ABSTRACT
Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, convergent studies have provided evidence that host genetic background may contribute to the development of severe coronavirus disease (COVID-19). Here, we summarize how some genetic variations, such as in SARS-CoV-2 receptor angiotensin-converting enzyme 2 or interferon signaling pathway, may help to understand why some individuals can develop severe COVID-19.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/metabolism , Peptidyl-Dipeptidase A/geneticsABSTRACT
BACKGROUND: In the realm of biomedical research, the growing volume, diversity and quantity of data has escalated the demand for statistical analysis as it is indispensable for synthesizing, interpreting, and publishing data. Hence the need for accessible analysis tools drastically increased. StatiCAL emerges as a user-friendly solution, enabling researchers to conduct basic analyses without necessitating extensive programming expertise. RESULTS: StatiCAL includes divers functionalities: data management, visualization on variables and statistical analysis. Data management functionalities allow the user to freely add or remove variables, to select sub-population and to visualise selected data to better perform the analysis. With this tool, users can freely perform statistical analysis such as descriptive, graphical, univariate, and multivariate analysis. All of this can be performed without the need to learn R coding as the software is a graphical user interface where all the action can be performed by clicking a button. CONCLUSIONS: StatiCAL represents a valuable contribution to the field of biomedical research. By being open-access and by providing an intuitive interface with robust features, StatiCAL allow researchers to gain autonomy in conducting their projects.
Subject(s)
Biomedical Research , Software , User-Computer Interface , Computational Biology/methods , Data Management/methods , Data Interpretation, StatisticalABSTRACT
PURPOSE OF REVIEW: There is still a need of biomarkers in the induction and neoadjuvant settings for squamous cell carcinoma of the head and neck (SCCHN). The objective of this concise review article is to give an overview on both predictive and prognostic biomarkers potentially useful for the management of SCCHN. RECENT FINDINGS: Human papilloma virus (HPV) positivity translated by the presence of the protein indicator p16 is synonymous of favorable prognosis SCCHN. However, there is some disparity for disease evolution among p16 positive SCCHN. A lack of correlation between immunohistochemistry (IHC) and precise quantification of active epidermal growth factor receptors (EGFRs) may explain the absence of link between EGFR expression performed by IHC and response to EGFR targeting therapies reported in SCCHN. Circulating tumor cells (CTCs) have the property to share the main somatic mutations and genetic rearrangements with the primary tumors. A particular potential interest lies on the possibility to predict patient outcome based on a single-CTC analysis. SUMMARY: This short review indicates that key biological marker reflecting disease outcome is not yet emerging for a clinical use in SCCHN. Hopes can be put into the so-called liquid biopsies incorporating circulating tumor cells and circulating tumor DNA.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Neoplastic Cells, Circulating , Humans , Head and Neck Neoplasms/genetics , Squamous Cell Carcinoma of Head and Neck , Carcinoma, Squamous Cell/pathology , Biomarkers , ErbB Receptors/genetics , ErbB Receptors/metabolism , Biomarkers, Tumor/metabolismABSTRACT
This ABIGENE pharmacokinetic (PK) study sought mainly to characterize the unchanged drug PK during long-term abiraterone acetate (AA) administration in advanced prostate cancer patients (81 patients). It was observed that individual AA concentrations remained constant over treatment time, with no noticeable changes during repeated long-term drug administration for up to 120 days. There was no correlation between AA concentrations and survival outcomes. However, a significant association between higher AA concentrations and better clinical benefit was observed (p = 0.041). The safety data did not correlate with the AA PK data. A significant positive correlation (r = 0.40, p < 0.001) was observed between mean AA concentration and patient age: the older the patient, the higher the AA concentration. Patient age was found to impact steady-state AA concentration: the older the patient, the higher the mean AA concentration. Altogether, these data may help to guide future research and clinical trials in order to maximize the benefits of AA metastatic castration-resistant prostate cancer patients.
