Project description:Breast cancer is one of the most frequent malignancies. The aim of the article is to analyse the cost-utility ratio and budgetary impact of talazoparib treatment for patients with locally advanced or metastatic gBRCA + breast cancer from the perspective of the Spanish National Health System. Analyses were based on the EMBRACA clinical trial and the model was constructed according to "partitioned survival analysis". Two scenarios were considered in order to compare talazoparib with the alternatives of capecitabine, vinorelbine and eribulin: 1. Chemotherapy in patients pre-treated with anthracyclines/taxanes and, 2. A second- and subsequent-line treatment option. Treatment types following relapse were recorded in the mentioned clinical trial. The effectiveness measure used was quality-adjusted life years (QALY). The average health cost of patients treated at 43 months with talazoparib was 84,360.86€, whilst current treatment costs were 26,683.90€. The effectiveness of talazoparib was 1.93 years of survival (1.09 QALY) relative to 1.58 years (0.83 QALY) in the treatment group. The incremental cost-utility ratio was 252,420.04€/QALY. This represents the additional cost required to earn an additional QALY when changing from regular treatment to talazoparib. Regarding budgetary impact, the number of patients susceptible to receiving treatment with between 94 and 202 talazoparib was estimated, according to scenario and likelihood. The 3-year cost difference was between 6.9 and 9 million euros. The economic evaluation conducted shows an elevated incremental cost-utility ratio and budgetary impact. Taking these results into account, the price of talazoparib would have to be lower than that taken as a reference to reach the cost-utility thresholds.
Project description:Antimicrobial resistance is a major public health problem globally. Likewise, forms of tuberculosis (TB) resistant to first- and second-line TB medicines present a major challenge for patients, healthcare workers and healthcare services. In November 2019, the World Health Organization (WHO) convened an independent international expert panel to review new evidence on the treatment of multidrug- (MDR) and rifampicin-resistant (RR) TB, using the Grading of Recommendations Assessment, Development and Evaluation approach.Updated WHO guidelines emerging from this review, published in June 2020, recommend a shorter treatment regimen for patients with MDR/RR-TB not resistant to fluoroquinolones (of 9-11 months), with the inclusion of bedaquiline instead of an injectable agent, making the regimen all oral. For patients with MDR-TB and additional fluoroquinolone resistance, a regimen composed of bedaquiline, pretomanid and linezolid may be used under operational research conditions (6-9 months). Depending on the drug-resistance profile, extent of TB disease or disease severity, a longer (18-20 months) all-oral, individualised treatment regimen may be used. In addition, the review of new data in 2019 allowed the WHO to conclude that there are no major safety concerns on the use of bedaquiline for >6 months' duration, the use of delamanid and bedaquiline together and the use of bedaquiline during pregnancy, although formal recommendations were not made on these topics.The 2020 revision has highlighted the ongoing need for high-quality evidence and has reiterated the need for clinical trials and other research studies to contribute to the development of evidence-based policy.
Project description:One year into the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic, the 2020 San Antonio Breast Cancer Symposium (SABCS) was another large congress held in a virtual format. Despite these circumstances, clinically relevant data were presented, and this short review focuses on developments in the fields of triple-negative breast cancer (TNBC) and metastatic HER2-positive breast cancer. A quality-of-life (QoL) analysis from IMPassion031 showed that adding atezolizumab to neoadjuvant chemotherapy was not associated with a detrimental effect on QoL, while the burden of treatment-induced side effects increased with each cycle of neoadjuvant therapy in both treatment arms. KEYNOTE-355 evaluated the addition of pembrolizumab to chemotherapy as first-line treatment in metastatic TNBC (mTNBC); a significant improvement of progression-free survival (PFS) was reported in the pembrolizumab arm. At the 2020 SABCS, results with respect to different chemotherapy backbones were reported and the benefit of pembrolizumab was maintained irrespective of the type of taxane. Disappointingly, the phase III IPATunity130 study could not confirm a PFS improvement with the AKT inhibitor ipatasertib when added to paclitaxel as first-line treatment in mTNBC. A biomarker analysis from the phase III ASCENT study showed that the antibody-drug conjugate sacituzumab govitecan was superior to chemotherapy by investigator's choice independent of Trop‑2 expression and BRCA mutation status. In HER2-positive breast cancer, the PRECIOUS trial suggested a small albeit significant benefit with reinduction of pertuzumab in later treatment lines in patients progressing on prior dual HER2-blockade in the first- or second-line setting. The HER2-specific tyrosine kinase inhibitor tucatinib when added to trastuzumab and capecitabine was shown to improve PFS and overall survival (OS) over trastuzumab and capecitabine alone in pretreated patients in the randomized HER2CLIMB trial; this benefit was apparently independent of hormone-receptor expression. An update from the DESTINY-Breast01 trial reported a median PFS of 19.4 months with trastuzumab deruxtecan in heavily pretreated patients. Finally, an analysis from the PERTAIN trial with > 6 years median follow-up showed excellent OS in patients with luminal B/HER2-positive receiving first-line trastuzumab/pertuzumab in combination with endocrine therapy suggesting that chemotherapy-free treatment is an option in highly selected patients.
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being the sixth leading cause of mortality worldwide and the fourth in Europe. Globally, it has a mortality/incidence ratio of 98%, and the 5‑year survival rate in Europe is only 3%. Although risk factors, such as obesity, diabetes mellitus, smoking, alcohol consumption and genetic factors, have been identified, the causes of PDAC remain elusive. Additionally, the only curative treatment for PDAC is surgery with negative margins. However, upon diagnosis, ~30% of the patients already present with locally advanced disease. In these cases, a multidisciplinary approach is required to improve disease‑related symptoms and prolong patient survival. In the present article, a comprehensive review of PDAC epidemiology, physiology and treatment is provided. Moreover, guidelines on patient treatment are suggested. Among the different available therapeutic options for the treatment of advanced PDAC, results are modest, most likely due to the complexity of the disease, and so the prognostic remains poor. Molecular approaches based on multi‑omics research are promising and will contribute to groundbreaking personalized medicine. Thus, economic investment that promotes research of pancreatic cancer will be critical to the development of more efficient diagnostic and treatment strategies.
