need of a prospective, multicenter cohort, which was designed and implemented accordingly. Show less
As a result of our ageing population, breast cancer is becoming a disease of the elderly. Unfortunately, most studies investigating the efficacy of treatment do not include older patients and are... Show moreAs a result of our ageing population, breast cancer is becoming a disease of the elderly. Unfortunately, most studies investigating the efficacy of treatment do not include older patients and are not representative for the older population. In this thesis, we investigated whether there is variation in treatment and survival among older women with breast cancer in five European countries. Moreover, we study the long term efficacy of two types of adjuvant endocrine therapy in postmenopausal women. In addition, the effect of age and comorbidities on breast cancer death in the presence of competing mortality is studied. Finally, we investigate whether other endpoints in clinical studies might be more relevant for the older population and we introduce a new endpoint for clinical research in the older population with cancer. Show less
Uveal melanoma (UM) is an aggressive intraocular tumor with a high propensity to metastasize. Accurate prognostication is relevant for patient counselling, planning of follow-up and... Show moreUveal melanoma (UM) is an aggressive intraocular tumor with a high propensity to metastasize. Accurate prognostication is relevant for patient counselling, planning of follow-up and stratification of patients in clinical trials. Discoveries of prognostically relevant genetic markers in the last few decades have fuelled the advancement of prognostication in UM considerably. In this thesis, we explored ways of improving genetic prognostication in UM, evaluated the effect of irradiation on chromosome testing, and investigated the association of DNA repair genes and epigenetic regulators with prognosis. We reveal that chromosome markers of high malignancy such as monosomy 3 and chromosome 8q gain are less often observed in patients who die due to metastases at a late stage. We demonstrate that combining the AJCC staging and chromosome 3 and 8q status results in enhanced risk stratification. We provide evidence that supports the taking of biopsies before radiotherapy is applied since chromosome testing seems to fail more often in irradiated tumors. Furthermore, we show that evaluating the role of DNA repair and epigenetics in uveal melanoma can help in unraveling the biology of uveal melanoma and identifying new markers for prognostication. Show less
