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Background: Increasing health literacy (HL) in children could be an opportunity for a more health literate future generation. The aim of this scoping review is to provide an overview of how HL is conceptualized and described in the context of health promotion in 9-12-year-old children., Methods: A systematic and comprehensive search for 'health literacy' and 'children' and 'measure' was performed in accordance with PRISMA ScR in PubMed, Embase.com and via Ebsco in CINAHL, APA PsycInfo and ERIC. Two reviewers independently screened titles and abstracts and evaluated full-text publications regarding eligibility. Data was extracted systematically, and the extracted descriptions of HL were analyzed qualitatively using deductive analysis based on previously published HL definitions., Results: The search provided 5,401 original titles, of which 26 eligible publications were included. We found a wide variation of descriptions of learning outcomes as well as competencies for HL. Most HL descriptions could be linked to commonly used definitions of HL in the literature, and some combined several HL dimensions. The descriptions varied between HL dimensions and were not always relevant to health promotion. The educational setting plays a prominent role in HL regarding health promotion., Conclusion: The description of HL is truly diverse and complex encompassing a wide range of topics. We recommend adopting a comprehensive and integrated approach to describe HL dimensions, particularly in the context of health promotion for children. By considering the diverse dimensions of HL and its integration within educational programs, children can learn HL skills and competencies from an early age., (© 2024. The Author(s).)

Objective: Three-dimensional organoid cell cultures have been established for a variety of human cancers. For most rare cancers, including salivary gland cancer (SGC), these models are lacking, despite the great unmet need to study cancer biology in these diseases. Therefore, we aimed to develop patient-derived organoid (PDO) models for different subtypes of SGC., Methods: Tumor samples of SGC patients were processed and embedded in Matrigel. Successful PDOs (expandable > 1*10 6 cells) were phenotypically characterized using immunohistochemistry (IHC) and genotypically by gene fusion analysis and by targeted and whole-exome sequencing. Successfully established PDOs were subjected to small-scale drug screening., Results: Out of 37 attempts, 7 viable short-term PDOs were established (19 % success rate; 3 salivary duct carcinoma, 3 adenoid cystic carcinoma and 1 mucoepidermoid carcinoma). Each PDO showed close phenotypical mimicry to parental tissue. Genotypic characterization revealed that in each PDO > 97.6 % of all COSMIC annotated variants and all MYB, MYBL1 and NFIB gene rearrangements were retained. Drug screening was proven feasible in all PDOs., Conclusion: We present the first comprehensively characterized short-term SGC PDO models for three subtypes of SGC with close phenotypic and genotypic resemblance to parental tissue, which can be used for drug screening applications., Competing Interests: Declaration of Competing Interest GL, WvB, GWV, TWA, OvH, AvEvG, JAS: these authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CvH: has been member of advisory boards for Bayer, Bristol-Myers Squibb, Ipsen, MSD, Regeneron, and Philips Molecular Pathway Diagnostics and has received research grants from AstraZeneca, Bristol-Myers Squibb, MSD, Merck, Ipsen, Novartis, and Sanofi., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cabozantinib is registered in fixed 60 mg dose. However, 46% to 62% of patients in the registration studies needed a dose reduction due to toxicity. Improved clinical efficacy has been observed in renal cell carcinoma patients (RCC) with a cabozantinib exposure greater than 750 μg/L. In our study we explored the cabozantinib exposure in patients with different tumour types. We included RCC patients from routine care and salivary gland carcinoma (SGC) patients from a phase II study with ≥1 measured C min at steady-state. The geometric mean (GM) C min at the starting dose, at 40 mg and at best tolerated dose (BTD) were compared between both tumour types. Forty-seven patients were included. All SGC patients (n = 22) started with 60 mg, while 52% of RCC patients started with 40 mg. GM C min at the start dose was 1456 μg/L (95% CI: 1185-1789) vs 682 μg/L (95% CI: 572-812) (P < .001) for SGC and RCC patients, respectively. When dose-normalised to 40 mg, SGC patients had a significantly higher cabozantinib exposure compared to RCC patients (C min 971 μg/L [95% CI: 790-1193] vs 669 μg/L [95% CI: 568-788]) (P = .005). Dose reductions due to toxicity were needed in 91% and 60% of SGC and RCC patients, respectively. Median BTD was between 20 to 30 mg for SGC and 40 mg for RCC patients. GM C min at BTD were comparable between the SGC and the RCC group, 694 μg/L (95% CI: 584-824) vs 583 μg/L (95% CI: 496-671) (P = .1). The observed cabozantinib exposure at BTD of approximately 600 μg/L is below the previously proposed target. Surprisingly, a comparable exposure at BTD was reached at different dosages of cabozantinib for SGC patients compared to RCC patients Further research is warranted to identify the optimal