1. Risk Stratification in Stage II Colon Cancer Patients Ramzi Amri, MD, PhD; Liliana G Bordeianou, MD, MPH; and David L Berger, MD Massachusetts General Hospital, Division of General and Gastrointestinal Surgery. Harvard Medical School, Department of Surgery. 96 th Annual Meeting of the New England Surgical Society September 25 - 27, 2015, Newport, Rhode Island

2. Stage II colon cancer: definition Invasion at least through muscularis propria (=stage IIA  T3 tumors) Higher substages: –IIB for T4a tumors: invasion through the serosa –IIC for T4b tumors: direct invasion into adjacent organs No lymph node involvement (stage III) or distant metastasis (stage IV)

3. Introduction Stage II colon cancer remains prognostically heterogenous, 1 despite introduction of: –AJCC stage subdivisions –ASCO 2 /NCCN 3 risk profiles (based on grade, lymph node yield and margin status) Decisions regarding adjuvant therapy are difficult Risk of both under- and overtreatment  We aim introduce a risk stratifying score based on readily-available factors that can help in decisions regarding adjuvant therapy 1. Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart AK. Revised TN categorization for colon cancer based on national survival outcomes data. J. Clin Oncol. 2010;28(2):264–271. 2. Benson AB, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J. Clin. Oncol. 2004;22(16):3408–3419. 3. Engstrom PF, Arnoletti JP, Benson AB, et al. NCCN Clinical Practice Guidelines in Oncology: colon cancer. J Natl Compr Canc Netw 2009;7(8):778–831.

4. Methods I ncluded: Surgical colon cancer patients at MGH 2004-2011 313 consecutive stage II patients Association of Survival, DFS with 5 risk factors: High baseline CEA (>5ng/L) High grade disease (<50% well-differentiated) Large vessel invasion Perineural invasion Extramural Vascular Invasion (EMVI) Assessment of factors individually, and as a stratified cumulative score (0, 1, 2-3, 4+) Adjusted for AJCC substage, adjuvant chemotherapy status (Cox Regression)

5. Results: incidence and overlap Majority IIA, high risk factors incidence range: 16-33% Substantial variations in rates within substages Limited overlap: strong correlation EMVI and large vessel insvasion (r=0.59), other correlations r<0.25) Stage-for-stage rates (% of any 2 simultaneously present)

6. Results: outcomes per risk factor

7. Results: risk score and outcomes

8. Summary of findings  The number of high risk factors present form strata incrementally associated with higher risks of recurrence and mortality Independent of stage II subcategory Independent of adjuvant chemotherapy status Inflection point at 2+ factors: One in 4 patients without adjuvant chemotherapy develop recurrence Mortality rises to ~7% to >30%

9. Discussion Limitations Predominance of stage IIA patients 1 in 3 patients lacked baseline CEA, therefore score could not be computed for all patients Conclusion:  This score provides a readily-available prognostic tool that helps in treatment decisions after surgery in stage II colon cancer patients

10. Questions? Disclosures: None. Contact: E: ramri@mgh.harvard.edu W: hsph.me/ramri Slides: bit.ly/AmriNESS2015