Exploratory analysis of a prognosis predictive formula for metastatic colorectal cancer treated with chemotherapy.

Abstract

757 Background: Progression free survival (PFS) has been recognized as a surrogate outcome in the therapy for metastatic or recurrent colorectal cancer (mCRC). As molecular targeted therapies have become to be widely used, new surrogate outcome such as early tumor shrinkage (ETS; the relative change in the sum of longest diameters of target lesions at week 8 compared to baseline) and deepness of response (DpR; the relative change in the sum of longest diameters of target lesions at the nadir compared to baseline) are proposed. However, their validity has not been fully proven. We conducted to develop a new prognosis predictive formula consisting of the three factors, DpR, ETS and PFS, in the first-line chemotherapy of mCRC. Methods: We retrospectively evaluated mCRC patients who started any chemotherapy from 2005 to 2010. Estimated ETS (eETS), instead of ETS, was defined as the estimated relative change of target lesions at week 8 calculated from first image assessment. DpR was defined as above. Predictive formulae of prognosis were examined by single and multiple regression analysis. Results: 63 patients were enrolled. KRAS status were as follows; wild type; 33, mutant; 17, unknown; 13. Chemotherapies were performed as follows; oxaliplatin-based plus bevacizumab; 34, irinotecan-based plus bevacizumab; 6, oxaliplatin-based plus anti-EGFR antibody; 2, oxaliplatin-based; 17, irinotecan-based; 4. Median of DpR, eETS, PFS and overall survival (OS) were 26.5%, 15.4%, 236 days and 571 days, respectively. PFS showed a correlation with OS (r2= 0.434), while DpR and eETS were less correlated with OS (r2= 0.228, 0.082). PFS and eETS were thus chosen as variables for the prediction formula of prognosis. However, the present formula did not show an apparent increased R2 value compared with the formula consisted of PFS alone (adjusted R2= 0.442 vs 0.425), indicating that the present formula could not provide more accurate prediction. In the stratified subgroups according to treatment regimen and KRAS status, the formula did not show remarkable change in R2 value. Conclusions: The present formulae including DpR and eETS does not have superior predicting potential to PFS alone for prognosis of the whole mCRC patients.