Tag: statistics

Target Oncol. 2022 Oct 14. doi: 10.1007/s11523-022-00916-8. Online ahead of print.

ABSTRACT

BACKGROUND: The combination of trifluridine-tipiracil and bevacizumab was compared with trifluridine-tipiracil monotherapy in a randomized, open-label, phase II trial, resulting in a statistically significant and clinically relevant improvement in progression-free survival (PFS), with tolerable toxicity in patients with refractory metastatic colorectal cancer (mCRC); however, evidence supporting the role of this combination in a real-world setting is limited.

OBJECTIVE: The aim of our work was to provide further evidence on the activity and safety of this combination in a real-world series of Western mCRC patients refractory or intolerant to previous therapies.

PATIENT AND METHODS: We conducted a retrospective, observational study of patients with mCRC refractory or intolerant to standard therapies. Patients were treated with trifluridine-tipiracil and bevacizumab. Previous therapy with fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, aflibercept, regorafenib, and cetuximab or panitumumab (only RAS wild-type) was allowed, as was previous participation in clinical trials. Clinicopathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS), PFS, and safety data were retrospectively collected and analyzed.

RESULTS: We recorded 31 patients treated between 1 December 2017 and 30 June 2022. Median age was 69 years (range 38-82 years), 39% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1, tumor location was left-sided in 77% of cases, 54% had synchronous presentation, 35% were RAS mutant, 3% were BRAF mutant, and 71% underwent primary tumor resection; 64% of patients had liver metastases, 55% had lung metastases, and 23% had peritoneal carcinomatosis. The median number of previous treatment lines was 2 (range 0-5), and 84% of patients received at least one previous anti-angiogenic agent. The ORR and DCR were 3% and 71%, respectively. With a median follow-up of 8 months (range 2-39), median PFS was 6 months (95% confidence interval [CI] 3.1-8.9 months) and median OS was 14 months (95% CI 10.1-17.8 months). Adverse events of any grade were reported in 58% of patients. The most common grade 3-4 toxicities were neutropenia (19%) and anemia (6%); 35% of patients required either dose delays or dose reductions due to toxicity. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was administered either on first or subsequent cycles of treatment in 35% of patients. No treatment-related deaths occurred. Sixty percent of the patients who discontinued treatment eventually received one or more lines of subsequent therapy.

CONCLUSIONS: Our series provides further evidence on the activity and safety of the combination of trifluridine-tipiracil and bevacizumab in a real-world series of Western refractory mCRC patients.

PMID:36239883 | DOI:10.1007/s11523-022-00916-8

Cancer Causes Control. 2022 Oct 14. doi: 10.1007/s10552-022-01639-x. Online ahead of print.

ABSTRACT

PURPOSE: Prostate cancer (PCa) is the most commonly diagnosed cancer in men, resulting in a large cancer burden given a relatively higher 5-year survival rate of patients after cancer diagnosis. The underlying etiology of prostate cancer is not well understood. Chronic inflammation plays a significant role in carcinogenesis overall and may be involved in the development of PCa, but immune-related biomarker studies in prostate cancer are limited.

METHODS: The associations of serum concentrations of cytokines, systemic immune biomarkers, with risk of PCa were assessed in a randomly selected sub-cohort (n = 798, mean age = 73 years) of the Osteoporotic Fractures in Men (MrOS) study, a prospective cohort of older men. At baseline, we measured serum interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of PCa was calculated for higher tertile levels of measured individual cytokines relative to the lowest tertile using Cox proportional hazards regression models.

RESULTS: After an average 6 years of follow-up, 59 men developed incident PCa. Men in the middle or highest tertile of IL-10 had a statistically significant 50% lower risk of PCa compared to the lowest tertile (hazard ratio = 0.50, 95% confidence interval = 0.30-0.84). There was no significant association between any of the other cytokines measured and PCa risk.

CONCLUSION: IL-10, an anti-inflammatory cytokine, was associated with lower risk of PCa. Further research of IL-10 and inflammation in relation to PCa development is warranted.

PMID:36239865 | DOI:10.1007/s10552-022-01639-x

Metabolomics. 2022 Oct 14;18(10):78. doi: 10.1007/s11306-022-01941-4.