Subject(s)
Abiraterone Acetate , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Abiraterone Acetate/pharmacokinetics , Abiraterone Acetate/therapeutic use , Abiraterone Acetate/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Middle Aged , Aged, 80 and over , Follow-Up Studies , Neoplasm Metastasis , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosageABSTRACT
BACKGROUND: Diagnostic value of 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine ([18F]FDOPA) PET in patients with suspected recurrent gliomas is recognised. We conducted a multicentre prospective study to assess its added value in the practical management of patients suspected of recurrence of high grade gliomas (HGG). METHODS: Patients with a proven HGG (WHO grade III and IV) were referred to the multidisciplinary neuro-oncology board (MNOB) during their follow-up after initial standard of care treatment and when MRI findings were not fully conclusive. Each case was discussed in 2 steps. For step 1, a diagnosis and a management proposal were made only based on the clinical and the MRI data. For step 2, the same process was repeated taking the [18F]FDOPA PET results into consideration. A level of confidence for the decisions was assigned to each step. Changes in diagnosis and management induced by [18F]FDOPA PET information were measured. When unchanged, the difference in the confidence of the decisions were assessed. The diagnostic performances of each step were measured. RESULTS: 107 patients underwent a total of 138 MNOB assessments. The proposed diagnosis changed between step 1 and step 2 in 37 cases (26.8%) and the proposed management changed in 31 cases (22.5%). When the management did not change, the confidence in the MNOB final decision was increased in 87 cases (81.3%). Step 1 had a sensitivity, specificity and accuracy of 83%, 58% and 66% and step 2, 86%, 64% and 71% respectively. CONCLUSION: [18F]FDOPA PET adds significant information for the follow-up of HGG patients in clinical practice. When MRI findings are not straightforward, it can change the management for more than 20% of the patients and increases the confidence level of the multidisciplinary board decisions.
Subject(s)
Brain Neoplasms , Glioma , Humans , Prospective Studies , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/therapy , Radiopharmaceuticals , Positron-Emission Tomography/methods , Sensitivity and Specificity , Dihydroxyphenylalanine , Neoplasm Recurrence, Local , Glioma/diagnostic imaging , Glioma/therapyABSTRACT
PURPOSE: We evaluated the prognostic value of immunotherapy-induced organ inflammation observed on 18FDG PET in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs). METHODS: Data from patients with IIIB/IV NSCLC included in two different prospective trials were analyzed. 18FDG PET/CT exams were performed at baseline (PETBaseline) and repeated after 7-8 weeks (PETInterim1) and 12-16 weeks (PETInterim2) of treatment, using iPERCIST for tumor response evaluation. The occurrence of abnormal organ 18FDG uptake, deemed to be due to ICPI-related organ inflammation, was collected. RESULTS: Exploratory cohort (Nice, France): PETInterim1 and PETInterim2 revealed the occurrence of at least one ICPI-induced organ inflammation in 72.8% of patients, including midgut/hindgut inflammation (33.7%), gastritis (21.7%), thyroiditis (18.5%), pneumonitis (17.4%), and other organ inflammations (9.8%). iPERCIST tumor response was associated with improved progression-free survival (p < 0.001). iPERCIST tumor response and immuno-induced gastritis assessed on PET were both associated with improved overall survival (OS) (p < 0.001 and p = 0.032). Combining these two independent variables, we built a model predicting patients' 2-year OS with a sensitivity of 80.3% and a specificity of 69.2% (AUC = 72.7). Validation cohort (Genova, Italy): Immuno-induced gastritis (19.6% of patients) was associated with improved OS (p = 0.04). The model built previously predicted 2-year OS with a sensitivity and specificity of 72.0% and 63.6% (AUC = 70.7) and 3-year OS with a sensitivity and specificity of 69.2% and 80.0% (AUC = 78.2). CONCLUSION: Immuno-induced gastritis revealed by early interim 18FDG PET in around 20% of patients with NSCLC treated with ICPI is a novel and reproducible imaging biomarker of improved OS.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Gastritis , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/therapy , Fluorodeoxyglucose F18 , Humans , Immunologic Factors , Immunotherapy/adverse effects , Inflammation/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/therapy , Positron Emission Tomography Computed Tomography/methods , Prognosis , Prospective Studies , Retrospective StudiesABSTRACT
