Tsikitis, Vassiliki L.

4013 Background: Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB & III) colon cancer. We hypothesized that stage I & IIA colon cancer patients would experience similar benefits. Methods: Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I & IIA; 537 patients) and late (stage IIB & III; 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by χ2 test. Results: Salvage rates for early and late stage disease patients with recurrence were the same (35.9% versus 37%, p=0.9 respectively). Median survival following second surgery after recurrence was 35.8 months late stage and 51.2 months for early stage patients respectively. Sites of first recurrence did not significantly differ between late and early stage disease: liver (37.4% vs. 27.2%); lung (29.7% vs.23.6%); intraabdominal (24.2% vs.10.9%); and locoregional (12.1% vs.10.9%). Methods of first detection of recurrence were also not significantly different: CEA (37.4% vs. 29.1%); CT scan (26.4% vs. 23.6%); chest X-ray (12.1% vs. 7.3%); and colonoscopy (8.8% vs. 12.7%), for late versus early stage disease, respectively. Conclusions: Patients with early stage colon cancer have similar sites of recurrence, and receive similar benefit from post-recurrence therapy as later stage patients; implementation of existing surveillance guidelines for early stage patients is appropriate. No significant financial relationships to disclose.

498 Background: Prior study, demonstrating differential immunohistochemical EGFR expression between the primary colon cancer and the liver metastasis, suggested possible molecular differences between the two tumor sites. This questions the relevance of obtaining genomic information from the primary tumor to guide adjuvant treatment. In this study we examine whether there are genomic differences specific to metastatic nodes versus the paired colon primary samples. Methods: Using 30 primary and lymph node metastasis pairs (dissected for >80% tumor from paraffin embedded tissue), we obtained a dataset of copy number derived from the Affymetrix Oncoscan Molecular Inversion Probe platform. Using the Nexus Copy Number software for processing, we used the default automatic segmentation of the copy number data with a threshold for calling copy number gains/losses of 2.3/1.7. Subsequently we applied the Wilcoxon signed-rank test in order to find regions showing copy number imbalance that differ between the paired nodes and tumors correcting for multiple comparisons by performing permutation-based estimation of the false discovery rate permuting the samples 100 times. Results: Using 40 ng of total DNA from paraffin embedded tumor from primary and tumor in positive nodes, we obtained high quality, genome wide copy number data. Using FDR < 0.1, we identified four chromosomal segments that showed statistically significant increased likelihood of copy number gains in the primary tumor compared to the tumor-containing node. Thirty five percent of tumor-bearing lymph nodes were copy number normal at the EGFR locus whereas the corresponding primary tumor showed amplification at 7p11.2 (includes the EGFR gene). A similar pattern was observed for 8q24, 14q11.2, and 20q12-q13; regions associated with aggressive tumor behavior. Conclusions: Our results demonstrate four significant differences between the primary tumor and lymph node metastasis and in all cases the metastasis were copy number normal compared to the copy number gain observed in the primary tumor. These results support the importance to examine differences at the genome level between the metastatic tumor site and the primary.

Purpose Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB and III) colon cancer. We hypothesized that stage I and IIA colon cancer patients would experience similar benefits. Patients and Methods Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I and IIA, 537 patients) and late (stage IIB and III, 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by χ2 test. Results Salvage rates for early- and late-stage disease patients with recurrence were the same (35.9% v 37%; P = .9, respectively). Median survival after second surgery after recurrence was 51.2 and 35.8 months for early- and late-stage patients, respectively. Single sites of first recurrence did not significantly differ between early and late stage, but multiple sites of recurrence occurred less often in early-stage patients (3.6% v 28.6%, for early v late, respectively; P < .001). Methods of first detection of recurrence were not significantly different: carcinoembryonic antigen (29.1% v 37.4%), computed tomography scan (23.6% v 26.4%), chest x-ray (7.3% v 12.1%), and colonoscopy (12.7% v 8.8%), for early versus late stage disease, respectively. Conclusion Patients with early-stage colon cancer have similar sites of recurrence, and receive similar benefit from postrecurrence therapy as late-stage patients; implementation of surveillance guidelines for early-stage patients is appropriate.