Systematic Review on the Effectiveness and Outcomes of Nivolumab Treatment Schemes in Advanced and Metastatic Cervical Cancer.

Advanced and metastatic cervical cancer remains a formidable challenge in oncology, with immune checkpoint inhibitors such as the PD-1 inhibitor nivolumab emerging as a potential therapeutic option. This systematic review rigorously assesses the effectiveness and outcomes of various nivolumab treatment regimens within this patient cohort, drawing from clinical trials and real-world evidence up to December 2023. Following a comprehensive search across PubMed, Scopus, and Embase, four studies were deemed eligible, involving a collective total of 80 patients. One preliminary trial data were excluded from the final analysis, as well as four other proceedings and abstracts on the efficacy and safety of nivolumab on advanced cervical cancer. The patients' average age across these studies was 48 years, with an average of 38% having an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Notably, 64% of all patients were positive for high-risk HPV, and 71% exhibited PD-L1 positivity, indicating a substantial target population for nivolumab. The analysis revealed a pooled objective response rate (ORR) of 48%, with a disease control rate (DCR) averaging 71%. Moreover, progression-free survival (PFS) at 6 months was observed at an average rate of 50%, reflecting the significant potential of nivolumab in managing advanced stages of the disease. The review highlights the influence of PD-L1 status on response rates and underscores the enhanced outcomes associated with combination therapy approaches. By delineating the variability in treatment efficacy and pinpointing key factors affecting therapeutic response and survival, this systematic review calls for further investigations to refine nivolumab's clinical application, aiming to improve patient outcomes in advanced and metastatic cervical cancer.

Exploring the Influence of Age, Gender and Body Mass Index on Colorectal Cancer Location.

Background and objectives: The global burden of non-communicable diseases like obesity and cancer, particularly colorectal cancer (CRC), is increasing. The present study aimed to investigate the association between CRC location (proximal vs. distal) and patient demographic factors including age, sex, and BMI, as well as cancer stage at diagnosis. Materials and Methods: In this cross-sectional study, data from 830 patients diagnosed with CRC were analyzed. The variables included age, sex, weight, height, BMI, cancer location, and cancer stage at diagnosis. Patients were stratified into three age groups and three BMI categories, and we analyzed the association between cancer location and these variables using Chi-squared tests and multivariate logistic regression. Results: The rectum and ascending colon were the most common locations of malignant neoplasms. No statistically significant differences in cancer location across age groups were observed. Significant differences were found in the BMI across age groups, particularly in the normal weight and overweight categories. Normal weight and obese patients had a higher proportion of Stage 3 and Stage 4 cancers. Obesity emerged as a significant predictor for rectal cancer in a multivariate logistic regression analysis, with an odds ratio of 1.56. However, no significant associations were found between cancer location and other factors like age, gender, or cancer stage. Conclusions: Our study revealed that normal weight and obese patients had a higher proportion of Stage 3 and Stage 4 cancers, with obesity emerging as a significant predictor for rectal cancer. It is important to note that while obesity was found to be a significant predictor for rectal cancer, the development and location of colorectal cancer is likely influenced by various factors beyond those studied here. Therefore, further research is needed to investigate the roles of other potential risk factors, like loss of SIRT6 and adipose tissue homeostasis. Additionally, inflammation associated with microbiota in the colorectal mucosa, systemic gene expression, and visceral obesity may also play important roles in the development and progression of colorectal cancer. Understanding these intricate relationships is crucial for better screening, disease prognosis, and management strategies.

Associations between Body Mass Index and Prostate Cancer: The Impact on Progression-Free Survival.

Background and objectives: This study aimed to evaluate the impact of body mass index on PCa outcomes in our institution and also to find if there are statistically significant differences between the variables. Materials and Methods: A retrospective chart review was performed to extract information about all male patients with prostate cancer between 1 February 2015, and 25 October 2022, and with information about age, weight, height, follow-up, and PSA. We identified a group of 728 patients, of which a total of 219 patients resulted after the inclusion and exclusion criteria were applied. The primary endpoint was progression-free survival, which was defined as the length of time that the patient lives with the disease, but no relapses occur, and this group included 105 patients. In this case, 114 patients had a biological, local or metastatic relapse and were included in the progression group. Results: Our study suggests that prostate cancer incidence rises with age (72 ± 7.81 years) in men with a normal BMI, but the diagnostic age tends to drop in those with higher BMIs, i.e., overweight, and obese in the age range of 69.47 ± 6.31 years, respectively, 69.1 ± 7.51 years. A statistically significant difference was observed in the progression group of de novo metastases versus the absent metastases group at diagnostic (p = 0.04). The progression group with metastases present (n = 70) at diagnostic had a shorter time to progression, compared to the absent metastases group (n = 44), 18.04 ± 11.37 months, respectively, 23.95 ± 16.39 months. Also, PSA levels tend to diminish with increasing BMI classification, but no statistically significant difference was observed. Conclusions: The median diagnostic age decreases with increasing BMI category. Overweight and obese patients are more likely to have an advanced or metastatic prostate cancer at diagnosis. The progression group with metastatic disease at diagnostic had a shorter time to progression, compared to the absent metastases group. Regarding prostate serum antigen, the levels tend to become lower in the higher BMI groups, possibly leading to a late diagnosis.

