Frank Stenner-Liewen

Universitätsspital Basel · Klinik für Onkologie

Background Tumor lysis syndrome (TLS) is a potentially life‐threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate‐lowering treatments, and a steroid prophase st...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients with melanoma, although long-term responses seem restricted in patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of secondary resistance...

Purpose To assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration–resistant prostate cancer (mCRPC) patients treated with ¹⁷⁷ Lutetium-PSMA I&T therapy. Methods Single-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety...

Aims Primary bone diffuse large B‐cell lymphoma (PB‐DLBCL) is not recognized as a separate entity by the current classification systems. Here we define and highlight its distinctive clinical presentation, morphology, phenotype, gene expression profile (GEP), and molecular genetics. Methods We collected 27 respective cases and investigated their ph...

Sarcomatoid Urothelial Bladder Cancer (SARC) is a rare and aggressive histological subtype of bladder cancer for which therapeutic options are limited and experimental models are lacking. Here, we report the establishment of a long-term 3D organoid-like model derived from a SARC patient ( SarBC-01 ). SarBC-01 emulates aggressive morphological, phen...

Tumor lysis syndrome (TLS) is a life-threatening condition caused by the rapid destruction of malignant cells, leading to imbalances in electrolytes and posing risks such as acute kidney injury, arrhythmia, and seizures. This retrospective study aimed to evaluate the incidence of TLS in a cohort of 94 patients with advanced-stage aggressive B-cell...

The management of prostate cancer is undergoing rapid changes in all disease settings. Novel imaging tools for diagnosis have been introduced, and the treatment of high-risk localized, locally advanced and metastatic disease has changed considerably in recent years. From clinical and health-economic perspectives, a rational and optimal use of the a...

Introduction: Primary mediastinal large B-cell lymphoma (PMBL) is a rarely occurring lymphoid malignancy, which typically affects young adults and presents itself as an anterior mediastinal mass. Gene expression profiling, as well as somatic genetic analysis revealed that it is closely related to classical Hodgkin lymphoma, whereas morphologically...

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is not recognized as a separate entity by the current classification systems. Here, we define and highlight its distinctive clinical presentation, morphology, phenotype, gene expression profile (GEP) and molecular genetics. We collected 27 respective cases and investigated their phenotype, perfo...

183 Background: Radionuclide therapy targeting the prostate specific membrane antigen ( ¹⁷⁷ Lu-PSMA therapy) has proven to be an effective treatment in men with metastatic castration resistant prostate cancer (mCRPCs). Despite representing a significant therapeutic breakthrough, a critical unmet need in ¹⁷⁷ Lu-PSMA therapy, is a prognostic biomarke...

LBA443 Background: The 2 primary endpoints of the CheckMate 274 trial were met as nivolumab (NIVO) improved disease-free survival (DFS) versus placebo (PBO) in the intent-to-treat (ITT) population and in patients with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. We report extended follow-up data. Methods: CheckMate 274 is a phase 3, dou...

Background: In the treatment of advanced Hodgkin Lymphoma (aHL), based on guidelines a multitude of treatment options are available. The availability of PET guided decision-making and new therapeutic agents increase the complexity of the decision-making process. Methods: Thirteen experts of Swiss university and cantonal hospitals in Switzerland...

Background and purpose Chemotherapy-induced neutropenia and neutrophil-to-lymphocyte ratio (NLR) are potentially useful prognostic markers in patients with metastatic castration-resistant prostate cancer (mCRPC). This post hoc analysis investigated whether these markers can be utilized for dose considerations and evaluated the prognostic impact of...

Approximately 420 men are diagnosed with germ-cell cancer (GCC) in Switzerland each year. Recent international guidelines outline management issues, but many aspects remain controversial in an area of highly individualised treatments. Even more than in other tumour types, in GCC the challenge is to choose exactly the correct treatment for an indivi...

Hodgkin lymphoma (HL) in older patients appears to be a different disease compared with younger patients with historically lower survival rates. This is related to a variety of factors, including increased treatment‐related toxicity, the presence of comorbidities and biologic differences. In order to better assess the clinical characteristics, trea...

Background The NLR could be established as an important prognostic marker for the outcome of mCRPC patients treated with chemotherapy, steroids and novel androgen receptor directed therapies. Thus far the value of the NLR as a biomarker in the context of therapeutic radionuclides has never been explored. Methods The pivotal phase III trial of Ra...

Since 2016, a next-generation sequencing (NGS) panel targeting 68 genes frequently mutated in lymphoid malignancies is an accredited part of routine diagnostics at the Institute of Pathology in Basel, Switzerland. Here, we retrospectively evaluate the feasibility and utility of integrating this NGS platform into routine practice on 80 diagnostic ca...

