Correlations between Demographic, Clinical, and Paraclinical Variables and Outcomes in Patients with KRAS-Mutant or KRAS Wild-Type Metastatic Colorectal Cancer-A Retrospective Study from a Tertiary-Level Center in Romania.

Colorectal cancer (CRC) is a significant global public health concern and its characteristics in Eastern Europe are underexplored. In this retrospective study, data of 225 patients with metastatic colorectal cancer (mCRC) from the Colțea Clinical Hospital's Oncology Department in Bucharest were analyzed between 2015 and 2023. They were divided into two groups based on the presence of KRAS mutation. The primary objective of the study was to investigate whether the presence of KRAS mutations influenced the prognosis of mCRC and to identify any demographic, clinical, or paraclinical factors associated with KRAS mutations in stage IV CRC. The overall survival for the entire study population was 29 months. There was a trend towards increased survival in the KRAS wild-type group (31 months) compared to the KRAS-mutant group (26 months), but this difference did not reach statistical significance. We found that lower levels of education, advanced T stage, advanced N stage, and M1 stage at diagnosis negatively impacted prognosis. Real-world data are crucial in shaping public policy strategies to better support patients with metastatic CRC. Understanding the correlations between the demographic, clinical, and paraclinical variables and the outcomes in mCRC patients with KRAS-mutant and KRAS wild-type colorectal cancer is essential for improving patient care and treatment strategies in Romania and beyond.

Restricted Mean Survival Time-Can It Be a New Tool in Assessing the Survival of Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors?

BACKGROUND: Lung cancer (LC) is the first and most lethal cancer in the world; identifying new methods to treat it, such as immune checkpoint inhibitors (ICIs), is needed. ICIs treatment is very effective, but it comes bundled with a series of immune-related adverse events (irAEs). Restricted mean survival time (RMST) is an alternative tool for assessing the patients' survival when the proportional hazard assumption (PH) fails. METHODS: We included in this analytical cross-sectional observational survey patients with metastatic non-small-cell lung cancer (NSCLC), treated for at least 6 months with ICIs in the first- and second-line settings. Using RMST, we estimated the overall survival (OS) of patients by dividing them into two groups. A multivariate Cox regression analysis was performed to determine the impact of the prognostic factors on OS. RESULTS: Seventy-nine patients were included (68.4% men, mean age 63.8), and 34/79 (43%) presented irAEs. The OS RMST of the entire group was 30.91 months, with a survival median of 22 months. Thirty-two out of seventy-nine (40.5%) died before we ended our study. The OS RMST and death percentage favored the patients who presented irAEs (long-rank test, p = 0.036). The OS RMST of patients with irAEs was 35.7 months, with a number of deaths of 12/34 (35.29%), while the OS RMST of the patients without irAEs was 17 months, with a number of deaths of 20/45 (44.44%). The OS RMST by the line of treatment favored the first line of treatment. In this group, the presence of irAEs significantly impacted the survival of these patients (p = 0.0083). Moreover, patients that experienced low-grade irAEs had a better OS RMST. This result has to be cautiously regarded because of the small number of patients stratified according to the grades of irAEs. The prognostic factors for the survival were: the presence of irAEs, Eastern Cooperative Oncology Group (ECOG) performance status and the number of organs affected by metastasis. The risk of dying was 2.13 times higher for patients without irAEs than for the patients who presented irAEs, (CI) 95% of 1.03 to 4.39. Moreover, by increasing the ECOG performance status by one point, the risk of death increased by 2.28 times, with a CI 95% of 1.46 to 3.58, while the involvement of more metastatic organs was associated with a 1.60 times increase in the death risk, with a CI 95% of 1.09 to 2.36. Age and the type of tumor were not predictive for this analysis. CONCLUSIONS: The RMST is a new tool that helps researchers to better address the survival in studies with ICIs treatment where the PH fails, and the long-rank test is less efficient due to the existence of the long-term responses and delayed treatment effects. Patients with irAEs have a better prognosis than those without irAEs in the first-line settings. The ECOG performance status and the number of organs affected by metastasis must be considered when selecting patients for ICIs treatment.

