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Background: Availability of potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) has pushed the median survival of ALK+ non-smallcell lung cancer (NSCLC) patients to over five years. In particular, second-generation ALK TKI have demonstrated superiority compared to the first-generation compound crizotinib and are meanwhile standard first-line treatment. However, clinical courses of individual patients vary widely, with secondary development of drug resistance and intracranial progression remaining important problems. While these limitations highlight the need for better disease monitoring and additional therapeutic tools, molecular tumor features are increasingly recognized as crucial determinants of clinical outcome. This trial aims to optimize management of ALK+ NSCLC by analyzing the efficacy of second-generation ALK inhibitors in conjunction with deep longitudinal phenotyping across two treatment lines.Methods/design: In this exploratory prospective phase II clinical trial, newly diagnosed ALK+ NSCLC patients will be randomized into two treatment arms, stratified by presence of brain metastases and ECOG performance status: brigatinib (experimental arm) vs. any other approved second-generation ALK TKI. Tumor tissue and blood samples will be collected for biomarker analysis at the beginning and throughout the study period to investigate baseline molecular tumor properties and analyze the development of acquired drug resistance. In addition, participating investigators and patients will have the possibility of fast-track molecular tumor and ctDNA profiling at the time of disease progression using state-of-the-art next-generation sequencing (NGS), in order to support decisions regarding next-line therapy.Discussion: Besides supporting therapeutic decisions for enrolled patients, the ABP trial primarily aims to deepen the understanding of the underlying biology and facilitate development of a framework for individualized management of ALK+ NSCLC according to molecular features. Patients with low molecular risk and the perspective of a "chronic disease" will be distinguished from "high-risk" cases, molecular properties of which will be utilized to elaborate improved methods of non-invasive monitoring and novel preclinical models in order to advance therapeutic strategies.Trial Registration: Clinicaltrials.gov , NCT04318938. Registered March 182,020, https://www.clinicaltrials.gov/ct2/show/NCT04318938 Eudra-CT, 2019-001828-36. Registered September 302,019, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-001828-36. [ABSTRACT FROM AUTHOR]

Background and Objective: Objective of this study was to determine whether the diagnostic accuracy of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) is sufficient for use among schoolchildren aged 8‐12 years. Methods: This prospective cohort study on diagnostic accuracy with calibrated examiners was conducted among 533 children of both sexes aged 8‐12 years, with and without TMD symptoms, selected randomly from the Rhein‐Neckar district. Self‐reporting of non‐dental facial pain was used as the reference standard, against which we calculated the following for the pain‐related items of the DC/TMD (index test): sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, accuracy and 95% Wilson Score confidence intervals. We also calculated the area under the receiver‐operating characteristic (AUROC) curve displaying sensitivity and specificity. Results: Our final sample consisted of 282 children, half of whom reported having facial pain and 3.2% reported sounds from the temporomandibular joints (TMJs). Despite high specificity (90.78%; 95% confidence interval (CI): [84.86%; 94.53%]), sensitivity of the adapted DC/TMD for pain on maximum jaw opening was poor (37.59%; 95% CI: [30.02%; 45.81%]). For pain on palpation, more similar values were recorded for sensitivity (74.47%; 95% CI: [66.69%; 80.95%]) and specificity (70.21%; 95% CI: [62.21%; 77.14%]). The diagnostic odds ratio was >1 for both examinations. The AUROC for pain on opening was 68.39% (95% CI: [62.62%; 74.16%]), and for pain on palpation, it was 74.63% (95% CI: [69.45%; 79.81%]), whereas the combination of both resulted to an AUROC of 74.09% (95% CI: [68.96%; 79.21%]). It was not possible to measure the diagnostic accuracy of the DC/TMD regarding TMJ sounds or jaw‐opening limitations, as they occurred too rarely in our sample. Conclusion: In this study, the diagnostic accuracy of the DC/TMD for TMD‐related pain in children was lower than that recorded for adults in previous studies. [ABSTRACT FROM AUTHOR]

