المؤلفون: DeTemple, Viola K., Hassel, Jessica C., Sachse, Michael M., Grimmelmann, Imke, Leiter, Ulrike, Gebhardt, Christoffer, Eckardt, Julia, Pföhler, Claudia, Angela, Yenny, Hübbe, Hanna, Gutzmer, Ralf

مصطلحات موضوعية: ddc:610, advanced basal cell carcinoma, hedgehog inhibitor reinduction, sequential treatment, checkpoint inhibition

الوصف: For patients with advanced basal cell carcinoma (aBCC) first-line treatment with hedgehog inhibitors (HHIs) and second-line treatment with PD1 inhibitors (PD1i) is available, offering combination and sequencing options. Here, we focus on the efficacy and safety of HHI reinduction after PD1i failure. Retrospective data analysis was performed with 12 patients with aBCC (locally advanced (n = 8)/metastatic (n = 4)). These patients (male:female 6:6, median age 68 years) initially received HHIs, leading to complete/partial response (66%) or stable disease (33%). Median treatment duration was 20.8 (2–64.5) months until discontinuation due to progression (n = 8), adverse events (n = 3), or patient request (n = 1). Subsequent PD1 inhibition (pembrolizumab 42%, cemiplimab 58%) yielded a partial response (8%), stable disease (33%), or progression (59%). Median treatment duration was 4.1 (0.8–16.3) months until discontinuation due to progression (n = 9), adverse events (n = 1), patient request (n = 1), or missing drug approval (n = 1). HHI reinduction resulted in complete/partial response (33%), stable disease (50%), or progression (17%). Median treatment duration was 3.6 (1–29) months. Response duration in the four responding patients was 2–29+ months. Thus, a subgroup of patients with aBCC responded to reinduction of HHI following PD1i failure. Therefore, this sequential treatment represents a feasible treatment option.

العلاقة: Cancers 14 (21): 5469 (2022); http://nbn-resolving.org/urn:nbn:de:bsz:291--ds-379428Test; hdl:20.500.11880/34297; http://dx.doi.org/10.22028/D291-37942Test

الإتاحة: https://doi.org/10.22028/D291-37942Test
https://doi.org/10.3390/cancers14215469Test
http://nbn-resolving.org/urn:nbn:de:bsz:291--ds-379428Test

المؤلفون: Schnabl, Saskia Maria, Garbe, Claus, Breuninger, Helmut, Walter, Vincent, Aebischer, Valentin, Eckardt, Julia, Ghoreschi, Franziska Carola, Häfner, Hans‐Martin, Scheu, Alexander

المصدر: Journal of the European Academy of Dermatology and Venereology ; volume 37, issue 1, page 65-74 ; ISSN 0926-9959 1468-3083

الوصف: Background Due to demographic change and increased UV exposure, the number of dermatosurgical procedures in the elderly is increasing. Data on the occurrence of systemic side effects during and after treatment with tumescent local anaesthesia are limited and do not refer to details such as volume and composition of local anaesthetics or epinephrine additive. Objectives The aim of this study was to investigate the risk of systemic side effects in elderly patients undergoing skin tumour surgery with tumescent local anaesthesia. Methods Investigation of systemic complications in patients (≥75 years) who underwent head and neck skin tumour surgery under tumescent local anaesthesia at the Department of Dermatology, University Medical Centre Tübingen, between October 2018 and March 2020. Results In total 782 patients (479 males, 303 females) with a mean age of 83.3 years (range: 75.1–102.2 years) could be included. A total of 2940 procedures were performed. Patients were assigned to two groups. The old–old group (≥75–84 years) included 491 patients and the oldest–old group (≥85 years) included 291 patients. The total inpatient stay and thus mean follow‐up period was 4.9 days (range 1–28 days). 92.0% (719/782) suffered from pre‐existing comorbidities. Systemic complications occurred in 10.2% (80/782; old–olds: 8.6%, oldest–olds: 13.1%). Hypertensive crisis (>180/120 mmHg) requiring intervention (6.7%) that occurred intraoperatively or during the inpatient stay was the most frequent systemic complication. Cardiac arrhythmias occurred postoperatively in 0.8% of cases. No life‐threatening complications directly related to tumescent local anaesthesia were found. Conclusions Skin tumour surgery in tumescent local anaesthesia for the elderly is safe, and complications caused by general anaesthesia can be avoided. Systemic complications can occur, but are usually mild, are caused by pre‐existing diseases and perioperative excitement, and can be rapidly detected and well treated by monitoring. There is no direct ...

