Background: The Heng et al JCO 2009 prognostic model was developed in the age of VEGF-targeted therapy and this study serves as an external validation while comparing its performance to other models. Methods: 1,028 previously unanalyzed patients were used to externally validate the prognostic criteria for overall survival (OS). The model’s discriminatory value was compared to four other prognostic models using C-indices and Net Reclassification Improvement (NRI) (Pencina et al 2008). NRI indicates how the Heng et al model improves upon other models by reclassifying a percentage of patients (pts) into the more correct risk group based on the observed OS at 2 years. Results: The median OS of all pts was 18.8 mons. On multivariable analysis, the pre-identified Heng’s risk factors (anemia, thrombocytosis, neutrophilia, hypercalcemia, Karnofsky performance status <80% and time from diagnosis to treatment < 1 year) continue to be independent predictors of poor OS (p<0.05). When pts were segregated into 3 risk categories, the median OS was 44, 21 and 8 mons in the favorable (17% of pts), intermediate (52%) and poor (31%) risk groups, respectively (p<0.0001, C-index=0.664). The NRI demonstrated that the Heng model was able to more accurately reclassify pts by a net of 23% and 9.7% of pts compared to the French and MSKCC models and was less accurate in reclassifying 13% of pts when compared to the CCF model (but lower c-index) based on observed 2-year OS (see table). Sensitivity analyses with 5 imputation datasets for missing data produced similar results. Conclusions: The Heng et al model was derived in the targeted therapy era and is now externally validated. The c-index is similar to other models primarily derived in the era of immunotherapy or early VEGF-targeted therapy.
Median OS in mons (% of pts) |
|||||
---|---|---|---|---|---|
Favorable | Intermediate | Poor | C-index | NRI* | |
Heng et al JCO 2009 | 44 (17%) | 21 (52%) | 8 (31%) | 0.664 | |
CCF (Choueiri Cancer 2007) | 33 (34%) | 18 (37%) | 9 (29%) | 0.662 | -13% |
French (Escudier ASCO 2008) | 49 (5%) | 21 (67%) | 7 (28%) | 0.638 | 23% |
IKCWG (Royston ASCO 2007) | 35 (14%) | 24 (50%) | 8 (36%) | 0.668 | 3.2% |
Motzer JCO 2002 | 44 (19%) | 18 (59%) | 7 (22%) | 0.657 | 9.7% |
*Comparing the Heng model with others.
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