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.

Challenges and Limitations of Endocrine Toxicity Evaluation in Non-Small Cell Lung Cancer Patients Treated with Immunotherapy-Retrospective Study from a Tertiary-Level Hospital in Romania.

(1) Background: The endocrine system has become a prominent target to autoimmune damage during treatment with immune checkpoint inhibitors (ICIs) in cancer patients. Real-world data regarding endocrine immune-related adverse events (irAEs) are needed to explore their impact in cancer patients. An analysis was conducted to evaluate endocrine irAEs caused by ICIs, besides the challenges and limitations of daily medical practice in oncology in Romania. (2) Methods: This was a retrospective cohort study of lung cancer patients treated with ICIs at Coltea Clinical Hospital, Bucharest, Romania, from 1 November 2017 to 30 November 2022. Endocrine irAEs were identified through endocrinological assessment and were distinguished as any occurring endocrinopathy during treatment with ICIs and related to immunotherapy. Descriptive analyses were performed. (3) Results: Of 310 cancer patients treated with ICIs, we identified 151 with lung cancer. From this cohort, 109 NSCLC patients qualified for baseline endocrine estimation and 13 patients (11.9%) developed endocrine irAEs, such as hypophysitis (4.5%), thyroid disorder (5.5%) and primary adrenal insufficiency (1.8%), with one or more endocrine glands being affected. There might be a correlation between endocrine irAEs and duration of ICI treatment. (4) Conclusions: Early diagnosis and adequate management of endocrine irAEs may be challenging in lung cancer patients. A high incidence of endocrine irAEs is expected with the growing use of ICIs, and because not all endocrine events are immune-related, cooperation between oncologists and endocrinologists is crucial in the management of these patients. More data are needed to confirm the correlation between endocrine irAEs and the efficacy of ICIs.

The impact of RAS mutation on the treatment strategy of colorectal cancer.

Kirsten rat sarcoma (KRAS) is the most frequently mutated oncogene in colorectal cancer, being present in 30% of patients with localized disease and in almost half of the patients that develop metastatic disease. While the development of chemotherapy doublets and targeted therapy have improved survival in recent years, KRAS mutation still has a controversial role regarding its prognostic and predictive value both in the adjuvant and in the metastatic setting. The impact of KRAS mutation on treatment strategy remains to be better defined. The development of new KRAS inhibitors promising new treatment options is on the horizon.

Aspects Regarding the Influence of Obesity on the Molecular Characteristics of Breast Tumors.

The influence of excess adipose tissue on the evolution and prognosis of breast cancer has been evaluated in numerous papers over the years. The ways in which obesity can influence the development, progression, and prognosis of this neoplasia are complex and requires the design of new studies, both clinical and preclinical. The aim of this study is to highlight a possible correlation between obesity-specific tumor microenvironment markers (adipokine or leptin) and the different histological subtypes and aggressive characteristics of breast tumors. We prospectively monitored the prognostic values of 39 patients diagnosed with breast cancer who received oncologic-specific treatment or are in follow-up regarding some obesity markers. Our analysis included parameters such as age, body mass index, immunohistochemical characteristics, and plasma concentration of leptin. The methodology was designed to reveal a possible correlation between obesity (quantified by measuring body mass index and waist circumference), the plasma level of leptin, and breast tumor immunohistochemical characteristics. The patients diagnosed with aggressive tumors subtypes (HER2-positive and triple-negative) had a significantly higher body mass index than patients diagnosed with luminal type tumors (32 kg/sqm versus 27 kg/sqm), the difference being 5 kg/sqm. In patients with non-luminal type breast tumors (HER2-positive and triple-negative), serum concentration of leptin is 55 pg/ml compared to 48 pg/ml in luminal type, statistically significant, p=0.0168. Leptin plays an important role in the connection of specific microenvironment tumors to breast cancer. An increased serum concentration of this adipokine was found in patients with HER2-positive and triple-negative breast tumors compared with luminal-type breast tumors, which could open new directions in the research of breast cancer prognosis in obese patients.

Level of education, background and clinical stage as prognostic factors according to RMST function in patients with early and locally advanced breast cancer: a single institution experience from Romania.

Background and aims: Our aim is to examine the relationship between the level of education, background, tumor size and lymph node status on the treatment outcome in a group of patients with early and locally advanced breast cancer (BC) by using the restricted mean survival time (RMST), which summarizes treatment effects in terms of event-free time over a fixed period of time. Methods: We evaluated the prognostic values in 143 patients treated for early BC at Elias University Emergency Hospital, Bucharest, Romania and followed up for a maximum of 36 months. The protocol was amended to include the levels of education (gymnasium, high school, or university), the background (urban or rural) and the clinical stage (primary tumor (T) and regional nodes (N)). The methodology consisted in using a Kaplan-Meier analysis and RMST for the entire sample and Cox regression, for the variables with statistical influence. The principal endpoints of the study were overall survival (OS) and progression free survival (PFS). Results: The level of education had impact both on RMST OS (35.30 vs. 26.70) and death HR (hazard ratio) in the group of patients with general school level, compared with those with graduated university. In this study, the urban or rural background did not impact the outcome, probably because in this study we included predominantly patients from urban areas (83%). Although clinical tumor size measurements did not impact the outcome, the clinical staged lymph node influenced both OS (p=0.0500) and PFS (p=0.0006) for the patients with palpable or imaging proof of lymph node involvement of station 2 or 3. Conclusions: RMST provides an intuitive and explicit way to express the effect of those risk factors on OS and PFS in a cohort of early breast cancer patients. Low level of education and high-grade clinical lymph node status negatively influences the outcome of this cohort of BC patients.

The importance of androgen receptors in breast cancer.

BACKGROUND AND AIM: Breast cancer (BC) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. For the breast malignant tumors there are numerous targeted therapies, depending on the receptors expressed. Regulating the process of epithelial-mesenchyme transcription, the steroid nuclear receptors are important in invasion and progression of BC cells. Till now, it is known that androgen receptor (AR) is present in about 60-80% of BC cells but, unfortunately, there is no targeted therapy available yet. METHODS: We revised the recent literature that included the AR mechanism of action in patients diagnosed with breast cancer, the preclinical, retrospective and clinical studies and the aspects related to the prognosis of these patients, depending on the molecular subtype. RESULTS: A total of 12 articles were eligible for this review. AR positivity was assessed using immunohistochemistry. Herein, neither 1 nor 10% cut-points were robustly prognostic. AR was an independent prognostic marker of BC outcome, especially in triple negative BC group. CONCLUSION: AR is a potential targeted pathway which can improve the prognostic of AR positive patients with BC. Further preclinical and clinical studies are necessary to clarify the mechanism of action and to establish the drugs which can be used, either alone or in combination.

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.