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

The global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories:A systematic analysis for the Global Burden of Disease Study 2019

Importance Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.Objective To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence Review The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.Findings In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and Relevance In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Predicting the Feasibility of Curative Resection in Low Rectal Cancer: Insights from a Prospective Observational Study on Preoperative Magnetic Resonance Imaging Accuracy

Background and Objectives: A positive pathological circumferential resection margin is a key prognostic factor in rectal cancer surgery. The point of this prospective study was to see how well different MRI parameters could predict a positive pathological circumferential resection margin (pCRM) in people who had been diagnosed with rectal adenocarcinoma, either on their own or when used together. Materials and Methods: Between November 2019 and February 2023, a total of 112 patients were enrolled in this prospective study and followed up for a 36-month period. MRI predictors such as circumferential resection margin (mCRM), presence of extramural venous invasion (mrEMVI), tumor location, and the distance between the tumor and anal verge, taken individually or combined, were evaluated with univariate and sensitivity analyses. Survival estimates in relation to a pCRM status were also determined using Kaplan–Meier analysis. Results: When individually evaluated, the best MRI predictor for the detection of a pCRM in the postsurgical histopathological examination is mrEMVI, which achieved a sensitivity (Se) of 77.78%, a specificity (Sp) of 87.38%, a negative predictive value (NPV) of 97.83%, and an accuracy of 86.61%. Also, the best predictive performance was achieved by a model that comprised all MRI predictors (mCRM+ mrEMVI+ anterior location+ p Conclusions: The use of selective individual imaging predictors or combined models could be useful for the prediction of positive pCRM and risk stratification for local recurrence or distant metastasis

Landscape of Immunotherapy Options for Colorectal Cancer: Current Knowledge and Future Perspectives beyond Immune Checkpoint Blockade

Colorectal cancer is the third most prevalent malignancy in Western countries and a major cause of death despite recent improvements in screening programs and early detection methods. In the last decade, a growing effort has been put into better understanding how the immune system interacts with cancer cells. Even if treatments with immune checkpoint inhibitors (anti-PD1, anti-PD-L1, anti-CTLA4) were proven effective for several cancer types, the benefit for colorectal cancer patients is still limited. However, a subset of patients with deficient mismatch repair (dMMR)/microsatellite-instability-high (MSI-H) metastatic colorectal cancer has been observed to have a prolonged benefit to immune checkpoint inhibitors. As a result, pembrolizumab and nivolumab +/− ipilimumab recently obtained the Food and Drug Administration approval. This review aims to highlight the body of knowledge on immunotherapy in the colorectal cancer setting, discussing the potential mechanisms of resistance and future strategies to extend its use

The Landscape of Nanovectors for Modulation in Cancer Immunotherapy

Immunotherapy represents a promising strategy for the treatment of cancer, which functions via the reprogramming and activation of antitumor immunity. However, adverse events resulting from immunotherapy that are related to the low specificity of tumor cell-targeting represent a limitation of immunotherapy’s efficacy. The potential of nanotechnologies is represented by the possibilities of immunotherapeutical agents being carried by nanoparticles with various material types, shapes, sizes, coated ligands, associated loading methods, hydrophilicities, elasticities, and biocompatibilities. In this review, the principal types of nanovectors (nanopharmaceutics and bioinspired nanoparticles) are summarized along with the shortcomings in nanoparticle delivery and the main factors that modulate efficacy (the EPR effect, protein coronas, and microbiota). The mechanisms by which nanovectors can target cancer cells, the tumor immune microenvironment (TIME), and the peripheral immune system are also presented. A possible mathematical model for the cellular communication mechanisms related to exosomes as nanocarriers is proposed

Immunotherapy-Related Publications in Colorectal Cancer: A Bibliometric Analysis

Patients with microsatellite-instability-high (MSI-H) or mismatched repair-deficient colorectal cancer (CRC) appear to be responsive to checkpoint inhibitors. This study aimed to assess research trends in CRC immunotherapy. Publication patterns of articles covering immunotherapies in CRC in the Web of Science Core Collection database were retrospectively examined using VOS viewer software (version 1.6.16) prior to 25 May 2021. Ultimately, 3977 records were identified that were published between 1975 and 2021, which received a total of 128,681 citations (an average of 32.36 citations per item), with a noticeable rise in 2014. The majority of articles were published in the US (35.8%), China (17.7%), and Germany (9.4%). Publications mainly originated from the Institut National de la Santé Et De La Recherche Medicale Inserm, followed by the University of Texas System and Harvard University; however, Johns Hopkins University received the most citations (18,666 for 69 publications). The Journal of Clinical Oncology issued the most publications (n = 146), while the most referenced item (7724 citations) was published in the New England Journal of Medicine in 2012. The most common keywords were associated with tumors (expression and microsatellite instability) or immune system components (t-cells/dendritic cells). The findings demonstrate the scientific community’s interest in the MSI-H subtype of colorectal tumors and how immunotherapy may be employed more successfully to treat metastatic CRC