Background The phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. Objective We investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary efficacy of the combination of copanlisib, an intravenous, pan-class I PI3K inhibitor, with the anti-EGFR monoclonal antibody cetuximab in recurrent and/or metastatic HNSCC patients in a phase I dose-escalation trial. Patients and methods Copanlisib was given intravenously on days 1, 8, and 15 of 28-day cycles at the dose of 45 mg and 30 mg, in combination with standard doses of weekly cetuximab (400 mg/m2 loading dose followed by 250 mg/m2 on days 8, 15, and 22, and weekly thereafter). Results Three patients received copanlisib 45 mg, of whom two experienced grade 3 hyperglycemia during Cycle 1 that met the DLT criteria. Eight patients were then treated with copanlisib at the dose of 30 mg. Because of the occurrence of hyperglycemia, a premedication with metformine was introduced on the day of the injections. No DLTs were reported at this dose level. The trial was stopped early because of the unfavourable toxicity profile of the combination. Among eight evaluable patients for response, four patients (50%) had disease stabilization according to RECIST1.1 as best response. Conclusion Copanlisib combined with cetuximab demonstrated unfavorable toxicity and limited efficacy in heavily pretreated recurrent and/or metastatic HNSCC patients.Trial registration NCT02822482, Date of registration: June 2016.
Subject(s)
Antineoplastic Agents/therapeutic use , Head and Neck Neoplasms/drug therapy , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Quinazolines/therapeutic use , Squamous Cell Carcinoma of Head and Neck/drug therapy , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Area Under Curve , Cetuximab/therapeutic use , Dose-Response Relationship, Drug , Female , Half-Life , Humans , Male , Maximum Tolerated Dose , Middle Aged , Phosphoinositide-3 Kinase Inhibitors/administration & dosage , Phosphoinositide-3 Kinase Inhibitors/adverse effects , Phosphoinositide-3 Kinase Inhibitors/pharmacokinetics , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Pyrimidines/pharmacokinetics , Quinazolines/administration & dosage , Quinazolines/adverse effects , Quinazolines/pharmacokineticsABSTRACT
OBJECTIVES: To assess patient needs and concerns after head and neck squamous cell carcinoma (HNSCC) treatment and their possible correlations with long-term quality of life (QoL) and to examine the potential impact of psychological distress on these results. METHODS: Alive and disease-free HNSCC patients at least 1 year after treatment were enrolled in this cross-sectional multicentric study and completed the EORTC QLQ-C30 and H&N35 QoL questionnaires, the head and neck cancer-specific patient concerns inventory (PCI-HN) questionnaire and the hospital anxiety and depression scale (HADS). Correlations between QoL outcomes and patient needs and concerns were investigated using Spearman's correlation tests. RESULTS: Seventy-two patients were enrolled in the study. Fear of cancer recurrence was the main patient concern followed by dental, salivary, fatigue, speech, and eating problems. The leading patient needs in terms of consultation were to be referred to the surgeon, the speech, and swallow therapist and the oral rehabilitation team. The number of patient concerns correlated negatively (r < .40) with functioning scales score and positively (r > .40) with general and head and neck symptoms. Psychological distress was the main determinant of QoL outcomes (p < .0001). We found a significant impact of gender (p = .002) on the number of patient concerns, and of patient age (p = .003) on the number of staff members selected by patients. CONCLUSION: Identification of patient needs and concerns along with multidisciplinary management of persistent symptoms and psychological distress seem essential steps towards improving QoL of HNSCC patients.
