1. Results Abstract Analysis of Prognostic Web-based Models for Stage II and III Colon Cancer: A Population-based Validation of Numeracy and Adjuvant! Online S Gill, C Loprinzi, H Kennecke, A Grothey, G Nelson, R Woods, C Speers, S Alberts, A Bardia and D Sargent Analysis of Prognostic Web-based Models for Stage II and III Colon Cancer: A Population-based Validation of Numeracy and Adjuvant! Online S Gill, C Loprinzi, H Kennecke, A Grothey, G Nelson, R Woods, C Speers, S Alberts, A Bardia and D Sargent BC Cancer Agency, Vancouver, Canada and Mayo Clinic, Rochester, MN Background: To aid in decisions regarding adjuvant therapy (AT) for resected high-risk colon cancer (CC), two prognostic (prog) models are in common use: the Mayo Clinic NUM calculator developed from a pooled data analysis of 7 randomized 5FU-based AT trials, and ADJ! developed using SEER data. This study examines the accuracy of NUM and ADJ! utilizing an independent population-based dataset of patients (pts) referred to the BC Cancer Agency (BCCA). Methods: Demographic, disease and treatment data for pts with stage II/III CC referred to the BCCA from 1995-1996 + 1999-2002 were collected. Observed (obs) 5-year relapse free survival (RFS) and overall survival (OS) were compared to predicted estimates (pred) using NUM and ADJ! both overall and for all prog subgroups as defined by T stage, N stage, tumor grade and age with >= 10 pts. Data are presented in a descriptive manner and using confidence intervals. Results: Median follow-up was 5.6 yrs for 2033 pts - 53% male, median age 68y, 40% N0, 45% treated with Surgery alone. The mean percentages of 5 year pred outcomes for each of the two models and the actual Kaplan Meier mean survivals are presented in the table. The percentage correct predictions of 5 y status is also presented, with correctness deemed accurate if the pt was alive and predicted to be alive >=50% as determined by each model or dead while the respective tool predicted <50% possibility of being alive. For surgery alone treated patients, ADJ!pred were more often closer to what was observed, as compared to NUM pred, in the prog subgroups (for RFS 56%, OS88%). For surgery + 5-FU, within these subgroups, NUMpred were more often closer to what was observed, as compared to ADJ!pred, for RFS (62%) and for OS (55%) Conclusions: In this independent population-based validation, NUM and ADJ! have acceptable and similar reliability with modest over-estimations of 5y RFS and OS. Both models thus appear to be useful adjuvant decision aids. Predicting the absolute benefit of AT for an individual patient can be complex depending upon baseline prognosis, efficacy of treatment, competing risks and patient preferences To individualize decisions regarding AT, prognostic decision models have been developed for colon cancer. Two web-based calculators are currently available: Numeracy – www.mayoclinic.com/calcs (Gill JCO 2004) Model developed using pooled data set of 7 randomized trials Adjuvant! On-line – www.adjuvantonline.com Model developed using population-SEER data to calculate baseline prognosis for patients treated with surgery alone The validity of the assumptions inherent in these prognostic tools has not been previously validated. Table 1: Demographics of BCCA cohort Methods Table 2: Observed and Predicted Outcomes with % correct predictions Figure: 5% Prediction Interval Plot: 5 year OS for Surgery + 5FU Background Patients with resected stage II and III CC referred to the BCCA between 1995-1996 and 1999-2003 were identified from the BC Colorectal Cancer Outcomes Unit (CRCOU) Information abstracted from the CRCOU database included demographics, disease status, treatment and outcome information (as measured from diagnosis date to observed first relapse and, date and cause of death if applicable) Predicted RFS and OS estimates were derived for each included patient using Numeracy and Adjuvant! (using a default comorbidity assumption of ‘Minor Problems’) Observed 5 yr RFS and OS were compared to predicted estimates from Numeracy and Adjuvant! for all relevant subgroups defined by T stage, N stage, grade and age with >= 10pts Data are presented in a descriptive manner % correct predictions of 5y status for each model are presented Correctness deemed accurate if pt alive and predicted to be alive by >=50% or dead with a predicted <50% possibility of being alive Surgery Alone N=924 Surgery + 5FU, N=1109 Total N=2033 Median Age73y65y68y Male Gender51%55%53% T1/2 stage2.5%8.9%6% T383%73%78% T414%18%16% N0 stage67%17%40% N125%60%44% N28%20%15% High Grade15%16% Median follow-up 5.6 years All pts treated with AT received 5FU/LV Adjuvant/Numeracy Predicted CRCOU Observed MetricMean % of 5 year outcomes% correct predictions NUMADJ!Observed (95% CI) NUMADJ! Surgery alone Overall, N=924 OS67.1%64.3%61.4% (58.2-64.9) 66.1%68.8% RFS60.7%60.1%57.5% (54.2-61.0) 65.1%66.3% N0 (stage II), N=621 OS76.4%74.0%72.4% (68.7-76.3) 68.5%69.4% RFS70.4%70.5%67.7% (63.8-71.7) 63.1%65.0% Surgery + 5FU Overall, N=1109 OS66.5%66.4%63.6% (60.7-66.7) 64.4%63.0% RFS60.7%63.3%57.3% (54.3-60.4) 58.2%58.7% N0 (stage II), N=193 OS78.6%80.1%71.5% (64.9-78.8) 66.2% RFS72.1%76.9%66.1% (59.4-73.6) 59.0%59.7% Conclusions 5yr RFS5yr OS NumeracyAdjuvant!NumeracyAdjuvant! Surg Alone44%56%12%88% Surg + 5FU62%38%55%45% Table 3: Percent Closer rate of Observed to Predicted Across Prognostic Subgroups Cell level analysis (>10pts) by age, T, N, grade In this independent population-based validation, Numeracy and Adjuvant! demonstrate acceptable and similar reliability with modest over-estimations of 5 yr RFS and OS These findings are based on a 5-FU treated population, and not FOLFOX. Both models are useful adjuvant decision-aids