KRAS mutation status and primary tumors location were correlated with single-site metastasis (liver, lung, and peritoneum) and dual-site metastases (liver-peritoneum, liver-lung, and lung-peritoneum).
The mutant allele frequency of KRAS in metachronous metastases was higher in 6 cases (mean difference =% 25.5% (range, 9.5%-58.0%)) and lower in 3 cases (mean difference = 9.3% (range, 8.0-10.0%) compared with each of their primary tumors.
The mutant allele frequency of KRAS in metachronous metastases was higher in 6 cases (mean difference =% 25.5% (range, 9.5%-58.0%)) and lower in 3 cases (mean difference = 9.3% (range, 8.0-10.0%) compared with each of their primary tumors.
The features associated with the mucinous histologic subtype were independent predictors for shorter OS, including BRAF (HR, 1.74; 95% CI, 1.35-2.25; P < .001) and KRAS (HR, 1.42; 95% CI, 1.22-1.65; P < .001) mutations, right-sided location (HR, 1.20; 95% CI, 1.04-1.39; P = .01), and synchronous metastases (HR, 2.92; 95% CI, 2.49-3.42; P < .001).
Treatments including the monoclonal antibodies showed a cost per month of PFS gained of 2823 € (FOLFIRI with cetuximab in KRAS wild-type patients and liver-only metastases), of € 15,822 (FOLFOX with panitumumab in KRAS wild type), and of 13,383 € (FOLFOX with bevacizumab).
Methods The data of patients with lung metastases from colon cancer who underwent SABR were retrospectively evaluated according to the following inclusion criteria: number of metastases ≤3; lung oligometastases from colon cancer in patients who underwent SABR; patients receiving previous chemotherapy alone or in combination with bevacizumab; Karnofsky performance status >80; life expectancy >6 months; at least 6 months' follow-up after SABR; presence of KRAS mutation.
The following algorithm was applied: "(colorectal OR rectal OR colon OR colonic) AND (liver OR hepatic) AND (metastasis OR metastases) AND (gene OR mutation OR KRAS OR BRAF OR SMAD4 OR RAS OR TP53 OR P53 OR APC OR PI3K OR MSI OR EGFR OR MACC1 OR microsatellite)."
In conclusion, our studies demonstrate how KRAS inhibits the tumor suppressor RKIP, thus offering novel justification for targeting RKIP as a strategy to overcome KRAS-induced tumor metastasis and chemoresistance in PDAC.
The present study aimed to investigate whether c-mesenchymal epithelial transition factor (C-MET) overexpression combined with <i>RAS</i> (including <i>KRAS, NRAS</i> and <i>HRAS</i>) or <i>BRAF</i> mutations were associated with late distant metastases and the prognosis of patients with colorectal cancer (CRC).
Targeted analysis of recurrent mutations thus presents a useful complement to the existing diagnostic tool kit, and correlations of EGFR in LMD and KRAS in solid metastases suggest that molecular distinctions or systemic treatment pressure underpin the differences in growth patterns within the brain.
The present review will focus on potential roles of gene heterogeneity in KRAS pathway in the development of CRC metastasis to lung and clinical therapies, which would lead to better understanding of the metastatic control and benefit to the treatment of metastases.
<i>Conclusions.</i> Although the number of patients analysed was limited, we found that the addition of cetuximab significantly improves the outcomes in KRAS wild type patients with unresectable colorectal cancer liver-confined metastases.
TP53 and BRAF<sup>V</sup><sup>600E</sup> adjMAFs were higher in metastases as compared to primary tumors, and high KRAS adjMAFs were found in CRC metastases of patients with KRAS wild-type primary tumors previously exposed to EGFR antibodies.
This study enrolled 457 patients with surgically resected primary and corresponding metastatic CRC (499 synchronous metastases and 57 metachronous metastases) and seven local recurrences, and KRAS/BRAF mutation and MSI status were analysed for these tumours.
Displacement loop instability occurred significantly more frequently in lymph node metastases and distant metastases of patients with early colorectal cancer onset age <60 years ( p = 0.0122 and p = 0.0129), was found with a significant high rate in a small cohort of TP53-mutated distant metastases ( p = 0.0418), and was associated with TP53 wild-type status of primary tumors ( p = 0.0009), but did not correlate with KRAS, NRAS, BRAF, or PIK3CA mutations.
Patients with intrapulmonary metastasis had significantly increased KRAS mutation frequency compared to those with extrapulmonary metastases (35% vs 26.5%, p = 0.0125).
In particular, mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS), alone or in combination with tumor protein p53 gene (TP53) mutations, were associated with decreased survival probability and with the occurrence of local metastases at recurrence.
Survival was independently and unfavourably affected by the following variables: poor performance status, short time from initial diagnosis of metastases to the start of regorafenib, low initial regorafenib dose, >3 metastatic sites, presence of liver metastases, and KRAS mutations.
Mutational frequencies were significantly higher in patients with lung metastases compared with those with liver and ovary/bladder metastases (p = 0.039), however, KRAS mutation status was not associated with an increased risk of relapsed in the lung.