Christian MENZER's публикаций (20)

PRO-CTCAE reveals under-recognition of dermatologic symptom burden in hospitalized cancer patients.

May, 2023

Dermatologic adverse events (dAEs) occur frequently in hospitalized patients and can significantly reduce quality of life. Physicians grade dAEs using the Common Terminology Criteria of Adverse Events (CTCAE). However, they often underestimate symptom frequency and severity. The patient-reported outcomes (PRO) version of the CTCAE (PRO-CTCAE) was developed to assess symptoms from the patient's perspective. In this study, we assessed the patient-reported burden of dAEs via the PRO-CTCAE questionnaire and compared results with dAE assessment by treating oncologists and dermatologists. Подробнее

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

Laser therapy as a treatment for chronic radiation fibrosis.

Jan, 2023

Chronic radiation fibrosis (CRF) is a long-term sequala of radiation therapy that has a significant impact on patient quality of life. There is no standard of care or single therapeutic modality that has been found to be consistently effective. Подробнее

Lasers in surgery and medicine

Consensus on the clinical management of chronic radiation dermatitis and radiation fibrosis: a Delphi survey.

Dec, 2022

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The British journal of dermatology Загрузить больше  

Adjuvant nivolumab plus ipilimumab or nivolumab alone versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): final results of a randomised, double-blind, phase 2 trial.

Oct, 2022

The IMMUNED trial previously showed significant improvements in recurrence-free survival for adjuvant nivolumab plus ipilimumab as well as for adjuvant nivolumab alone in patients with stage IV melanoma with no evidence of disease after resection or radiotherapy. Here, we report the final analysis, including overall survival data. Подробнее

Lancet (London, England)

Treatment of Indolent Cutaneous B-Cell Lymphoma with Intralesional or Intravenous Rituximab.

Sep, 2022

Indolent cutaneous B-cell lymphomas (CBCL) are a rare disease for which the therapeutic recommendations are based on clinical reports. Recommendations for solitary lesions include surgery or irradiation. However, the high relapse rates may require less invasive repeatable therapy. This study seeks to retrospectively assess the efficacy of intralesional rituximab (ILR) for indolent CBCL when compared with intravenous rituximab (IVR). Patients treated for indolent CBCL with ILR or IVR at the Division of DermatoOncology of the University Hospital Heidelberg were eligible for this study. Characteristics of lymphoma, treatment response, and adverse events were assessed. Twenty-one patients, 67% male at a median age of 52 (range 17-80), were included. Nineteen (90%) had only localized lymphoma (stage T1 and T2). Complete response was achieved in 92% (11/12) of ILR after a median of one cycle (three injections) and 78% (7/8) of IVR patients after a median of six cycles. Half of ILR patients and 78% of IVR patients showed relapse after a median of 15 and 23 months, respectively. Adverse reactions were usually mild and were limited to the first injection of ILR. One patient with IVR contracted a pulmonary infection. ILR may be an alternative to the intravenous administration of rituximab for localized indolent CBCL. Подробнее

Cancers

Targeted Therapy for Melanomas Without BRAF V600 Mutations.

Jun, 2022

Modern therapy of advanced melanoma offers effective targeted therapeutic options in the form of BRAF plus MEK inhibition for patients with BRAF V600 mutations. For patients lacking these mutations, checkpoint inhibition remains the only first-line choice for treatment of metastatic disease. However, approximately half of patients do not respond to immunotherapy, requiring effective options for a second-line treatment. Advances in genetic profiling have found other possible target molecules, especially a wide array of rare non-V600 BRAF mutations which may respond to available targeted therapy.More information on the characteristics of such mutants is needed to further assess the efficacy of targeted therapies in the metastatic and adjuvant setting of advanced melanoma. Thus, it may be helpful to classify known BRAF mutations by their kinase activation status and dependence on alternative signaling pathways. While BRAF V600 mutations appear to have an overall more prominent role of kinase activity for tumor growth, non-V600 BRAF mutations show great differences in kinase activation and, hence, response to BRAF plus MEK inhibition. When BRAF-mutated melanomas rely on additional signaling molecules such as RAS for tumor growth, greater benefit may be expected from MEK inhibition than BRAF inhibition. In other cases, mutations of c-kit or NRAS may serve as important pharmacological targets in advanced melanoma. However, since benefit from currently available targeted therapies for non-V600 mutants is usually inferior regarding response and long-term outcome, checkpoint inhibitors remain the standard recommended first-line therapy for these patients.Herein, we review the current clinical data for characteristics and response to targeted therapy of melanomas lacking a V600 BRAF mutation. Подробнее

Current treatment options in oncology

Efficacy of laser CO treatment for refractory lymphedema secondary to cancer treatments.

