Chapter 4 56 This thesis focuses on the evaluation of the optimal allocation and duration of adjuvant chemotherapy in stage II colon cancer. Using decision-analytic modelling, we evaluated the cost-effectiveness of different strategies to allocate adjuvant chemotherapy in stage II colon cancer patients. In addition, we evaluated the optimal treatment duration in these patients. This chapter briefly describes colon cancer epidemiology and the importance of optimizing treatment strategies in stage II colon cancer. Subsequently, it explains why adjuvant chemotherapy allocation is considered as a medical dilemma in stage II colon cancer by discussing treatment effectiveness, the selection of high-risk patients, the optimal treatment duration and the health risks of adjuvant chemotherapy. Furthermore, the advantages of decision-analytic modelling to address the challenge of adjuvant chemotherapy allocation and optimal treatment duration in stage II colon cancer are discussed. Finally, the aims and outline of this thesis are described. Colon cancer Colon cancer is the fourth most commonly diagnosed cancer worldwide, after lung-, breast- and prostate cancer, with around 1.1 million new cases and 0.6 million deaths in 2018.1 The incidence of colon cancer varies widely by world region and is highest in western countries, which is probably due to differences in lifestyle compared to non-Western countries.1 Worldwide, the incidence and mortality rates are higher in men compared to women. In the Netherlands, colon cancer is an important health problem as well. The incidence has more than doubled in the last thirty years; from 4,600 new cases in 1989 to 9,800 cases in 2018.2 The average age of a colon cancer patient is 69 years at the moment of diagnosis. In addition, more than 30% of all newly diagnosed patients are aged 75 or older.2 Thus, colon cancer mainly affects elderly patients. Given the aging population in the Netherlands in combination with an unfavourable change in lifestyle, such as a decrease in physical activity and an increase in alcohol consumption, the risk to develop colon cancer is increasing. On the other hand, the Dutch colorectal cancer screening program was introduced in 2014, which hopefully will ensure a decrease in colon cancer mortality in the long term. Shift in colon cancer stage distribution Using the tumor-node-metastasis (TNM) system, four disease stages are distinguished to classify the extensiveness of colon cancer.3 In this thesis, we focus on stage II colon cancer, which means that the tumor has grown through the colon wall, but has not spread to regional lymph nodes or distant organs. The proportion of stage II colon cancer patients was 26% in 2018 in the Netherlands. Due to the introduction of the Dutch national colorectal cancer screening program, the proportion of stage II colon cancer patients slightly decreased. To illustrate, in 2013 28% of the colon cancer patients were diagnosed with stage II disease.4 Medical dilemma’s in stage II colon cancer treatment The standard treatment of stage II colon cancer patients is surgical resection. The overall prognosis after surgical resection is relatively good. To illustrate, the QUASAR trial reported in 2007 5-year survival rates of 76% and 80% for disease-free survival (DFS) and overall survival (OS), respectively.5 However, the stage II colon cancer population is heterogeneous regarding the risk to develop a recurrence. Therefore, adjuvant chemotherapy is recommended in national and international guidelines to optimize survival probabilities for those patients with a high risk of recurrence.6-8 Notwithstanding these recommendations, there are still three important knowledge gaps. Firstly, 8 1 Chapter 1 149602 Jongeneel BNW.indd 8 04-06-2021 13:47 Left page (even page number) Book 17 x 24 cm (B5 - 17,6 x 25 cm) of adjuvant chemotherapy allocation and optimal treatment duration in stage II colon discussed. Finally, the aims and outline of this thesis are described. Colon cancer Colon cancer is the fourth most commonly diagnosed cancer worldwide, after lung-, b prostate cancer, with around 1.1 million new cases and 0.6 million deaths in 2018.1 The in colon cancer varies widely by world region and is highest in western countries, which is pr to differences in lifestyle compared to non-Western countries.1 Worldwide, the inci mortality rates are higher in men compared to women. In the Netherlands, colon cancer is an important health problem as well. The incidence has doubled in the last thirty years; from 4,600 new cases in 1989 to 9,800 cases in 2018.2 The a of a colon cancer patient is 69 years at the moment of diagnosis. In addition, more than newly diagnosed patients are aged 75 or older.2 Thus, colon cancer mainly affects elder Given the aging population in the Netherlands in combination with an unfavourable change such as a decrease in physical activity and an increase in alcohol consumption, the risk to de cancer is increasing. On the other hand, the Dutch colorectal cancer screening program was in 2014, which hopefully will ensure a decrease in colon cancer mortality in the long term. Shift in colon cancer stage distribution Using the tumor-node-metastasis (TNM) system, four disease stages are distinguished to extensiveness of colon cancer.3 In this thesis, we focus on stage II colon cancer, which mea tumor has grown through the colon wall, but has not spread to regional lymph nodes or dist The proportion of stage II colon cancer patients was 26% in 2018 in the Netherlands. introduction of the Dutch national colorectal cancer screening program, the proportion colon cancer patients slightly decreased. To illustrate, in 2013 28% of the colon cancer pa diagnosed with stage II disease.4 Medical dilemma’s in stage II colon cancer treatment The standard treatment of stage II colon cancer patients is surgical resection. The overa after surgical resection is relatively good. To illustrate, the QUASAR trial reported in 2 survival rates of 76% and 80% for disease-free survival (DFS) and overall survival (OS), re However, the stage II colon cancer population is heterogeneous regarding the risk to recurrence. Therefore, adjuvant chemotherapy is recommended in national and in guidelines to optimize survival probabilities for those patients with a high risk of re Notwithstanding these recommendations, there are still three important knowledge ga 8 149602 Jongeneel BNW.indd 8
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