Tumor Thickness at Tumor-Normal Interface (TNI): A Novel Pathologic Indicator of Chemotherapy Response in Hepatic Colorectal Metastases (HCRM)
A Agarwal, S Kopetz, P Boonsirikamchai, YS Chun, H Wang, JN Vauthey, EM Loyer, DM Maru. MD Anderson Cancer Center, Houston
Background: Progress in treatment of HCRM demands pathologic indicators of therapy response. Pathologic response;one of the best predictor of disease free survival (DFS) has limitation of low reproducibly among pathologists. Based on observation of majority of residual tumor cells seen at the TNI, we hypothesized that the tumor thickness at the TNI correlate with radiologic and pathologic response and DFS.
Design: This study included 119 patients (M/F= 1.8, median age 56 years) with resected HCRM (moderately differentiated adenocarcinoma) following preoperative chemotherapy ± Bevacizumab. Imaging response was assessed by the RECIST criteriae in 50 patients. The pathologic response was categorized as complete (no tumor cells), major (<50% residual tumor cells) and minor (>50% residual tumor cells), as published previously. All H&E sections from the tumors were reviewed by two pathologists and maximum tumor thickness comprised of uninterrupted layers of tumor cells was measured perpendicular to the TNI in millimeter. In tumors where entire section has tumor without stroma, the highest thickness measured on a glass slide was utilized for analysis. The maximum tumor thickness <0.5mm was considered as <0.5mm without additional measurement. For specimen with >1 tumor, average residual tumor and maximum thickness at TNI were used.
Results: Seventy-six received oxaliplatin based chemotherapy, 43 received irinotecan based chemotherapy and 90 received Bevacizumab. The imaging response was complete in 14, partial in 32 and progression in 4. The complete pathologic response was seen in 9, major response in 52 and minor response in 58. Median tumor thickness at TNI was 2mm (IQR 0.5 to 6mm). The tumor thickness correlated with pathologic (Spearman r=0.81, p<0.01) and radiologic response (Spearman r=0.37, p<0.01). Cut of thickness of 3mm differentiated minor vs. major/complete pathologic response (sensitivity 0.85, specificity 0.89). Tumor thickness correlated with the DFS as continuous variable in log-transformed analysis and lower thickness predicted better DFS (p=0.02). In the Cox regression analysis tumor thickness was a better predictor of DFS than pathologic response. The tumor thickness did not correlate with the type of cytotoxic chemotherapy, but was smaller in patients treated with bevacizumab (p=0.04).
Conclusions: Tumor thickness measured at TNI is potentially a new prognostic factor for therapy response and survival outcome in patients with HCRM.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 72, Tuesday Afternoon