Search

INTRODUCTION: In recent years, the number of general practices contributing to the Clinical Practice Research Datalink (CPRD) database GOLD is decreasing. Therefore, for research questions addressing for instance novel treatments requiring up-to-date data, sample size will become an important consideration in study feasibility. In recent years, CPRD Aurum, containing information of practices that use EMIS software, has become an additional data source that is being used for CPRD studies. In order to establish whether Aurum is suited to act as data source for future studies in the field of lung cancer research, we aimed to compare characteristics between patients with lung cancer in Aurum and GOLD.METHODS: A retrospective study was performed comparing characteristics and overall survival (OS) of patients with lung cancer in Aurum and GOLD. To further evaluate similarity, hypothetical eligibility of these patients in Aurum and GOLD was compared for 11 randomized clinical trials (RCTs).RESULTS: Baseline characteristics registered in Aurum and GOLD were largely similar, with some clinically irrelevant differences for previous malignancies, deviant laboratory values and drug use. Median OS was 9.8 and 9.0 months for patients in Aurum and GOLD, respectively. Potential RCT eligibility varied between 49.4% and 79.5% and 49.1% and 78.1% for patients in Aurum and GOLD, respectively. Mortality rates and the comparison of the obtained HRs per hypothetical eligibility cohort per RCT were similar in Aurum and GOLD.CONCLUSION: This study showed that data of patients with lung cancer in Aurum and GOLD are largely comparable, suggesting that Aurum is suitable for future epidemiological lung cancer research.

Radboud University, 06 maart 2023, Promotores : Caron, S., Heskes, T.M., Contains fulltext : 289688.pdf (Publisher’s version ) (Closed access)

Item does not contain fulltext

Item does not contain fulltext, Het merendeel van de kinderen vindt het lastig om over traumatische ervaringen te spreken en zal er niet op eigen initiatief over beginnen. Terwijl praten over trauma met belangrijke anderen en vervolgens passende emotionele steun krijgen, de kans op het ontwikkelen van een posttraumatische stressstoornis (PTSS) verkleint. De omgeving is aan zet om dit gesprek aan te gaan maar die voelt zich - vooral bij jonge kinderen - vaak handelingsverlegen. Het project 'Ik wil je iets vertellen' is een reactie op de dagelijkse behandelpraktijk, waarin zowel getraumatiseerde kinderen als volwassenen regelmatig vertellen dat ze als jong kind niet konden delen met anderen wat ze hadden meegemaakt. Het bestaat uit een prentenboek en website die ingezet kunnen worden als hulpmiddel om het gesprek aan te gaan over nare ervaringen, van alledaagse vervelende gebeurtenissen tot trauma’s. Het prentenboek heeft als doel om kinderen te stimuleren om over nare ervaringen te vertellen en voorlezers - of dit nu ouders, docenten of hulpverleners zijn - te helpen om hier goed op te reageren.

Introduction: EGFR tyrosine kinase inhibitor improved the survival of patients with metastatic EGFR mutation-positive (EGFRm+) NSCLC. Despite high response rates, resistance develops inevitably in every patient. In up to 13%, HER2 protein overexpression is found on progression. We hypothesized that dual blockade of EGFR and HER2 by osimertinib combined with trastuzumab-emtansine (T-DM1) could reinduce tumor responses. Methods: In this multicenter, single-arm, phase 1-2 study (NCT03784599), patients with EGFRm+ NSCLC, progressing on osimertinib and HER2 overexpression were included. Patients were treated with T-DM1 3.6 mg/kg (intravenously) every 3 weeks and osimertinib 80 mg once a day. Primary end points were objective response rate (ORR) at 12 weeks and safety. Responses were assessed every 6 weeks (Response Evaluation Criteria in Solid Tumors 1.1). Sample size was calculated using Simon's two-stage minimax design (H0 = 41%, H1 > 55%, 80% power, one-sided type I error 10%: a ORR 16 of 36 was needed to proceed to 58 patients). Results: From January 2019 to April 2021, 27 patients were enrolled. ORR after 12 weeks of treatment was 4% (1 of 27). Median progression-free survival was 2.8 months (95% confidence interval: 1.4–4.6 mo). Most frequent treatment-related adverse events of any grade were fatigue, diarrhea, and nausea, among these, grade 3 in four patients. There were no grade 4 or 5 therapy-related adverse events. Conclusions: TRAEMOS (Trastuzumab-Emtansine and Osimertinib) is the first trial combining T-DM1 and osimertinib in patients with EGFRm+ NSCLC to target HER2 overexpression at osimertinib resistance. Safety profile was favorable compared with cytotoxic chemotherapy; but treatment revealed limited efficacy. Further clinical evaluation of this regimen is not warranted.