Subject(s)
Head and Neck Neoplasms , Percutaneous Coronary Intervention , Psychological Distress , Cross-Sectional Studies , Head and Neck Neoplasms/therapy , Humans , Neoplasm Recurrence, Local , Quality of Life , Surveys and QuestionnairesABSTRACT
In therapeutic research, the safety and efficacy of pharmaceutical products are necessarily tested on humans via clinical trials after an extensive and expensive preclinical development period. Methodologies such as computer modeling and clinical trial simulation (CTS) might represent a valuable option to reduce animal and human assays. The relevance of these methods is well recognized in pharmacokinetics and pharmacodynamics from the preclinical phase to postmarketing. However, they are barely used and are poorly regarded for drug approval, despite Food and Drug Administration and European Medicines Agency recommendations. The generalization of CTS could be greatly facilitated by the availability of software for modeling biological systems, by clinical trial studies and hospital databases. Data sharing and data merging raise legal, policy and technical issues that will need to be addressed. Development of future molecules will have to use CTS for faster development and thus enable better patient management. Drug activity modeling coupled with disease modeling, optimal use of medical data and increased computing speed should allow this leap forward. The realization of CTS requires not only bioinformatics tools to allow interconnection and global integration of all clinical data but also a universal legal framework to protect the privacy of every patient. While recognizing that CTS can never replace 'real-life' trials, they should be implemented in future drug development schemes to provide quantitative support for decision-making. This in silico medicine opens the way to the P4 medicine: predictive, preventive, personalized and participatory.
Subject(s)
Clinical Trials as Topic , Drug Development , Medical Oncology , Neoplasms/therapy , Biomedical Research , Computational Biology , Computer Simulation , Drug Approval/legislation & jurisprudence , Europe , Health Policy , Humans , Product Surveillance, Postmarketing , United StatesABSTRACT
Background Checkpoint inhibitors bring marked benefits but only in a minority of patients and may also be associated with severe adverse events. Treatment outcome still cannot be faithfully predicted. The following study hypothesized that host genetics could be applied as predictive biomarkers for checkpoint inhibitor response and immune-related adverse events. We conducted a study based on germinal polymorphisms from genes coding for proteins involved in immune regulation. Methods Germinal DNA was obtained from advanced cancer patients treated with anti-PD-1/PD-L1 checkpoint inhibitors. DNA was genotyped using a custom panel of 166 single nucleotide polymorphisms covering 86 preselected immunogenetic-related genes. Computational analysis using a GTEX portal was made to determine potential expression Quantitative Trait Loci in tissues. Results Ninety-four consecutive patients were included. Objective response rate (complete or partial response) was significantly correlated to tumor microenvironment-related SNPs concerning CCL2, NOS3, IL1RN, IL12B, CXCR3 and IL6R genes. Toxicity were linked to target-related gene SNPs including UNG, IFNW1, CTLA4, PD-L1 and IFNL4 genes. The Area Under the ROC curve (AUC) was 0.81 (95% CI: 0.72-0.9) for response and 0.89 (95% CI: 0.76-1.00) for toxicity. In silico functionality exploring pointed rs4845618 (IL6R), rs10964859 (IFNW1) and rs3087243 (CTLA4) as potentially impacting gene expression. Conclusion These results strongly support a role for distinct immunogenetic-related gene SNPs able to predict efficacy and safety of anti-PD1/PD-L1 therapies. The results highlight the existence of patient-specific, germinal biomarkers able predict response to checkpoint inhibitor efficacy and, possibly, to predict treatment-related adverse events.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Biomarkers, Tumor/genetics , Germ-Line Mutation , Immunogenetics , Neoplasms/mortality , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Immunotherapy , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Pharmacogenomic Testing , Prognosis , Retrospective Studies , Survival RateABSTRACT
AIM: Second ipsilateral breast tumor event (2ndIBTE) occurring after primary radio-surgical treatment can be treated by either salvage mastectomy or 2nd conservative treatment (2ndCT) including an accelerated partial breast re-irradiation (APBrI). We analyzed the impact of the GEC-ESTRO APBI classification (GAC) on the oncological outcome after APBrI. MATERIALS AND METHODS: Between 2000 and 2016, 159 patients (pts) underwent a 2ndCT. After lumpectomy, APBrI was performed using either low-dose (30-55 Gy reference isodose) or high-dose rate brachytherapy (28-34 Gy). Oncological outcome including 3rdIBTE, regional (RFS) or metastasis-free survival (MFS), specific (SS) and overall survival (OS) was analyzed according to GAC. Univariate (UVA) and multivariate analyses (MVA) were conducted to identify significant prognostic factors for 3rdIBTE. RESULTS: With a median follow-up of 71 months (range 62-85 months), 60 pts (42%), 61 pts (42.7%) and 22 pts (15.4%) were classified as low-risk (LR), intermediate-risk (IR) and high-risk (HR), respectively. For the whole cohort, 6-year 3rdIBTE-free survival, RFS, MFS, SS and OS rates were 97.4, 96.4, 90.3, 92.9 and 91.2%, respectively. Six-year 3rdIBTE-free survival rates for LR, IR and HR were 100, 95.8 and 92.9%, respectively (p = 0.003), while no significant differences were found between the three GAC groups for RFS, MFS, SS. In UVA, lympho-vascular invasion (p = 0.009), positive margins (p = 0.0001) and GAC high-risk group (p = 0.001) were considered as significant prognostic factors for 3rdIBTE, while, in MVA, high-risk group (p = 0.009) was the only prognostic factor. CONCLUSION: In case of 2ndIBTE, GAC could be used as a decision helping tool to discuss conservative or radical treatment options. Patient information remains crucial in order to accurately define the salvage therapy modalities.