Mar, 2022

Lymphedema is a frequent debilitating condition among cancer patients. Daily supportive treatment may be necessary without long-term improvement. We describe two cases with chronic refractory lymphedema treated with fractional 10,600 nm CO laser. A 61-year-old female with locally advanced cervical cancer presented with postsurgical edematous swelling of the vulva and mons pubis and recurring cellulitis due to chronic lymphangiectasia. After six treatments of fractional CO laser, she noticed an 80% reduction of lymphorrea, swelling, and frequency of cellulitis. A 32-year old melanoma patient presented with refractory right lower leg lymphedema post right inguinal lymph node dissection and radiation. After fractional CO laser, she noted increased softness of her inguinal scar and a decrease of the lower leg edema. Fractional CO laser may be useful in addressing chronic refractory lymphedema. Further research should confirm our findings to consider fractional laser as a standard method in the treatment of chronic lymphedema. Подробнее

Lasers in surgery and medicine

Expression of p53 up-regulated modulator of apoptosis (PUMA) in non-melanoma skin cancer of long-term immunosuppressed solid organ transplant recipients compared to immunocompetent patients.

Oct, 2021

The risk of UV radiation (UVR)-induced non-melanoma skin cancer (NMSC) is dramatically increased in immunosuppressed organ transplant recipients compared to immunocompetent patients. In the skin, p53 up-regulated modulator of apoptosis (PUMA) is a central regulator of apoptosis in response to UVR damage and immune response regulation. Data on the expression of PUMA in patients with NMSC relative to immune status is limited To study differences in the expression and distribution of PUMA in cutaneous SCC and BCC by immunohistochemistry between immunocompetent patients and organ transplant recipients, and the effect of CsA-containing immunosuppressive maintenance regimens on this expression. PUMA expression in SCC (n = 34) and BCC (n = 20) was analysed comparatively by immunohistochemical staining in matched cohorts of 27 immunocompetent patients and 27 organ transplant recipients SCC and BCC showed unequivocal positive PUMA expression, however, there was no significant difference in NMSC between organ transplant recipients and immunocompetent patients. A 17% reduction in staining score for PUMA in SCC, but not in BCC, of organ transplant recipients treated with a cyclosporin (CsA)-containing regimen was noted compared to organ transplant recipients without chronic CsA intake (p = 0.0381) PUMA expression in SCC, but not BCC, is significantly reduced by CsA-containing therapy, suggesting a disturbance of apoptosis by iatrogenic immunosuppression with a divergent impact on SCC and BCC. Подробнее

European journal of dermatology : EJD

Bimatoprost drug delivery with fractional laser and microneedling for the management of COVID-19 prone positioning-induced facial atrophy and hypopigmentation.

Sep, 2021

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JAAD case reports

Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial.

05, 2020

Nivolumab and ipilimumab, alone or in combination, are widely used immunotherapeutic treatment options for patients with advanced-ie, unresectable or metastatic-melanoma. This criterion, however, excludes patients with stage IV melanoma with no evidence of disease. We therefore aimed to evaluate the safety and efficacy of adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus a placebo in this patient population. Подробнее

Lancet (London, England)

Inpatient Management of Mucocutaneous GVHD.

Dec, 2019

Graft-versus-host disease (GVHD) is an immune mediated disorder affecting 30 - 70% of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT), and is a major cause of morbidity and non-relapse mortality (NRM) [1]. Dermatologists play a critical role in acute and chronic GVHD, as skin involvement is common and often the earliest involved site of disease [2]. Подробнее

Current dermatology reports

Targeted Therapy in Advanced Melanoma With Rare Mutations.

11, 2019

BRAF/MEK inhibition is a standard of care for patients with V600E/K-mutated metastatic melanoma. For patients with less frequent mutations, however, efficacy data are limited. Подробнее

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis.

12, 2018

Immune checkpoint inhibitors (ICIs) are now a mainstay of cancer treatment. Although rare, fulminant and fatal toxic effects may complicate these otherwise transformative therapies; characterizing these events requires integration of global data. Подробнее

JAMA oncology

Immunotherapy with ipilimumab plus nivolumab in a stage IV melanoma patient during pregnancy.

11, 2018

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European journal of cancer (Oxford, England : 1990)

Granulomatous skin reactions after tumour vaccine in two patients.

Mar, 2018

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Journal of the European Academy of Dermatology and Venereology : JEADV

[Dermoscopically conspiciuous pigmented lesion on the forehead of a young male patient].

Dec, 2017

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Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete

African tick-bite fever - a tantalizing souvenir from South Africa.

Oct, 2017

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Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG

Mechano-insensitive nociceptors are sufficient to induce histamine-induced itch.

Jul, 2013

The nerve fibres underlying histamine-induced itch have not been fully elucidated. We blocked the lateral femoral cutaneous nerve and mapped the skin area unresponsive to mechanical stimulation, but still sensitive to electrically induced pain. Nerve block induced significantly larger anaesthetic areas to mechanical (100 mN pin-prick, 402 ± 61 cm²; brush, 393 ± 63 cm²) and heat pain stimuli (401 ± 53 cm²) compared with electrical stimulation (352 ± 62 cm², p < 0.05), whereas the anaesthetic area tested with 260 mN (374 ± 57 cm²) did not differ significantly. Histamine was applied by iontophoresis (7.5 mC) at skin sites in which mechanical sensitivity was blocked, but electrical stimulation was still perceived 30 min after the nerve block (n = 9). In these areas iontophoresis of histamine provoked itching in 8/9 subjects with a mean maximum of 4.6 ± 1 (on an 11-point rating scale). Histamine-induced itch can thus be perceived at skin sites where input from mechano-sensitive polymodal nociceptors is blocked. In conclusion, input from mechano-insensitive nociceptors is sufficient to generate histamine-induced itch. Подробнее

Acta dermato-venereologica

Discriminative sensory characteristics of the lateral femoral cutaneous nerve after mepivacaine-induced block.

