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  • 1
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2010-12)
    Abstract: Tyrosine kinase inhibitors (TKI) have enriched the therapeutic options in patients with renal cell carcinoma (RCC), which frequently induce morphological changes in tumors. However, only little is known about the biological activity of TKI. Circulating endothelial cells (CEC) have been associated with endothelial damage and, hence, may serve as a putative marker for the biological activity of TKI. The main objective of our study was to evaluate the predictive value of CEC, monocytes, and soluble vascular endothelial growth factor receptor (sVEGFR)-2 in RCC patients receiving sunitinib treatment. Methods Analyses of CEC, monocytes, and sVEGFR-2 were accomplished for twenty-six consecutive patients with metastatic RCC who received treatment with sunitinib (50 mg, 4 wks on 2 wks off schedule) at our institution in 2005 and 2006. Results In RCC patients CEC are elevated to 49 ± 44/ml (control 8 ± 8/ml; P = 0.0001). Treatment with sunitinib is associated with an increase in CEC within 28 days of treatment in patients with a Progression free survival (PFS) above the median to 111 ± 61 (P = 0.0109), whereas changes in patients with a PFS below the median remain insignificant 69 ± 61/ml (P = 0.1848). Monocytes and sVEGFR2 are frequently altered upon sunitinib treatment, but fail to correlate with clinical response, defined by PFS above or below the median. Conclusions Sunitinib treatment is associated with an early increase of CEC in responding patients, suggesting superior endothelial cell damage in these patients as a putative predictive biomarker.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2041352-X
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  • 2
    In: European Journal of Cancer, Elsevier BV, Vol. 93 ( 2018-04), p. 150-153
    Type of Medium: Online Resource
    ISSN: 0959-8049
    RVK:
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 1120460-6
    detail.hit.zdb_id: 1468190-0
    detail.hit.zdb_id: 82061-1
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  • 3
    In: Clinical and Experimental Neuroimmunology, Wiley, Vol. 12, No. 2 ( 2021-05), p. 127-134
    Abstract: Immune checkpoint inhibitor (ICI) therapy has revolutionized the management of multiple cancers with previously poor prognosis. Despite its efficacy the therapy is associated with a wide spectrum of immune‐related adverse events (irAEs) including neurological deficits ranging from peripheral neuropathy, myopathy, and myasthenic syndromes to encephalopathy or meningitis. Up to now, neurological irAEs, especially those with central nervous system (CNS) involvement, have been reported rather sporadically. Symptoms can be unspecific, which results in a diagnostic challenge. Methods In the study at hand, we report 5 patients who presented with symptoms of the CNS during ICI therapy indicating autoimmune encephalitis. Results Symptoms ranged from headache and hallucinations to symptoms of the brainstem to cerebellar syndrome. Radiological findings according to brain magnetic resonance imaging were unspecific, and analysis of autoantibodies remained negative in all cases. All patients underwent lumbar puncture, and examination of the cerebrospinal fluid revealed an elevated cell count, and thus an indication of inflammation, in 4 cases (80%). Consequently, all patients received high‐dose steroid treatment, and symptoms of all patients with elevated cerebrospinal fluid cell count significantly improved. Conclusions We demonstrate that symptoms of immune checkpoint inhibitor–induced encephalitis can be unspecific, and radiological findings are often inconspicuous. Thus, cerebrospinal fluid analysis is the most important examination to achieve a correct diagnosis, which in turn is decisive for a rapid start of therapy.