exposure and starting dose to balance efficacy and toxicity., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Aim: Because the tyrosine kinases c-MET and vascular endothelial growth factor receptors (VEGFR) are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in patients with recurrent/metastatic (R/M) SGC., Patients and Methods: A single-centre phase II study was conducted. Patients with immunohistochemical c-MET-positive R/M SGC were included in three cohorts: adenoid cystic carcinoma (ACC); salivary duct carcinoma (SDC) and other miscellaneous SGCs. No prior systemic treatments were required. Patients started cabozantinib 60 mg once daily. The primary outcome was the objective response rate (ORR). Secondary outcomes included survival, safety and quality of life. Per Simon-two-stage design, depending on efficacy, a maximum of 43 patients would be included., Results: In total, 25 patients were included until premature closure owing to severe toxicity. Six patients (24%) had grade 3-5 wound complications, occurring at a median of 7.1 months on cabozantinib treatment (range 2.1-12.6). Remarkably, four of these six patients developed this complication in the area prior exposed to high-dose radiotherapy. Other grade ≥3 adverse events in >1 patient were hypertension (20%), diarrhoea (8%) and dehydration (8%). Twenty-one patients were evaluable for response; 1/15 ACC (ORR: 7%); 1/4 SDC and 0/2 patients with other miscellaneous SGC responded. Median progression-free survival was 9.4 months (95% confidence interval [CI] 7.4-11.4 months), 7.2 months (95%CI 0.0-15.1) and 6.9 months (95%CI 0.0-15.1), respectively., Conclusion: This study showed too many severe cabozantinib-associated wound complications in patients with SGC, especially in prior irradiated areas. Therefore, the study closed prematurely. The efficacy in the limited number of evaluable patients was low to moderate., Trial Registration: This trial was registered on ClinicalTrials.gov: NCT03729297., Competing Interests: Conflict of interest statement WvB reported no conflict of interest to declare. MU reported no conflict of interest to declare. SK reported no conflict of interest to declare. TD reported no conflict of interest to declare. SW receives research funding from BMS, MSD, Pfizer, Roche, Nextcure, AstraZeneca, Bayer and Lily. MJ reported no conflict of interest to declare. SP reported no conflict of interest to declare. AvE reported no conflict of interest to declare. CvH: Advisory (institution): Bayer, Bristol-Myers Squibb, Ipsen, MSD and Regeneron. Research grant (institution): Astra Zeneca, Bristol-Myers Squibb, MSD, Merck, Ipsen, Novartis and Sanofi. Ipsen Pharmaceuticals: this funding source had no role in the design of this study and did not have any role during its execution, analyses and interpretation of the data. Ipsen provided courtesy review of the article for scientific accuracy and fair balance. The authors were free to accept or decline the feedback provided., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland cancer. Androgen receptor (AR) (96%) and HER2 (29-46%) expression, and a high propensity for regional lymph node metastases are hallmarks of the disease. We hypothesized that c-MET, E-cadherin, PSMA tumor and PSMA neovascular expression may be prognostic factors in SDC., Materials and Methods: Expression levels of these proteins were established on tissue microarrays containing 165 primary SDC tumor specimens. Association with survival was studied with Kaplan-Meier curves, and univariable and multivariable Cox regression models. Furthermore, association with lymph node status, AR and HER2 expression, and gender was studied., Results: We found that patients with high PSMA tumor expression showed a significantly longer overall survival (OS) (median 83 vs. 43 months, P = 0.022), a trend towards a longer DFS (median 51 vs. 22 months, P = 0.094), and significantly reduced hazard ratio for death in the univariable Cox regression model (HR 0.46, P = 0.034). In the multivariable model only a high number of tumor-positive lymph nodes and high age (>80) at diagnosis were prognostic for poor OS. High PSMA tumor expression was also significantly associated with low N-stage (P = 0.001) and expression was higher in women versus men (P = 0.029). High PSMA tumor expression and E-cadherin loss were significantly associated with strong and weak AR-expression, respectively (P = 0.033 and P = 0.007). None of the factors were significantly associated with HER2 expression., Conclusion: c-MET, E-cadherin, and tumor and neovascular PSMA expression are no independent prognostic factors in SDC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Adenoid cystic carcinoma is a rare cancer that arises from secretory glands. Metastases are mainly seen in the lungs and bones. Cardiac metastases are extremely rare; only 1 case has previously been described. In this patient, cardiac metastases were suspected based on CT imaging. Tumor imaging by Ga-prostate-specific membrane antigen (PSMA)-11 PET is mainly used in prostate cancer patients but is also of interest in adenoid cystic carcinoma patients because of high PSMA-ligand uptake in salivary glands. Ga-PSMA-11 PET imaging supported the suspicion of cardiac metastases, because the cardiac lesions showed similar tracer uptake compared with other metastases.

