Association between health-related quality-of-life results, outcomes of efficacy and drug approvals: a meta-research study of randomized phase III trials in oncology.

BACKGROUND: Despite the interest from the scientific community and regulatory agencies, limited data are available on the association between health-related quality-of-life (QoL) results, outcome of efficacy and drug approvals. MATERIALS AND METHODS: We updated the previously published meta-research study of phase III clinical trials in patients with solid tumours treated with systemic treatments, published from 2012 to 2021 in 11 selected journals. For the present analysis, we focused on studies conducted in the advanced setting. The primary outcome was the association of global QoL results with study primary endpoints (EP1), overall survival (OS) and progression-free survival (PFS), while a secondary outcome was the frequency of positive global QoL results among treatments approved by regulatory agencies [European Medicines Agency (EMA)/Food and Drug Administration (FDA)]. A descriptive analysis was carried out and the association between QoL results and characteristics of studies and of publications was tested. RESULTS: Five hundred and ninety-two eligible publications were identified from 2012 to 2021. The primary endpoint was OS in 298 clinical trials (50.3%) and PFS in 304 clinical trials (51.4%). A positive result in EP1 analysis was reported in 124 trials (41.6%) with OS as EP1 and in 182 trials (59.5%) with PFS as EP1. Among studies with positive OS and PFS, global QoL results were positive in 39 (31.5%) and 45 studies (24.7%), respectively. FDA and EMA approvals were available for 143 (24.2%) and 142 studies (24%), respectively. Among these, global QoL results were positive in 55 (38.5%) and 56 studies (39.4%), respectively. QoL results were available for most drugs approved by regulatory agencies, but the proportion of approvals with positive global QoL results was not significantly increased from 2012-2016 to 2017-2021. CONCLUSIONS: Despite QoL data being available for most cancer treatments recently approved by regulatory agencies, QoL improvement has been demonstrated in a minority of studies with positive results in the primary endpoint.

Subgroup analyses in randomized phase III trials of systemic treatments in patients with advanced solid tumours: a systematic review of trials published between 2017 and 2020.

BACKGROUND: Subgroup analyses of randomized controlled trials are very common in oncology; nevertheless, the methodological approach has not been systematically evaluated. The present analysis was conducted with the aim of describing the prevalence and methodological characteristics of the subgroup analyses in randomized controlled trials in patients with advanced cancer. METHODS: A systematic literature search using PubMed was carried out to identify all phase III randomized controlled trials conducted in adult patients affected by locally advanced or metastatic solid tumours, published between 2017 and 2020. RESULTS: Overall, 253 publications were identified. Subgroup analyses were reported in 217 (86%) publications. A statistically significant association of presence of subgroup analysis with study sponsor was observed: subgroup analyses were reported in 157 (94%) for-profit trials compared with 60 (70%) non-profit trials (P < 0.001). Description of the methodology of subgroup analysis was completely lacking in 82 trials (38%), only cited without methodological details in 100 trials (46%) and fully described in 35 trials (16%). Forest plot of subgroup analyses for the primary endpoint was available in 195 publications (77%). Among publications with reported forest plots, the median number of subgroups for primary endpoint was 19 (range 6-78). Out of the 217 publications with subgroup analyses, authors discuss the heterogeneity of treatment effect among different subgroups in 173 publications (80%), although a formal test for interaction for subgroup analysis of primary endpoint was reported for at least one variable only in 60 publications (28%). Correction for multiplicity was explicitly carried out only in nine trials (4%). CONCLUSIONS: The very high prevalence of subgroup analyses in published papers, together with their methodological weaknesses, makes advisable an adequate education about their correct presentation and correct reading. More attention about proper planning and conduction of subgroup analysis should be paid not only by readers, but also by authors, journal editors and reviewers.

What is the accuracy of the surgical guide in the planning of orthognathic surgeries? A systematic review.

