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Background: The purpose of the FDZL-MRinCLM study (NCT03088163) is to evaluate the feasibility of early parameter change assessed by diffusion kurtosis imaging of magnetic resonance (MR-DKI) in predicting clinical response to chemotherapy and investigate its prognostic value in patients with colorectal liver metastases (CLM).

Introduction: RAS mutations in metastatic colorectal cancer (mCRC) are clearly associated with lack of benefit from anti-EGFR drugs. Recent data suggest that these mutations may affect the pattern of metastatic spread. The aim of our study was to investigate if KRAS mutant mCRC has a distinct pattern of metastatization. Methods: We conducted a retrospective study including patients with mCRC with KRAS mutational analysis performed between 2010 and 2012. Exon 2 KRAS mutations are routinely analyzed for treatment decision in our centre by therascreen® or cobas® assays. We excluded those patients with no clinical data available. SPSS was used for the statistical analysis. Results: 203 patients with clinical and molecular characterization by exon 2 KRAS mutation were included in the analysis. The median age was 63 years old and 142 patients (70%) were male. At the time of colorectal cancer diagnosis, 133 patients (65.5%) had advanced disease, and 70 patients (34.5%) were diagnosed with non-advanced CRC but tumor relapsed with distant metastasis. Tumors were located in the colon in 144 patients (70.9%), mainly in the sigma (76 patients, 37.4%). Regarding the metastatic sites, liver was the most common site of metastasis (124 patients, 61.1%). Fifty-seven patients had lung metastasis (28.1%), 32 patients (15.8%) had distant lymph nodes metastasis and 29 patients (14.3%) had peritoneal metastasis. Other distant metastasis sites were adrenal glands (1%), bone (2%), central nervous system (CNS) (0.5%) and ovary (3.9%). KRAS mutation was detected in 95 patients (46.8%). Median overall survival was 35.6 months, with no difference observed between KRAS mutant and KRAS wild-type tumors (29.6 months vs 40.8 months, p-value = 0.162). Lung metastases were more frequent in exon 2 KRAS mutant tumors (34.7% vs 22.2%, odds ratio = 3.92, p-value = 0.048), although this was more evident in rectal cancer. Metastases in liver, lymph nodes, adrenal glands, bone, peritoneum and ovary were not associated with KRAS mutational status. We have also observed that mutations in KRAS were related to a more extensive disease, metastases were more frequently present in 2 or more locations in KRAS mutant tumors (33.7% vs 21.3%, p-value = 0.048). Conclusion: Molecular features together with their clinical characteristics (more frequent lung metastasis and extended disease) suggest that the biology of these tumors is different from other genomically-defined groups. Nevertheless, KRAS mutation does not significantly impact survival in the metastatic setting.

was 33 vs 13 months for cetuximab-treated vs untreated patients with PODXL high tumours receiving first line combination chemotherapy and second line. Silencing of PODXL in vitro led to a reduction of EGFR expression, whereas silencing of EGFR did not affect PODXL levels. Moreover, silencing of PODXL but not EGFR rendered CRC cells more resistant to cetuximab compared to control cells.Conclusions: PODXL is an independent biomarker of poor prognosis also in mCRC, and its link with the EGFR axis is further confirmed. These findings bear potential clinical significance for further improved treatment stratification of patients with mCRC.Legal entity responsible for the study: The authors.