ABSTRACT

INTRODUCTION: Premature adrenarche (PA) for long time was considered a benign condition but later has been connected to various diseases in childhood and adulthood which remains controversial.

OBJECTIVE: To investigate the effect of premature adrenarche on the metabolic phenotype, and correlate the clinical and biochemical data with the metabolic profile of children with PA.

METHODS: Nuclear magnetic resonance (NMR)-based untargeted and targeted metabolomic approach in combination with multivariate and univariate statistical analysis applied to study the metabolic profiles of children with PA. Plasma, serum, and urine samples were collected from fifty-two children with Idiopathic PA and forty-eight age-matched controls from the division of Pediatric Endocrinology of the University Hospital of Patras were enrolled.

RESULTS: Metabolomic results showed that plasma and serum glucose, myo-inositol, amino acids, a population of unsaturated lipids, and esterified cholesterol were higher and significantly different in PA children. In the metabolic profiles of children with PA and age-matched control group a gradual increase of glucose and myo-inositol levels was observed in serum and plasma, which was positively correlated their body mass index standard deviation score (BMI SDS) values respectively. Urine ¹H NMR metabolic fingerprint of PA children showed positive correlation and a clustering-dependent relationship with their BMI and bone age (BA) respectively.

CONCLUSION: This study provides evidence that PA driven metabolic changes begin during the childhood and PA may has an inductive role in a BMI-driven increase of specific metabolites. Finally, urine may be considered as the best biofluid for identification of the PA metabolism as it reflects more clearly the PA metabolic fingerprint.

PMID:36239863 | DOI:10.1007/s11306-022-01941-4

Mol Cell Biochem. 2022 Oct 14. doi: 10.1007/s11010-022-04579-x. Online ahead of print.

ABSTRACT

Mutation or overexpression renders pan-RAS (rat sarcoma) proteins insensitive to inactivation. Activated pan-RAS communicates signal from the cell surface receptor to activate RAS-MAPK/ERK (RAS-mitogen-activated protein kinases/extracellular signal regulated kinases) signaling and orchestrates epithelial-to-mesenchymal transition-activating transcription factors (EMT-ATFs) reprogramming to induce EMT. Owing to limited studies available in bladder cancer, the present study is taken up to examine the expressions of the EMT-associated markers in pan-RAS-pERK1/2 (pan-RAS-phosphoERK1/2)-positive well-characterized cohort of forty-two non-muscle invasive bladder cancer (NMIBC) and forty-five muscle invasive bladder cancer (MIBC) patients. Immunohistochemical staining was performed on paraffin embedded tissue sections to determine the immunolevels and cellular localization of marker proteins. Semi-quantitative expressions of pan-RAS, pERK1/2, and EMT markers (E-cadherin, Vimentin, N-cadherin, Snail, Slug Twist, and Zeb1) were statistically examined with clinicohistopathological profile of the patients using SPSS, version 20.0 software. The study documents the diagnostic relevance of immunohistochemical expressions of pan-RAS-pERK1/2/EMT-associated markers in order to stratify NMIBC and MIBC patients. Follow-up studies supported the role of altered EMT phenotype in pan-RAS-pERK1/2-activated positive tumors with disease aggressiveness. To the best of our knowledge, our study is the first concluding the impact of altered EMT phenotype via pan-RAS-pERK1/2 axis on the short survival outcome [short overall survival (OS) (p = 0.04), short progression-free survival (PFS) (p = 0.02) and short cancer-specific survival (CSS) (p = 0.03)] of muscle invasive bladder cancer patients.

PMID:36239855 | DOI:10.1007/s11010-022-04579-x

Cell Mol Neurobiol. 2022 Oct 14. doi: 10.1007/s10571-022-01292-7. Online ahead of print.