Subject(s)
Breast Neoplasms/diagnosis , Neoplasms, Second Primary/diagnosis , Adult , Aged , Aged, 80 and over , Brachytherapy/adverse effects , Breast Neoplasms/etiology , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Clinical Decision-Making , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Decision Trees , Disease Management , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Grading , Neoplasm Staging , Neoplasms, Second Primary/etiology , Neoplasms, Second Primary/mortality , Neoplasms, Second Primary/therapy , Radiotherapy Dosage , Retrospective StudiesABSTRACT
Jérôme Barriere was inadvertently missing in the original version of this article. He has participated to the study design, protocol writing and inclusion of a significant number of patients.
ABSTRACT
PURPOSE: This study aimed to assess the therapeutic impact and diagnostic accuracy of 18F-DOPA PET/CT in patients with glioblastoma or brain metastases. METHODS: Patients with histologically proven glioblastoma or brain metastases were prospectively included in this monocentric clinical trial (IMOTEP). Patients were included either due to a clinical suspicion of relapse or to assess residual tumor infiltration after treatment. Multimodality brain MRI and 18F-DOPA PET were performed. Patients' data were discussed during a Multidisciplinary Neuro-oncology Tumor Board (MNTB) meeting. The discussion was first based on clinical and MRI data, and an initial diagnosis and treatment plan were proposed. Secondly, a new discussion was conducted based on the overall imaging results, including 18F-DOPA PET. A second diagnosis and therapeutic plan were proposed. A retrospective and definitive diagnosis was obtained after a 3-month follow-up and considered as the reference standard. RESULTS: One hundred six cases were prospectively investigated by the MNTB. All patients with brain metastases (N = 41) had a clinical suspicion of recurrence. The addition of 18F-DOPA PET data changed the diagnosis and treatment plan in 39.0% and 17.1% of patients' cases, respectively. Concerning patients with a suspicion of recurrent glioblastoma (N = 12), the implementation of 18F-DOPA PET changed the diagnosis and treatment plan in 33.3% of cases. In patients evaluated to assess residual glioblastoma infiltration after treatment (N = 53), 18F-DOPA PET data had a lower impact with only 5.7% (3/53) of diagnostic changes and 3.8% (2/53) of therapeutic plan changes. The definitive reference diagnosis was available in 98/106 patients. For patients with tumor recurrence suspicion, the adjunction of 18F-DOPA PET increased the Younden's index from 0.44 to 0.53 in brain metastases and from 0.2 to 1.0 in glioblastoma, reflecting an increase in diagnostic accuracy. CONCLUSION: 18F-DOPA PET has a significant impact on the management of patients with a suspicion of brain tumor recurrence, either glioblastoma or brain metastases, but a low impact when used to evaluate the residual glioblastoma infiltration after a first-line radio-chemotherapy or second-line bevacizumab.
