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.

Spiritual Care for Cancer Patients at the End-of-Life.

BACKGROUND: Spiritual care for patients at the end of life is an important element in their holistic care. The aim of this study is to assess the opinions of cancer patients with limited prognosis about the importance of faith in fighting illness and the factors contributing to a better adjustment to illness and to their self-reconciliation and spiritual well-being. MATERIAL AND METHODS: This study used a specially designed questionnaire for cancer patients with limited prognosis. The 30 respondents were patients with an estimated prognosis of less than 1 month, cared for in a unit with palliative and home care beds. RESULTS: The patients emphasized the importance of family as a supporter in the fight against disease (90%), followed by faith (66.7%) and a care team (63.3%). The most common concerns expressed were related to the course of their disease, family distress, fear of death, and the Russian-Ukrainian war. CONCLUSION: Family and faith represent important factors in supporting and caring for a patient at the end-of-life. Patients who felt spiritually at peace and were supported in their faith by family and a priest had a better spiritual state.

Therapeutic Obstinacy in End-of-Life Care-A Perspective of Healthcare Professionals from Romania.

BACKGROUND: End-of-life care raises ethical, moral, legal and economic dilemmas, especially when physicians have to decide whether to initiate or to stop treatments that may be considered disproportionate and futile. AIM: To explore the opinion of health care professionals involved in end-of-life patient care on interventions considered disproportionate and futile at this stage of care, the causes and factors of pressure leading to such situations, and possible solutions to reduce the phenomenon. MATERIAL AND METHOD: The study used an adapted, designed questionnaire intended for health professionals caring for patients at the end of life. The 128 respondents were physicians, nurses, psychologists and social workers who expressed their opinions about therapeutic obstinacy in end-of-life care. RESULTS: The results of the research highlight the role of the family as a pressure factor, the causes related to the non-acceptance of the prognosis and diagnosis of a terminal condition, fear of death and ignorance of the patient's wishes. Interventions considered disproportionate at the end of life were cardiopulmonary resuscitation, mechanical ventilation, transfusion of blood derivatives, complex diagnostic investigations and the establishment of gastrostomy/jejunostomy in the last days of life. CONCLUSIONS: End-of-life therapeutic obstinacy is a reality in end-of-life care, and healthcare professionals face many ethical challenges in this process. Care decisions must be made together with the patient and their family, respecting the rights, dignity and respect of all parties involved in the process.

Long-Term Survival in BRCA1 Mutant Advanced Ovarian Cancer: Unveiling the Impact of Olaparib.

Ovarian cancer is one of the most frequent malignancies in women. The treatment landscape underwent significant changes as new agents were introduced in ovarian cancer management over the last decade. We present two cases of long responses to Olaparib in BRCA (BReast CAncer gene) mutant ovarian cancer patients. The first case belongs to a 42-year-old female diagnosed with advanced ovarian carcinoma with a rare germinal mutation (BRCA1 c.68_69delAG, commonly found in descendants of Ashkenazi Jewish populations, but also Arabic and Asian ones) and a significant family history of ovarian and breast cancers. After poorly tolerated neoadjuvant chemotherapy, the patient underwent total hysterectomy, bilateral adnexectomy, and intraperitoneal hyperthermic chemotherapy. After eight months, the disease progressed, and first-line platinum chemotherapy was administered. Although not well-tolerated (grade 3 anemia, allergic reactions), chemotherapy resulted in a partial response, and given the patient's characteristics, maintenance with Olaparib was recommended. Treatment is ongoing (total current duration 69 months) and tolerated well (grade 1 side effects). This case illustrates the long-term benefits that novel therapies like Olaparib may offer in patients with platinum-sensitive relapsed ovarian cancer harboring a rare BRCA mutation. The second case highlights a 55-year-old postmenopausal woman diagnosed with ovarian cancer, FIGO stage IVA. Initial treatment included six cycles of chemotherapy, which led to a partial response, followed by interval debulking surgery and another four cycles of chemotherapy. Subsequent Olaparib maintenance therapy post BRCA1 mutation identification contributed to a significant progression-free survival of 65 months until disease recurrence and secondary cytoreductive surgery, showcasing the effectiveness of PARP inhibitors in personalized oncology treatment of ovarian cancer.

The Use of Artificial Intelligence in Predicting Chemotherapy-Induced Toxicities in Metastatic Colorectal Cancer: A Data-Driven Approach for Personalized Oncology.

BACKGROUND: Machine learning models learn about general behavior from data by finding the relationships between features. Our purpose was to develop a predictive model to identify and predict which subset of colorectal cancer patients are more likely to experience chemotherapy-induced toxicity and to determine the specific attributes that influence the presence of treatment-related side effects. METHODS: The predictor was general toxicity, and for the construction of our data training, we selected 95 characteristics that represent the health state of 74 patients prior to their first round of chemotherapy. After the data were processed, Random Forest models were trained to offer an optimal balance between accuracy and interpretability. RESULTS: We constructed a machine learning predictor with an emphasis on assessing the importance of numerical and categorical variables in relation to toxicity. CONCLUSIONS: The incorporation of artificial intelligence in personalizing colorectal cancer management by anticipating and overseeing toxicities more effectively illustrates a pivotal shift towards more personalized and precise medical care.

Real Check RIO: A Real-World Analysis of Nivolumab in First Line Metastatic Melanoma Assessing Efficacy, Safety and Predictive Factors.

We performed a retrospective study on 51 metastatic melanoma patients treated with Nivolumab in first line, at the Regional Institute of Oncology (RIO) Iasi, Romania between April 2017 and December 2019. We studied the efficacy and safety of anti-PD-1 immune checkpoint inhibitor therapy on a treatment-naive population. After a median follow-up of 36 months, the median progression free survival (PFS) was 26 months (95% CI, 15-36) and the median overall survival (OS) was 31 months (95% CI, 20.1-41.8). At 12 months after the initiation of immunotherapy, the percentage of patients alive was 70%, and at 24 months 62.5%. The most common adverse events observed were dermatological (23.5%) and grade ≥3 was identified in 4 (6.8%) patients. Multivariate analysis indicated that the presence of liver metastases (HR 4.42; 95% CI: 1.88-10.4, p = 0.001) and a neutrophils/lymphocytes ratio (NLR) were associated with poor survival (HR 3.21; 95% CI: 1.04-9.87, p = 0.04). Although retrospective data on a small group of patients were analyzed, we can conclude that our results in RIO are similar to those described in clinical trials and other real-world studies. Our study highlights the potential usefulness of liver metastases and NLR as novel predictive factors in clinical decision-making.