Neoadjuvant chemotherapy for radiation associated angiosarcoma (RAAS) of the breast: A retrospective single center study.

Background: Radiation associated angiosarcoma (RAAS) of the breast is a rare malignancy with poor survival. Optimal treatment strategies remain uncertain due to a lack of data, and vary between surgery alone and a combination of surgery with (neo)adjuvant chemotherapy (NACT) and/or re-irradiation. The aim of this study was to evaluate the potential benefit of taxane based NACT.

Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products.

Adoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has proven highly effective for treating solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy for yet unknown reasons. Defining markers that correlate with high tumor-reactivity of the autologous TIL products is thus key for achieving better tailored immunotherapies.

Effective generation of tumor-infiltrating lymphocyte products from metastatic non-small-cell lung cancer (NSCLC) lesions irrespective of location and previous treatments.

Background: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Because current treatment regimens show limited success rates, alternative therapeutic approaches are needed. We recently showed that treatment-naïve, stage I/II primary NSCLC tumors contain a high percentage of tumor-reactive T cells, and that these tumor-reactive T cells can be effectively expanded and used for the generation of autologous tumor-infiltrating T cell (TIL) therapy.

Challenges and controversies patients and (health care) professionals experience in managing vaginal, vulvar, penile or anal cancer: The SILENCE study.

Objective: Patients with vaginal, vulvar, penile or anal cancer experience deteriorated psychosocial functioning and decreased Quality of Life (QoL). The aims of this study were to explore (1) the challenges and controversies patients experience in managing vaginal, vulvar, penile or anal cancer; their unmet needs; and how this affects their psychosocial functioning and (2) the gaps health care professionals (HCPs) experience in providing psychosocial support and potential improvements in care.

Methods: Semi-structured interviews with patients with vaginal, vulvar, penile or anal cancer and with HCPs were conducted.

Functional Screen for microRNAs Suppressing Anchorage-Independent Growth in Human Cervical Cancer Cells.

The progression of anchorage-dependent epithelial cells to anchorage-independent growth represents a critical hallmark of malignant transformation. Using an in vitro model of human papillomavirus (HPV)-induced transformation, we previously showed that acquisition of anchorage-independent growth is associated with marked (epi)genetic changes, including altered expression of microRNAs. However, the laborious nature of the conventional growth method in soft agar to measure this phenotype hampers a high-throughput analysis.

Developing a dynamic simulation model to support the nationwide implementation of whole genome sequencing in lung cancer.

Background: This study shows how dynamic simulation modeling can be applied in the context of the nationwide implementation of Whole Genome Sequencing (WGS) for non-small cell lung cancer (NSCLC) to inform organizational decisions regarding the use of complex and disruptive health technologies and how these decisions affect their potential value.

Methods: Using the case of the nationwide implementation of WGS into clinical practice in lung cancer in the Dutch healthcare system, we developed a simulation model to show that including service delivery features across the diagnostic pathway can provide essential insight into the affordability and accessibility of care at the systems level. The model was implemented as a hybrid Agent-Based Model and Discrete-Event Simulation model in AnyLogic and included 78 hospital agents, 7 molecular tumor board agents, 1 WGS facility agent, and 5313 patient agents each year in simulation time.

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial.

Background: While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response.

Whole genome sequencing in oncology: using scenario drafting to explore future developments.

Background: In oncology, Whole Genome Sequencing (WGS) is not yet widely implemented due to uncertainties such as the required infrastructure and expertise, costs and reimbursements, and unknown pan-cancer clinical utility. Therefore, this study aimed to investigate possible future developments facilitating or impeding the use of WGS as a molecular diagnostic in oncology through scenario drafting.

Methods: A four-step process was adopted for scenario drafting.

T cells expanded from renal cell carcinoma display tumor-specific CD137 expression but lack significant IFN-γ, TNF-α or IL-2 production.

Metastatic renal cell carcinoma (RCC) has a poor prognosis. Recent advances have shown beneficial responses to immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies. As only a subset of RCC patients respond, alternative strategies should be explored.

Delta-Like Ligand-Notch1 Signaling Is Selectively Modulated by HPV16 E6 to Promote Squamous Cell Proliferation and Correlates with Cervical Cancer Prognosis.

Human papillomavirus (HPV) drives high-grade intraepithelial neoplasia and cancer; for unknown reasons, this occurs most often in the cervical transformation zone. Either mutation or HPV E6-driven inhibition of Notch1 can drive neoplastic development in stratified squamous epithelia. However, the contribution of Notch1 and its Delta-like ligands (DLL) to site susceptibility remains poorly understood.

Adenocarcinoma of the Uterine Cervix Shows Impaired Recruitment of cDC1 and CD8 T Cells and Elevated β-Catenin Activation Compared with Squamous Cell Carcinoma.

Purpose: Adenocarcinoma of the uterine cervix is the second most common type of cervical cancer after squamous cell carcinoma (SCC). Although both subtypes are treated similarly, patients with adenocarcinoma have a worse prognosis. In this study, immunologic features of the tumor microenvironment in these two subsets were pursued with potential therapeutic implications.

Repeatability of arterial input functions and kinetic parameters in muscle obtained by dynamic contrast enhanced MR imaging of the head and neck.

