Fig. 1
Study group definition. 1 Intended CTx regimen was chosen from among the following: CapeOX (oxaliplatin 130 mg/m2 IV day 1, capecitabine 1000 mg/m2 twice daily per os (PO) for 14 days, repeat every 3 weeks); CapeIRI (irinotecan 250 mg/m2 day 1, capecitabine 1000 mg/m2 twice daily PO for 14 days, repeat every 3 weeks); FOLFOX4 (oxaliplatin 85 mg/m2 intravenous (IV) day 1, Leucovorin 200 mg/m2 IV days 1 and 2, 5- fluorouracil 400 mg/m2 IV bolus on day 1 and 2, 5- fluorouracil 600 mg/m2 22-h continuous infusion days 1 and 2, repeat every 2 weeks); FOLFIRI (irinotecan 180 mg/m2 IV day 1, Leucovorin 400 mg/m2 IV day 1, 5- fluorouracil 400 mg/m2 IV bolus day 1, then 5- fluorouracil 1200 mg/m2 /d continuous infusion days 1 and 2, repeat every 2 weeks). Bevacizumab was administered on the first day of each cycle at a dose of 5 mg/kg IV in combination with the 2-week regimen and at a dose of 7.5 mg/kg IV with the 3-week regimen. 2 KRAS status was not tested (not yet performed or not ordered during the enrollment period) for mCRC patient management; KRAS testing was performed by ISO 15189-accredited methods; specifically 2008 - December 2011 by real time PCR method using TheraScreen (DxS); January 2012 – May 2013 using the Cobas® KRAS Mutation Test (Roche Diagnostics). 3 prior malignancy except for locally curable cancers such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast, curatively treated with no evidence of disease for ≥3 years. 4 active, known, or suspected autoimmune disease requiring systemic treatment with immunosuppressive medication including chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis). 5 active infection at the time of blood collection including clinically significant non-healing or healing wound, ulcer. * exclusion criterion applicable if appears before the blood collection. ** exclusion criterion applicable if appears before the achievement of objective clinical response