RESUMO
BACKGROUND: Predicting prognosis in refractory metastatic colorectal cancer (mCRC) patients is needed to guide decision making. The Colon Life nomogram was developed to predict 12-week mortality in refractory mCRC patients. The aim of this study is to validate the Colon Life nomogram in last line/refractory patients receiving trifluridine/tipiracil (FTD/TPI) in daily practice. METHODS: The validation cohort consists of 150 QUALITAS study patients, an observational substudy of the Prospective Dutch CRC cohort, who were treated with FTD/TPI between 2016 and 2019. Model performance was assessed on discrimination, calibration, and clinical usefulness. The additional prognostic value of baseline quality of life (QoL) and thymidine kinase (TK1) expression in tissue was explored. RESULTS: Of the 150 patients, 25 (16.7%) died within 12 weeks of starting FTD/TPI treatment. The C-statistic was 0.63 (95% C.I. 0.56-0.70). The observed/expected ratio was 0.52 (0.37-0.73). The calibration intercept and slope were -1.06 (-1.53 to -0.58) and 0.41 (0.01-0.81), respectively, which indicated overestimation of 12-week mortality by the nomogram. Decision curve analysis showed the nomogram did not yield a positive net benefit at clinically meaningful thresholds for predicted 12-week mortality. Addition of QoL to the nomogram improved the C-statistic to 0.85 (0.81-0.89). TK1 expression was associated with progression-free survival but not with overall survival. CONCLUSION: We demonstrated evident miscalibration of the Colon Life nomogram upon external validation, which hampers its use in clinical practice. We recommend conducting a study with a sufficiently large sample size to update the Colon Life nomogram or to develop a new model including QoL.
RESUMO
BACKGROUND: The RECOURSE trial (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) demonstrated an overall survival (OS) benefit of trifluridine/tipiracil (FTD/TPI) vs placebo in refractory metastatic colorectal cancer (mCRC). Given the limited benefit of later line treatments, we developed the Colon Life nomogram to assess the 12-week death probability in the refractory setting. METHODS: This post hoc analysis of RECOURSE included patients with available data to calculate the nomogram score: Eastern Cooperative Oncology Group Performance Status, primary tumor resection, lactate dehydrogenase, and peritoneal metastases. The nomogram calibration was assessed by calibration plots and C-index. The nomogram prognostic and predictive ability was assessed by Cox model analyses and the nomogram score predictive value was explored according to the cutoff identified at maximum value of the Youden index in time-dependent receiver operating characteristic curve analysis. RESULTS: Overall, 251 trial patients were evaluable: 90 in the placebo arm and 161 in the FTD/TPI arm. The calibration was optimal in the placebo arm (C-index 0.807) and suboptimal in the FTD/TPI arm (0.657). The cutoff of the nomogram score of 23 showed the best discriminative ability for 12-week OS (hazard ratio 3.46, 95% confidence interval 2.17-5.51 for scores 40 vs 15) and had maximum value of the Youden index (0.381). Median OS and 3-month PFS were 9.0 vs 7.5 months and 39.3% vs 5.2%, respectively, for FTD/TPI vs placebo in the low-risk group (score <23) and 4.8 vs 3.4 months and 22.3% vs 9.8% in the high-risk group (score ⩾23) (interaction NS). CONCLUSION: The Colon Life nomogram is an accurate tool for estimating life expectancy in refractory mCRC. The benefit of FTD/TPI was independent of the predicted risk of early death.