Background: Quantification of pharmacokinetic parameters in dynamic contrast enhanced (DCE) MRI is heavily dependent on the arterial input function (AIF). In the present patient study on advanced stage head and neck squamous cell carcinoma (HNSCC) we have acquired DCE-MR images before and during chemo radiotherapy. We determined the repeatability of image-derived AIFs and of the obtained kinetic parameters in muscle and compared the repeatability of muscle kinetic parameters obtained with image-derived AIF's versus a population-based AIF.

Polyfunctional tumor-reactive T cells are effectively expanded from non-small cell lung cancers, and correlate with an immune-engaged T cell profile.

Non-small cell lung cancer (NSCLC) is the second most prevalent type of cancer. With the current treatment regimens, the mortality rate remains high. Therefore, better therapeutic approaches are necessary.

Variation in the time to treatment for stage III and IV non-small cell lung cancer patients for hospitals in the Netherlands.

Objectives: Increased emphasis on molecular diagnostics can lead to increased variation in time to treatment (TTT) for patients with stage III and IV non-small cell lung cancer. This article presents the variation in TTT for advanced NSCLC patients observed in Dutch hospitals before the widespread use of immunotherapy. The aim of this article was to explore the variation in TTT between patients, as well as between hospitals.

The great debate at "Melanoma Bridge 2018", Naples, December 1st, 2018.

The great debate session at the 2018 Melanoma Bridge congress (November 29-December 1, Naples, Italy) featured counterpoint views from experts on three topical issues in melanoma. These were whether overall survival should still be the main endpoint for clinical trials in melanoma, whether anti-cytotoxic T-lymphocyte-associated antigen (CTLA)-4 is still the optimal choice of drug to use in combination with an anti-programmed death (PD)/PD-ligand (L)-1 agent, and the place of adjuvant versus neoadjuvant therapy in patients with melanoma. These three important debates are summarised in this report.

Early cost-effectiveness of tumor infiltrating lymphocytes (TIL) for second line treatment in advanced melanoma: a model-based economic evaluation.

Background: An emerging immunotherapy is infusion of tumor infiltrating Lymphocytes (TIL), with objective response rates of around 50% versus 19% for ipilimumab. As an Advanced Therapeutic Medicinal Products (ATMP), TIL is highly personalized and complex therapy. It requests substantial upfront investments from the hospital in: expensive lab-equipment, staff expertise and training, as well as extremely tight hospital logistics.

A prediction model relating the extent of intraoperative fascia preservation to erectile dysfunction after nerve-sparing robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is performed in patients with prostate cancer. Unfortunately, 10-46% of patients may still suffer from limited erectile function (EF) after RARP. This study aimed to develop a prediction model based on the extent of fascia preservation (FP) and postoperative EF after RARP.

Bioorthogonally Applicable Fluorescence Deactivation Strategy for Receptor Kinetics Study and Theranostic Pretargeting Approaches.

The availability of a receptor for theranostic pretargeting approaches was assessed by use of a new click-chemistry-based deactivatable fluorescence-quenching concept. The efficacy was evaluated in a cell-based model system featuring both membranous (available) and internalized (unavailable) receptor fractions of the clinically relevant receptor chemokine receptor 4 (CXCR4). Proof of concept was achieved with a deactivatable tracer consisting of a CXCR4-specific peptide functionalized with a Cy5 dye bearing a chemoselective azide handle (N -Cy5-AcTZ14011).

Incidence of small bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

Background And Study Aims: Lynch syndrome (LS) patients have an increased risk of small bowel cancer. The question is whether surveillance will lead to early detection of (pre)malignant lesions. We recently reported on prevalence of small bowel neoplasia (SBN) in LS patients as assessed by video capsule endoscopy (VCE).

Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics.

Background: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for and evaluation; e.g. fluorescence or nuclear medicine.

Overview of Thoracic Oncology Trials in Cooperative Groups Around the Globe.

Survival rates of patients with either early and advanced stage non-small-cell lung cancer (NSCLC) have improved with newer systemic therapy and radiation techniques, including combination regimens, targeted therapies, and immunotherapies. The cancer cooperative groups have historically played a critical role in the advancement of NSCLC therapy. Annually, representatives from cooperative groups worldwide convene at the International Lung Cancer Congress (ILCC).

Decisions on Further Research for Predictive Biomarkers of High-Dose Alkylating Chemotherapy in Triple-Negative Breast Cancer: A Value of Information Analysis.

Objectives: To inform decisions about the design and priority of further studies of emerging predictive biomarkers of high-dose alkylating chemotherapy (HDAC) in triple-negative breast cancer (TNBC) using value-of-information analysis.

Methods: A state transition model compared treating women with TNBC with current clinical practice and four biomarker strategies to personalize HDAC: 1) BRCA1-like profile by array comparative genomic hybridization (aCGH) testing; 2) BRCA1-like profile by multiplex ligation-dependent probe amplification (MLPA) testing; 3) strategy 1 followed by X-inactive specific transcript gene (XIST) and tumor suppressor p53 binding protein (53BP1) testing; and 4) strategy 2 followed by XIST and 53BP1 testing, from a Dutch societal perspective and a 20-year time horizon. Input data came from literature and expert opinions.