Algemeen 15 1 e the large number of RCTs that have evaluated adjuvant treatment effectiveness in colon cancer ts, the effectiveness in the stage II population remains unclear, mainly due to insufficient power studies for the stage II population. Furthermore, over the years the number of examined regional nodes per patients increased as this provides important information about the patients’ osis, which resulted in a migration of disease stage.9 That is, a patient that was classified as stage ore the increasing number of evaluated lymphnodes, could possibly be classified as stage III in a recently conducted study. Secondly, there is no consensus on which high-risk features should be into account to select stage II colon cancer patients for adjuvant chemotherapy. Thirdly, there is onvincing data for the optimal duration of adjuvant treatment in stage II colon cancer patients ared to stage III colon cancer. Moreover, when deliberating on the optimal treatment choice in II colon cancer, it is important to explicitly take into account the fact that there are also health associated with adjuvant chemotherapy. To guide the clinical decision making process, the tial health gain of adjuvant treatment should be carefully balanced against the potential harms. arizing, the identification of patients that require adjuvant chemotherapy as well as the optimal ment duration remains challenging. Below the three knowledge gaps are discussed in more detail. fect of adjuvant chemotherapy in stage II colon cancer eatment effect of adjuvant chemotherapy in stage II colon cancer has been evaluated in several mized clinical trials (RCTs) during the last decades. IMPACT was the first collaboration that cted a pooled analysis of 1,016 patients with stage II colon cancer from 5 RCTs, which compared rouracil-leucovorin (FU-LV) treated group to a control group. The group that was treated with demonstrated a small, statistically non-significant improvement in 5-year DFS and OS. The DFS were 76% versus 73% and the OS rates were 82% versus 80% for the FU-LV group compared to ntrol group, respectively.10 Subsequently, in 2004 another meta-analysis was conducted in which patients were included with stage II or III colon cancer from 7 RCTs (the 5 RCTs included in CT and two additional RCTs), which compared FU-LV to a control group. In a stage II colon cancer oup analysis (n=1,440), a small but significant difference of 4% (76% versus 72%, p=0.049) was for DFS and a small non-significant difference of 1% in OS (81% versus 80%, p=0.113).11 7, results of the QUASAR trial became available. In the QUASAR trial, 3,239 resected stage I (1%), %) and III (8%) patients were included of which 71% was diagnosed with colon cancer and 29% ectal cancer. Patients were randomized to a FU-LV arm (with or without levamisole) or a control The QUASAR trial demonstrated a relative risk of recurrence of 0.78 (95% CI, 0.67-0.91) and a e risk of OS of 0.82 (95% CI, 0.70-0.95) for FU-LV treated patients compared to observation. The rs reported an improvement in OS of 3.6% for FU-LV compared to observation within 5-year -up, which was assessed as having limited clinical impact.5 After the QUASAR trial, the MOSAIC SABP-07 trials were conducted to evaluate the benefit of the addition of oxaliplatin to FU-LV OX) in stage II and III colon cancer. In the secondary analysis of stage II colon cancer patients only 9), the MOSAIC trial reported a statistically non-significant improvement in DFS with a hazard HR) of 0.84 (95%CI: 0.62-1.14) for FOLFOX compared to FU-LV. However, the HR for OS was 1 CI: 0.70-1.41), indicating equal survival probabilities in both groups.12 In the NSABP C-07 trial, 1 General introduction 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 Pagina met aflopende navigatie tabjes. Het cijfer staat op 5 mm van het eindformaat Aflopend beeldelement
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