WHAT IS THIS SUMMARY ABOUT?: In this article, we summarize results from the ongoing phase 3 CheckMate 76K clinical study published online in Nature Medicine in October 2023. The study goal was to learn whether nivolumab works as an adjuvant therapy (that is, helps to keep cancer from coming back when it is given after surgery) for stage 2 melanoma (skin cancer) that has not spread to other parts of the body. Nivolumab is an immunotherapy that activates a person's immune system so it can destroy cancer cells. In melanoma, staging describes the severity of the cancer. Melanoma staging ranges from 0 (very thin and confined to the upper layer of the skin) to 4 (spread to distant parts of the body), with earlier stages removed by surgery. The people in this study had stage 2 melanoma that had not spread to the lymph nodes or other organs in the body. HOW WAS THE STUDY DESIGNED?: People 12 years and older with stage 2 melanoma that had not spread and had been removed by surgery were included in CheckMate 76K. People were randomly assigned to receive either nivolumab (526 patients) or placebo (264 patients). A placebo resembles the test medicine but does not contain any active medicines. The researchers assessed whether people who received nivolumab lived longer without their cancer returning and/or spreading to other parts of their bodies (compared with placebo) and if nivolumab was well tolerated. WHAT WERE THE RESULTS?: Researchers found that people who received nivolumab were 58% less likely to have their cancer return and 53% less likely of having their cancer spread to distant parts of their body, compared with placebo. These reductions in risk with nivolumab were seen in different subgroups of people with a range of characteristics, and regardless of how deep the melanoma had gone into the skin. People taking nivolumab had more side effects than those taking placebo, but most were mild to moderate and manageable. WHAT DO THE RESULTS MEAN?: Results from CheckMate 76K support the benefit of using nivolumab as a treatment option for people with stage 2 melanoma post-surgery.
- MeSH
- ipilimumab terapeutické užití MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- melanom * patologie MeSH
- nádory kůže * farmakoterapie chirurgie etiologie MeSH
- nivolumab MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients with resected stage IIB/C melanoma randomized 2:1 (stratified by tumor category) to nivolumab 480 mg or placebo every 4 weeks for 12 months. The primary endpoint was investigator-assessed recurrence-free survival (RFS). Secondary endpoints included distant metastasis-free survival (DMFS) and safety. At 7.8 months of minimum follow-up, nivolumab significantly improved RFS versus placebo (hazard ratio (HR) = 0.42; 95% confidence interval (CI): 0.30-0.59; P < 0.0001), with 12-month RFS of 89.0% versus 79.4% and benefit observed across subgroups; DMFS was also improved (HR = 0.47; 95% CI: 0.30-0.72). Treatment-related grade 3/4 adverse events occurred in 10.3% (nivolumab) and 2.3% (placebo) of patients. One treatment-related death (0.2%) occurred with nivolumab. Nivolumab is an effective and generally well-tolerated adjuvant treatment in patients with resected stage IIB/C melanoma. ClinicalTrials.gov identifier: NCT04099251 .
- MeSH
- adjuvancia imunologická MeSH
- dvojitá slepá metoda MeSH
- lidé MeSH
- maligní melanom kůže MeSH
- melanom * farmakoterapie chirurgie MeSH
- nádory kůže * farmakoterapie chirurgie MeSH
- nivolumab MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
The combination of liquid biomarkers from a single blood tube can provide more comprehensive information on tumor development and progression in cancer patients compared to single analysis. Here, we evaluated whether a combined analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and circulating cell-free microRNA (miRNA) in total plasma and extracellular vesicles (EV) from the same blood sample is feasible and how the results are influenced by the choice of different blood tubes. Peripheral blood from 20 stage IV melanoma patients and five healthy donors (HD) was collected in EDTA, Streck, and Transfix tubes. Peripheral blood mononuclear cell fraction was used for CTC analysis, whereas plasma and EV fractions were used for ctDNA mutation and miRNA analysis. Mutations in cell-free circulating DNA were detected in 67% of patients, with no significant difference between the tubes. CTC was detected in only EDTA blood and only in 15% of patients. miRNA NGS (next-generation sequencing) results were highly influenced by the collection tubes and could only be performed from EDTA and Streck tubes due to hemolysis in Transfix tubes. No overlap of significantly differentially expressed miRNA (patients versus HD) could be found between the tubes in total plasma, whereas eight miRNA were commonly differentially regulated in the EV fraction. In summary, high-quality CTCs, ctDNA, and miRNA data from a single blood tube can be obtained. However, the choice of blood collection tubes is a critical pre-analytical variable.
