Showing papers by "Markus Meissner published in 2022"

Immune Checkpoint Inhibitor-Induced Cerebral Pseudoprogression: Patterns and Categorization

Abstract: Background The inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system. Methods We screened our hospital information system to identify patients with any in-house ICI treatment for any tumor disease during the years 2007-2019. All patients with cerebral MR imaging (cMRI) of sufficient diagnostic quality were included. cMRIs were retrospectively analyzed according to immunotherapy response assessment for neuro-oncology (iRANO) criteria. Results We identified 12 cases of cerebral pseudoprogression in 123 patients treated with ICIs and sufficient MRI. These patients were receiving ICI therapy for lung cancer (n=5), malignant melanoma (n=4), glioblastoma (n=1), hepatocellular carcinoma (n=1) or lymphoma (n=1) when cerebral pseudoprogression was detected. Median time from the start of ICI treatment to pseudoprogression was 5 months. All but one patient developed neurological symptoms. Three different patterns of cerebral pseudoprogression could be distinguished: new or increasing contrast-enhancing lesions, new or increasing T2 predominant lesions and cerebral vasculitis type pattern. Conclusion Cerebral pseudoprogression followed three distinct patterns and was detectable in 3.2% of all patients during ICI treatment and in 9.75% of the patients with sufficient brain imaging follow up. The fact that all but one of the affected patients developed neurological symptoms, which would be classified as progressive disease according to iRANO criteria, mandates vigilance in the diagnosis and treatment of ICI-induced cerebral lesions.

Impact of the Covid‐19 pandemic on melanoma and non‐melanoma skin cancer inpatient treatment in Germany – a nationwide analysis

Abstract: SARS‐CoV‐2 has massively changed the care situation in hospitals worldwide. Although tumour care should not be affected, initial reports from European countries were suggestive for a decrease in skin cancer during the first pandemic wave and only limited data are available thereafter.

Factors Associated with Hemorrhage of Melanoma Brain Metastases after Stereotactic Radiosurgery in the Era of Targeted/Immune Checkpoint Inhibitor Therapies

Abstract: Simple Summary Melanoma brain metastases (MBM) have a high propensity for hemorrhage (HA) after treatment. Our retrospective analysis evaluated factors associated with HA of MBM after robotic stereotactic radiosurgery (SRS) in the era of modern systemic therapy, and to the best of our knowledge, this is the first study focusing on this side effect. A total of 55 patients with 279 MBM were treated. The use of anticoagulants was the only predictive factor, both for radiologically evident HA and HA causing grade 3 toxicity. The interval between the administration of systemic therapy and SRS was also significant with regard to HA causing grade 1 toxicity, but it appears that the combination was safe, at least concerning grade 3 toxicity. We believe that our study is a useful contribution to the current literature, as it provides insights regarding the factors that correlate with HA. Abstract We aimed to evaluate the factors associated with hemorrhage (HA) of melanoma brain metastases (MBM) after Cyberknife stereotactic radiosurgery (SRS) in the modern era of systemic therapy. A total of 55 patients with 279 MBM were treated in 93 fractions. The median age, SRS dose, radiological follow-up, and time to HA were 60.4 years, 20 Gy, 17.7 months, and 10.7 months, respectively. Radiologically evident HA was documented in 47 (16.8%) metastases. Of the 55 patients, 25 (45.4%) suffered an HA. Among those, HA caused grade 3 toxicity in 10 patients (40%) and grade 1 symptoms in 5 patients (20%). Ten patients (40%) with HA experienced no toxicity. Logistic regression revealed the use of anticoagulants and the administration of systemic therapy within 7/15 days from SRS to be predictive for HA. When considering the HA causing grade 3 symptomatology, only the use of anticoagulants was significant, with the delivery of whole brain radiation therapy (WBRT) before the HA narrowly missing statistical significance. Our retrospective analysis showed that the administration of modern systemic therapy within 7/15 days from SRS may contribute to HA of MBM, though it appears safe, at least concerning grade 3 toxicity. The use of anticoagulants by the time of SRS significantly increased the risk of HA.

Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Re-Induction following Resistance or Toxicity

Abstract: Simple Summary The era of immune checkpoint blockade (ICB) with nivolumab and pembrolizumab (anti-PD-1) alone or in combination with ipilimumab (anti-CTLA-4) has led to prolonged survival in patients with cutaneous melanoma (CM). However, the response to ICB is low in patients with uveal melanoma (UM). This retrospective multicenter study examines the effectiveness of re-induction with ICB in patients with metastatic UM. A re-induction was recorded when ICB treatment was initiated a second time after a first ICB treatment was discontinued due to resistance or toxicity. We compared two cohorts (re-induction of ICB vs. once-only ICB) and present evidence for the clinical activity of a re-induction with ICB in a small subgroup of patients. Abstract Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95% CI: 11.1–23.8) versus 9.4 months (cohort B, 95% CI: 6.1–14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities.

