569 Background: We have previously identified a multigene expression model of tumor radiosensitivity with validation in four independent cohorts (breast, rectal, esophageal, and head and neck). This model predicts a radiosensitivity index (RSI) that is directly proportional to tumor radioresistance, (RSI, high index = radioresistance). The purpose of this study was to assess differences in RSI between primary colon cancer and metastases. Methods: Patients were identified from our institutional IRB-approved prospective observational protocol. A total of 704 metastatic and 1,362 primary lesions were obtained from a de-identified meta-data pool. Gene expression was obtained from Affymetrix Hu-RSTA-2a520709 microarrays. RSI was calculated using the previously published ranked based algorithm. An independent cohort of 38 lung and liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiotherapy (SBRT) was used for validation. Results: The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors compared with 54% of primaries were in the RSI-radioresistant (RSI-RR) peak, suggesting that metastatic tumors may be slightly more radioresistant than primaries (p=0.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radioresistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31), p<0.0001. These findings were confirmed when the analysis was restricted to lesions from the same patient (n=69). In our independent cohort of lung and liver metastases, lung metastases had an improved outcome over patients with liver metastases (2 yr local control, lung vs. liver metastases; 100% vs. 74.0%, p=0.027). Conclusions: Assessment of radiosensitivity between primary and metastatic tissues of colon cancer histology, reveals significant differences based on anatomical location of metastases. These initial results warrant validation in a larger clinical cohort.
Embryonic origin of primary colon cancer predicts survival in patients undergoing ablation for colorectal liver metastases
