bluuebunny/crossref_metadata_2025 huggingface dataset:
The Challenge of Mediastinal Staging
Authors: Ceron Loris , Michieletto Lucio , Zamperlin Andrea , Mancino Laura ,   Director, Pulmonology Unit, Ospedale dellAngelo Venice-Mestre,   Senior Registrar, Pulmonology Unit, Ospedale dellAngelo Venice-Mestre,   Senior Registrar, Pulmonology Unit, Ospedale dellAngelo Venice-Mestre,   Senior Registrar, Pulmonology Unit, Ospedale S Bortolo Vicenza
Published: October 2015

Lung cancer staging is a crucial step in both correct prognosis and therapy. Mediastinal staging in particular is usually accomplished using imaging techniques such as computed tomography and 18Fglucose positron-emission tomography, minimally invasive techniques, i.e. transbronchial needle aspiration with or without ultrasound guidance (endobronchial ultrasound) and transoesophageal ultrasound-guided fine needle aspiration and surgical procedures, i.e. mediastinoscopy, thoracoscopy. Each of these techniques has its own sensitivities, specificities and predictive values that must be thoroughly considered within the staging route, with the aim of achieving the best result with the least resource consumption and the least discomfort to the patient; the correct evaluation of a negative result on the basis of its predictive value is essential as well. In this article we suggest a mathematical model that can predict the probability of nodal metastasis after a certain number of diagnostic procedures has been performed, providing an objective way of evaluating whether a patient is fit for surgery or, conversely, whether further investigations are required.
Magnetic Resonance Imaging Findings of Radiation-induced Changes After Treatment of Malignant Gliomas and Metastases with a Particular Emphasis on Radiation Necrosis
Authors: Alonso Raquel Cano , la Peña Mar Jimenez de , Rodriguez Manuel Recio , Arranz Javier Carrascoso , Vega Fernandez Vicente Martinez de , Moreno Javier Pardo ,   General Radiologist,   Deputy Chief,   Deputy Chief,   Deputy Chief,   Chief of Service, Department of Diagnostic Imaging,   Deputy Chief, Department of Neurology, Hospital Universitario Quirón Madrid
Published: October 2015

New contrast-enhancing lesions discovered on routine follow-up brain imaging at or near the site of previously treated primary or metastatic brain tumours represent a clinical and radiological challenge, as radiation necrosis and tumoral recurrence often present at standard magnetic resonance imaging (MRI) with overlapping imaging features. Since the advent of combined therapy, including surgery and/or radiotherapy and chemotherapy, the post-treatment radiological assessment has been made earlier, with a subsequent higher incidence of early radionecrosis and a potential risk of mistaking it for disease progression. Therefore, both clinical and imaging follow-up are essential. This article briefly describes and illustrates the temporal patterns and spectrum of MR findings of radiation-induced brain injury and considers practical aspects of conventional and advanced MR sequences (diffusion-weighted imaging, perfusion MR and MR spectroscopy), with a particular emphasis on the distinction between tumoral recurrence and radiation necrosis.
Leukaemic Transformation of Philadelphia-chromosome-negative Myeloproliferative Neoplasms — A Review of the Molecular Background
Authors: Thoennissen Nils H , Koeffler H Phillip ,   Post-doctoral Researcher, Division of Hematology/Oncology, Cedars-Sinai Medical Center,   Director, Division of Hematology/Oncology, Cedars-Sinai Medical Center, and Deputy Director of Cancer Research, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
Published: October 2015

Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs), including polycythaemia vera (PV), primary myelofibrosis (PMF) and essential thrombocythaemia (ET), are clonal haematopoietic stem cell disorders characterised by proliferation of one or more myeloid cell lineages. They are closely associated with theJAK2V617F mutation, whose detection is used as a clonal marker in the differential diagnosis of MPN. Despite recent improvements in the molecular diagnosis and therapeutic regimen of these chronic disorders, haematological evolution to blast phase remains a major cause of long-term mortality. The mechanism of MPN transformation is still a matter of some controversy because of insufficient insights into the underlying molecular pathogenesis. The purpose of this article is to summarise the increasing data concerning the mechanism of leukaemic evolution of patients diagnosed with chronic MPN. Chromosomal abnormalities and genes that have been shown to play a potential causative role in chronic-phase acceleration are discussed, as are aberrations that may serve as prognostic markers in the blast phase of MPN.
Musculoskeletal Pathologies in Children with Haemophilia Evaluated using a Standardised Physical Joint Scoring System to Assess Disability
Authors: Trakymiene Sonata Saulyte ,   Paediatric Haematologist/Oncologist, Department of Paediatric Haematology/Oncology, Vilnius University Childrens Hospital, and Faculty of Medicine, Vilnius University
Published: October 2015

Repeated bleeding into the joints leads to the development of chronic and progressive joint disease in 90% of people with severe haemophilia. Owing to recurrent haemarthroses, musculoskeletal outcome remains an important hallmark of treatment efficacy in haemophilia. Physical joint assessment is commonly used to measure structural and functional joint damage. With the development and introduction of prophylaxis, the most widely used instruments for the assessment of haemophilic arthropathy were found to lack sensitivity to detect the earliest signs of joint disease. To address these inadequacies, a new international consensus tool, the Haemophilia Joint Health Score (HJHS), was developed. The HJHS appears to be a sensitive, reliable and valid tool. However, the HJHS needs further evaluation in various patient populations to assess its applicability and usefulness.
Difficult Decisions in Cancer Care — Conducting an Ethics Case Analysis
Authors: Gallagher Ann , Gannon Craig ,   Reader in Nursing Ethics, Faculty of Health and Medical Sciences, Division of Health and Social Care, University of Surrey,   Consultant, Palliative Care, Princess Alice Hospice
Published: October 2015

In everyday oncology practice, practitioners make a wide range of ethical decisions. Many of these decisions will seem straightforward, with those involved agreeing on the right course of action. Other decisions will be difficult, with conflicting perspectives regarding the wishes, needs and best interests of patients. This article suggests an ethical framework to facilitate the decision-making of practitioners in relation to challenging practice situations. We provide an anonymised ‘ethics case’ to examine one difficult decision made by a hospice team. The four-quadrant approach can be used to facilitate reflection and collaborative decision-making.
The Evolving Role of Chemotherapy and Predictive Markers in Early-stage Non-small-cell Lung Cancer
Authors: Humke Eric W , Wakelee Heather ,   Instructor of Medicine,   Assistant Professor of Medicine, Department of Medicine, Division of Oncology, Stanford Cancer Center, Stanford University School of Medicine
Published: October 2015

Lung cancer continues to be the leading cause of cancer mortality worldwide. The utility of traditional chemotherapy has reached a plateau in both the metastatic and adjuvant settings. However, we have entered an era of better targeting of both traditional cytotoxic agents and newer compounds for select subsets of patients based on genetic analysis of the tumour. Substantial evidence supports the use of adjuvant chemotherapy in both stage II and stage III non-small-cell lung cancer (NSCLC), but it remains unclear which combination of either traditional or targeted therapies will work best for an individual patient. The use of chemotherapy and targeted therapies in patients with resected stage I NSCLC remains controversial because we cannot predict who benefits from its usage. This article focuses on the evolving role of predictive biomarkers in early-stage NSCLC and summarises the trials that are prospectively evaluating the use of those biomarkers to individualise treatment of NSCLC.
Hormonal Treatment of Metastatic Endometrial Stromal Sarcomas
Authors: Kitayama Jonathan M , Shimizu David , Terada Keith Y ,   Pathology Resident, University of Hawaii Pathology Residency Program,   Assistant Professor, Department of Pathology, University of Hawaii, John A Burns School of Medicine,   Associate Professor, Department of Obstetrics and Gynecology, and Director, Gynecologic Oncology, University of Hawaii, John A Burns School of Medicine
Published: October 2015

