Digging in real-word electronic database for assessing CDK 4/6 inhibitors adherence in breast cancer patients from Romania.

Introduction: It is imperative for patients to respect the prescribed treatments to achieve the anticipated clinical outcomes, including the outpatients receiving oral anti-cancer drugs such as selective cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). With the introduction of three CDK 4/6i drugs in the Romanian pharmaceutical market in 2018, our study aimed to evaluate medication adherence and the influencing factors among patients undergoing treatment with palbociclib, ribociclib, or abemaciclib for advanced or metastatic breast cancer. Methods: Medication adherence was assessed using the Proportion of Days Covered (PDC) method, and Spearman correlation analysis was conducted to explore the relationships between adherence, age, gender, and follow-up duration. Results: The study enrolled 330 breast cancer patients, with an average follow-up period of 14.6 ± 12.5 months for palbociclib, 10.6 ± 7.1 months for ribociclib, and 8.6 ± 6.4 months for abemaciclib-treated patients. A small proportion of patients demonstrated non-adherence: 12.8% for palbociclib, 14.6% for ribociclib, and 14.7% for abemaciclib. Among patients receiving palbociclib, there was no significant correlation between adherence, age (rho = 0.07, p = 0.35), or gender (rho = -0.144, p = 0.054). However, a significant correlation was found with the duration of follow-up (rho = -0.304, p < 0.0001). Similar results were observed for patients receiving ribociclib or abemaciclib. Most patients received combination therapy with letrozole (46%) and exemestane (13%) for palbociclib, letrozole (48%) and fulvestrant (19%) for ribociclib, and fulvestrant (39%) and letrozole (27%) for abemaciclib, Discussion: High adherence rates were observed among patients treated with CDK 4/6i drugs, with no significant differences noted among the three drugs in this class. However, the collected patient data was limited, lacking information on adverse reactions that could potentially lead to treatment discontinuation, as determined by the oncologist's decision not to prescribe. Consequently, a comprehensive understanding of all factors contributing to the low adherence levels is hindered.

Homologous Recombination Deficiency Score Determined by Genomic Instability in a Romanian Cohort.

The Homologous Recombination Deficiency (HRD) Score, determined by evaluating genomic instability through the assessment of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST), serves as a crucial biomarker for identifying patients who might benefit from targeted therapies, such as PARP inhibitors (PARPi). This study aimed to investigate the efficacy of HRD testing in high-grade serous ovarian carcinoma, tubal, and peritoneal cancer patients who are negative for somatic BRCA1 and BRCA2 mutations and to evaluate the impact of HRD status on Bevacizumab and PARPi therapy response. A cohort of 100 Romanian female patients, aged 42-77, was initially selected. Among them, 30 patients had unsuitable samples for HRD testing due to insufficient tumor content or DNA integrity. Using the OncoScan C.N.V. platform, HRD testing was successfully performed on the remaining 70 patients, with 20 testing negative and 50 testing positive for HRD. Among the HRD-positive patients, 35 were eligible for and benefited from PARPi maintenance therapy, resulting in a median progression-free survival (PFS) increase from 4 months to 8.2 months. Our findings support the importance of HRD testing in ovarian cancer patients, demonstrating the potential therapeutic advantage of PARPi therapy in HRD-positive patients without somatic BRCA1/2 mutations.

A systematic review of clinical trials of treatment regimens in HER2-amplified metastatic colorectal cancer.

INTRODUCTION: Targeting HER2 has led to a revolution in therapy for cancers such as breast and gastric cancer, HER2 amplification is rarer (just 2-6%) in colorectal cancer (CRC) and efforts to target this receptor have lagged. Despite recent FDA approval for the first directed therapy combination for HER2 amplified metastatic CRC, the EMA has not yet authorized any such treatment and this represents a persistent unmet need in Europe and beyond. Here, we review data from trials targeting HER2 amplification, the latest target for CRC therapy. AREAS COVERED: PubMed, Cochrane Library, EMBASE, and clinicaltrials.gov were reviewed systematically for possible manuscripts from inception to 1 July 2022. Results: A total of seven studies comprised of 284 locally advanced/mCRC patients receiving HER2 targeting agents were included in this systematic review. Most of the studies (n = 5) were non-randomized phase 2 trials, one phase 2/3 randomized controlled trial, and one phase 2a multiple-basket study. The outcomes consisted in the analysis of HER2 targeting agents and ORR, PFS, OS benefit, and toxicities of the therapy. EXPERT OPINION: Anti-HER2 therapy exhibits a favorable toxicity profile compared with other targeted approaches; however, there is work to be done on optimizing patient selection and understanding resistance mechanisms.