Background: Endobronchial ultrasound elastography that provides information on tissue stiffness may help distinguish malignant from benign mediastinal and hilar lymph nodes. Objectives: In this prospective trial, we assessed the diagnostic value of elastographic images and the interobserver agreement in its evaluation. Method: Elastographic images from 77 lymph nodes in 65 patients were reviewed by 3 pneumologists. The elastographic image was classified based on the predominant colour: predominantly green, intermediary, and predominantly blue. With 2 or 3 interobserver matches, the corresponding elastographic image was correlated with the pathological result obtained from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and/or other invasive procedures. Results: All 3 reviewers had agreement in classifying elastographic images in 45% (35/77). Overall, the interobserver agreement among the 3 readers for classifying elastographic pattern was found to be moderate (Fleiss Kappa index = 0.519; 95% CI = [0.427; 0.611]). On cytological/histological evaluation, 55 lymph nodes were malignant and 22 were benign. In classifying "green" as benign and "blue" as malignant, the sensitivity and specificity were 71% (95% CI = [54%; 85%]) and 67% (95%-CI = [35%; 90%]), respectively. Conclusions: Elastography will not replace invasive EBUS-TBNA due to a moderate interobserver agreement and insufficient sensitivity and specificity. However, elastography will, maybe, present an additional feature to identify malignant lymph nodes in the context of clinical, radiological, and cytological results. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to retrospectively assess the survival rate and stability of periodontally compromised and mobile anterior mandibular teeth after splinting in patients under supportive periodontal therapy (SPT).Materials and Methods: Thirty-nine patients with splinted anterior mandibular teeth and SPT (≥1 visit/year) for 3-15 years were re-examined. Periodontal status, patient and tooth-related factors were assessed retrospectively before (baseline) and 3 years after splinting (n = 39 patients, 162 splinted teeth). For patients with splints inserted for more than 3 years, retrospective data after 5 (n = 30), 7 (n = 24), 10 (n = 16), 12 (n = 8) and 15 years (n = 4) was included, if available. At baseline, splinted teeth included at least one tooth with increased mobility combined with clinical attachment loss (CAL) ≥ 5 mm and ≥50% relative bone loss (RBL). Baseline RBL of splinted teeth was assessed for all patients. Change in RBL was assessed after 10 years, if available.Results: No splinted tooth was lost within the first 3 years after splinting. One splinted tooth was lost 7 years after baseline and one 12 years after baseline. After 3 years mean(SD) periodontal probing depth of splinted teeth decreased from 3.39(1.41) mm to 2.12(0.37) mm and mean(SD) CAL from 5.61(1.66) mm to 5.09(1.67) mm and remained stable over the observation period. No change in RBL was observed over a 10-year period (p = .213). The survival rate of the splints until fracture or debonding was 74.4% after 3 years.Conclusions: Periodontally compromised splinted teeth show a high survival-rate and periodontal stability during SPT. [ABSTRACT FROM AUTHOR]

Background: Multimorbid patients receiving polypharmacy represent a growing population at high risk for negative health outcomes. Tailoring is an approach of systematic intervention development taking account of previously identified determinants of practice. The aim of this study was to assess the effect of a tailored program to improve the implementation of three important processes of care for this patient group: (a) structured medication counseling including brown bag reviews, (b) the use of medication lists, and (c) structured medication reviews to reduce potentially inappropriate medication.Methods: We conducted a cluster-randomized controlled trial with a follow-up time of 9 months. Participants were general practitioners (GPs) organized in quality circles and participating in a GP-centered care contract of a German health insurance. Patients aged >50 years, suffering from at least 3 chronic diseases, receiving more than 4 drugs, and being at high risk for medication-related events according to the assessment of the treating GP were enrolled. The tailored program consisted of a workshop for GPs and health care assistants, educational materials and reminders for patients, and the elaboration of implementation action plans. The primary outcome was the change in the degree of implementation between baseline and follow-up, measured by a summary score of 10 indicators. The indicators were based on structured surveys with patients and GPs.Results: We analyzed the data of 21 GPs (10 - intervention group, 11 - control group) and 273 patients (130 - intervention group, 143 - control group). The increase in the degree of implementation was 4.2 percentage points (95% confidence interval: -0.3, 8.6) higher in the intervention group compared to the control group (p = 0.1). Two of the 10 indicators were significantly improved in the intervention group: medication counseling (p = 0.017) and brown bag review (p = 0.012). Secondary outcomes showed an effect on patients' self-reported use of medication lists when buying drugs in the pharmacy (p = 0.03).Conclusions: The tailored program may improve implementation of medication counseling and brown bag review whereas the use of medication lists and medication reviews did not improve. No effect of the tailored program on the combined primary outcome could be substantiated. Due to limitations of the study, results have to be interpreted carefully. The factors facilitating and hindering successful implementation will be examined in a comprehensive process evaluation.Trial Registration Number: ISRCTN34664024 , assigned 14/08/2013. [ABSTRACT FROM AUTHOR]