الإتاحة: https://doi.org/10.1111/jdv.18588Test

المؤلفون: Eckardt, Julia, Schroeder, Christopher, Martus, Peter, Armeanu-Ebinger, Sorin, Kelemen, Olga, Gschwind, Axel, Bonzheim, Irina, Eigentler, Thomas, Amaral, Teresa, Ossowski, Stephan, Rieß, Olaf, Flatz, Lukas, Garbe, Claus, Forschner, Andrea

المساهمون: Eberhard Karls Universität Tübingen

المصدر: Journal of Cancer Research and Clinical Oncology ; volume 149, issue 2, page 833-840 ; ISSN 0171-5216 1432-1335

مصطلحات موضوعية: Cancer Research, Oncology, General Medicine

الوصف: Background High tumor mutational burden (TMB) is associated with a favorable outcome in metastatic melanoma patients treated with immune checkpoint inhibitors. However, data are limited in the adjuvant setting. As BRAF mutated patients have an alternative with targeted adjuvant therapy, it is important to identify predictive factors for relapse and recurrence-free survival (RFS) in patients receiving adjuvant anti-PD-1 antibodies. Methods We evaluated 165 melanoma patients who started adjuvant anti-PD-1 antibody therapy at our center between March 2018 and September 2019. The initial tumor stage was assessed at the beginning of therapy according to the 8th edition of the AJCC Cancer Staging Manual. Tumor and normal tissue of the high-risk stages IIIC/D/IV were sequenced using a 700 gene NGS panel. Results The tumor stages at the beginning of adjuvant anti-PD-1 therapy were as follows: N = 80 stage IIIA/B (48%), N = 85 stage IIIC/D/IV (52%). 72/165 patients (44%) suffered a relapse, 44/72 (61%) with only loco regional and 28/72 (39%) with distant metastases. Sequencing results were available from 83 to 85 patients with stage IIIC/D/IV. BRAF mutation status (HR 2.12, 95% CI 1.12–4.08; p = 0.022) and TMB (HR 7.11, 95% CI 2.19–23.11; p = 0.001) were significant and independent predictive factors for relapse-free survival (RFS). Conclusion BRAF mutation status and TMB were independent predictive factors for RFS. Patients with BRAF V600E/K mutation and TMB high had the best outcome. A classification based on BRAF mutation status and TMB is proposed to predict RFS in melanoma patients with adjuvant anti-PD-1 therapy.

الإتاحة: https://doi.org/10.1007/s00432-022-03939-wTest

المؤلفون: Lodde, Georg, Forschner, Andrea, Hassel, Jessica, Wulfken, Lena M., Meier, Friedegund, Mohr, Peter, Kähler, Katharina, Schilling, Bastian, Loquai, Carmen, Berking, Carola, Hüning, Svea, Schatton, Kerstin, Gebhardt, Christoffer, Eckardt, Julia, Gutzmer, Ralf, Reinhardt, Lydia, Glutsch, Valerie, Nikfarjam, Ulrike, Erdmann, Michael, Stang, Andreas, Kowall, Bernd, Roesch, Alexander, Ugurel, Selma, Zimmer, Lisa, Schadendorf, Dirk, Livingstone, Elisabeth

مصطلحات موضوعية: ddc:610

الوصف: Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9% (95% CI 74–80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26% lower in patients >65 years (RR 0.74, 95% CI 68–80). The most common reasons against adjuvant treatment given by patients were age (29.4%, 95% CI 24–38), and fear of adverse events (21.1%, 95% CI 16–28) and impaired quality of life (11.9%, 95% CI 7–16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9% (95% CI 47–59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI.

