Incidence and Clinical Features of Pseudoprogression in Brain Metastases After Immune-Checkpoint Inhibitor Therapy: A Retrospective Study.

Pseudoprogression is known to occur after immune-checkpoint inhibitor (ICI) therapy in brain metastasis and can complicate clinical decision-making. Still, its incidence, timing, and clinical presentation remain unclear. A retrospective cohort study in melanoma and non-small cell lung cancer brain metastasis patients was conducted to address this.

Heterogeneity of CD8 T-Cell Changes in Advanced Melanomas After Initiation of Immunotherapy.

Whole-body CD8 T-cell PET imaging can detect spatial and temporal localization of CD8 T cells. To obtain insight into early CD8 T-cell response to immunotherapy in patients with melanoma, a highly immunogenic tumor, we performed serial PET imaging with the 1-armed CD8 antibody tracer ZED88082A. Immunotherapy-naïve adult patients with stage IV melanoma underwent PET scanning 2 d after receiving 10 mg of ZED88082A intravenously at baseline and 6-8 wk after initiation of standard-of-care immunotherapy.

Transcriptional pattern enriched for synaptic signaling is associated with shorter survival of patients with high-grade serous ovarian cancer.

Bulk transcriptomic analyses of high-grade serous ovarian cancer (HGSOC) so far have not uncovered potential drug targets, possibly because subtle, disease-relevant transcriptional patterns are overshadowed by dominant, non-relevant ones. Our aim was to uncover disease-outcome-related patterns in HGSOC transcriptomes that may reveal novel drug targets. Using consensus-independent component analysis, we dissected 678 HGSOC transcriptomes of systemic therapy naïve patients-sourced from public repositories-into statistically independent transcriptional components (TCs).

Evaluation of BRCA1/2 testing rates in epithelial ovarian cancer patients: lessons learned from real-world clinical data.

Identification of somatic and germline BRCA1/2 pathogenic variants in epithelial ovarian cancer (EOC) patients is essential for determining poly-(ADP-ribose)-polymerase (PARP) inhibitor sensitivity and genetic predisposition. In the Netherlands, BRCA1/2 testing changed to a tumor-first approach to efficiently identify both somatic and germline pathogenic variants in all patients. Here, we performed an in-depth evaluation of the first four years of the tumor-first test-pathway.

Quality of life, neurocognitive functioning, psychological issues, sexuality and comorbidity more than 2 years after commencing immune checkpoint inhibitor treatment.

Background: Increasing numbers of patients diagnosed with advanced cancer survive long-term after treatment with immune checkpoint inhibitors (ICIs). To design adequate interventions for these survivors, knowledge regarding quality of life (QOL) and its association with long-term and late effects of ICI treatment is required. Therefore, this study aimed to evaluate QOL, neurocognitive function, psychological issues, sexuality, and comorbidities in patients surviving at least 2 years after commencing ICI treatment.

[Help with nibs and mabs: targeted cancer therapies for non-oncologists].

Targeted therapies, including monoclonal antibodies and small molecules, are increasingly important components of oncological treatments. Targeted therapies are designed to tackle cancer cell pathogenesis at specific points essential to tumour survival and growth. These drugs can result in both on- and off-target side effects which are frequently clinically relevant.

Change in Metabolic Markers and the Risk of Skin Cancer: Results from the Lifelines Cohort Study in the Netherlands.

Background: Skin cancers are the most common cancers in Caucasians, and their incidence is rising. Although metabolic and anthropometric markers play a role in cancer development, the relationship between metabolic and anthropometric changes in skin cancer remains unclear. This study aimed to examine possible associations between these changes and the risk of skin cancer.

A comparison of real-world data on adjuvant treatment in patients with stage III BRAF V600 mutated melanoma - Results of systematic literature research.

Background: Over the past decade, PD-1-based immune checkpoint inhibitors (ICI) and targeted therapies (TT) with BRAF and MEK inhibitors transformed melanoma treatment. Both are widely used in the adjuvant setting. However, for patients with a BRAF V600 mutation, the optimal adjuvant therapy remains unclear due to the lack of head-to-head comparison studies.

Elevations of Cardiac Troponin in Patients Receiving Immune Checkpoint Inhibitors: Data From a Prospective Study.

Background: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer. However, immune-related adverse events are prevalent in patients receiving ICI therapy. A serious immune-related adverse event is ICI-myocarditis, which is complex to diagnose given that the significance of early symptoms and biomarker trajectories, such as high-sensitivity troponin T (hs-TnT) are unclear.

Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study.

Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response.

B cells critical for outcome in high grade serous ovarian carcinoma.

Recent work has shown evidence for the prognostic significance of tumor infiltrating B cells (B-TIL) in high grade serous ovarian carcinoma (HGSOC), the predominant histological subtype of ovarian cancer. However, it remains unknown how the favorable prognosis associated with B-TIL relates to the current standard treatments of primary debulking surgery (PDS) followed by chemotherapy or (neo-)adjuvant chemotherapy (NACT) combined with interval debulking surgery. To address this, we analyzed the prognostic impact of B-TIL in relationship to primary treatment and tumor infiltrating T cell status in a highly homogenous cohort of HGSOC patients.

Serous Tubal Intraepithelial Carcinoma After Neoadjuvant Chemotherapy: A Report of 2 Cases.