Subject(s)
Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Clinical Decision-Making , Dihydroxyphenylalanine/analogs & derivatives , Interdisciplinary Communication , Positron Emission Tomography Computed Tomography , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Glioblastoma/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Male , Middle AgedABSTRACT
BACKGROUND: In stage III non-small cell lung cancer (NSCLC) treated with concomitant chemoradiotherapy, there is a high rate of relapse. Some of these relapses are only local and can be treated by stereotactic ablative radiation therapy (SABR). Previous studies reporting outcome after SABR reirradiation of the thorax consisted of a heterogeneous population of various lung cancer stages or even different types of cancer. The purpose of study is to evaluate toxicity and outcome of this strategy in locally relapsed stage III NSCLC only. METHODS: From February 2007 to November 2015, 46 Stage III NSCLC patients treated with SABR, for lung recurrence following conventionally fractionated radiation therapy (CFRT), were retrospectively analyzed. RESULTS: Median follow-up was 47.3 months (1-76.9). The 2 and 4-year progression-free survival (PFS), and overall survival (OS) were of 25.5%/8.6 and 48.9%/30.8%, respectively. Highest presenting toxicity in patients (grade 1 through 5) was: 13 (28.3%), 7 (15.2%), 1 (2.2%), 0 and 2 (4.4%), with deaths due to hemoptysis (n = 1) and alveolitis (n = 1). Although the Biological Effective Dose (at Planning Tumor Volume isocenter) was lower for central tumors treated for an in-field relapse (n = 21, 116 Gy versus 168 Gy, p = 0.005), they had no significant difference in OS than the remaining cohort, but with a higher rate of grade 2-5 toxicities (OR = 0.22, [0.06-0.8], p = 0.02). CONCLUSION: Reirradiation with SABR for local relapse in patients previously treated for stage III NSCLC, is feasible and associated with good outcome. This is also true for central tumors treated for an in-field relapse, but should be radiated with caution to mitigate toxicity.
Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Radiosurgery/adverse effects , Re-Irradiation/adverse effects , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome , Tumor BurdenABSTRACT
Extracellular vesicles (EVs) have been shown to play an important role in intercellular communication as carriers of DNA, RNA and proteins. While the intercellular transfer of miRNA through EVs has been extensively studied, the stability of extracellular miRNA (ex-miRNA) once engulfed by a recipient cell remains to be determined. Here, we identify the ex-miRNA-directed phenotype to be transient due to the rapid decay of ex-miRNA. We demonstrate that the ex-miR-223-3p transferred from polymorphonuclear leukocytes to cancer cells were functional, as demonstrated by the decreased expression of its target FOXO1 and the occurrence of epithelial-mesenchymal transition reprogramming. We showed that the engulfed ex-miRNA, unlike endogenous miRNA, was unstable, enabling dynamic regulation and a return to a non-invasive phenotype within 8 h. This transient phenotype could be modulated by targeting XRN1/PACMAN exonuclease. Indeed, its silencing was associated with slower decay of ex-miR-223-3p and subsequently prolonged the invasive properties. In conclusion, we showed that the 'steady step' level of engulfed miRNA and its subsequent activity was dependent on the presence of a donor cell in the surroundings to constantly fuel the recipient cell with ex-miRNAs and of XRN1 exonuclease, which is involved in the decay of these imported miRNA.
Subject(s)
Epithelial-Mesenchymal Transition/genetics , Exoribonucleases/metabolism , MicroRNAs/metabolism , Microtubule-Associated Proteins/metabolism , Neoplasms/genetics , RNA Stability , Cell Line, Tumor , Exosomes/metabolism , Humans , Neoplasm Invasiveness , Neoplasms/enzymology , Neoplasms/metabolism , Neoplasms/pathology , Neutrophils/metabolismABSTRACT
BACKGROUND: Providing cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate the information given to patients undergoing total pharyngolaryngectomy (TPL) as well as the evolution and predictors of patient quality of life (QoL). METHODS: We conducted a prospective multicentric study on patients undergoing TPL for a locally advanced laryngeal/hypopharyngeal cancer. All patients completed the EORTC QLQ-INFO25, QLQ-C30, and QLQ-H&N35 questionnaires, before and after surgery. RESULTS: This study enrolled 46 patients. Between the pre- and post-therapeutic periods, we observed no significant changes in the global QLQ-INFO25 and QLQ-C30 scores. However, we found a significant deterioration in 4 QLQ-INFO25 scales/items and in social functioning, as well as an increase of sense, speech, and social contact problems. N-stage and professional activity were significant predictors of preoperative QLQ-INFO25 scores. Younger age was significantly associated with financial difficulties, whereas professional activity and lower education level were significant predictors of xerostomia and swallowing problems, respectively. CONCLUSION: In patients undergoing TPL, we observed significant changes in QLQ-INFO25 scores between the pre- and post-treatment periods and, particularly, a deterioration of patient satisfaction with the information received. Several clinical factors were identified as significant predictors of QLQ-INFO25 and QoL scores.