وصف الملف: application/pdf

العلاقة: https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23958Test; urn:nbn:de:bvb:20-opus-239583; https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-239583Test; https://doi.org/10.3390/cancers13102319Test; https://opus.bibliothek.uni-wuerzburg.de/files/23958/cancers-13-02319-v2.pdfTest

الإتاحة: https://doi.org/10.3390/cancers13102319Test
https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23958Test
https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-239583Test
https://opus.bibliothek.uni-wuerzburg.de/files/23958/cancers-13-02319-v2.pdfTest

المؤلفون: Eckardt, Julia, Häfner, Hans‐Martin, Kofler, Katrin, Mroz, Gabi, Scheu, Alexander, Schulz, Claudia, Kofler, Lukas

المصدر: JDDG: Journal der Deutschen Dermatologischen Gesellschaft ; volume 19, issue 4, page 536-543 ; ISSN 1610-0379 1610-0387

الوصف: Summary Background Sentinel lymph node biopsy (SLNB) is useful for staging of patients with melanoma. Although SLNB is mostly performed under general anesthesia (GA), tumescence local anesthesia (TLA) can also be used. However, less data are available regarding feasibility of SLNB under TLA. Here we present a post‐operative follow‐up of 150 patients. Patients and Methods We prospectively analyzed data from 150 patients with primary cutaneous malignant melanoma. We assessed pain, post‐operative complications and patients’ satisfaction after SLNB under TLA. Results 32 % of the patients reported post‐operative pain within the first 48 h after SLNB. Seroma was the most frequent complication, as 29 seromas after SLNB were observed. Wound infection was observed in 3.3 % of the patients. 98.7 % of the patients were satisfied with SLNB under TLA. Conclusions SLNB under TLA is a safe and feasible option and should be considered for patients with melanoma. Especially with multimorbid or elderly patients, the risks of GA can be avoided.

الإتاحة: https://doi.org/10.1111/ddg.14351Test

المؤلفون: Eckardt, Julia, Häfner, Hans‐Martin, Kofler, Katrin, Mroz, Gabi, Scheu, Alexander, Schulz, Claudia, Kofler, Lukas

المصدر: JDDG: Journal der Deutschen Dermatologischen Gesellschaft ; volume 19, issue 4, page 536-544 ; ISSN 1610-0379 1610-0387

الوصف: Zusammenfassung Hintergrund Für die Stadieneinteilung von Patienten mit malignem Melanom ist die Wächterlymphknotenbiopsie (WLKB) eine wichtige Methode. Meist erfolgt die WLKB in Vollnarkose (VN). Sie kann auch in Tumeszenz‐Lokalanästhesie (TLA) durchgeführt werden, jedoch liegen wenige Daten zur WLKB in TLA vor. In dieser Studie wurden die Daten von 150 Patienten mit WLKB in TLA ausgewertet. Patienten und Methodik Die Daten von 150 Patienten mit malignem Melanom der Haut wurden prospektiv analysiert. Schmerzen, Komplikationen und die Patientenzufriedenheit nach WLKB in TLA wurden ausgewertet. Ergebnisse 32 % der Patienten berichteten über postoperative Schmerzen innerhalb der ersten 48 Stunden nach WLKB. Das Serom war die häufigste Komplikation. Es traten 29 Serome nach WLKB auf. Eine Wundinfektion wurde bei 3,3 % der Patienten beobachtet. 98,7 % der Patienten waren mit der WLKB in TLA zufrieden. Schlussfolgerungen WLKB in TLA ist eine sichere und praktikable Option und sollte bei Patienten mit Melanom in Betracht gezogen werden. Insbesondere bei multimorbiden oder älteren Patienten können die Risiken der VN vermieden werden.

