Clinical, Pathological and Molecular Insights on KRAS, NRAS, BRAF, PIK3CA and TP53 Mutations in Metastatic Colorectal Cancer Patients from Northeastern Romania.

Mutations in RAS, BRAF, PIK3CA, and TP53 are well-established genetic abnormalities in metastatic colorectal cancer (mCRC). However, limited information is available for patients from Eastern Europe, including Romania. In this retrospective analysis, we investigated 104 mCRC patients from the Northeastern region of Romania to determine the frequency, distribution, coexistence, and clinicopathological and molecular correlations of these mutations. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). Patients with KRAS mutant tumors and wild-type TP53 genotype were found to have no personal history of gastrointestinal cancer (p = 0.02, p = 0.007). KRAS mutations in exon 3 were associated with the female gender (p = 0.02) and the absence of lymph node invasion (p = 0.02). PIK3CA mutations were linked to the absence of lymph node invasion (p = 0.006). TP53 mutations were associated with KRAS mutations in exon 2 (p = 0.006), ulcerated histopathologic type (p = 0.04), and G2 differentiation (p = 0.01). It provides novel insights into genetic variations specific to the population from Northeastern Romania, which has been underrepresented in previous studies within Eastern Europe. Furthermore, our findings enable the development of genetic profiles in a developing country with limited access to specialized genetic tests and facilitate comparisons with other populations.

Combined Anti-PD-1 and Anti-CTLA-4 Treatment in Stage IV Melanoma Patients: A Bicentric Analysis of Real-World Data and a Modern Treatment Scenario Proving Lactate Dehydrogenase's Usefulness.

BACKGROUND: This retrospective study evaluates patients with stage IV melanoma treated with nivolumab and ipilimumab combination therapy from two regional oncology centers in Romania from the year 2019 to the end of 2022. METHODS: The data were analyzed in SAS for Windows, V9.4. LDH means were stratified by the number of metastatic sites before treatment and compared using an independent sample T-test. The survival curves were estimated using the Kaplan-Meier method, and the survival distributions were compared with the log-rank test. The effects of the main clinical and pathological variables on OS and PFS were investigated with Cox regression. RESULTS: The LDH mean for patients with three or more metastases before treatment was significantly higher than that for patients with only one metastatic site. The Kaplan-Meier curve of OS in all evaluable patients enrolled in the study resulted in a median OS of 346 days (95% CI: 150) and a median PFS of 211 days (95% CI: 113-430). A total of 45.3% of the patients experienced adverse events during the nivolumab + ipilimumab treatment, with some of them having multiple organ systems involved. DISCUSSION: The OS values were lower than those reported in approved clinical trials, but the results show a marked improvement when compared to the results obtained by chemotherapy regimens previously used in these scenarios. CONCLUSION: This study provides real-world insights into the survival data and safety profiles of combination therapy with anti-PD-1 antibodies and anti-CTLA-4 antibodies.