Apr, 2013

Background and objectives Unmyelinated C-fibres comprise the largest group of somatic afferents and have demonstrated a crucial role not only in the perception of high-threshold mechanically, thermally or chemically induced pain, but also in non-harmful low-threshold mechanical stimuli [1,2]. The objective of our study was to characterize differential sensitivity changes of C-fibre related subclasses of high-threshold and low-threshold polymodal nociceptors and low-threshold mechanoreceptors to the local anaesthetic (LA) mepivacaine during nerve block of the purely sensory lateral femoral cutaneous nerve (LFCN) in human. We assumed a diverse response of different classes of afferents to the two different concentrations of the LA mepivacaine (Scandicaine). Methods In a double-blind randomized experimental setting, an ultrasound-guided nerve block of the LFCN was performed in 10 healthy male subjects, each with two different concentrations of mepivacaine (0.5 and 1%). Responsiveness of afferent nerve fibres to different noxious and non-noxious stimuli was tested by Quantitative Sensory Testing (QST) 30, 180, and 300 min after nerve block. Both LA concentrations of mepivacaine were compared for time course of the areas of anaesthesia for the tested sensory modalities. Results Initial extension of anaesthetic areas at 30 min did not differ between both LA concentrations. At 180 min only the anaesthetic areas to nociceptive stimuli were reduced at the site of lower mepivacaine injection (260mN: 204mm2 (18; 244; median difference and 95% confidence interval; p < 0.05), heat: 276mm2 (3; 305)). In contrast, no significant differences were found between the two concentration when non-nociceptive stimuli were used (100mN: 187mm2 (4; 240), p >0.05, brush: 159mm2 (-59; 202)). Conclusion Equal initial sizes of anaesthesia areas for all sensory modalities can be explained by supramaximal perineural LA molecule concentration in both administered mepivacaine dosages. Upon washout of the LA nociceptive function is restored faster as compared to non-nociceptive sensation and higher concentration of the LA are required to maintain the analgesia. Quantitative sensory testing is able to detect different susceptibility of low threshold mechanosensors and subtypes of nociceptive C-fibres to mepivacaine. Using painful mechanical, heat and electrical stimulation different classes of nociceptors will be activated. The analgesic areas to electrical stimulation were particularly small; one might therefore hypothesize that the proposed protocol allows to also differentiate mechano-insensitive ("silent") and mechanosensitive ("polymodal") nociceptors. Implications QST is a non-invasive method to functionally examine sensory modalities and their pharmacological modulation in humans. The method is sufficiently sensitive to differentiate the analgesic properties of mepivacaine at 0.5 and 1% and might also be adequate to different classes of nociceptors. Further development of nociceptive stimuli including supra-threshold encoding characteristics will enable to investigate peripheral analgesic effects more specifically and thus might help to design new analgesics with preferential effect on high frequency discharge of nociceptors. Подробнее

Scandinavian journal of pain

Evaluation of radio-immunotherapy sequence on immunological responses and clinical outcomes in patients with melanoma brain metastases (ELEKTRA).

2022

In patients with melanoma brain metastases (MBM), a combination of radiotherapy (RT) with immune checkpoint inhibitors (ICI) is routinely used. However, the best sequence of radio-immunotherapy (RIT) remains unclear. In an exploratory phase 2 trial, MBM patients received RT (stereotactic or whole-brain radiotherapy depending on the number of MBM) combined with ipilimumab (ipi) ± nivolumab (nivo) in different sequencing (Rad-ICI or ICI-Rad). Comparators arms included patients treated with ipi-free systemic treatment or without RT (in MBM-free patients). The primary endpoints were radiological and immunological responses in the peripheral blood. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Of 106 screened, 92 patients were included in the study. Multivariate analysis revealed an advantage for patients starting with RT (Rad-ICI) for overall response rate (RR: p = .007; HR: 7.88 (95%CI: 1.76-35.27)) and disease control rate (DCR: p = .036; HR: 6.26 (95%CI: 1.13-34.71)) with a trend for a better PFS (p = .162; HR: 1.64 (95%CI: 0.8-3.3)). After RT plus two cycles of ipi-based ICI in both RIT sequences, increased frequencies of activated CD4, CD8 T cells and an increase in melanoma-specific T cell responses were observed in the peripheral blood. Lasso regression analysis revealed a significant clinical benefit for patients treated with Rad-ICI sequence and immunological features, including high frequencies of memory T cells and activated CD8 T cells in the blood. This study supports increasing evidence that sequencing RT followed by ICI treatment may have better effects on the immunological responses and clinical outcomes in MBM patients. Подробнее

Oncoimmunology