Subject(s)
Hypopharyngeal Neoplasms , Laryngeal Neoplasms , Laryngectomy/education , Patient Education as Topic , Pharyngectomy/education , Postoperative Complications/psychology , Quality of Life , Aged , Female , Humans , Hypopharyngeal Neoplasms/psychology , Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/psychology , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Male , Middle Aged , Patient Education as Topic/methods , Patient Education as Topic/statistics & numerical data , Patient Satisfaction , Pharyngectomy/methods , Prospective Studies , Surveys and QuestionnairesABSTRACT
BACKGROUND: The randomized controlled trial (RCT) is the gold standard to objectively assess the effect of treatments. To help improve the quality of RCTs, experts established a list of recommendations, the CONsolidated Standards of Reporting Trials (CONSORT) Statement. In this study, we evaluated the implementation of the CONSORT Statement in the field of high-grade gliomas in adult patients and looked for criteria associated with higher quality of RCTs. MATERIALS AND METHODS: We searched all high-grade gliomas RCTs published in PubMed between January 1990 and December 2016. The quality of these RCTs was assessed by completing a modified CONSORT Score (CS). RESULTS: Ninety-six published RCTs were identified. The median CS was 19.5 on a scale of 0-33. Items were not equally reported. Items regarding the method of randomization or the blinding were reported in less than 25% of RCTs. However, the CS has constantly improved over the years. Before the implementation of the CONSORT Statement in 1996, the median CS was 13, whereas it was 17 for the period 1996-2004 and 22 after 2005. A higher CS was observed when RCTs were published in a journal with an impact factor above 10 (p < .001) or after 2010 (p = .001), when the primary outcome was clearly defined (p < .001) and for RCTs that enrolled more than 200 patients (p = .004). CONCLUSION: Although there has been a steady improvement in the CS over the years in the field of high-grade gliomas, a major effort must be made in the reporting methods for randomization and blinding. IMPLICATIONS FOR PRACTICE: This study showed that the quality of reporting of randomized control trials (RCTs) concerning the treatment of high-grade gliomas is poor. Factors associated with a better quality of reports were identified and should be incorporated into the design of future RCTs. When clinicians read the results of RCTs, they should be aware of the possible inadequate reporting from these trials and take it into account for the management of their patients. This study identifies how RCTs can be improved in their reporting but also in their design, in order to advance care for patients with high-grade gliomas in the future.
Subject(s)
Brain Neoplasms/therapy , Glioma/therapy , Randomized Controlled Trials as Topic , Research Report/standards , Data Accuracy , Humans , PublishingABSTRACT
BACKGROUND: The benefits of supervised physical activity programs in cardiac rehabilitation have been amply demonstrated, but the quantity of physical activity often declines quickly once supervision ends. This trial assesses the effectiveness of an experimental intervention drawing on habit formation theory to maintain physical activity. METHODS: Cardiovascular patients (N = 47) were randomly assigned to one of two groups. The first group participated in two supervised physical activity (SPA) sessions per week for 20 weeks. The second group was offered a progressively autonomous physical activity (PAPA) program as follows: the same supervised program as the SPA group for 10 weeks and then a further 10 weeks with one supervised session replaced by a strategy to build and sustain the habit of autonomous physical activity. The International Physical Activity Questionnaire (IPAQ; Craig et al. Med Sci Sports Exerc 35(8):1381-1395, 2003) was used to measure the quantity of physical activity, which was the primary outcome. The number of participants was limited, and we thus took multiple IPAQ measurements (at 0, 5, 7, 9 and 12 months after the start of the intervention) and used a mixed model for analysis. Physical condition, automaticity of the physical activity behavior, motivation, and quality of life were examined for changes. RESULTS: No significant between-group differences were noted for physical activity behaviors after the program, physical condition, motivation, or behavioral automaticity. The PAPA group nevertheless completed more PA sessions during the intervention, and their quality of life was significantly higher than that of the SPA group at 12 months. CONCLUSION: Although the number of supervised sessions was lower, the progressively autonomous PA program resulted in the same or even higher positive outcomes than the fully supervised PA program. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77313697 , retrospectively registered on 20 November 2015.
