Impact of age, tumor characteristics, and treatment on local control and disease outcome in early stage breat cancer : an EORTC translational research project

Dit proefschrift behelst een aantal klinische studies met betrekking tot de behandeling van borstkanker. Zowel aspecten van de locoregionale behandeling, d.w.z. chirurgie en bestraling, als van de systemische behandeling, d.w.z. chemotherapie en hormonale therapie, worden belicht. Het proefschrift bestaat uit drie delen. Het eerste deel behelst de rol van de timing van chemotherapie t.o.v. de operatie bij de behandeling van borstkanker. Hieruit blijkt onder meer dat het geven van chemotherapie voorafgaand aan de operatie leidt tot "krimpen" van het gezwel en derhalve tot een stijging in het aantal borstsparende behandelingen. In deel twee wordt de rol van de locoregionale behandeling, d.w.z. chirurgie en bestraling, bij borstkanker bestudeerd. Tevens worden potenti_le voorspellende factoren voor het optreden van een lokaal recidief bestudeerd. Met name jonge vrouwen die borstsparende therapie ondergaan blijken een verhoogd risico te hebben op het optreden van een lokaal recidief. Het optreden van het lokale recidief lijkt voorspeld te kunnen worden door overexpressie van de tumorcel marker, genaamd PS6K. In deel drie wordt dieper ingegaan op vrouwen jonger dan veertig jaar met borstkanker. Deze groep vrouwen heeft een slechte prognose vergeleken met oudere vrouwen en de oorzaak hiervoor is onduidelijk. Derhalve wordt op dit moment geadviseerd om iedere vrouw jonger dan 35 jaar met borstkanker te behandelen met chemotherapie. In deel 3 wordt aangetoond dat er wel degelijk jonge vrouwen te identificeren zijn met een goede prognose waarbij de vraag gesteld kan worden of het geven van chemotherapie bij deze vrouwen wel noodzakelijk is.LEI Universiteit LeidenChirurgische oncologi

Examiners’ perceptions in surgical education: the blind spot in the assessment of OSCEs

Surgical oncolog

The effect of stereoscopic Augmented Reality visualization on learning anatomy and the modifying effect of visual-spatial abilities: a double-center randomized controlled trial

Health and self-regulatio

Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial

Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated. Partial regression of cutaneous metastases was observed in 8 patients and stable disease in 1 patient, reaching the statistical endpoint of treatment efficacy. Continued treatment induced clinical response in 11 patients, including complete responses in three patients. Seven patients developed vitiligo-like depigmentation on areas of skin that were not treated with MI therapy, indicating a systemic effect of MI therapy. Melanoma-specific antibody responses were induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in 11 of 15 patients tested. These systemic immune responses were significantly increased during therapy as compared to baseline in responding patients. This study shows that MI therapy induces local and systemic anti-melanoma immunity and local regression of cutaneous metastases in 38% of patients, or 52% during prolonged therapy. This study provides proof-of-concept of MI therapy, a low-cost, broadly applicable and well-tolerated treatment for cutaneous melanoma metastases, attractive for further clinical investigation

Management of soft tissue sarcomas in extremities: variation in treatment recommendations and surveillance according to specialty and continent

Background This study aimed to provide an insight into clinical decision-making and surveillance strategy of sarcoma specialists for patients with primary soft tissue sarcoma of the extremities (eSTS). The secondary aim was to quantify the role of patient- and tumor-specific factors in the perioperative management. Methods Members of sarcoma societies were sent a Web-based 21-item survey about eSTS management. The survey concerned only primary resectable high-grade eSTS in adults. Results The study enrolled 396 respondents. The majority of the surgical specialists thought the evidence for perioperative chemotherapy (CTX) for high-grade eSTS was insufficient. Radiotherapy (RTX) was less frequently offered in Asia than in North America and Europe. The specialties and continents also differed regarding the importance of patient and tumor characteristics influencing RTX and CTX recommendation. For surveillance after initial treatment outpatient visits, chest computed tomography (CT) scans, and magnetic resonance images of the extremity were the methods primarily used. The specialists in North America preferred chest CT scan over chest x-ray, whereas those in Asia and Europe had no clear preference. Discussion Specialty and continent are important factors contributing to the variation in clinical practice, treatment recommendations, and surveillance of patients with primary resectable high-grade eSTS.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Stereoscopic three-dimensional visualisation technology in anatomy learning: A meta-analysis