The Bidirectional Relationship between Pulmonary Tuberculosis and Lung Cancer.

Lung cancer and pulmonary tuberculosis are two significant public health problems that continue to take millions of lives each year. They may have similar symptoms and, in some cases, are diagnosed simultaneously or may have a causal relationship. In tuberculosis disease, the chronic inflammation, different produced molecules, genomic changes, and fibrosis are believed to be important factors that may promote carcinogenesis. As a reverse reaction, the development of carcinogenesis and the treatment may induce the reactivation of latent tuberculosis infection. Moreover, the recently used checkpoint inhibitors are a debatable subject since they help treat lung cancer but may lead to the reactivation of pulmonary tuberculosis and checkpoint-induced pneumonitis. Pulmonary rehabilitation is an effective intervention in post-tuberculosis patients and lung cancer patients and should be recommended to improve outcomes in these pathologies.

Diagnostic Accuracy of Machine-Learning Models on Predicting Chemo-Brain in Breast Cancer Survivors Previously Treated with Chemotherapy: A Meta-Analysis.

We performed a meta-analysis of chemo-brain diagnostic, pooling sensitivities, and specificities in order to assess the accuracy of a machine-learning (ML) algorithm in breast cancer survivors previously treated with chemotherapy. We searched PubMed, Web of Science, and Scopus for eligible articles before 30 September 2022. We identified three eligible studies from which we extracted seven ML algorithms. For our data, the χ2 tests demonstrated the homogeneity of the sensitivity's models (χ2 = 7.6987, df = 6, p-value = 0.261) and the specificities of the ML models (χ2 = 3.0151, df = 6, p-value = 0.807). The pooled area under the curve (AUC) for the overall ML models in this study was 0.914 (95%CI: 0.891-0.939) and partial AUC (restricted to observed false positive rates and normalized) was 0.844 (95%CI: 0.80-0.889). Additionally, the pooled sensitivity and pooled specificity values were 0.81 (95% CI: 0.75-0.86) and 0.82 (95% CI: 0.76-0.86), respectively. From all included ML models, support vector machine demonstrated the best test performance. ML models represent a promising, reliable modality for chemo-brain prediction in breast cancer survivors previously treated with chemotherapy, demonstrating high accuracy.

Trifluridine/tipiracil as a therapeutic option in real life setting of metastatic colorectal cancer: An efficacy and safety analysis.

Background: In the phase III RECOURSE trial, the orally administered combination trifluridine/tipiracil (FTD/TPI) demonstrated a survival benefit and an acceptable safety profile, earning approval as a third-line therapy in metastatic colorectal cancer (mCRC). This study aimed to assess the efficacy and safety of FTD/TPI in daily clinical practice in Romanian population. Methods: A single-center, retrospective, and observational study analyzed patients with mCRC that received chemotherapy with trifluridine/tipiracil between May 2019 and May 2022 at the Oncology Institute Prof. Dr. Ion Chiricuța in Cluj-Napoca, Romania. Study endpoints included safety, and median progression-free survival (PFS). Results: In this Romanian cohort (n = 50) the most common treatment-emergent adverse event was haematological toxicity (76%): anemia (50%), leucopenia (38%), neutropenia (34%), and thrombocytopenia (30%), followed by fatigue (60%), and abdominal pain (18%). Overall, the median progression-free survival was 3.85 months (95% CI: 3.1-4.6 months). PFS was significantly correlated with the number of FTD/TPI administrations and prior surgery. Conclusion: Our study corroborated the previously described safety profile for FTD/TPI in the third-line setting, and demonstrated relatively superior mPFS.

How Much Burnout and Coping Influence Quality of Life among Young Oncology Providers in Romania during the COVID-19 Pandemic.

This study aims to investigate the correlations between burnout, coping strategies, and quality of life among young oncology healthcare workers in Romania during the COVID-19 pandemic. We collected the data using an online questionnaire consisting of sociodemographic questions, the Maslach Burnout Inventory, the COPE questionnaire, and the 15D instrument. A total of 122 healthcare providers responded to our survey. We evaluated the differences in the scores among the three groups of healthcare workers in oncology under 40 years old: medical oncologists (n = 87), radiation oncologists (n = 11), and oncology nurses (n = 24). Finally, we conducted a correlation analysis between the dimensions of burnout, coping, and quality of life. Overall, the medical oncologists exhibited much higher burnout levels than nurses in the COVID-19 pandemic outbreak, having statistically significant higher levels of emotional exhaustion, depersonalization, and lack of personal achievement. Some factors were inversely associated with burnout: active approach, planning, positive interpretation and growth, and acceptance. Our findings illustrated a very good level of health-related quality of life (average = 0.93, SD = 0.06), and no statistically significant differences were found in the quality of life between the three groups. This study was the first to identify the profile of young oncology providers in Romania. Our findings may be relevant in creating preventive strategies for burnout and increasing the quality of life in Romanian young oncology providers in future crises.