Serous tubal intraepithelial carcinoma (STIC) is regarded as the origin of most high-grade serous carcinomas (HGSC). After a diagnosis of isolated STIC, risk of developing HGSC is substantial. Since surveillance cannot detect HGSC in time to cure the disease, there is no consensus on the optimal treatment after a diagnosis of isolated STIC, but chemotherapy is considered one of the possible strategies.

Long-term outcome of high-grade serous carcinoma established in risk-reducing salpingo-oophorectomy specimens in asymptomatic BRCA1/2 germline pathogenic variant carriers.

Objective: The aim of this study was to describe the long-term outcome of asymptomatic BRCA1/2 germline pathogenic variant (GPV) carriers with high-grade serous carcinoma (HGSC) in their risk-reducing salpingo-oophorectomy (RRSO) specimen.

Methods: In a previously described cohort of asymptomatic BRCA1/2 GPV carriers derived from the Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) study, women with HGSC at RRSO were identified. Main outcome was ten-year disease-free survival (DFS).

Cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma: prospective real-world data from the DRUG Access Protocol.

Background: The DRUG Access Protocol provides patients with cancer access to registered anti-cancer drugs that are awaiting reimbursement in the Netherlands and simultaneously collects prospective real-world data (RWD). Here, we present RWD from PD-1 blocker cemiplimab in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (laCSCC; mCSCC).

Methods: Patients with laCSCC or mCSCC received cemiplimab 350 mg fixed dose every three weeks.

Everolimus decreases [U-C]glucose utilization by pyruvate carboxylase in breast cancer cells in vitro and in vivo.

Reprogrammed metabolism is a hallmark of cancer, but notoriously difficult to target due to metabolic plasticity, especially in response to single metabolic interventions. Combining mTOR inhibitor everolimus and mitochondrial complex 1 inhibitor metformin results in metabolic synergy in in vitro models of triple-negative breast cancer. Here, we investigated whether the effect of this drug combination on tumor size is reflected in changes in tumor metabolism using [U-C]glucose labeling in an MDA-MB-231 triple negative breast cancer xenograft model.

Immune checkpoint inhibitor-mediated polymyalgia rheumatica versus primary polymyalgia rheumatica: comparison of disease characteristics and treatment requirement.

Objectives: To compare clinical characteristics, imaging findings and treatment requirements of patients with immune checkpoint inhibitor-mediated polymyalgia rheumatica (ICI-PMR) and primary PMR.

Methods: This single centre, retrospective cohort study compared ICI-PMR in patients with cancer (n = 15) to patients with primary PMR (n = 37). A comparison was made between clinical symptoms, laboratory markers, ultrasonography, 18F-FDG-PET/CT findings and treatment requirements related to PMR.

Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol.

Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors.

A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors.

The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry.

CINOVA: a phase II study of CPC634 (nanoparticulate docetaxel) in patients with platinum resistant recurrent ovarian cancer.

Objective: Recurrent platinum-resistant ovarian cancer has a poor prognosis with limited therapeutic options. Sub-therapeutic intra-tumoral drug concentrations may add to therapy resistance. CPC634 (docetaxel entrapped in CriPec nanoparticles) was designed to enhance tumor accumulation of drug with localized drug release at the target site to increase therapeutic efficacy.

Pharmacological inhibition of MEK1/2 signaling disrupts bile acid metabolism through loss of Shp and enhanced Cyp7a1 expression.

The RAS-MAPK signaling pathway is one of the most frequently dysregulated pathways in human cancer. Small molecule inhibitors directed against this pathway have clinical activity in patients with various cancer types and can improve patient outcomes. However, the use of these drugs is associated with adverse effects, which can result in dose reduction or treatment interruption.

Whole-body CD8 T cell visualization before and during cancer immunotherapy: a phase 1/2 trial.

Immune checkpoint inhibitors (ICIs), by reinvigorating CD8 T cell mediated immunity, have revolutionized cancer therapy. Yet, the systemic CD8 T cell distribution, a potential biomarker of ICI response, remains poorly characterized. We assessed safety, imaging dose and timing, pharmacokinetics and immunogenicity of zirconium-89-labeled, CD8-specific, one-armed antibody positron emission tomography tracer ZED88082A in patients with solid tumors before and ~30 days after starting ICI therapy (NCT04029181).

The Value of Glycemic Control Prior to Cancer Diagnosis on All-Cause Mortality among Patients with Type 2 Diabetes in Dutch Primary Care.

Background: Poor glycemic control prior to cancer diagnosis for patients with preexisting type 2 diabetes (T2DM) may predict a worse cancer diagnosis. We investigated the association between pre-diagnosis glycemic control and all-cause mortality in patients with T2DM who develop cancer.

Methods: This prospective cohort study linked data from three sources covering 1989 to 2019: a T2DM benchmarking database, the Netherlands Cancer Registry, and the Personal Records Database.

Towards less mutilating treatments in patients with advanced non-melanoma skin cancers by earlier use of immune checkpoint inhibitors.

Merkel cell carcinoma (MCC), advanced cutaneous squamous cell carcinoma (cSCC), and advanced basal cell carcinoma (BCC) are rare, and the often frail patients may require potentially mutilating local treatments. Immune checkpoint inhibitors (ICIs) are effective in melanoma and are moving towards the neoadjuvant setting. This systematic review explores data supporting the transition of ICIs from the metastatic to the (neo)adjuvant setting non-melanoma skin cancer (NMSC) and describes how knowledge from melanoma can be utilized.