- MeSH
- cirkulující nádorová DNA krev MeSH
- extracelulární vezikuly genetika metabolismus ultrastruktura MeSH
- lidé MeSH
- melanom krev patologie MeSH
- mikro RNA krev genetika MeSH
- mutace MeSH
- nádorové biomarkery krev genetika MeSH
- nádorové buněčné linie MeSH
- nádorové cirkulující buňky metabolismus MeSH
- senioři MeSH
- staging nádorů MeSH
- tekutá biopsie přístrojové vybavení metody MeSH
- transmisní elektronová mikroskopie MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
As the development of the Internet and social media has led to pervasive data collection and usage practices, consumers' privacy concerns have increasingly grown stronger. While previous research has investigated consumer valuation of personal data and privacy, only few studies have investigated valuation of different privacy aspects (e.g., third party sharing). Addressing this research gap in the literature, the present study explores Internet users' valuations of three different privacy aspects on a social networking service (i.e., Facebook), which are commonly captured in privacy policies (i.e., data collection, data control, and third party sharing). A total of 350 participants will be recruited for an experimental online study. The experimental design will consecutively contrast a conventional, free-of-charge version of Facebook with four hypothetical, privacy-enhanced premium versions of the same service. The privacy-enhanced premium versions will offer (1) restricted data collection on side of the company; (2) enhanced data control for users; and (3) no third party sharing, respectively. A fourth premium version offers full protection of all three privacy aspects. Participants' valuation of the privacy aspects captured in the premium versions will be quantified measuring willingness-to-pay. Additionally, a psychological test battery will be employed to examine the psychological mechanisms (e.g., privacy concerns, trust, and risk perceptions) underlying the valuation of privacy. Overall, this study will offer insights into valuation of different privacy aspects, thus providing valuable suggestions for economically sustainable privacy enhancements and alternative business models that are beneficial to consumers, businesses, practitioners, and policymakers, alike.
- Publikační typ
- časopisecké články MeSH
- MeSH
- imidazoly terapeutické užití toxicita MeSH
- klinické zkoušky, fáze III jako téma * metody využití MeSH
- lidé MeSH
- melanom * farmakoterapie sekundární terapie MeSH
- metastázy nádorů farmakoterapie genetika terapie MeSH
- multicentrické studie jako téma MeSH
- oximy škodlivé účinky terapeutické užití MeSH
- placeba MeSH
- protoonkogenní proteiny B-raf * genetika izolace a purifikace MeSH
- pyridony terapeutické užití toxicita MeSH
- pyrimidinony škodlivé účinky terapeutické užití MeSH
- randomizované kontrolované studie jako téma metody využití MeSH
- statistika jako téma MeSH
- výsledky a postupy - zhodnocení (zdravotní péče) trendy využití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: The accuracy of diagnosis of skin cancer and especially of early malignant melanoma is most important to reduce its morbidity and mortality. Previous pilot studies using electrical impedance measurements indicate statistically significant accuracies for the detection of skin cancer. OBJECTIVES: The aim of this study is to investigate the accuracy of electrical impedance spectra to distinguish between malignant melanoma and benign skin lesions using an automated classification algorithm. PATIENTS/METHODS: Electrical impedance spectra were measured in a multi-centre study at 12 clinics around Europe. Data from 285 histologically analysed lesions were used to train an algorithm to sort out lesions for automatic detection of melanoma. Another data cohort of 210 blinded lesions (148 various benign lesions and 62 malignant melanomas where 38 being from Breslow thickness ≤1 mm) from 183 patients was thereafter used to estimate the accuracy of the technique. RESULTS: Observed sensitivity to malignant melanoma is 95% (59/62) and observed specificity 49% (72/148). CONCLUSIONS: The results suggest that electrical impedance spectra can distinguish between malignant melanoma and benign skin lesions. Although it is indicated that the accuracy of the device is clinically promising, the overall performance, and the sensitivity to thin malignant melanomas, must be improved and thoroughly validated before the instrument can be used as a routine stand-alone diagnostic decision support tool. The technique is under revision to further improve the reproducibility, specificity and sensitivity.
- MeSH
- algoritmy * MeSH
- impedanční spektroskopie metody MeSH
- lidé MeSH
- melanom diagnóza MeSH
- nádory kůže diagnóza MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Maďarsko MeSH
- Německo MeSH
- Spojené království MeSH
- Švédsko MeSH