الإتاحة: https://doi.org/10.1111/ddg.14351_gTest

المؤلفون: Eckardt, Julia, Aebischer, Valentin, Häfner, Hans-Martin, Kofler, Lukas, Pietschke, Katharina, Forchhammer, Stephan

المصدر: Der Hautarzt; 20240101, Issue: Preprints p1-4, 4p

المؤلفون: Eckardt, Julia, Schroeder, Christopher, Martus, Peter, Armeanu-Ebinger, Sorin, Kelemen, Olga, Gschwind, Axel, Bonzheim, Irina, Amaral, Teresa, Ossowski, Stephan, Riess, Olaf, Flatz, Lukas, Garbe, Claus, Forschner, Andrea Lydia

الوقت: 610

العلاقة: http://dx.doi.org/10.1007/s00432-022-03939-wTest; http://hdl.handle.net/10900/146993Test; http://dx.doi.org/10.15496/publikation-88334Test

الإتاحة: https://doi.org/10.15496/publikation-88334Test
https://doi.org/10.1007/s00432-022-03939-wTest
http://hdl.handle.net/10900/146993Test

المؤلفون: Lodde, Georg C., Hassel, Jessica, Wulfken, Lena M., Meier, Friedegund, Mohr, Peter, Kähler, Katharina, Hauschild, Axel, Schilling, Bastian, Loquai, Carmen, Berking, Carola, Hüning, Svea, Eckardt, Julia, Gutzmer, Ralf, Reinhardt, Lydia, Glutsch, Valerie, Nikfarjam, Ulrike, Erdmann, Michael, Beckmann, Catharina L., Stang, Andreas, Kowall, Bernd, Galetzka, Wolfgang, Roesch, Alexander, Ugurel, Selma, Zimmer, Lisa, Schadendorf, Dirk, Forschner, Andrea, Livingstone, Elisabeth

المساهمون: Deutsche Forschungsgemeinschaft

المصدر: European Journal of Cancer ; volume 191, page 112957 ; ISSN 0959-8049

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.ejca.2023.112957Test
https://api.elsevier.com/content/article/PII:S095980492300309X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S095980492300309X?httpAccept=text/plainTest

المؤلفون: Niens, Janna, Reh, Fabienne, Çoban, Büşra, Cichewicz, Karol, Eckardt, Julia, Liu, Yi-Ting, Hirsh, Jay, Riemensperger, Thomas D.

الوقت: 570

الوصف: Parkinson’s disease (PD) results from a progressive degeneration of the dopaminergic nigrostriatal system leading to a decline in movement control, with resting tremor, rigidity and postural instability. Several aspects of PD can be modeled in the fruit fly, Drosophila melanogaster, including a-synuclein-induced degeneration of dopaminergic neurons, or dopamine (DA) loss by genetic elimination of neural DA synthesis. Defective behaviors in this latter model can be ameliorated by feeding the DA precursor L-DOPA, analogous to the treatment paradigm for PD. Secondary complication from L-DOPA treatment in PD patients are associated with ectopic synthesis of DA in serotonin (5-HT)-releasing neurons, leading to DA/5-HT imbalance. Here we examined the neuroanatomical adaptations resulting from imbalanced DA/5-HT signaling in Drosophila mutants lacking neural DA. We find that, similar to rodent models of PD, lack of DA leads to increased 5-HT levels and arborizations in specific brain regions. Conversely, increased DA levels by L-DOPA feeding leads to reduced connectivity of 5-HT neurons to their target neurons in the mushroom body (MB). The observed alterations of 5-HT neuron plasticity indicate that loss of DA signaling is not solely responsible for the behavioral disorders observed in Drosophila models of PD, but rather a combination of the latter with alterations of 5-HT circuitry.

العلاقة: https://resolver.sub.uni-goettingen.de/purl?gro-2/59024Test; https://resolver.sub.uni-goettingen.de/purl?gs-1/14799Test

الإتاحة: https://doi.org/10.3389/fnsys.2017.00076Test
https://resolver.sub.uni-goettingen.de/purl?gro-2/59024Test
https://resolver.sub.uni-goettingen.de/purl?gs-1/14799Test