Hidradenitis suppurativa—Pitfalls of long‐term immunosuppressive treatment with tumor necrosis factor (TNF)‐α inhibitors

Abstract: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by inflamed lesions in forms of nodules, abscesses and sinus tracts with consecutive scarring in predominantly but not compulsory apocrine-gland bearing parts of the body such as axillary, inguinal or anogenital. The exact pathogenesis remains unclear to date. Follicular hyperkeratosis results in follicle occlusion and eventually rupture with destructive inflammation; but also pathological signaling of TNFα and IL-17 seem to be relevant. Even if the primary (auto-)inflammatory process is not triggered by a bacterial infection, skin microbiome of HS patients is altered, promoting a bacterial biofilm maintaining inflammatory processes. Depending on disease severity and comorbidities, different treatment approaches with either medical agents, for example, immunosuppressive therapy with biologics versus surgical approaches should be considered individually. However, management of HS patients often remains challenging. An increased overall risk of cancer in patients with HS has been described repeatedly and particularly the development of squamous cell carcinoma (SCC) secondary to chronic inflammation is a serious complication. The tumors are typically localized gluteal, perianal and perineal, while displaying a high incidence of local recurrences despite wide surgical excisions. Whether immunosuppressive treatment with biologics is associated with an increased risk of developing nonmelanoma skin cancer (NMSC) in patients with psoriasis or HS is still controversially discussed. HS patients under TNF-α inhibitors and the occurrence of a SCC throughout have been described. However, the underlying disease itself, that is, HS, in terms of pathogenesis and clinical course with longstanding inflammation increases the risk of developing a SCC. To what extent the immunosuppressive therapy eventually affects the tumor genesis remains unclear. Case 1: A 38-year-old male suffered from severe HS (Hurley stage III), showing recurrent absceding inflammation in both axillae, groins as well as anogenital. Over time, he received sequential wide local excisions and repeated systemic antibiotic treatment. Since June 2014, the patient was started on adalimumab in alternating dosage. In March 2020, the patient presented a severe worsening of his anogenital involvement with an extensive inflammation in form of widespread abscesses and fistulas accompanied by a decline of his general condition. Besides febrile temperatures, laboratory findings showed persistently elevated inflammatory markers and an anemia of chronic disease. MRI confirmed vast abscess formations perianal, transsphincteric, within the right ischio-anal fossa as well as urogenital with a fistula from the perineum into the scrotum (Figure 1). Clinical condition gradually declined further impending a septic course. Under antibiotic protection multiple abscess incisions and drainages were performed by our general surgical colleagues immediately. An intraoperative wound swab revealed growth of multiple anaerobic bacteria (Finegoldia magna, Eggerthia catenaformis, Petponiphils lacrimalis). To stabilize his clinical condition and prior to a planned

Functional Downregulation of PD-L1 and PD-L2 by CpG and non-CpG Oligonucleotides in Melanoma Cells

Abstract: Simple Summary Although metastatic melanoma is still not a curable disease, targeting of immunologically relevant checkpoints represents a turning point in the treatment. Particularly, targeting the interaction between PD-L1 and its referring receptor PD-1 with antibodies has been shown to activate T-cell function abrogating the evasion of tumor cells from immune recognition. Here, we present another approach that interferes with this system by showing that treatment of melanoma cells with oligonucleotides reduces the expression of PD-L1 (and PD-L2) on tumor cells. Specifically, non-CpG-6-PTO, an ODN that forms superstructures known as G-quartets, has been found to inhibit the interferon-γ-induced signaling cascade which fosters PD-L1 expression. These findings suggest a new therapeutic strategy to interfere with one of the most important immune checkpoints. Abstract The clinical application of immune checkpoint inhibitors represents a breakthrough progress in the treatment of metastasized melanoma and other tumor entities. In the present study, it was hypothesized that oligonucleotides (ODNs), known as modulators of the immune response, have an impact on the endogenous expression of checkpoint molecules, namely PD-L1 and PD-L2 (PD-L1/2). IFNγ-stimulated melanoma cells (A375, SK-Mel-28) were treated with different synthetically manufactured oligonucleotides which differed in sequence, length and backbone composition. It was found that a variety of different ODN sequences significantly suppressed PD-L1/2 expression. This effect was dependent on length and phosphorothioate (PTO) backbone. In particular, a sequence containing solely guanines (nCpG-6-PTO) was highly effective in downregulating PD-L1/2 at the protein, mRNA and promoter levels. Mechanistically, we gave evidence that ODNs with G-quartet-forming motifs suppress the interferon signaling axis (JAK/STAT/IRF1). Our findings identify a subset of ODNs as interesting pharmacological compounds that could expand the arsenal of targeted therapies to combat the immunological escape of tumor cells.

Microscale nuclear magnetic resonance gradient chip

Abstract: We propose a design, micro fabrication process, and nuclear magnetic resonance (NMR) based evaluation, of a magnetic field gradient chip. The uni-axial linear z-gradient coil design was computed by a stream-function method, with the optimisation goal to exhibit minimum power dissipation. The gradient coils were implemented on two bi-planes, which were built-up with Cu electroplating in combination with photo definable dry-film laminates. In the presented fabrication process, the initial seed layer served as a self-aligning back-side mask to define the electroplating mould, and also to implement resistive temperature detectors. The coil design and the electroplating process were tailored to enhance the electroplated height to construct low-resistive coils. Thermographic imaging in combination with the integrated temperature sensors allowed for investigating the heat-up, in order to analyse the current rating of the coil dual stack. The gradient coil was assembled with a radio frequency micro coil in a flip-chip configuration. To demonstrate the field linearity, a micro-engineered phantom was fabricated and subjected to a one-dimensional NMR experiment.

Exploring the most visible websites on cutaneous T‐cell lymphoma—revealing limited quality of patient health information on the internet

Abstract: Patients diagnosed with cancer frequently search the Internet for health information. Yet, the quality of CTCL online information has not been investigated so far.