Background: Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group.Methods/design: This prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70 years or older and/or "frail" (Charlson Comorbidity Index > 1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG > 1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score: "fit" patients are allocated to combination CT (carboplatin/nab-paclitaxel) and "less fit" patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either four cycles of CT or two cycles of CT followed by two cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks. The primary endpoint is the rate of treatment-related grade III/IV adverse events (Common Terminology Criteria for Adverse Events (CTCAE) V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential "frail" and "elderly" patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers.Discussion: The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.Trial Registration: ClinicalTrials.gov, NCT03345810; initially registered on 17 November 2017. Eudra-CT, 2016-003963-20; initially registered on 3 January 2017. [ABSTRACT FROM AUTHOR]

Background: Conventional whole brain radiotherapy (WBRT) has been established as the treatment standard in patients with cerebral metastases from small-cell lung cancer (SCLC), however, it has only modest efficacy and limited prospective data is available for WBRT as well as local treatments such as stereotactic radiosurgery (SRS).Methods/design: The present single-center prospective randomized study, conducted at Heidelberg University Hospital, compares neurocognitive function, as objectively measured by significant deterioration in Hopkins Verbal Learning Test - Revised total recall at 3 months. Fifty-six patients will be randomized to receive either SRS of all brain metastases (up to ten lesions) or WBRT. Secondary endpoints include intracranial progression (local tumor progression and number of new cerebral metastases), extracranial progression, overall survival, death due to brain metastases, local (neurological) progression-free survival, progression-free survival, changes in other cognitive performance measures, quality of life and toxicity.Discussion: Recent evidence suggests that SRS might be a promising treatment option for SCLC patients with brain metastases. The present trial is the first to prospectively investigate the treatment response, toxicity and neurocognition of WBRT and SRS in SCLC patients.Trial Registration: Clinicaltrials.gov NCT03297788 . Registered September 29, 2017. [ABSTRACT FROM AUTHOR]

Objectives: The goals of the present study were to prospectively analyze salvage surgery with microvascular reconstruction in recurrent squamous cell carcinoma of the oral cavity (OSCC) in terms of oncological outcome and quality of life.Patients and Methods: From 2012 to 2015, 28 patients underwent salvage surgery due to recurrent OSCC or second primary OSCC without the option of curative re-irradiation. Endpoints were disease-specific survival and progression-free survival after 12 months. The survival was estimated by using the Kaplan-Meier blotting. Quality of life data (European Organization for Research and Treatment of Cancer - EORTC: QLQ-C30 and QLQ-H&N35) was assessed at baseline and subsequently every 3 months up to one year.Results: Estimated 1-year-survival was 68.4% and progression-free survival was 38.5%. Overall quality of life was significantly reduced three months after salvage surgery [baseline (mean 64.15) versus time 1 (mean 53.04); p = 0.002]. However, the patients experienced a recovery within the first year [baseline (mean 64.15) versus time 4 (mean 70.33); p = 0.176]. Furthermore, the sensation of pain is significantly reduced after salvage surgery [baseline (mean 47.53) versus time 2 (mean 31.25); p = 0.036]. Microvascular reconstruction success rate was 93.1%.Conclusion: Salvage surgery is a curative treatment option in recurrent and intensively pretreated OSCC. Microvascular reconstruction is feasible with acceptable morbidity and high success rates. Quality of life can be preserved. Further studies combining checkpoint inhibition with salvage surgery are justified. [ABSTRACT FROM AUTHOR]