New Targeted Therapies and Combinations of Treatments for Cervical, Endometrial, and Ovarian Cancers: A Year in Review.

This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year (the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting). Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecological malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review.

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.

Diagnostic Value of Artificial Intelligence-Assisted Endoscopic Ultrasound for Pancreatic Cancer: A Systematic Review and Meta-Analysis.

We performed a meta-analysis of published data to investigate the diagnostic value of artificial intelligence for pancreatic cancer. Systematic research was conducted in the following databases: PubMed, Embase, and Web of Science to identify relevant studies up to October 2021. We extracted or calculated the number of true positives, false positives true negatives, and false negatives from the selected publications. In total, 10 studies, featuring 1871 patients, met our inclusion criteria. The risk of bias in the included studies was assessed using the QUADAS-2 tool. R and RevMan 5.4.1 software were used for calculations and statistical analysis. The studies included in the meta-analysis did not show an overall heterogeneity (I2 = 0%), and no significant differences were found from the subgroup analysis. The pooled diagnostic sensitivity and specificity were 0.92 (95% CI, 0.89-0.95) and 0.9 (95% CI, 0.83-0.94), respectively. The area under the summary receiver operating characteristics curve was 0.95, and the diagnostic odds ratio was 128.9 (95% CI, 71.2-233.8), indicating very good diagnostic accuracy for the detection of pancreatic cancer. Based on these promising preliminary results and further testing on a larger dataset, artificial intelligence-assisted endoscopic ultrasound could become an important tool for the computer-aided diagnosis of pancreatic cancer.

The importance of BMP6 marker within the process of epithelial-mesenchymal transition in the pleomorphic adenoma of the salivary gland.

The pleomorphic adenoma is the most frequently encountered tumor of the salivary glands, representing between 45% and 75% of the total number of the tumors of the salivary glands. According to the literature, there are many studies on the immunohistochemical aspects of the myoepithelial cells, present in the pleomorphic adenoma of the salivary gland. A big diversity of mono and polyclonal antibodies, such as the cytokeratins, muscular proteins and other markers, has been used. In our study, we investigated the immunohistochemical aspect of bone morphogenetic protein 6 (BMP6) marker concerning 15 cases of pleomorphic adenomas of the salivary glands. In the immunohistochemical study, we used the paraffin blocks that served for obtaining the sections necessary for the classical histopathological processing by means of the usual stainings. The immunohistochemical study used the enzymatic detection and the LSAB 2 (Labeled Streptavidin-Biotin 2) System technique as the working method. In order to underline the process of epithelial-mesenchymal transition, we also used double sequential immunohistochemical reactions. By the use of the BMP6 marker, we intended to evaluate the reactivity of the various tumor components in the pleomorphic adenomas of the salivary gland, for this marker, taking into consideration its possible involvement in the process of the epithelial-mesenchymal transition. The maximum reactivity for BMP6 was recorded at the level of the normal, excretory, intratubular units, in the luminal cells of the proliferative ductal units, in the myxoid matrix, the cytoplasm of the myxoid stellate cells and the plasmacytoid matrix and the cytoplasm of the chondroid lacunar cells. Some of the cells belonging to the solid, proliferative areas, some of the abluminal cells, that are part of the proliferative ductal units and certain myxoid stellate or plasmocytoid cells contain the S100 protein, which would indicate the existence of some processes of mesenchymal epithelial÷myoepithelial transdifferentiation in the development of this type of salivary tumor. The BMP6 expression is specific to the serous acini salivary cells, which are the most specialized epithelial salivary gland cells. The study demonstrated that the mesenchymal epithelial÷myoepithelial potential of transdifferentiation of the luminal cells that make up the proliferative units is certified by the immunohistochemical expression of some BMP6 purely mesenchymal protein cells.

Determination of VEGFR-2 (KDR) 604A>G Polymorphism in Pancreatic Disorders.