ABSTRACT

The dorsal hippocampus is involved in behavioral avoidance regulation. It is unclear how experiences such as the neonatal stress of maternal deprivation (MD) and post-weaning environmental enrichment (EE) affect avoidance behavior and the dorsal hippocampal parameters, including neuronal morphology, corticotrophin-releasing hormone (CRH) signaling, and oxytocin receptor (OTR) level. In male BALB/c mice, we found that MD impaired avoidance behavior in the step-on test compared to non-MD and EE rearing conditions could alleviate that partially. MD increased neuronal branches in the CA1 but decreased synaptic connection levels in the CA2, CA3, and DG. Meanwhile, MD increased the CA1’s OTR levels, which negatively correlated with nucleus densities. MD also increased the CA1’s and CA2’s CRH levels, which positively correlated with CRHR1 levels. However, MD statistically elevated the CA3’s CRH receptor 1 (CRHR1) levels, which negatively correlated with nucleus densities and, probably, synaptic connection levels in the CA3. The additive effects of MD and EE maintained similar CRH levels and CRHR1 levels as well as OTR levels in the hippocampal areas as the additive of non-MD and non-EE. However, the presence of MD and EE still decreased the CA1’s neuronal branches and the CA2’s and DG’s synaptic connection levels. The study illustrates how MD and EE affect avoidance behaviors, hippocampal neuron morphology, and CRH and OTR levels. The results indicate that the late-life environmental improvement partially restores the alterations in dorsal hippocampal areas induced by early life stress.

PMID:36239833 | DOI:10.1007/s10571-022-01292-7

Oral Maxillofac Surg. 2022 Oct 14. doi: 10.1007/s10006-022-01123-5. Online ahead of print.

ABSTRACT

PURPOSE: Three-dimensional surgical planning (3-DSP) is becoming commonplace in the management of benign and malignant disease for oral and maxillofacial surgery practice within the last decade. Surgeons utilize a virtual “wrap” to preoperatively delineate and define maxillofacial tumor resection margins. The investigators hypothesized that the use of a wrap is a predictable method to obtain negative bony margins.

METHODS: The investigators implemented a retrospective chart review. The sample was composed of patients over the age of 18 treated at John Peter Smith Health Network and Parkland/UT Southwestern Medical Center who obtained 3-DSP for the pathology of the head and neck, involving the bone, with a virtual wrap utilized for bony margins. The proportion of cases was calculated, descriptive statistics were reported, and binomial exact calculation was performed for confidence intervals. The primary variable analyzed was bony margin status on final histopathology, involved or uninvolved, based on the pathology report.

RESULTS: The sample was composed of 39 cases, one of which was excluded due to aborting the preplanned 3-DSP. Of the 38 included cases, one had involved bony margin on final histopathology (2.6%; 95% confidence limits, 0.1%, 13.8%). There were 16 malignant cases (42%) and 22 benign cases (58%). When stratified by pathology, 1 out of the 16 malignant cases (6.3%; 95% confidence interval, 0.2%, 30%) and 0 out of the 22 benign cases (95% confidence interval, 0%, 15.4%) had an involved bony margin on final histopathology.

CONCLUSION: The results of this preliminary study suggest three-dimensional surgical planning with wrap margins is a predictable method to obtain negative bony margins in benign and malignant disease of the maxillofacial complex. Further studies will focus on compiling prospective data to solidify the accuracy and predictability of using a wrap to obtain negative bony margins.

PMID:36239829 | DOI:10.1007/s10006-022-01123-5

Eur Arch Otorhinolaryngol. 2022 Oct 14. doi: 10.1007/s00405-022-07671-6. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect of surgical procedures (transoral laser microsurgery (TLM) and open partial laryngectomy (OPL)) on the prognosis of patients with early laryngeal cancer.

METHODS: A total of 760 patients diagnosed with early laryngeal cancer (T1-2N0M0) and treated with TLM (n = 416) or OPL (n = 344) between 2004 and 2015 were abstracted from the SEER database. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (SIPTW) were performed to obtain comparable cohorts. The survival rates were estimated by the Kaplan-Meier method, and compared using the log-rank test. Univariate and multivariate Cox regression analyses with a false discovery rate (FDR) correction were applied to contrast the association between two surgical approaches and overall survival (OS) and disease-specific survival (DSS).

