The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379). The main exposure was DP phenotype (DP/non-DP), as assessed by two independent pathologists. DP cases were defined by immunohistochemistry as >70% expression of moderate or strong intensity for both MMP-7 and pIGF-1R. Primary endpoint: progression-free survival (PFS); secondary endpoints: OS and response rate. PFS and OS were adjusted by baseline characteristics using multivariate Cox models. We analyzed 67 patients (30 non-DP, 37 DP) in the PULSE trial and 181 patients in the POSIBA trial (158 non-DP, 23 DP). Response rates and PFS were similar between groups in both studies. DP was associated with prolonged OS in PULSE (adjusted HR: 0.23; 95%CI: 0.11-0.52; P=.0004) and with shorter OS in POSIBA (adjusted HR: 1.67; 95%CI: 0.96-2.90; P=.07). A differential effect of anti-EGFRs on survival by DP phenotype was observed. Panitumumab might be more beneficial for RAS-WT mCRC patients with DP phenotype, whereas cetuximab might improve OS in non-DP.

Background: Body composition assessment using computed tomography (CT) scans may be hampered by software costs. To facilitate its implementation in resource-limited settings, two open-source segmentation programs (Horos and CoreSlicer) were transversally validated in colorectal cancer patients. Methods: Contrast-enhanced abdominal CT scans were analyzed following the Alberta protocol. The Cross-Sectional Area (CSA) and intensities of skeletal muscle tissue (MT), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intramuscular adipose tissue (IMAT) were measured. The Skeletal Muscle Index (SMI) was calculated. Cutoff points were applied to the SMI, MT intensity, and VAT CSA to define muscle atrophy, myosteatosis, and abdominal obesity. The inter-software agreement was evaluated using different statistical tools. Results: A total of 68 participants were measured. The MT CSA and SMI displayed no differences. The MT CSA agreement was excellent, and both programs provided equal muscle atrophy prevalences. CoreSlicer underestimated the MT intensity, with a non-significant myosteatosis prevalence increase (+5.88% and +8.82%) using two different operative definitions. CoreSlicer overestimated the CSA and intensity in both VAT and SAT, with a non-significant increase (+2.94%) in the abdominal obesity prevalence. Conclusions: Both software programs were feasible tools in the study group. The MT CSA showed great inter-software agreement and no muscle atrophy misdiagnosis. Segmentation differences in the MT intensity and VAT CSA caused limited diagnostic misclassification in the study sample.