Endometrial sarcomas account for 1015% of all uterine sarcomas. These tumours are composed of uniform cells that resemble the stromal cells of proliferative endometrium. As endometrial sarcomas are rare, accounting for less than 1% of all gynaecological malignancies, there is an absence of clinical trials and treatment guidelines do not exist. It is well-known that low-grade endometrial stromal sarcomas (LGESS) are often oestrogen-receptor- (OR) and progesterone-receptor- (PR) positive. This provides a potential target for treatment, similar to other hormonally sensitive tumours. This article reviews the literature in terms of current management strategies for LGESS, particularly the data in terms of hormonal therapy.
Image-guided Radiotherapy Based on Kilovoltage Cone-beam Computed Tomography — A Review of Technology and Clinical Outcome
Authors: Guckenberger Matthias ,   Radiation Oncologist and Vice Chairman, Department of Radiation Oncology, University Hospital Würzburg
Published: October 2015

In this article an overview about the technology and clinical application of gantry-mounted kilovoltage cone-beam computed tomography (CBCT) systems for image-guided high-precision radiotherapy is provided. The emphasis will be on the body sites that are most frequently targeted in daily clinical routine (prostate, lung and head-and-neck region).
Platelets — From Function to Dysfunction in Essential Thrombocythaemia
Authors: Andrews Robert K , Berndt Michael C , Elalamy Ismael ,   Associate Professor, Australian Centre for Blood Diseases, Monash University,   Director, Biomedical Diagnostic Institute, Dublin City University,   Professor, Haematology Department, Hôpital Tenon Paris University VI
Published: October 2015

Platelets are an important component of blood. The main biological role of platelets is to respond to vascular injury and promote thrombus formation to prevent bleeding. However, we now know that platelets also have additional functions in a variety of processes such as immunity, inflammation, coagulation, atherogenesis and tumour metastasis. Platelet disorders commonly lead to defects in haemostasis. Of particular interest is the myeloid proliferative disorder, essential thrombocythaemia (ET). In ET the increased number of platelets leads to an increased risk of blood clot formation and subsequent thrombohaemorrhagic complications. Here we provide a general review of platelet function and activation, as well as more detailed information on the dysfunction of platelets in patients with ET.
Long-term Efficacy of Rituximab Treatment in Thrombotic Thrombocytopenic Purpura
Authors: Chemnitz Jens M , Hallek Michael , Scheid Christof ,   Specialist,   Professor of Medicine, Director and Chair, Department of Internal Medicine I, University of Cologne,   Professor of Medicine, Director and Chair, Department of Internal Medicine I, University of Cologne
Published: October 2015

The use of therapeutic plasma exchange has reduced mortality rates in thrombotic thrombocytopenic purpura (TTP) from 90 to 1020%. However, TTP is a potentially lethal disorder, and management of patients with TTP refractory to plasma exchange or frequently recurrent disease is difficult. In those cases, rituximab might be a therapeutic option, although current data are based primarily on case reports and smaller case series. While initial response rates to rituximab are reported to be high, long-term follow-up data of patients treated with rituximab are rare; however, it is important to estimate the safety and benefit of this treatment. In this article we focus on current experience with rituximab in the treatment of TTP, including recent results with long-term follow-up.
The HemoRec Database as an Example of a Rare Diseases Registry
Authors: Zdziarska Joanna , Chojnowski Krzysztof , Klukowska Anna , Łętowska Magdalena , Mital Andrzej , Musiał Jacek , Podolak-Dawidziak Maria , Windyga Jerzy , Ovesna Petra , Brabec Petr , Zawilska Krystyna ,   Department of Haematology, Jagiellonian University Medical College,   Department of Haematology, Medical University of Lodz,   Department of Paediatrics, Haematology and Oncology, Warsaw Medical University,   Institute of Haematology and Transfusion Medicine, Warsaw,   Department of Haematology and Transplantology, Medical University of Gdansk,   Department of Medicine, Jagiellonian University Medical College,   Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University,   Institute of Haematology and Transfusion Medicine, Warsaw,   Institute of Biostatistics and Analyses, Masaryk University,   Institute of Biostatistics and Analyses, Masaryk University,   Department of Internal Diseases and Haematology, J Strus Hospital, Karol Marcinkowski University of Medical Sciences
Published: October 2015