    Type of Medium: Online Resource
    ISSN: 1759-1961 , 1759-1961
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2508135-4
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  • 4
    In: Clinical Genitourinary Cancer, Elsevier BV, Vol. 15, No. 2 ( 2017-04), p. 280-290.e3
    Type of Medium: Online Resource
    ISSN: 1558-7673
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2466266-5
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  • 5
    In: Journal of Oncology, Hindawi Limited, Vol. 2020 ( 2020-12-07), p. 1-9
    Abstract: Therapy with immune checkpoint inhibitors (ICIs) has improved overall survival and cancer-related morbidity of cancer treatment even in cancer entities with poor prognosis. Since the approval of the first ICI, ipilimumab, for treatment of advanced melanoma by the Food and Drug Administration (FDA) in 2011, the spectrum of indications and approved ICIs has grown, rapidly. Up to now, seven different ICIs for more than 20 indications are available. However, their mechanisms of action can lead to immune-related adverse events (irAEs). In particular, neurological irAEs are clinically relevant. Although they are rare, an early and accurate diagnosis is challenging and neurological disease course and sequelae are potentially fatal. Between 08/2017 and 03/2020, 31 patients received ICI treatment at Hannover Medical School and presented with neurological adverse events (N-irAEs). Treated malignancies were metastatic melanoma, bronchial carcinoma, and urothelial cell carcinoma. All patients received comprehensive neurological diagnostics including clinical examination and magnetic resonance imaging (MRI). Cerebrospinal fluid (CSF) analysis was obtained in 21 patients and electroneurography was performed in 22 patients. Although N-irAEs were suspected in all 31 patients, 11 patients had other conditions leading to neurological symptoms including tumor metastases in seven patients and hemorrhagic or ischemic stroke in four patients. In the following, these patients are referred to as the differential diagnosis (DD) group. Patients with N-irAEs suffered from immune mediated neuropathy (9/20), myositis and/or myasthenic syndrome (6/20), or encephalitis/cerebellitis (5/20). Except for cell count, CSF results did not differ between the N-irAEs and the DD group. Symptoms related to N-irAEs are rather unspecific potentially mimicking other tumor-related symptoms such as metastases. Patients with malignancy are predominantly not treated by neurologists. Because of the complexity of neurological symptoms, detailed neurological investigations in specialized institutions are necessary in patients with new neurological symptoms and need to be critically discussed with treating oncologists.
    Type of Medium: Online Resource
    ISSN: 1687-8469 , 1687-8450
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2461349-6
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  • 6
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 11 ( 2019-10-24), p. 1777-
    Abstract: Immune checkpoint inhibitor (ICI) therapy has revolutionized the management of various cancers with previously poor prognosis. Despite its great efficacy, the therapy is associated with a wide spectrum of immune-related adverse events (irAE) including neurological symptoms which can affect all parts of the central and peripheral nervous system. Even though these events are rare, they are of high relevance as the rate of residual symptoms or even fatal outcomes is remarkable. To provide a detailed overview of neurological adverse events associated with immune checkpoint-inhibitor therapy we conducted a literature search. While focusing on ipilimumab, nivolumab, and pembrolizumab therapy, all available case reports as well as larger case series and clinical trials have been considered. Eighty-two case reports about checkpoint-inhibitor therapy induced symptoms of the peripheral nervous system have been published, while only 43 case reports addressed central nervous system abnormalities. The frequency of immune checkpoint-inhibitor therapy inducing neurological adverse events is about 1% in larger studies. Especially neuromuscular adverse events exhibit distinct clinical and diagnostic characteristics. Additionally, several affected patients presented with overlap-syndromes, which means that symptoms and diagnostic findings indicating myositis, myasthenia gravis, and neuropathy were present in one individual patient at the same time. Thus, neurological and particularly neuromuscular adverse events of immune checkpoint-inhibitor therapy may constitute a new disease entity.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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  • 7
    In: Cancer Medicine, Wiley, Vol. 12, No. 8 ( 2023-04), p. 9373-9383
    Abstract: Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune‐related adverse events (irAE). Especially ICI‐mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing. Methods A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut‐off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed. Results nAE of any grade were observed in 31% of the patients ( n  = 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher‐grade nAE had significantly elevated serum‐concentrations of monocyte chemoattractant protein 1 (MCP‐1) and brain‐derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE ( p   〈  0.01 and p   〈  0.05). Conclusion Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP‐1 and BDNF are potentially the first clinical‐class nAE predictors for patients under ICI therapy.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2659751-2
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