BACKGROUND: To investigate the true accuracy of the surgical guide in the planning of orthognathic surgeries, which are performed worldwide. MATERIAL AND METHODS: A systematic search was conducted in the PubMed database, Web of science, Scopus and Embase, covering August 2020 to January 2021. Studies that included patients with dentofacial deformity including anteroposterior, vertical and asymmetry problems who were undergoing an orthognathic surgery procedure were included; QUADAS-2 was used to determine the risk of bias by analyzing the quality of the studies. A PRISMA (flowchart) was created to show the study selection, keywords, nomination processes, and inclusion and exclusion criteria. RESULTS: Eleven studies were selected for qualitative and quantitative synthesis. All studies evaluated described high precision of the surgical guide, where the lowest error values were represented by the CAD/CAM technique. CONCLUSIONS: The planning and printing errors related to the guide were all less than 2 mm, and the absolute averages of the errors related to virtual planning in the analysis of the different plans were less than 1 mm. Finally, the measurement of the ANB angle obtained equivalent results between the virtual planning and the traditional.

Overexpression of ALDH1 and EMT marker profile are linked with unfavorable outcome in head and neck cancer.

BACKGROUND: The aim of this research was to assess the expression of aldehyde dehydrogenase 1 (ALDH1) and epithelial-mesenchymal transition (EMT) markers in head and neck squamous cell carcinoma (HNSCC), and to correlate them with the clinical and histopathological parameters of a patient cohort with follow-up over an 8-year period. MATERIAL AND METHODS: For this, seventeen HNSCC and non-neoplastic adjacent epithelium (AE) samples were subjected to laser microdissection and real-time PCR to evaluate the mRNA expression of ALDH1, E-cadherin (E-CAD), N-cadherin (N-CAD), and vimentin (VIM). Also, immunohistochemistry was performed for ALDH1, E-CAD, N-CAD, and VIM in the tumor center (TC), invasion front (IF), and AE of the seventeen samples. Mann-Whitney, Kruskal-Wallis and Chi-square tests were used to correlate the mRNA and immunohistochemical expression with different variables, considering p<0.05. Kaplan-Meier curves were produced for local recurrence, regional metastasis and treatment. RESULTS: A mRNA overexpression of ALDH1 in primary tumors was associated with regional metastasis and a high ALDH1 immunostaining was related to metastasis and a worse patient outcome. Additionally, a favorable outcome was associated with the transition phase and an unfavorable outcome was associated with EMT event. An overall 26.9 months was observed with longer survival associated with surgery and radiotherapy. CONCLUSIONS: However, due to the intense variability inherent to the indicator proteins in the EMT process, the complete profile markers related to this biological process should be continuous investigated.

Evaluation of cone beam computed tomography and periapical radiography in the diagnosis of root resorption.

BACKGROUND: This study aimed to evaluate the accuracy of cone beam computed tomography (CBCT) and periapical radiography in diagnosing root resorption and verify the influence of filling material in detecting these lesions. METHODS: Digital periapical radiographs and CBCT images of patients with root resorption and a history of dental trauma from a radiology clinic were reviewed retrospectively. The sample comprised 40 teeth with root resorption and 20 normal teeth as controls. Images were analysed by two radiologists and two endodontists. The sensitivity, specificity and accuracy were determined. The kappa coefficient assessed interobserver agreement and the t test determined significant differences between the imaging methods. RESULTS: The accuracy of CBCT in diagnosing external (P = 0.0144) and internal (P = 0.0038) inflammatory resorption was significantly higher than for periapical radiography. For replacement resorption, no statistical difference was noted (P > 0.05). In endodontically treated teeth, CBCT was statistically superior in diagnosing root resorption (P = 0.0138). CONCLUSIONS: CBCT was superior to digital periapical radiography in diagnosing external and internal inflammatory root resorption after dental trauma and can be considered in the differential diagnosis of resorptive lesions in teeth with endodontic treatment.