Heritable defects in telomere and mitotic function selectively predispose to sarcomas.

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls.

Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST).

Purpose: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital.

Immune checkpoint inhibitors: current status.

The use of immune checkpoint inhibitors (ICIs) is growing rapidly in oncology and palliative care clinicians and other generalists will increasingly see patients who are receiving, or who have received ICI. For optimal care, it is important that clinicians have a basic understanding of the unique nature of ICI as anticancer treatments, including patterns of response, potential issues with concurrent corticosteroid use and the wide range of possible immune-related adverse effects (IrAEs). This paper, informed by a recent literature search, provides a succinct yet comprehensive overview of ICI, with a particular focus on IrAE, highlighting that some are potentially life-threatening and/or can develop a long time, sometimes years, after even a short course of an ICI.

Imbalance Associated With Cisplatin Chemotherapy in Adult Cancer Survivors: A Clinical Study.

Objective: This study investigated balance problems and vestibular function in adult cancer survivors who had completed cisplatin chemotherapy treatment.

Study Design: Observational cross-sectional study.

Setting: Tertiary care center.

Long-term outcomes with intensive induction chemotherapy (carboplatin, bleomycin, vincristine and cisplatin/bleomycin, etoposide and cisplatin) and standard bleomycin, etoposide and cisplatin in poor prognosis germ cell tumours: A randomised phase II trial (ISRCTN53643604).

Background: Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. An intensive regimen, CBOP/BEP (carboplatin, bleomycin, vincristine and cisplatin/BEP), met response targets in a randomised, phase II trial (74% complete response or partial response marker negative, 90% confidence interval (CI) 61%-85%).

Aim: To assess long-term outcomes and late toxicity associated with CBOP/BEP.

Navigating the "Optimal Implantation Depth" With a Self-Expandable TAVR Device in Daily Clinical Practice.

Objectives: This study sought to predict whether different methods of calculating the implantation depth (ID) influence clinical and hemodynamic outcome reporting in patients undergoing transcatheter aortic valve replacement (TAVR) with a self-expandable device.

Background: Different approaches exist to calculate the ID, which may influence uniform and reliable reporting because the updated Valve Academic Research Consortium (VARC-2) criteria do not provide specific instructions.

Methods: The clinical and hemodynamic outcomes of 258 patients undergoing TAVR with a third-generation self-expandable device were analyzed with regard to the method used to assess the ID as follows: arithmetic mean, the arithmetic mean of the measured distances from the noncoronary cusp and the left coronary cusp to the distal prosthesis end; noncoronary cusp distance, the distance from the noncoronary cusp to the distal prosthesis end; and deepest edge, the deepest edge of the distal prosthesis end.

Micro-dislodgement during transcatheter aortic valve implantation with a contemporary self-expandable prosthesis.

Objectives: To evaluate the incidence, risk factors and the clinical outcome of micro-dislodgement (MD) with a contemporary self-expandable prosthesis during transcatheter aortic valve implantation.

Methods: MD was defined as movement of the prosthesis of at least 1.5 mm upwards or downwards from its position directly before release compared to its final position.

The Latest Evolution of the Medtronic CoreValve System in the Era of Transcatheter Aortic Valve Replacement: Matched Comparison of the Evolut PRO and Evolut R.

Objectives: The aim of this study was to investigate the hemodynamic and clinical performance of the Evolut PRO compared with its direct predecessor, the Evolut R.

Background: Recently, the newest commercially available generation of the self-expandable Medtronic CoreValve prosthesis, the CoreValve Evolut PRO, was introduced to the market. This prosthesis is based on the previous Evolut R model and specifically designed to mitigate paravalvular leakage.

Developing an integrated rehabilitation model for thoracic cancer services: views of patients, informal carers and clinicians.

Background: Access to rehabilitation to prevent disability and optimise function is recommended for patients with cancer, including following cancer diagnosis. Models to integrate rehabilitation within oncology services as cancer treatment commences are required, but must be informed by those they are intended to support. We aimed to identify views of patients, carers and clinicians to develop and refine a rehabilitation model to be tested in a feasibility trial for people newly diagnosed with lung cancer or mesothelioma.

Salvage Chemotherapy With Gemcitabine, Paclitaxel, Ifosfamide, and Cisplatin for Relapsed Germ Cell Cancer.

Background: Metastatic germ cell tumors remain potentially curable when treated with salvage chemotherapy at first relapse. In the present phase I/II study, we sought to improve on the response rate and duration of the TIP (paclitaxel, ifosfamide, cisplatin) regimen by adding gemcitabine (Gem-TIP).

Materials And Methods: Twenty patients were recruited after failure of first-line cisplatin-containing chemotherapy.

Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3: European Organization for Research and Treatment of Cancer (EORTC) phase II trial 90101 'CREATE'.

Background: Alveolar soft part sarcoma (ASPS) is an orphan malignancy associated with a rearrangement of transcription factor E3 (TFE3), leading to abnormal MET gene expression. We prospectively assessed the efficacy and safety of the MET tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic ASPS.

Patients And Methods: Eligible patients with reference pathology-confirmed ASPS received oral crizotinib 250 mg bd.

Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation.

