Algemeen 37 despite the large number of RCTs that have evaluated adjuvant treatment effectiveness in colon cancer patients, the effectiveness in the stage II population remains unclear, mainly due to insufficient power in the studies for the stage II population. Furthermore, over the years the number of examined regional lymphnodes per patients increased as this provides important information about the patients’ prognosis, which resulted in a migration of disease stage.9 That is, a patient that was classified as stage II before the increasing number of evaluated lymphnodes, could possibly be classified as stage III in a more recently conducted study. Secondly, there is no consensus on which high-risk features should be taken into account to select stage II colon cancer patients for adjuvant chemotherapy. Thirdly, there is less convincing data for the optimal duration of adjuvant treatment in stage II colon cancer patients compared to stage III colon cancer. Moreover, when deliberating on the optimal treatment choice in stage II colon cancer, it is important to explicitly take into account the fact that there are also health risks associated with adjuvant chemotherapy. To guide the clinical decision making process, the potential health gain of adjuvant treatment should be carefully balanced against the potential harms. Summarizing, the identification of patients that require adjuvant chemotherapy as well as the optimal treatment duration remains challenging. Below the three knowledge gaps are discussed in more detail. The effect of adjuvant chemotherapy in stage II colon cancer The treatment effect of adjuvant chemotherapy in stage II colon cancer has been evaluated in several randomized clinical trials (RCTs) during the last decades. IMPACT was the first collaboration that conducted a pooled analysis of 1,016 patients with stage II colon cancer from 5 RCTs, which compared a fluorouracil-leucovorin (FU-LV) treated group to a control group. The group that was treated with FU-LV demonstrated a small, statistically non-significant improvement in 5-year DFS and OS. The DFS rates were 76% versus 73% and the OS rates were 82% versus 80% for the FU-LV group compared to the control group, respectively.10 Subsequently, in 2004 another meta-analysis was conducted in which 3,302 patients were included with stage II or III colon cancer from 7 RCTs (the 5 RCTs included in IMPACT and two additional RCTs), which compared FU-LV to a control group. In a stage II colon cancer subgroup analysis (n=1,440), a small but significant difference of 4% (76% versus 72%, p=0.049) was found for DFS and a small non-significant difference of 1% in OS (81% versus 80%, p=0.113).11 In 2007, results of the QUASAR trial became available. In the QUASAR trial, 3,239 resected stage I (1%), II (91%) and III (8%) patients were included of which 71% was diagnosed with colon cancer and 29% 1 General introduction Pagina met aflopende navigatie tabjes. Het cijfer staat op 5 mm van het eindformaat CHAPTER 2 Estimating adjuvant treatment effects in stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data Gabriëlle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, Marjolein J.E. Greuter and Veerle M.H. Coupé International Journal of Cancer. 2020 Jun 1;146(11):2968-2978 Estimating adjuvant treatment effects in stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data Gabrielle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, Marjolein J.E. Greuter and Veerle M.H. Coupé International Journal of Cancer. 2020 Jun 1;146(11):2968-2978 CHAPTER 2 149602 Jongeneel BNW.indd 19 04-06-2021 13:47 Door een afbeelding 3 mm verder door te laten lopen dan het eindformaat zal er bij beweging in het productieproces meer beeld in het afloopgebied ter compensatie zijn en is er geen kans op een witte lijn. Let op: deze extra ruimte rondom wordt later afgesneden. Zorg ervoor dat tekst of andere belangrijke beeldelementen niet te dicht bij deze ‘afsnijrand’ (eindformaat) staan en hou 5 mm afstand. Dus, heeft jouw document kleurvlakken, foto’s of andere beeldelementen die door moeten lopen tot de rand van de pagina (zie de hoofdstukpagina’s en ‘tabjes’ van deze handleiding), dan moet er in het document ‘afloop’ gecreëerd worden. Hoe je deze afloop instelt voor jouw document lees je vanaf pagina 50. Zie ook onderstaande voorbeelden ter illustratie. Aflopend beeldelement CHAPTER 2 Estimating adjuvant treatment effects in stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data Gabriëlle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, Marjolein J.E. Greuter and Veerle M.H. Coupé International Journal of Cancer. 2020 Jun 1;146(11):2968-2978 Gabrielle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, 04-06-2021 13:47
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