Antipsychotic polypharmacy in adult patients diagnosed with schizophrenia: A retrospective study.

Antipsychotic polypharmacy (APP) is a common practice in the treatment of schizophrenia. In this study, we aimed to identify the prevalence of APP in our department, as well as the trends associated with co-prescribing antipsychotics. We collected data from the medical records of all 193 inpatients diagnosed with schizophrenia who were admitted to Prof. Dr. Alexandru Obregia Clinical Psychiatry Hospital (Bucharest, Romania), Department 9, during January 2019-December 2019. Demographic characteristics of the patients, clinical diagnosis, psychiatric admission type and duration of hospitalization were examined. Data regarding the antipsychotic regimen at discharge and other psychotropic drugs used were collected. A total of 69 (35.75%) patients received more than 2 antipsychotics upon discharge. Patients treated with APP did not differ in regards to sex, age, education level, employment status, marital status, living situation, type of admission from those receiving antipsychotic monotherapy (APM). Prolonged hospitalization was found to be an independent predictor of APP (P=0.014). Most of the combinations used in our unit included clozapine (47.8%), and the most frequently used treatment in the APP group was the combination of paliperidone and clozapine (14.5%). In the APP group, 30 (43.5%) patients included in their regimen was a long-acting intramuscular antipsychotic. There was no significant difference in terms of the use of mood stabilizers, antiparkinsonian drugs or anxiolytics between the APP and the APM group; yet, a higher prevalence of antidepressant use, although not statistically significant (P=0.067), in the APP group compared to the APM group, was observed. The use of APP as a long-term regimen is a common practice in our department, as it is worldwide. There is a great need for randomized-control trials and evidence-based studies in order to define the safest and most effective combinations of antipsychotics and also the characteristics of patients that may benefit from these combinations.

Treatment Experience and Predictive Factors Associated with Response in Platinum-Resistant Recurrent Ovarian Cancer: A Retrospective Single-Institution Study.

Ovarian cancer (OC) represents the most common and lethal gynecologic malignancy, due to its increased incidence and mortality rate. It is usually diagnosed in advanced stages and, even though surgery and platinum-based treatments are initially efficient, recurrences emerge in over 70% of cases. Although there are multiple options of chemotherapy drugs from which to choose, little is known regarding the best strategy for prolonged survival. Thus, this study aimed to assess the effect that most frequently used chemotherapeutic regimens have upon time-to-treatment-failure (TTF) from the first line and beyond, considering clinical and biological factors which influence the treatment outcome of platinum-resistant recurrent OC. We retrospectively analyzed data from 78 patients diagnosed with platinum-resistant OC, who underwent chemotherapy-based treatment with or without anti-angiogenic therapy at OncoHelp Oncology Center, Romania (January 2016-February 2021). Our study identified positive predictive factors for TTF related to histology (serous carcinoma subtype), anthropometry (age over 60 for patients treated with topotecan with or without bevacizumab), renal function (creatinine levels between 0.65 and 1 mg/dL for patients treated with regimens containing bevacizumab and pegylated liposomal doxorubicin) and treatment choice (bevacizumab in combination with pegylated liposomal doxorubicin or topotecan used from the first line and beyond).

Predictors of the response to nivolumab immunotherapy in the second or subsequent lines for metastatic non-small cell lung cancers.