Cannabidiol (CBD) and ∆-tetrahydrocannabinol (THC) have well documented immunomodulatory effects in vitro, but not following oral administration in humans. Here we show that oral co-administration of cannabinoids with lipids can substantially increase their intestinal lymphatic transport in rats. CBD concentrations in the lymph were 250-fold higher than in plasma, while THC concentrations in the lymph were 100-fold higher than in plasma.

Is clarithromycin a potential treatment for cachexia in people with lung cancer? A feasibility study.

Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250mg twice daily or placebo for eight weeks.

Can body composition be used to optimize the dose of platinum chemotherapy in lung cancer? A feasibility study.

Purpose: Current methods of dosing platinum-based chemotherapy are suboptimal. Potentially, taking lean body mass into account may help. To inform the design of a future study, we first examined the feasibility and acceptability of such an approach using dual-energy X-ray absorptiometry (DEXA) and explored aspects suggestive of over- and under-dosing.

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines.

There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposure of patients to cannabis components has not been explored.

Extra-abdominal desmoid fibromatosis: A review of management, current guidance and unanswered questions.

Extra abdominal desmoid fibromatosis is a complex condition with many recognised treatments including active observation, hormonal therapy, chemotherapy, radiotherapy and surgical resection. There is large variation in the natural history of individual desmoid tumours, with some cases progressing aggressively and others regressing spontaneously when observed alone. This combined with an absence of accurate clinical predictors of a desmoid tumour's behaviour has led to difficulties in identifying which patients would benefit most from aggressive treatment, and which could be adequately managed with a policy of active observation alone.

Maintenance pazopanib versus placebo in Non-Small Cell Lung Cancer patients non-progressive after first line chemotherapy: A double blind randomised phase III study of the lung cancer group, EORTC 08092 (EudraCT: 2010-018566-23, NCT01208064).

Background: Switch maintenance is an effective strategy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Pazopanib is an oral, multi-targeted tyrosine kinase inhibitor (TKI). EORTC 08092 evaluated pazopanib given as maintenance treatment following standard first line platinum-based chemotherapy in patients with advanced NSCLC.

Nationwide trends in the current management of desmoid (aggressive) fibromatosis.

Aims: The optimal management of desmoid fibromatosis remains unclear, leading to significant variability in patient management. To assess this problem, the current approach of clinicians managing this complex condition in the UK was investigated.

Materials And Methods: A hypothetical case of intramuscular limb girdle desmoid fibromatosis in a fit 65-year-old patient was devised.

Results of a phase II pilot study of moderate dose radiotherapy for inoperable desmoid-type fibromatosis--an EORTC STBSG and ROG study (EORTC 62991-22998).

Background: To determine the activity of radiotherapy in patients with inoperable desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was carried out.

Materials And Methods: Patients with inoperable progressive disease of primary, recurrent or incompletely resected lesions received a dose of 56 Gy in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2 years and thereafter every 6 months.

Adenovirus-mediated hypoxia-targeted gene therapy using HSV thymidine kinase and bacterial nitroreductase prodrug-activating genes in vitro and in vivo.

Hypoxia is an important factor in tumor growth. It is associated with resistance to conventional anticancer treatments. Gene therapy targeting hypoxic tumor cells therefore has the potential to enhance the efficacy of treatment of solid tumors.

Severe sequence-specific toxicity when capecitabine is given after Fluorouracil and leucovorin.

Purpose: Options for single-agent fluoropyrimidine adjuvant therapy after bowel cancer resection include intravenous fluorouracil with leucovorin (FU/LV) or oral capecitabine. These treatments have similar efficacy but differ in convenience and toxicity. We therefore wished to compare their overall acceptability to patients.

Loading doses for costly cancer biologicals: a cause for concern or tilting at windmills?

The emergence of novel, effective but expensive biological therapies is significantly improving outcomes for many patients with cancer, but also substantially increasing treatment costs. Monoclonal antibodies with long half-lives have often been developed using loading doses to hasten the achievement of a therapeutic dose. Although the benefits of loading doses have not been proven, we caution against abandoning this practice on uncertain theoretical grounds.

Use of blood outgrowth endothelial cells as virus-producing vectors for gene delivery to tumors.

Cell-based delivery of therapeutic viruses has potential advantages over systemic viral administration, including attenuated neutralization and improved viral targeting. One of the exciting new areas of investigation is the potential ability of endothelial-lineage cells to deliver genes to the areas of neovascularization. In the present study, we compared two types of endothelial-lineage cells [outgrowth endothelial cells (OECs) and culture-modified mononuclear cells (CMMCs), also known as "endothelial progenitor cells"] for their ability to be infected with adenovirus and to home to the areas of neovascularization.

Expression of TCL1 in hematologic disorders.

Objective: TCL1, MTCP1 and TCL1b are three members of a new family of oncogenes that are expressed in T cell leukemias of ataxia telangiectasia patients (T-PLL, T-CLL). TCL1 is located at 14q32.1 and activated by juxtaposition to the alpha/delta-locus at 14q11 or beta-locus at 7q35 of the T cell receptor during the reciprocal translocations t(14;14)(q11;q32), t(7;14)(q35;q32), or inversion inv(14)(q11;q32).