This study describes an interlaboratory comparison (ILC) among nine (9) laboratories to evaluate and validate the standard operation procedure (SOP) for single-particle (sp) ICP-TOFMS developed within the context of the Horizon 2020 project ACEnano. The ILC was based on the characterization of two different Pt nanoparticle (NP) suspensions in terms of particle mass, particle number concentration, and isotopic composition. The two Pt NP suspensions were measured using icpTOF instruments (TOFWERK AG, Switzerland). Two Pt NP samples were characterized and mass equivalent spherical sizes (MESSs) of 40.4 ± 7 nm and 58.8 ± 8 nm were obtained, respectively. MESSs showed <16% relative standard deviation (RSD) among all participating labs and <4% RSD after exclusion of the two outliers. A good agreement was achieved between the different participating laboratories regarding particle mass, but the particle number concentration results were more scattered, with <53% RSD among all laboratories, which is consistent with results from previous ILC studies conducted using ICP-MS instrumentation equipped with a sequential mass spectrometer. Additionally, the capabilities of sp-ICP-TOFMS to determine masses on a particle basis are discussed with respect to the potential for particle density determination. Finally, because quasi-simultaneous multi-isotope and multi-element determinations are a strength of ICP-TOFMS instrumentation, the precision and trueness of isotope ratio determinations were assessed. The average of 1000 measured particles yielded a precision of below ±1% for intensity ratios of the most abundant Pt isotopes, i.e. 194Pt and 195Pt, while the accuracy of isotope ratios with the lower abundant isotopes was limited by counting statistics.

The full text of this thesis is not available due to privacy or embargo reasons.

Contains fulltext : 247406.pdf (Publisher’s version ) (Open Access)

Abstract Background This research evaluates the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) as add-on therapy to standard care for adults with schizophrenia from an Australian health system perspective. Methods A Markov model estimated costs in 2021 Australian dollars and Disability-Adjusted Life-Years (DALYs) averted with rTMS added to standard care compared to standard care alone over 12-months for adults aged 25–65 years with hallucinations in schizophrenia refractory to other therapies. rTMS effect size was sourced from a meta-analysis and converted to a relative risk using the Cochrane conversion method. Probabilistic sensitivity analysis evaluated uncertainty in effect size and disability weights. One-way sensitivity analyses varied rTMS session cost and effectiveness, time horizon and inpatient costs. Results The base-case average incremental cost-effectiveness ratio (ICER) was $87,310/DALY averted (95% UI: $10,157–$97,877). Reducing rTMS session cost to $100 lowered the ICER to $9,127/DALY (95% UI: Dominant–$50,699). A 4-year time horizon resulted in rTMS being less costly and more effective (Dominant) than standard care. Decreasing the 3-month probability of relapse with rTMS to 4.6% resulted in a 71% probability of rTMS being cost-effective. Conclusions Using a threshold of $50,000/ DALY averted, rTMS as add-on therapy to standard care for the treatment of refractory hallucinations in schizophrenia would not be considered a cost-effective treatment option compared to standard care

INTRODUCTION : The combination of IO-CT has become the standard of care for patients with aNSCLC with a low or intermediate programmed death-ligand 1 (PD-L1) expression (<50%), and an option for patients with high PDL1 (≥50%) expression. There are no data available on the subsequent line (L2) outcomes after IO-CT. We aimed to assess the outcomes of various L2 treatments after IO-CT in aNSCLC. [...]

Objectives: Exercise has been reported to alleviate disease as well as treatment impact in patients with lung cancer. Nevertheless, there is limited information available regarding the perception of lung cancer dedicated healthcare professionals' and their advice on exercise. Materials and Methods: An online survey exploring healthcare professionals' practice patterns, perceptions, barriers, and facilitators of exercise in patients with lung cancer was conducted within members of the EORTC Lung Cancer Group (LCG).Results: One hundred forty-one healthcare providers completed the survey, mainly medical and radiation oncologists. Overall, 63% of the study participants declared that they frequently assessed exercise level in their patients, and 43% of them reinforced the importance of exercise. However, only 10% referred patients to an exercise program or specialist. Although the majority of the respondents had a positive perception regarding the benefits and safety of exercise (even in patients with advanced disease and/or bone metastasis), two-thirds of clinicians reported not having adequate training about exercise counselling. Moreover, 53% reported to lack of knowledge of guidelines referring to exercise in patients with cancer. Several obstacles and facilitators to improve exercise promotion in lung cancer care were identified.Conclusion: Healthcare providers recognize the relevance and feasibility of exercise as part of cancer treatment intervention, but specific pathways to do the referral are frequently missing. Future structured and well-designed strategies and initiatives are needed to support an effective referral in order to implement exercise interventions routinely in clinical practice.

The standard of care for patients with stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CCRT) followed by one year of adjuvant durvalumab. Despite the survival benefit granted by immunotherapy in this setting, only 1/3 of patients is alive and disease free at 5 years. Novel treatment strategies are under development to improve patient outcomes in this setting: different anti-programmed death-(ligand) 1 (PD-(L)1) antibodies after CCRT, consolidation immunotherapy after sequential chemoradiotherapy (SCRT), induction immunotherapy before CCRT and immunotherapy concurrent with CCRT and/or SCRT. Cross-trial comparison is particularly challenging in this setting due to the different timing of immunotherapy delivery and the difference in patient in- and exclusion criteria. In this review, we present the results of clinical trials investigating immune therapy in unresectable stage III NSCLC and discuss in-depth their biological rationale, their pitfalls and potential benefits. Particular emphasis is placed on the potential mechanisms of synergism between chemotherapy, radiation therapy and different monoclonal antibodies, and how this affects the tumor immune micro-environment. The designs and questions tackled by ongoing clinical trials are also discussed. Last, we address open questions and unmet clinical needs, such as the necessity for predictive biomarkers (e.g. radiomics and ctDNA). Identifying distinct subsets of patients to tailor anti-cancer treatment is a priority, especially in a heterogeneous disease such as stage III NSCLC.