Project description:Ixabepilone (Ixempra) is a member of a new class of cytotoxic agents, the epothilones. Epothilones promote tubulin polymerization in vitro and demonstrate antitumor activity. This article reviews the preclinical and clinical data that have led to the approval of ixabepilone for patients with locally advanced or metastatic breast cancer for whom anthracycline and taxane treatments have failed.
Project description:Background and aimsAcute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy.MethodsThis executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (< 16 years old) patients.ConclusionsThe 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.
Project description:Locally advanced breast cancer (LABC) cases have a varying five-year survival rate, mainly influenced by the tumor response to chemotherapy. Paclitaxel activity (response rate) varies across populations from 21.5% to 84%. There are some reports on genetic traits and paclitaxel; however, there is still considerable residual unexplained variability. In this study, we aimed to test the association between eleven novel markers and tumor response to paclitaxel and to explore if any of them influenced tumor protein expression. We studied a cohort of 140 women with LABC. At baseline, we collected a blood sample (for genotyping), fine needle aspirates (for Western blot), and tumor measurements by imaging. After follow-up, we ascertained the response to paclitaxel monotherapy by comparing the percent change in the pre-, post- tumor measurements after treatment. To allocate exposure, we genotyped eleven SNPs with TaqMan probes on RT-PCR and regressed them to tumor response using linear modeling. In addition, we compared protein expression, between breast tumors and healthy controls, of those genes whose genetic markers were significantly associated with tumor response. After adjusting for multiple clinical covariates, SNPs on the LPHN2, ROBO1, SNTG1, and GRIK1 genes were significant independent predictors of poor tumor response (tumor growth) despite paclitaxel treatment. Moreover, proteins encoded by those genes are significantly downregulated in breast tumor samples.
Project description:Background and purposeTreatment planning of radiotherapy for locally advanced breast cancer patients can be a time consuming process. Artificial intelligence based treatment planning could be used as a tool to speed up this process and maintain plan quality consistency. The purpose of this study was to create treatment plans for locally advanced breast cancer patients using a Convolutional Neural Network (CNN).Materials and methodsData of 60 patients treated for left-sided breast cancer was used with a training, validation and test split of 36/12/12, respectively. The in-house built CNN model was a hierarchically densely connected U-net (HD U-net). The inputs for the HD U-net were 2D distance maps of the relevant regions of interest. Dose predictions, generated by the HD U-net, were used for a mimicking algorithm in order to create clinically deliverable plans.ResultsDose predictions were generated by the HD U-net and mimicked using a commercial treatment planning system. The predicted plans fulfilling all clinical goals while showing small (≤0.5 Gy) statistically significant differences (p < 0.05) in the doses compared to the manual plans. The mimicked plans show statistically significant differences in the average doses for the heart and lung of ≤0.5 Gy and a reduced D2% of all PTVs. In total, ten of the twelve mimicked plans were clinically acceptable.ConclusionsWe created a CNN model which can generate clinically acceptable plans for left-sided locally advanced breast cancer patients. This model shows great potential to speed up the treatment planning process while maintaining consistent plan quality.
Project description:BackgroundEribulin mesylate (ERI; Halaven®) is a microtubule inhibitor approved in the United States for metastatic breast cancer patients with at least two prior chemotherapy regimens for metastatic breast cancer, and in the European Union in locally advanced breast cancer or metastatic breast cancer patients who progressed after at least one chemotherapy for advanced disease. This network meta-analysis compared the efficacy and safety of ERI versus other chemotherapies in this setting.MethodsSystematic searches conducted in MEDLINE, Embase, and the Cochrane Central Register of Clinical Trials identified randomized controlled trials of locally advanced breast cancer/metastatic breast cancer chemotherapies in second- or later-line settings. Efficacy assessment included pre-specified subgroup analysis of breast cancer subtypes. Included studies were assessed for quality using the Centre for Reviews and Dissemination tool. Bayesian network meta-analysis estimated primary outcomes of overall survival and progression-free survival using fixed-effect models. Comparators included: capecitabine (CAP), gemcitabine (GEM), ixabepilone (IXA), utidelone (UTI), treatment by physician's choice (TPC), and vinorelbine (VIN).ResultsThe network meta-analysis included seven trials. Results showed that second- or later-line patients treated with ERI had statistically longer overall survival versus TPC (hazard ratio [HR]: 0.81; credible interval [CrI]: 0.66-0.99) or GEM+VIN (0.62; 0.42-0.90) and statistically longer progression-free survival versus TPC (0.76; 0.64-0.90), but statistically shorter progression-free survival versus CAP+IXA (1.40; 1.17-1.67) and CAP+UTI (1.61; 1.23-2.12). In triple negative breast cancer, ERI had statistically longer overall survival versus CAP (0.70; 0.54-0.90); no statistical differences in progression-free survival were observed in triple negative breast cancer.ConclusionsThis network meta-analysis suggests that ERI may provide an overall survival benefit in the overall locally advanced breast cancer/metastatic breast cancer populations and triple negative breast cancer subgroup compared to standard treatments. These findings support the use of ERI in second- or later-line treatment of patients with locally advanced breast cancer/metastatic breast cancer.