Rare diseases constitute a major burden on public health, mainly due to the high cost of therapy and logistical difficulties (for example, the need to organise a network of designated treatment centres). National and international registries of rare diseases facilitate data collection and analysis for demographic, economic and research purposes. They are also useful for treatment centres and other healthcare providers and pharmaceutical companies developing orphan drugs. We present the HemoRec database, implemented in 2006 in six European countries, as an example of an international registry of inherited bleeding disorders. HemoRec is used in 15 Polish treatment centres and stores data on 1,100 patients with inherited bleeding disorders (amounting to 24.9% of all patients registered in the Polish central registry held at the Institute of Haematology and Blood Transfusion in Warsaw). It can be developed in the future into a national platform of data collection and exchange in the network of Polish, and hopefully also European, haemophilia treatment centres.
Quality of Life in Elderly Patients with Urological Malignancies — A Review of Standard Questionnaires
Authors: Terret Catherine , Droz Jean-Pierre ,   Geriatric Oncologist, Department of Medical Oncology, Centre Léon-Bérard,   Consultant, Centre Léon-Bérard and Emeritus Professor of Medical Oncology, University Claude-Bernard Lyon 1
Published: October 2015

Quality of life (QOL) is a very complex subject and is difficult to measure in elderly patients. Only a few tools have been validated in this population: the Medical Outcome Study Short Form 36 (SF-36) and the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire QLQ-C30 with addition of the QLQ-ELD15 module. Other tools have been studied in genito-urinary tumours: the Functional Assessment of Cancer Therapy (FACT)General (FACT-G) and specific tools adapted for use in patients with kidney and bladder cancers. Moreover, different tools must be used in different clinical settings, such as localised or castration-refractory prostate cancers. Thus, there is an unmet need for both standardisation and co-ordination of QOL evaluation tools in genito-urinary cancers. The availability of good QOL tools would enable an increase in the efficiency of decision-making in these cancers where comparisons between the side effects of the different treatments are difficult.
A Review of Treatment in Non-small-cell Lung Cancer
Authors: Pallis Athanasios G ,   Medical Oncologist, Department of Medical Oncology, University General Hospital of Heraklion
Published: October 2015

Non-small-cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases. For patients with early-stage disease, surgery followed by adjuvant chemotherapy is the optimal treatment. For patients with locally advanced disease, the standard approach is chemoradiotherapy, since it offers a small but statistically significant prolongation in survival compared with the sequential approach. It should be noted, however, that this approach is associated with significant toxicity and it only applies to patients with good performance status. For patients with metastatic disease, chemotherapy represents the cornerstone of treatment and results in a median survival of approximately 10 months. Recently, the addition of bevacizumab or cetuximab to chemotherapy doublets and the use of gefitinib and erlotinib has improved the outcome in selected patients with advanced NSCLC. Hopefully, advances in understanding the molecular biology of cancer and mechanisms of tumourigenesis will facilitate the discovery and development of novel targeted agents and will further improve outcomes for these patients.
Symptomatic Spinal Metastases from Intracranial High-grade Glioma — Report of Four Cases and Review of the Literature
Authors: Powell James ,   Specialist Registrar, Velindre Cancer Centre, Velindre NHS Trust
Published: October 2015