Aims of the study: Atezolizumab is an approved therapy for urothelial carcinoma based on results from the IMvigor 210 and IMvigor211 phase II and III trials. The global SAUL study evaluated atezolizumab in a broader patient population more representative of real-world populations. Among approximately 1000 patients treated in SAUL, 25 were treated...

Abstract GOLPH2 (Golgi Phosphoprotein 2) is a protein with pro-oncogenic properties that has currently been identi ed as a prime target for tumour therapy. Its involvement in key oncogenic pathways like EGFR, mTOR/AKT, PI3K makes it a good candidate for therapeutic intervention. Several research groups have consistently reported that GOLPH2, when e...

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) such as programmed death ligand-1 (PD-L1) blockers offers pronounced clinical benefit with durable responses and a manageable safety profile. Patients with a high risk of immune-related adverse events are generally excluded from clinical trials testing ICI therapy. Thus, only a little in...

Background Golgi phosphoprotein 2 (GOLPH2) has been shown to be involved in chronic inflammatory processes and carcinogenesis. GOLPH2 is prominently overexpressed in hepatocellular carcinoma, melanoma, glioblastoma, prostate, lung, and colorectal cancer. With a low and tightly regulated expression in non-malignant tissues, GOLPH2 has been proposed...

e14137 Background: HLA open conformers (OC) are defined as HLA class I molecules lacking beta-2-microglobulin (β2m) and peptide. OC can be derived from different HLA I molecules such as HLA-B27, -B57, and –Cw08. OC have a different three dimensional structure when compared to their respective HLA/β2m/peptide counterpart and induce distinct immunolo...

Purpose: PD-(L)1-blocking antibodies have clinical activity in metastatic non-small cell lung cancer (NSCLC) and mediate durable tumor remissions. However, the majority of patients are resistant to PD-(L)1 blockade. Understanding mechanisms of primary resistance may allow prediction of clinical response and identification of new targetable pathway...

Selective digestive decontamination (SDD) with the oral, non-absorbable antimicrobial substances gentamicin, vancomycin and amphotericin B was optionally used at our institution to reduce the risk of gastrointestinal tract derived infections in multiple myeloma (MM) patients undergoing high-dose chemotherapy with subsequent autologous stem cell tra...

First generation immune checkpoint inhibitors including anti-CTLA-4 and anti-PD-1 antibodies have led to major clinical progress, yet resistance frequently leads to treatment failure. Thus, new targets acting on T cells are needed. CD33-related Siglecs are pattern recognition immune receptors binding to a range of sialoglycan ligands, which appear...

Over the last few years, there have been many changes in the management of patients with follicular lymphoma, resulting in improvements in progression-free survival and quality of life. In addition to established regimens such as radiotherapy and immunochemotherapy, new treatment options are on the horizon. Furthermore, even the use of established...

Follicular lymphoma (FL) is the most frequent indolent lymphoma in the Western world and is characterized in almost all cases by the t(14;18) translocation that results in overexpression of BCL2, an anti-apoptotic protein. The entity includes a spectrum of subentities that differ from an indolent to a very aggressive growth pattern. As a consequenc...

Patients with classical Hodgkin lymphoma (cHL) have an impaired cellular immune response as indicated by an anergic reaction against standard recall antigens and a diminished rejection reaction of allogeneic skin transplant. This clinical observation can be linked to the histopathological feature of cHL since the typical pattern of a cHL manifestat...

Background: Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. T...

Introduction In metastatic renal-cell carcinoma (mRCC), physicians have a plethora of therapeutic choices, with the latest addition of checkpoint inhibitors. However, many questions regarding the best use of the respective drugs remain unanswered. Therefore, it is important to examine and summarize the outcome of real-world experiences to understan...

Purpose:Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a...

Vinorelbine combined with filgrastim (r-metHuG-CSF) at a dose of 10 µg/kg of body weight (BW) per day is a reliable and well tolerated regimen for mobilization of hematopoietic progenitor cells (HPC) in patients with multiple myeloma. This prospective randomized phase 2 study was initiated to assess the feasibility of a reduced filgrastim dosage. V...

Background: The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with different regimens after first-line docetaxel, as well as disease progression. Patients and methods: Patients with mCRPC having received first-line chemotherapy with docetaxel were eli...

Background Stimulation of the immune system by targeting the PD-1/PD-L1 pathway can result in activation of anti-tumor immunity. Besides its clinical benefit immune checkpoint therapy leads to significant immune-related adverse events (irAEs). Some rare irAEs are not well described yet but are critical in patient management. Case presentation Here...

RNF41 (Ring Finger Protein 41) is an E3 ubiquitin ligase involved in the intracellular sorting and function of a diverse set of substrates. Next to BRUCE and Parkin, RNF41 can directly ubiquitinate ErbB3, IL-3, EPO and RARα receptors or downstream signaling molecules such as Myd88, TBK1 and USP8. In this way it can regulate receptor signaling and r...

