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Patients with metastatic Colorectal Cancer (mCRC), in which primary tumors are KRAS mutated, have no response to anti-EGFR therapy. However, less than half of mCRC patients with KRAS wild-type primary tumors respond to anti-EGFR therapy. Other downstream effectors of the EGFR pathway are being analyzed to fine-tune KRAS predictive value. However, as the primary tumor is the tissue of analysis that determines the use of anti-EGFR therapy in advanced disease, a high concordance in the status of these effectors between primary tumors and related metastases is required. We analyzed the concordances of downstream EGFR effectors in tumoral pairs of primaries and related metastases in a series of KRAS wild-type patients. One hundred seventeen tumoral pairs from patients with CRC were tested for KRAS mutational status. The level of concordance in the presence of KRAS mutations was 91% between the primary tumor and related metastases. The 70 pairs with KRAS wild-type primary tumors were further analyzed for BRAF and PIK3CA mutational status and for EGFR, PTEN and pAKT expression, and the number of concordant pairs was 70 (100%), 66 (94%), 43 (61%), 46 (66%) and 36 (54%), respectively. Our findings suggest that the mutational status of KRAS, BRAF and PIK3CA in the primary tumor is an adequate surrogate marker of the status in the metastatic disease. On the other hand, the immunohistochemical analysis of EGFR, PTEN and pAKT showed a much higher degree of discordance between primaries and related metastases.

NSCLC are seldom reported. Method: Consecutive patients with curative resected NSCLC and confirmed EGFR mutations at Fudan University Shanghai Cancer Center from January 2007 to December 2017, were retrospectively enrolled. The initial recurrence sites were recorded and categorized into five groups: thoracic recurrence, brain recurrence, neck recurrence, abdominal recurrence, and bone recurrence. The indicators of overall and site-specific recurrence were identified using the Cox regression model, where a panel of routinely used IHC markers (including Her2, Ki67, TTF-1, CK20, CK7, CK5/6, p53, RRM1, NapsinA, p40, syn, Bcl-2, CDX2, ERCC1 and p63) were incorporated. A nomogram was developed based on variables selected in multivariate analysis. The bootstrapping method (1000 repetitions) was applied to internally validate the nomogram Result: After a median follow-up of 32 (range, 5-122) months, disease recurrence was observed in 197(37.1%) out of the 531 patients, with a median recurrence-free survival (RFS) of 19 (95% CI, 16.63-21.37) months. Most patients (n¼136; 69.0%) had thoracic recurrence, followed by brain recurrence (n¼41; 20.8%), bone recurrence (n¼41; 20.8%), abdominal recurrence (n¼14; 7.1%), and neck recurrence (n¼13; 6.6%). Sex, tumor size, Ki67, and N stage were independent indicators of thoracic recurrence. Tumor size, N stage, CK20, and Syn were independent indicators of brain recurrence. N stage and Ki67 were independent indicators of bone recurrence. N stage was the independent indicator of abdominal recurrence and neck recurrence. Tumor size, Ki67, CK20, and N stage were independently associated with overall recurrence, and thus a nomogram predicting the 1-, 2-, and 3-year RFS probability was developed based on these four factors. The concordance index (C-index) was 0.723 (95% confidence interval, 0.675 to 0.771) and the calibration curves displayed good agreement between the predicted RFS and the actual observation.

hepatitis. They also contributed to all-grade hypothyroidism, hyperthyroidism and pneumonitis. These toxicities have significant impact on patients' quality of life, ultimately affecting patients' compliance. A timely intervention with proper supportive care is necessary.