Androgen deprivation therapy (ADT) is first-line palliative treatment in androgen receptor-positive (AR+) salivary duct carcinoma (SDC), and response rates are 17.6-50.0%. We investigated potential primary ADT resistance mechanisms for their predictive value of clinical benefit from ADT in a cohort of recurrent/metastatic SDC patients receiving palliative ADT (n = 30). We examined mRNA expression of androgen receptor (AR), AR splice variant-7, intratumoral androgen synthesis enzyme-encoding genes AKR1C3, CYP17A1, SRD5A1 and SRD5A2, AR protein expression, ERBB2 (HER2) gene amplification and DNA mutations in driver genes. Furthermore, functional AR pathway activity was determined using a previously reported Bayesian model which infers pathway activity from AR target gene expression levels. SRD5A1 expression levels and AR pathway activity scores were significantly higher in patients with clinical benefit from ADT compared to those without benefit. Survival analysis showed a trend toward a longer median progression-free survival for patients with high SRD5A1 expression levels and high AR pathway activity scores. The AR pathway activity analysis, and not SRD5A1 expression, also showed a trend toward better disease-free survival in an independent cohort of locally advanced SDC patients receiving adjuvant ADT (n = 14) after surgical tumor resection, and in most cases a neck dissection (13/14 patients) and postoperative radiotherapy (13/14 patients). In conclusion, we are the first to describe that AR pathway activity may predict clinical benefit from ADT in SDC patients, but validation in a prospective study is needed., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Rationale : Treatment options for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC), major subtypes of salivary gland cancer, are limited. Both tumors often show overexpression of prostate-specific membrane antigen (PSMA). In prostate cancer, PSMA-ligands labeled with 68 Ga or 177 Lu are used for imaging and therapy, respectively. Primary aim of this study in R/M ACC and SDC patients was to systematically investigate 68 Ga-PSMA-uptake by PET/CT imaging to determine if PSMA radionuclide therapy could be a treatment option. Methods : In a prospective phase II study, PET/CT imaging was performed 1 h post injection of 68 Ga-PSMA-HBED-CC in 15 ACC patients and 10 SDC patients. Maximum standardized uptake values (SUV) were determined in tumor lesions. Immunohistochemical PSMA expression was scored in primary tumors and metastatic tissue. Standard imaging (MRI or CT) was performed for comparison. Results : In ACC patients, SUV max ranged from 1.1 to 30.2 with a tumor/liver-ratio >1 in 13 out of 14 evaluable patients (93%). In SDC patients, SUV max ranged from 0.3 to 25.9 with a tumor/liver-ratio >1 in 4 out of 10 patients (40%). We found a large intra-patient inter-metastatic variation in uptake of 68 Ga-PSMA, and immunohistochemistry did not predict ligand uptake in ACC and SDC. Finally, PSMA-PET detected additional bone metastases compared to CT in 2 ACC patients with unexplained pain. Conclusion : In 93% of ACC patients and 40% of SDC patients we detected relevant PSMA-ligand uptake, which warrants to study PSMA radionuclide therapy in these patients. Additionally, our data provide arguments for patient selection and treatment timing. Finally, PSMA-PET imaging has added diagnostic value compared to CT in selected patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Salivary gland cancer (SGC) is a rare malignancy consisting of 22 subtypes with different genetic, histological and clinical characteristics. This rarity and heterogeneity makes systemic treatment of recurrent or metastatic (R/M) disease challenging. Use of chemotherapy is scarcely studied and chemotherapy at best has moderate effects. New therapeutic strategies are therefore warranted, but advances made in SGC are lagging behind on advances made in more common cancers. By unraveling tumor characteristics of SGC, such as genetic alterations and protein expression profiles, therapeutic strategies tailored to the patient's tumor can be rationalized. This genomic profiling and mapping of immunohistochemical expression profiles is essential in the search for a suitable treatment approach. Thereby, it alleviates the paucity in systemic treatment options and can significantly alter the prognosis of patients with R/M SGC. This review aims to give a comprehensive overview of known genetic alterations and expression profiles amenable for targeted therapy in every histological subtype of SGC. We discuss the remaining knowledge gaps and the implications of these targets for future studies and personalized treatments, thereby aiding clinicians faced with this rare and heterogeneous type of cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: Salivary duct carcinoma (SDC), an aggressive subtype of salivary gland cancer, is androgen receptor (AR)-positive in 67-96% of cases. In patients with locally recurrent and metastatic (R/M) AR-positive SDC, androgen deprivation therapy (ADT) has an overall response rate of 18-64.7%. In this study, we describe the efficacy of adjuvant ADT in patients with poor-risk (stage 4a) AR-positive SDC., Methods: This is a retrospective cohort study in which patients with stage 4a AR-positive SDC were offered adjuvant ADT, i.e. bicalutamide, luteinizing hormone-releasing hormone (LHRH) analogue or a combination of these after tumour resection. In the control group, data were collected on patients with stage 4a SDC who underwent a tumour resection but did not receive adjuvant ADT., Results: Twenty-two AR-positive SDC patients were treated with adjuvant ADT for a median duration of 12 months. The control group consisted of 111 SDC patients. After a median follow-up of 20 months in the ADT-treated patients and 26 months in the control group, the 3-year disease-free survival (DFS) was estimated as 48.2% (95% confidence interval [CI] 14.0-82.4%) and 27.7% (95% CI 18.5-36.9%) (P = 0.037). Multivariable Cox regression analysis showed a hazard ratio of 0.138 (95% CI 0.025-0.751, P = 0.022) for DFS and 0.064 (95% CI 0.005-0.764, P = 0.030) for overall survival (OS) in favour of the ADT-treated patients., Conclusion: Poor-risk, AR-positive SDC patients who received adjuvant ADT have a significantly longer DFS compared with patients in the control group, who did not receive adjuvant ADT. For OS, this was just below and above the significance level, in case there was or was no correction for confounders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Previous gait analysis studies of patients with an ankle arthrodesis have reported increased motion in the adjacent joints. However, of similar importance are the forces that act on the ipsi- and contralateral joints and the effect of ankle arthrodesis with regard to balance control. The purpose of the present study was to determine the joint moments and the amount of asymmetrical loading of the ankle and joints adjacent to the ankle in patients after successful ankle arthrodesis. Therefore, 8 patients with a painless ankle fusion were included and assessed using 4 functional tests: preferred and fast speed walking, a sit-to-stand test, and a balance test. The ground reaction force and ankle joint moment were smaller in the fused ankle. During the balance on foam test, the velocity of the center of pressure was significantly larger on the contralateral extremity. In conclusion, ankle arthrodesis leads to small asymmetries in joint moments during gait, indicating greater loading of the contralateral ankle. In addition, the unaffected leg compensates for the operated leg in balance control. Because of the small alterations, overuse of the contralateral ankle is not expected after ankle arthrodesis., (Copyright © 2018 The American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in-situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and-to a lesser extent-HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting., (© 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor-positive. Only limited data are available on androgen deprivation therapy (ADT)., Methods: Patients with advanced androgen receptor-positive salivary duct carcinoma treated with first-line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression-free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care., Results: Thirty-four of 35 patients who were ADT-treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT-treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P = .02)., Conclusion: We recommend ADT in advanced androgen receptor-positive salivary duct carcinoma given its response and clinical benefit. © 2017 Wiley Periodicals, Inc. Head Neck, 2017., (© 2017 The Authors Head & Neck Published by Wiley Periodicals, Inc.)

Objective: Assessing a diverse biomarker panel (NT-proBNP, TNF-α, galectin-3, IL-6, Troponin I, ST2 and sFlt-1) to detect subclinical cardiotoxicity after treatment with anthracyclines., Methods: Of 55 breast cancer patients biomarkers were assessed and echocardiography was performed one year after treatment with anthracyclines., Results: 29.1% of patients showed abnormal biomarker levels: NT-proBNP in 18.2%, TNF-α and Galectin-3 in 7.3%. IL-6, troponin I, ST2 and sFlt-1 were normal in all patients. A correlation between left ventricular ejection fraction (LVEF) and NT-proBNP was observed (r = -0.564, p ≤ 0.01)., Conclusion: The evaluated biomarkers do not contribute to early detection. Future research should focus on NT-proBNP.