Nivolumab Hypersensitivity Reactions a Myth or Reality in Solid Tumors-A Systematic Review of the Literature.

Immune-checkpoint inhibitors (ICIs) are the most effective treatments nowadays. Nivolumab was the second ICI used for treating solid tumors with amazing results. Patients treated with Nivolumab may react differently to this treatment. Some people tolerate this treatment very well without experiencing any adverse reactions, whilst some may have mild symptoms and a part of them can present severe reactions. In our research, we sought to identify the answers to four questions: 1. what type of cancer has more severe hypersensitivity reactions to Nivolumab, 2. what is the time frame for developing these severe reactions to Nivolumab, 3. whether it is best to continue or stop the treatment after a severe hypersensitivity reaction to Nivolumab and 4. what severe hypersensitivity reactions are the most frequent reported along Nivolumab treatment. This review also highlights another problem with regard to the usage of concomitant and prior medications or other methods of treatment (e.g., radiation therapy), which can also lead to severe reactions. Treatment with Nivolumab is very well tolerated, but patients should also be warned of the possibility of severe hypersensitivity reactions for which they should urgently see a doctor for a personalized evaluation. There are some options for individuals with severe hypersensitivity reactions, for eg. switching the medication or applying a desensitization protocol.

Correlation between Androgen Receptor Expression and Immunohistochemistry Type as Prognostic Factors in a Cohort of Breast Cancer Patients: Result from a Single-Center, Cross Sectional Study.

BACKGROUND: We investigated the correlation between the androgen receptor (AR) and immunohistochemistry (IHC) as a prognostic factor in breast cancer (BC). AR is expressed in 60-80% of BC. METHODS: We evaluated the prognostic values of AR expression among 143 patients with BC for 36 months. The protocol was amended to measure androgen, estrogen and progesterone receptor expression by IHC and the percentage of hormone positive nuclei was quantified. We determined and quantified the Her2/neu status using IHC and in situ hybridization. The methodology consisted in using a Kaplan-Meier analysis and restricted mean survival time up to 36 months. The principal endpoints of the study were overall survival (OS) and progression free survival (PFS). RESULTS: 57% of patients (n = 82) from our group had AR+ (≥ 1%). Patients with AR+ had better OS, 35.50 vs. 33.40 months, with p = 0.027. Moreover, PFS was prolonged for patients AR+, 32.60 vs. 30.50 months, with p = 0.38. Triple negative breast cancer (TNBC) patients had lower OS and no difference was observed for PFS. CONCLUSIONS: Both OS and PFS were favorably influenced by the presence of AR. TNBC had worse outcomes compared with patients with hormonal or/and Her 2/neu positive disease in terms of OS.

Histological Aspects and Quantitative Assessment of Ki67 as Prognostic Factors in Breast Cancer Patients: Result from a Single-Center, Cross Sectional Study.

Background and objectives: Our aim is to explore the relationship between the levels of protein encoded by Ki67 and the histopathological aspects regarding the overall survival and progression-free survival in a single university center. A secondary objective was to examine other factors that can influence these endpoints. New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. Ki67 is a nuclear protein associated with cell proliferation. Together with the histological type and tumor grade, it is used to appreciate the aggressiveness of the breast tumors. Materials and Methods: We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, in which we enrolled women with stage I to III breast cancer. The protocol was amended to include the immunohistochemistry determination of Ki67 and the histological aspects. The methodology consisted in using a Kaplan-Meier analysis for the entire sample and restricted mean survival time up to 36 months. Results: Both lower Ki67 and low tumor grade are associated with better prognosis in terms of overall survival (OS) and progression-free survival (PFS) for our patients' cohort. In our group, the histological type did not impact the time to progression or survival. Conclusions: Both overall survival and progression-free survival may be influenced by the higher value of Ki67 and less differentiated tumors. Further studies are needed in order to establish if the histologic type may impact breast cancer prognostic, probably together with other histologic and molecular markers.