Objectives: The features that contribute to the apparent effectiveness of three-dimensional visualisation technology [3DVT] in teaching anatomy are largely unknown. The aim of this study was to conduct a systematic review and meta-analysis of the role of stereopsis in learning anatomy with 3DVT. Methods: The review was conducted and reported according to PRISMA Standards. Literature search of English articles was performed using EMBASE, MEDLINE, CINAHL EBSCOhost, ERIC EBSCOhost, Cochrane CENTRAL, Web of Science and Google Scholar databases until November 2019. Study selection, data extraction and study appraisal were performed independently by two authors. Articles were assessed for methodological quality using the Medical Education Research Study Quality Instrument and the Cochrane Collaboration's tool for assessing the risk of bias. For quantitative analysis, studies were grouped based on relative between-intervention differences in instructional methods and type of control conditions. Results: A total of 3934 citations were obtained of which 67 underwent a full-text review. Ultimately, 13 randomised controlled trials were included in the meta-analysis. When interactive, stereoscopic 3D models were compared to interactive, monoscopic 3D models within a single level of instructional design, for example isolating stereopsis as the only true manipulated element in the experimental design, an effect size [ES] of 0.53 (95% confidence interval [CI] 0.26-0.80; P <.00001) was found. In comparison with 2D images within multiple levels of instructional design, an effect size of 0.45 (95% CI 0.10-0.81; P <.002) was found. Stereopsis had no effect on learning when utilised with non-interactive 3D images (ES = −0.87, 95% CI −2.09-0.35; P =.16). Conclusion: Stereopsis is an important distinguishing element of 3DVT that has a significant positive effect on acquisition of anatomical knowledge when utilised within an interactive 3D environment. A distinction between stereoscopic and monoscopic 3DVT is essential to make in anatomical education and research

Prognostic value of quantitative [F-18]FDG-PET features in patients with metastases from soft tissue sarcoma

Background: Prognostic biomarkers are pivotal for adequate treatment decision making. The objective of this study was to determine the added prognostic value of quantitative [F-18]FDG-PET features in patients with metastases from soft tissue sarcoma (STS). Methods: Patients with metastases from STS, detected by (re)staging [F-18]FDG-PET/CT at Leiden University Medical Centre, were retrospectively included. Clinical and histopathological patient characteristics and [F-18]FDG-PET features (SUVmax, SUVpeak, SUVmean, total lesion glycolysis, and metabolic tumor volume) were analyzed as prognostic factors for overall survival using a Cox proportional hazards model and Kaplan-Meier methods. Results: A total of 31 patients were included. SUVmax and SUVpeak were significantly predictive for overall survival (OS) in a univariate analysis (p = 0.004 and p = 0.006, respectively). Hazard ratios (HRs) were 1.16 per unit increase for SUVmax and 1.20 per unit for SUVpeak. SUVmax and SUVpeak remained significant predictors for overall survival after correction for the two strongest predictive clinical characteristics (number of lesions and performance status) in a multivariate analysis (p = 0.02 for both). Median SUVmax and SUVpeak were 5.7 and 4.9 g/mL, respectively. The estimated mean overall survival in patients with SUVmax > 5.7 g/mL was 14 months; otherwise, it was 39 months (p 4.9 g/mL, the estimated mean overall survival was 18 months; otherwise, it was 33 months (p = 0.04). Conclusions: In this study, SUVmax and SUVpeak were independent prognostic factors for overall survival in patients with metastases from STS. These results warrant further investigation of metabolic imaging with [F-18]FDG-PET/CT in patients with metastatic STS.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Screening for Hepatitis C Virus Reinfection Using a Behaviour-Based Risk Score among Men Who Have Sex with Men with HIV:Results from a Case–Control Diagnostic Validation Study

We assessed the predictive capacity of the HCV-MOSAIC risk score, originally developed for primary early HCV infection, as a screening tool for HCV reinfection in 103 men who have sex with men (MSM) with HIV using data from the MOSAIC cohort, including MSM with HIV/HCV-coinfection who became reinfected (cases, n = 27) or not (controls, n = 76) during follow-up. The overall predictive capacity of the score was assessed using the area under the receiver operating characteristic (AUROC) curve. The effects of covariates on the receiver operating characteristic (ROC) curve were assessed using parametric ROC regression. The score cut-off validated for primary early infection (≥2.0) was used, from which the sensitivity and specificity were calculated. The AUROC was 0.74 (95% confidence interval (CI) = 0.63–0.84). Group sex significantly increased the predictive capacity. Using the validated cut-off, sensitivity was 70.4% (95%CI = 49.8–86.2%) and specificity was 59.2% (95%CI: 47.3–70.4%). External validation from a cohort of 25 cases and 111 controls, all MSM with HIV, resulted in a sensitivity of 44.0% (95%CI = 24.4–65.1) and specificity of 71.2% (95%CI = 61.8–79.4). The HCV-MOSAIC risk score may be useful for identifying individuals at risk of HCV reinfection. In sexual health or HIV-care settings, this score could help guide HCV-RNA testing in MSM with a prior HCV infection.</p

Personalising sarcoma care using quantitative multimodality imaging for response assessment

Over the last decades, technological developments in the field of radiology have resulted in a widespread use of imaging for personalising medicine in oncology, including patients with a sarcoma. New scanner hardware, imaging protocols, image reconstruction algorithms, radiotracers, and contrast media, enabled the assessment of the physical and biological properties of tumours associated with response to treatment. In this context, medical imaging has the potential to select sarcoma patients who do not benefit from (neo-)adjuvant treatment and facilitate treatment adaptation. Due to the biological heterogeneity in sarcomas, the challenge at hand is to acquire a practicable set of imaging features for specific sarcoma subtypes, allowing response assessment. This review provides a comprehensive overview of available clinical data on imaging-based response monitoring in sarcoma patients and future research directions. Eventually, it is expected that imaging-based response monitoring will help to achieve successful modification of (neo)adjuvant treatments and improve clinical care for these patients. (C) 2021 The Royal College of Radiologists. Published by Elsevier Ltd.Biological, physical and clinical aspects of cancer treatment with ionising radiatio