Integration of Pathologic Findings With Clinical-Radiologic Tumor Measurements to Quantify Response to Neoadjuvant Chemotherapy

摘要

The aim of the project is to develop and test a new method to quantify the proportion (percent) of cancer that is residual after neoadjuvant chemotherapy using standard radiologic and/or clinical measures of tumor size that are integrated with pathologic information about the amount of cancer within each tumor. In years 1 and 2 we combined our measure of cancer cellularity with the radiological tumor measurements with the gross and microscopic pathologic changes in the breast and axillary lymph nodes after chemotherapy to determine a measure of relative breast cancer response. This Residual Cancer Index (RCI) closely correlated with T-stage and greater proportion of residual cancer (poor response) after paclitaxel, 5-FU, doxorubicin, and cyclophosphamide (T/FAC) was significantly related to low proliferation, bcl-2 overexpression, and tau overexpression. By the end of year 3 (June 2005) we had enlarged the evaluation to 103 patients who received T/FAC chemotherapy (6 months) and 61 patients who received FAC alone (3 months neoadjuvant then 3 months adjuvant), conducted an interim evaluation of distant relapse-free survival (DRFS) with respective median follow-up of 48 and 90 months, and compared the amount of residual cancer burden (RCB) at the completion of neoadjuvant treatment with the proportional reduction of cancer represented by RCI. We found that in both cohorts the new measures of response were significantly prognostic and outperformed the existing classification of response as pathologic complete response (pCR) versus residual disease (RD). There was no prognostic difference between RCI and RCB. Therefore, we have selected RCB to evaluate in a larger cohort of patients who received neoadjuvant T/FAC (n=243) or FAC or T alone (n=189) and for whom the pathologic material after treatment is available for review. We requested a one-year extension to complete this and extend the follow-up period.