Subject(s)
Cardiac Rehabilitation/methods , Cardiovascular Diseases/therapy , Exercise Therapy/methods , Exercise , Health Behavior , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/psychology , Female , Habits , Health Knowledge, Attitudes, Practice , Health Status , Humans , Male , Middle Aged , Motivation , Personal Autonomy , Quality of Life , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Physical activity programs (PAP) in patients with cardiovascular disease require evidence of cost-utility. To assess improvement in health-related quality of life (QoL) and reduction of health care consumption of patients following PAP, a randomized trial was used. METHODS: Patients from a health insurance company who had experienced coronary artery disease or moderate heart failure were invited to participate (N = 1891). Positive responders (N = 50) were randomly assigned to a progressively autonomous physical activity (PAPA) program or to a standard supervised physical activity (SPA) program. The SPA group had two supervised sessions per week over 5 months. PAPA group had one session per week and support to aid habit formation (written tips, exercise program, phone call). To measure health-related quality of life EQ-5D utility score were used, before intervention, 6 months (T6) and 1 year later. Health care costs were provided from reimbursement databases. RESULTS: Mobility, usual activities and discomfort improved significantly in both group (T6). One year later, EQ-5D utility score was improved in the PAPA group only. Total health care consumption in the intervention group decreased, from a mean of 4097 euros per year before intervention to 2877 euros per year after (p = 0.05), compared to a health care consumption of 4087 euros and 4180 euros per year, in the total population of patients (N = 1891) from the health insurance company. The incremental cost effectiveness ratio was 10,928 euros per QALYs. CONCLUSION: A physical activity program is cost-effective in providing a better quality of life and reducing health care consumption in cardiovascular patients. TRIAL REGISTRATION: ISRCTN77313697 , retrospectively registered on 20 November 2015.
Subject(s)
Cardiac Rehabilitation/economics , Cardiovascular Diseases/economics , Cardiovascular Diseases/therapy , Exercise Therapy/economics , Health Care Costs , Quality of Life , Aged , Cardiac Rehabilitation/methods , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/physiopathology , Cost-Benefit Analysis , Exercise Therapy/methods , Female , France , Health Resources/economics , Humans , Male , Middle Aged , Quality-Adjusted Life Years , Recovery of Function , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Sunitinib is one of the first-line standard treatments for metastatic clear cell renal cell carcinoma (ccRCC) with a median time to progression shorter than 1 year. The objective is to discover predictive markers of response to adapt the treatment at diagnosis. METHODS: Prospective phase 2 multi-centre trials were conducted in ccRCC patients initiating sunitinib (54 patients) or bevacizumab (45 patients) in the first-line metastatic setting (SUVEGIL and TORAVA trials). The plasmatic level of CXCL7 at baseline was correlated with progression-free survival (PFS). RESULTS: The cut-off value of CXCL7 for PFS was 250 ng ml-1. Patients with CXCL7 plasmatic levels above the cut-off at baseline (250 ng ml-1) had a significantly longer PFS (hazard ratio 0.323 (95% confidence interval 0.147-0.707), P=0.001). These results were confirmed in a retrospective validation cohort. The levels of CXCL7 did not influence PFS of the bevacizumab-treated patients. CONCLUSIONS: CXCL7 may be considered as a predictive marker of sunitinib efficacy for ccRCC patients.