NAACCR/IACR Combined Annual Conference 2019 Treatment of Stage IV Colon Cancer in the US: A Patterns of Care Analysis Xiang Gao1, Amanda Kahl2 , Paolo Goffredo1, Imran Hassan1, Mary Charlton2 1University of Iowa, Department of Surgery; 2University of Iowa, College of Public Health NAACCR/IACR Combined Annual Conference 2019

Disclosures The authors have nothing to disclose

Background - Colon Cancer 3rd most common cancer diagnosis 3rd leading cause of cancer-related deaths Lifetime risk Men: 1 in 22 Women: 1 in 24 Stage IV 5-year survival: 14% 77-90% present with unresectable disease Source: American Cancer Society. https://www.cancer.org/cancer/colon-rectal-cancer.html

Background - SEER POC 2014

Background - Stage IV Treatment Tumor resection, metastasectomy, neo/adjuvant chemotherapy Chemotherapy + biologics, then re-evaluate Chemotherapy + biologics Chemotherapy + biologics Colon resection if: imminent risk of obstruction, significant bleeding, perforation, or other significant tumor symptoms

Objective Examine the patient, tumor, and hospital factors associated with treatment regimens in stage IV colon cancer.

Methods - Study Population Patients aged >20 years Diagnosed in 2014 Stage IV colon- first and only cancer Sampling proportionate to registry size Connecticut, New Jersey, Iowa, Detroit, Kentucky, Louisiana, Atlanta, California, Hawaii, New Mexico, Seattle, Utah Oversampling of racial minorities

Methods - Treatment Variables Primary tumor resection (PTR, yes/no) Radiation (yes/no) Chemotherapy Targeted biologic agents Treatment groups: Resection plus chemotherapy Chemotherapy only Given within 7 weeks of diagnosis Resection only No treatment

Methods - Additional Variables Charlson Index SEER Registry region: Northeast: Connecticut, New Jersey North Central: Iowa, Detroit South: Kentucky, Louisiana, Atlanta West: California, Hawaii, New Mexico, Seattle, Utah

Methods - Statistical Analysis Treatment patterns by SEER region Chi-square tests Patient, tumor, hospital/region characteristics by treatment Multinomial logistic regression Patient, tumor, hospital/region characteristics by treatment with chemotherapy only as reference group Overall survival Kaplan-Meier Cox proportional hazards

Results SEER 18 Registry POC patients diagnosed with stage IV colon cancer in 2014 (N=1445) Exclude histologies that are not malignant neoplasm, carcinoma, adenocarcinona, mucinous adenocarcinoma, or signet ring cell carcinoma N=38 Stage IV adenocarcinoma of colon (N=1407)

Resection + Chemotherapy Results - Overall Population Total: 3336 weighted cases Mean age: 63 Male: 51% White: 63% Resection + Chemotherapy 41% Resection first 73% Chemotherapy first 13% Unknown sequence 14% Chemotherapy Only 23% Resection Only 16% No treatment 17% Surgery to metastasis 28%

Results - Patterns of Treatment by Region

Residency program status Results - Univariable Analysis by Treatment Group Patient Demographics Age at diagnosis Sex Race Insurance status Marital status Clinical characteristics Charlson Index Perforation Obstruction Hospital/registry characteristics Registry Region Hospital bed size Residency program status Treatment variables PTR and chemotherapy sequence Surgery to metastasis Radiation Chemotherapy VEGF inhibitor EGFR inhibitor Tumor characteristics Histology Grade T, N, M stages KRAS, BRAF status MSI

Results - Multinomial Regression Factors associated with PTR + Chemotherapy (vs chemotherapy only)

Results - Multinomial Regression Factors associated with PTR only (vs chemotherapy only)

Factors associated with no treatment (vs chemotherapy only) Results - Multinomial Regression Factors associated with no treatment (vs chemotherapy only)

Results - Kaplan Meier Overall Survival Median survival PTR + Chemotherapy: >24 months Chemotherapy Only: 14 months PTR only: 5 months No treatment: 2 months

Results - Cox Proportional Hazards Adjusted for: Age, sex, race, insurance status, marital status, Charlson Index, SEER region, hospital bed size, hospital residency status, tumor histology, grade, T, N, and M stages, KRAS, BRAF, MSI, perforation, obstruction, surgery to metastasis

Summary PTR + Chemo PTR only No treatment Node positive Lower metastatic burden + perforation + obstruction Married Small, non-academic hospitals PTR only Advanced T, N Lower metastatic burden + perforation + obstruction Older Medicaid Small hospitals No treatment Unknown genetic markers Older African American 57% of patients received PTR (+/- chemotherapy)

Conclusions Resection is frequently used in treatment of stage IV colon cancer Resection should be reserved to severe symptoms or curative intent Variation in treatment patterns by hospital factors Support for guideline implementation may be particularly beneficial in small, non-academic hospitals Variation in treatment patterns by race, insurance status, age Efforts that identify/address barriers to care, patient education

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