RESULTS: The 5-year OS for the TLM group was 79.5% versus 77.7% for the OPL group (P = 0.619). Similar results were revealed for the comparison of 5-year DSS rates (91.1% versus 91.5%, P = 0.891). After PSM and SIPTW balance the confounding factors, no significant difference was observed in the OS and DSS of patients treated with TLM compared to patients treated with OPL. The consistent results were still yielded (all P > 0.05), when stratified by gender, age, year of diagnosis, residence, household income, tumor site, T stage, differentiation, and adjuvant therapy.

CONCLUSION: This study provides strong evidence that there is no significant difference in the prognosis of early laryngeal carcinoma between the treatment of TLM and OPL, which may be helpful to guide the clinical decision-making of these patients.

PMID:36239784 | DOI:10.1007/s00405-022-07671-6

Childs Nerv Syst. 2022 Oct 14. doi: 10.1007/s00381-022-05669-3. Online ahead of print.

ABSTRACT

PURPOSE: Abusive head trauma (AHT) is a major cause of morbidity and mortality in children. Studies on pediatric head injury observe that AHT patients often have a higher incidence of malignant cerebral oedema and, overall, worse prognosis. There are limited studies with a focus on the outcome of decompressive surgery in children with AHT. This is a study undertaken to review our institutional experience on the role of decompressive surgery in AHT patients and objectively assess its outcomes, in corroboration with current literature.

METHODS: This is an ethics-approved, retrospective study. Inclusion criteria consist of all children with a diagnosis of AHT managed by the Neurosurgical Service, KK Women’s and Children’s Hospital. Demographical and clinical variables are incorporated in the statistical analyses.

RESULTS: From 2011 to 2021, a total of 7 patients required decompressive surgery for AHT. Mean age of the cohort was 17.1 months (with the majority of patients being male (n = 5, 71.4%). During the follow-up period, there was 1 mortality (14.3%), 3 patients developed cerebral palsy (42.9%), and 3 patients had post-traumatic epilepsy (42.9%). With regards to functional outcome, 4 patients (57.1%) had a favorable KOSCHI score at 6 months follow-up.

CONCLUSION: Decompressive surgery in children with AHT presents with its own unique challenges. We therein present our neurosurgical experience in decompressive surgery for this extremely vulnerable group of patients. Given the potential role of decompressive surgery in AHT, the development of an objective marker to select such patients who may benefit most from intervention should be the way forward.

PMID:36239781 | DOI:10.1007/s00381-022-05669-3

Nurs Educ Perspect. 2022 Oct 12. doi: 10.1097/01.NEP.0000000000001061. Online ahead of print.

ABSTRACT

This project aimed to explore the cultural competence of third-year undergraduate nursing students. A retrospective, quantitative, quasi-experimental design was used to collect data from 15 undergraduate students who took part in a three-week travel abroad community clinical to Thailand during 2019. Students engaged in reflective journaling. Data were collected before and after travel using the 20-item Cultural Intelligence Scale. Post mean scores were higher than presurveys, indicating that students improved on cultural competency overall. All subcategories showed a positive difference, and the results were overall statistically significant.

PMID:36239770 | DOI:10.1097/01.NEP.0000000000001061

J Natl Cancer Inst. 2022 Oct 14:djac157. doi: 10.1093/jnci/djac157. Online ahead of print.

ABSTRACT

BACKGROUND: There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC).

METHODS: The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values.

RESULTS: Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P < .001). Estrogen receptor-positive ILCs were of lower grade (grade 1 and 2: 90% in ILC vs 72% in IDC) but larger in size (T3 and 4: 14.3% in ILC vs 3.4% in IDC) (corrected P < .001), and since 1990, the mean ILC size detected at diagnosis increased yearly. Patients with estrogen receptor (ER)-positive ILC underwent statistically significantly more mastectomies compared with ER-positive IDC (57% vs 46%). Using Kaplan-Meier analysis, patients with ER-positive ILC had statistically significantly worse disease-free survival and overall survival than ER-positive IDC although 6 times more IDCs were classified as high risk by OncotypeDx Breast Recurrence Score assay.

CONCLUSIONS: This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management.

PMID:36239760 | DOI:10.1093/jnci/djac157