Checkpoint inhibitors represent the first therapeutic class to replace chemotherapy lines for the treatment of metastatic non-small cell lung cancer (NSCLC), due to improved overall survival and tolerability. Nivolumab, a fully human anti-programmed cell death-1 immunoglobulin G4 monoclonal antibody, is the first immune checkpoint inhibitor approved by the US Food and Drug Administration in 2014 for cases of metastatic melanoma and in 2015 for cases of squamous cell lung cancer and kidney cell cancer. The present study aimed to identify predictive markers (favorable or unfavorable) for time to treatment discontinuation using nivolumab in the second or subsequent line of therapy of metastatic NSCLC cases. Analysis of a group of 78 NSCLC patients treated with nivolumab allowed the identification of negative predictive markers, related to the presence of metastases (adrenal in men under 65 years, liver, brain and the number of metastatic sites) and the hematological profile (neutrophilia at the initiation of treatment and lymphocyte variation at 6 weeks of treatment).

Role of combining neutrophil-to-lymphocyte ratio and pretreatment body mass index in predicting progression-free survival in patients with non-small cell lung cancer treated with nivolumab.

Identifying markers capable of predicting outcomes in lung cancer patients treated with nivolumab represents a growing research interest. The combination of neutrophil-to-lymphocyte ratio (NLR) and body mass index (BMI) may help predict treatment efficacy. Thus, the present study aimed to investigate the influence of NLR and BMI on progression-free survival (PFS) in non-small-cell lung cancer (NSCLC) patients treated with nivolumab. A retrospective study was made on 80 patients with NSCLC that were treated with nivolumab at the OncoHelp Oncology Center, Timisoara, Romania after platinum-based chemotherapy, from January 2018 to April 2020. Patients were administered nivolumab at a dose of 3 mg/m2 or 240 mg total dose, every 2 weeks. The predictive impact of NLR (baseline at 2 and 4 weeks after the start of nivolumab) and BMI for disease progression was assessed. Median PFS for subjects with NLR <3 before treatment was 18.5 weeks, while in subjects with NLR ≥3 was 14 weeks (P=0.50). Median PFS for subjects with NLR2 <3 at 2 weeks after treatment was 21 weeks, while in subjects with NLR2 ≥3, PFS was 14 weeks (P=0.17). Median PFS for subjects with NLR4 <3 at 4 weeks after treatment was 23 weeks, while in subjects with NLR4 ≥3, PFS was 19 weeks (P=0.33). Multivariate analysis for the association with PFS showed that baseline NLR, male sex and BMI were associated independently, thus we could develop a significant statistical model [AUROC=0.76, 95% CI (0.45-0.89), P=0.03], a new predictive score for PFS. The assessment of NLR and BMI may represent simple and useful biomarkers; combining them and taking into consideration the male sex may predict PFS in patients with advanced NSCLC treated with nivolumab.

Anthropometry in the immunotherapy of cutaneous and ocular melanomas.

The height of the adult individual is a balance of the expression of some genetic factors (especially the Y-M 170 haplotype of the Y chromosome) and the environment (nutrition and morbidity during childhood). Higher height is associated with a low risk of developing coronary heart disease, hypertension, gastroesophageal reflux, diaphragmatic hernia, but with a higher risk for atrial fibrillation, venous thromboembolism, intervertebral disc pathology, vasculitis and cancer. The research consisted of a retrospective observational study on patients who received immunotherapy (IT) with nivolumab for cutaneous and ocular melanoma neoplasms. We intended to highlight the associations between the duration of immunotherapy and sex profiles, age, anthropometric data (height, weight). Even though the number of available cases was relatively small (42), an inverse association between the body mass index of the subjects and the duration of immunotherapy could be proved, a more expressed association in case of male patients.

Significance of metastatic topography for the immunotherapy of cutaneous and ocular melanomas.

PD-1 is expressed on the surface of activated T lymphocytes and belongs to the category of negative immune stimuli. Its blocking stimulates the immune response to tumor antigens. Ocular melanomas represent 3-4% of the total melanomas and have metastatic potential, especially to the liver but also to the lungs, skin, and bones. In the case of metastatic melanoma, immunotherapy has a unique role due to the lower frequencies of BRAF mutation in choroidal melanomas and consecutive exclusion from treatment with specific BRAF tyrosine kinase inhibitors. A retrospective observational study was performed in 42 patients who received immunotherapy (IT) with nivolumab for cutaneous and ocular metastatic melanomas, aimed at highlighting the association between the topography of metastases and the duration of immunotherapy until progressive disease. The results indicated the presence of liver metastases as a negative predictive factor for IT duration in patients with melanoma and the presence of lymphatic metastases as a predictive factor for longer IT in patients with melanoma under 65 years old.