@misc{Potocki_Paweł_Results_2024,
 author={Potocki, Paweł},
 address={Kraków},
 howpublished={online},
 year={2024},
 school={Rada Dyscypliny Nauki medyczne},
 language={pol; eng},
 abstract={Colorectal cancer (CRC) is a relevant health problem worldwide with unsatisfactory treatment outcomes. Anti-EGFR antibodies combined with chemotherapy doublets are effective in advanced disease. The KRAS and BRAF mutations define a subpopulation of patients with an inferior prognosis and are established negative predictive factors for anti-EGFR therapy. BRAF V600E-specific therapy has been approved and novel agents targeting KRAS G12C are being evaluated. Recently, a location of the primary tumor in the proximal or distant colon emerged as a factor that influences both the molecular makeup, clinical characteristics, and treatment outcomes in CRC. A better understanding of the populatlonal clinical characteristics and treatment patterns for both anti-EGFR and novel agents is needed. Real-world data may provide insight into those issues. A retrospective cross-sectional study was conducted on the clinical characteristics of metastatic CRC cases evaluated for RAS and BRAF mutations in a single laboratory. In 7604 evaluated cases, the prevalence of BRAF V600E was 6.77% and was associated with female sex primary in the right colon, high-grade, mucinous, signet cell, partially neuroendocrine histology, perineural, and vascular invasion. The ’ prevalence of KRAS G12C was 3.11% and was associated with primary in the left col on and with samples originating from brain metastases In 38,5%},
 abstract={of the cases, no mutation was detected which identified the population eligible for EGFR inhibition. A multicentre retrospective clinical study of patients treated with anti-EGFR antibodies - cetuximab or panitumumab in combination with FOLFOX or FOLF1R1 chemotherapy - was also conducted focusing on the impact of the primary tumor location. The objective response occurred in 68.3%, median depth of response was -47.9% and the median progression-free survival was 11.4 months. 15% of the patients analyzed had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment results in terms of the response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33-0.78, p = 0.010), and the median depth of response: -36.7% vs-50.0% (p= 0,038). There was only a borderline nonsignificant trend for inferior PFS in patients with proximal tumors. The OS data were incomplete. This work confirms the link between primary tumor location and molecular biology and clinical outcomes in CRC. It also establishes the expected prevalence of mutations that constitute resistance to EGFR inhibition and the expected outcomes of this treatment in a real-world dataset of Polish patients. The association of the BRAF V600E mutation with neuroendocrine histology and KRAS G12C with the left part of the intestine},
 abstract={and brain metastases are new findings and require further investigation, but potentially identify populations that are likely to benefit from new targeted therapies.},
 title={Results of targeted treatment in patients with colon cancer},
 type={Praca doktorska},
 keywords={colorectal cancer, KRAS G12C mutation, BRAF V600E mutation, real world data, anti-EGFR},
}