Random mutagenesis combined with MAPPIT, single mutants. Table representing all single RNF41 mutants resulting from the screen. Column 1 and 2 show the positions and mutations in RNF41. Column 3, 4 and 5 represent the relative MAPPIT signals of the preys tested against the RNF41 mutants, with EFH1A, a JAK2 binder, as a positive control. The relativ...

L163Q does not influence RNF41 auto-ubiquitination. HEK293T cells co-transfected with pMet7-vectors encoding Flag-tagged RNF41, L163Q, ΔCC or sol IL5Rα (mock), together with HA-ubiquitin were incubated overnight with 5μM MG132 and 25μM chlolorquine to inhibit proteasomal or lysosomal degradation. Flag immunoprecipitation followed by anti-HA stainin...

Statistical analysis of biological replicates from the data in Fig 4A and 4B. The Western Blots in Fig 4A and 4B, together with biological replicates, were quantified using Image J. (A) The ubiquitination signal was normalized for the amount of immunoprecipitated Flag-tagged VPS52 and compared between the mock, RNF41 and L163Q condition. A one-way...

Random mutagenesis combined with MAPPIT, specific single mutants. Table representing only the specific single mutants for interaction with VPS52 or ASB6. (XLSX)

Generation and origin of the constructs used in this paper. (XLSX)

L163Q specifically disrupts interaction with VPS52. MAPPIT analysis of HEK293T cells transiently co-transfected with a plasmid encoding an empty, VPS52, ASB6 or USP8 prey together with a RNF41 or L163Q bait. (TIF)

(A) Ectopic expression of RNF41 hampers VPS52 oligomerization. AlphaScreen analysis of HEK293T cells transiently co-transfected with a plasmid encoding an E-tagged and Flag-tagged VPS52 together with untagged WT RNF41, L163Q or sol IL5Rα (mock). Values are means ± s.d from triplicate samples from one of three representative experiments. Data and st...

Data and statistical analysis of biological replicates from AlphaScreen experiments in Figs 3E, 4E and S2. One-way ANOVA (randomized block design) showed a marginal significant difference (Fig 3E: P = 0.0983; Fig 4E: P = 0.1106; S2 Fig: P = 0.0693). (TIF)

e14523 Background: Cancer patients (pts) are at risk to develop complications when infected with seasonal influenza viruses. Current guidelines propose that pts on PD-1 directed therapies may receive concurrent inactivated influenza immunization if not medically contraindicated. In this observational study, we aimed to assess the vaccine induced im...

Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.

Background: We previously showed that mCRPC patients developing grade ≥3 neutropenia (NP) with cabazitaxel had a prolonged progression-free survival (PFS) and OS (Meisel EJC 2016; 56:93-100). A risk model combining the neutrophil-to-lymphocyte ratio (NLR) and grade ≥ 3 NP was built to distinguish patients with a poor, intermediate and good prognosi...

Background: Curative chemotherapy approaches in patients with malignancies and platelet (PLT) transfusion refractoriness due to alloimmunization may be hampered by the lack of suitable PLT donors. For these patients, transfusion of cryopreserved autologous PLTs is an option, but is time- and resource-consuming. We aimed at further simplifying this...

Background Enzalutamide is a second-generation androgen receptor (AR) inhibitor that binds to and blocks the AR with higher affinity than previously available AR inhibitors. High activity has been proven in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and in chemotherapy-naive patients with...

Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore lacking deeper insights into genome-wide lymph...

In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitor...

Background: Cabazitaxel significantly improves overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC) progressing during or after docetaxel, but is associated with a higher rate of grade ≥3 neutropenia compared with docetaxel. We thus examined the relationship between cabazitaxel-induced grade ≥3 neutropenia, bas...

Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data are not available for all clinical indications. Accordingly, the efficacy of the biosimilar filgrastim Zarzio® combined with vinorelbine for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma has not bee...

After more than two decades of almost no clinical advances for muscle-invasive bladder cancer (MIBC), exciting breakthrough research has been conducted in the last 2 yr. Among the findings, genome-wide next-generation sequencing (NGS) and gene expression profiling results for bladder cancer have profoundly added to our understanding of this disease...

Abstract OBJECTIVES: HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272) and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) pati...

Carbonic anhydrase 9 (CA9) and carbonic anhydrase 12 (CA12) were proposed as potential targets for cancer therapy more than 20 years ago. However, to date, there are only very few antibodies that have been described to specifically target CA9 and CA12 and also block the enzymatic activity of their targets. One of the early stage bottlenecks in iden...

We aimed to assess the efficacy of vinorelbine plus granulocyte colony-stimulating factor (G-CSF) for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma and to identify adverse risk factors for successful mobilization. Vinorelbine 35 mg/m2 was administered intravenously on day 1 in an outpatient setti...