Pancreatic disorders have a high prevalence worldwide. Despite the fact that screening methods became more effective and the knowledge we have nowadays about pancreatic diseases has enhanced, their incidence remains high. Our purpose was to determine whether single nucleotide polymorphism (SNP) of VEGFR-2/KDR (vascular endothelial growth factor receptor 2/kinase insert domain receptor) influences susceptibility to develop pancreatic pathology. Genomic DNA was extracted from blood samples collected from patients diagnosed with acute pancreatitis (n = 110), chronic pancreatitis (n = 25), pancreatic cancer (n = 82) and healthy controls (n = 232). VEGFR-2 (KDR) 604A>G (rs2071559) polymorphism frequency was determined with TaqMan allelic discrimination assays. Statistical assessment was performed by associating genetic polymorphism with clinical and pathological data. In both pancreatic disorders and healthy control groups the polymorphism we studied was in Hardy-Weinberg equilibrium. Association between increased risk for pancreatic disorders and studied polymorphism was statistically significant. KDR 604AG and AG + GG genotypes were more prevalent in acute pancreatitis and pancreatic cancer patients than in controls. These genotypes influence disease development in a low rate. No association was found between chronic pancreatitis and KDR 604AG and AG + GG genotypes. In Romanian cohort, we found an association between the KDR 604A→G polymorphism and acute pancreatitis and pancreatic cancer. Carriers of the -604G variant allele were more frequent among acute pancreatitis and pancreatic cancer than among controls, suggesting that KDR 604G allele may confer an increased risk for these diseases. In the future, more extensive studies on larger groups are necessary, in order to clarify the role of VEGFR2 polymorphisms in pancreatic pathology.

Rare thymic malignancy of B-cell origin - T-cell÷histiocyte-rich large B-cell lymphoma.

AIM: T-cell÷histiocyte-rich B-cell lymphoma is a rare type of diffuse large B-cell lymphoma reported as involving primarily the thymus only by one paper in the English literature. CASE PRESENTATION: A four and a half years old boy was admitted, after a sudden onset in the middle of the night, with superior vena cava syndrome, resuscitated cardiac and respiratory arrest and severe coma with Glasgow Coma Scale rate of 3. In spite of intensive treatment, the patient repeated twice the cardiac arrest and died sixteen hours after admittance. The autopsy confirmed the existence of a huge mediastinal mass, revealed by the prior to death computed tomography examination, and the thorough histopatological established the diagnosis of T-cell÷histiocyte-rich large B-cell lymphoma of the thymus with renal spread. DISCUSSION: The particularities of the presented case are the primary location of the lesion in the thymus, the age of the patient, very young, the lack of lymph nodes involvement and the rapid development of the disease until death without any possibility of therapeutic specific intervention. CONCLUSIONS: The case is the second reported in the literature with primary involvement of the thymus by this rare variant of diffuse large B-cell lymphoma. The histopatological examination is the golden standard for the diagnosis. Any clinical symptom of unexplained fatigue and dyspnea in a child should raise the clinician's suspicion of a mediastinal mass involving the thymus.

Particularities of associating viral hepatitis with pregnancy and mental disorders.

Pregnancy generates particular circumstances for all co-existent conditions. Associating pregnancy with liver diseases has distinct particularities. The authors will perform a presentation of the etiopathogenic, diagnosis and therapeutic conduct particularities regarding the association between pregnancy, chronic liver diseases and mental disorders. The three pathological entities are analyzed separately, followed by a study of a triple association. Associating pregnancy and mental disorders has been better studied due to a higher frequency of mental disorders, especially postpartum, but the triple association pregnancy, chronic hepatitis with viral etiology mainly, and mental disorders has been less analyzed. There is concluded that pregnancy, through the physiological changes it undergoes, as well as its pathology, represents a clearly influencing factor of the association with a chronic liver disease or with a mental disorder.

Amino acids from Mytilus galloprovincialis (L.) and Rapana venosa molluscs accelerate skin wounds healing via enhancement of dermal and epidermal neoformation.

Wound healing consists of re-epithelialization, contraction and formation of granulation and scar tissue. Amino acids from proteins are involved in these events, but their exact roles are not well understood. The present study was undertaken to investigate the anti-inflammatory effects of some amino acids from two molluscs, Mytilus galloprovincialis (L.) (Mediterranean mussel) and Rapana venosa (hard shell-clam) employed in induced skin burn injuries in Wistar rats. The treatment was evaluated in terms of essential amino acids composition which rendered the extracts very efficient in healing skin burns. The healing process was examined by periodic acid Schiff's, Verhoeff's Van Gieson and immunohistochemistry stains for collagen IV, CD 34 and CD 117 antibodies. According to the obtained results, as expressed by histological studies, the most abundant blood vessels, collagen fibres, basal and stem cells were found only for treated animals with amino acids from Rapana venosa extracts. The rich composition of amino acids from the two molluscs merits consideration as therapeutic agents in the treatment of skin burns.