Intraspinal (leptomeningeal or intramedullary) metastases from primary intracranial gliomas have been well documented in several clinical and pathological series; however, symptomatic intraspinal metastases remain rare. We conducted a retrospective search of cases of intraspinal metastases treated at our centre and report four cases of symptomatic intraspinal leptomeningeal and intramedullary metastases from an intracranial glioma. The mean age of the four cases was 43 years (range 2855 years). The intraspinal metastases were detected after a median time of 18.5 months after onset of the disease and the median survival time of the four patients from detection of spinal metastases was one month. Median overall survival of the four patients was 19 months. One patient was treated with surgery and all received radiotherapy treatment. Radiotherapy provided good initial palliation of pain but improvement in neurological deficits was limited.Overall, prognosis in cases of leptomeningeal and intramedullary metastases from primary intracranial glioma is very poor; however, this diagnosis should be considered in patients with malignant glioma presenting with new back pain and/or associated spinal neurological signs or symptoms. Radiotherapy provided relief of pain and some improvement in neurological function but no survival advantage. Clinical awareness and recognition of this entity will become increasingly important as local control of primary malignant glioma improves and corresponding improvements in outcome and prognosis of this disease are observed.
Adjuvant Chemotherapy in Patients with Osteosarcoma
Authors: Federman Noah , Tap William ,   Assistant Professor, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Jonsson Comprehensive Cancer Center,   Section Chief, Sarcoma Oncology, Melanoma and Sarcoma Service, Memorial Sloane-Kettering Cancer Center, Sarcoma Program, University of California, Los Angeles
Published: October 2015

Osteosarcoma is the most common primary malignant neoplasm of bone in children, adolescents and young adults. Prior to 1970, the outcome for patients with osteosarcoma was dismal, with only 1020 % of patients achieving long-term survival. The improvement in survival over the past four decades, now approaching 75 %, has largely been due to the addition of adjuvant chemotherapy to surgery. However, for patients that have metastatic osteosarcoma or recurrence of their cancer, the outlook is poor and the prognosis has not improved over the past several decades, despite the advent and use of newer chemotherapeutic agents and combinations. This review will focus on the current chemotherapeutic treatments of localised osteosarcoma, the controversies surrounding adjuvant therapy and future directions and additions to our armamentarium.
Novel Therapy of Relapsed and Refractory Classical Hodgkin’s Lymphoma
Authors: Derenzini Enrico , Buglio Daniela , Younes Anas ,   Postdoctoral Fellow,   Professor, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center,   Professor, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center
Published: October 2015

Classical Hodgkins lymphoma (HL) is generally considered a highly curable disease, with approximately 80 % of patients cured with standard first-line chemotherapy. The standard treatment approach for relapsed/refractory patients is second-line salvage chemotherapy followed by autologous stem cell transplantation (ASCT). About half of all patients undergoing ASCT are rescued and definitely cured by such an approach, but the outcome in patients relapsing or refractory to second-line chemotherapy and ASCT is dismal, with a median survival of less than three years. Therapeutic options for this subset of patients comprise tandem ASCT, reduced-intensity allogeneic stem cell transplantation (allo-SCT) and novel agents. Median overall and progression-free survival rates following allo-SCT have ranged from 27 to 56 % and from 18 to 39 %, respectively, with a treatment-related mortality ranging from 15 to 25 %. Several new compounds have been identified as promising agents for the treatment of patients with relapsed classical HL. These drugs have shown promising activity in a subset of heavily pre-treated relapsed/refractory patients, with response rates and disease control rates exceeding 40 and 70 %. If approved, these compounds will probably change the standard of care, making it possible to develop combination regimens with chemotherapy or other new agents, thus improving efficacy with a decreased toxicity profile.
Thalassaemia as a Hypercoagulable State
Authors: Cappellini Maria D ,   Professor of Medicine, Department of Internal Medicine, Fondazione IRCCS “Ca’ Granda” Ospedale Policlinico, University of Milan
Published: October 2015

Although the life expectancy of thalassaemia patients has markedly improved over the last few decades, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events, mainly in thalassaemia intermedia, has led to the identification of a hypercoagulable state in these patients. In this article, the molecular and cellular mechanisms leading to hypercoagulability in thalassaemia are highlighted, with a special focus on thalassaemia intermedia, being the type with the highest incidence of thrombotic events as compared with other types of thalassaemia. Clinical experience and available clues regarding optimal management are also discussed.
A Review of Targeted Therapies in the Management of Advanced-stage Hepatocellular Carcinoma
Authors: Hung Tony , Finn Richard S ,   Medical Student,   Assistant Professor of Medicine and Director, Translational Oncology Research Laboratory and Liver Cancer Research Program, Division of Hematology/Oncology, Geffen School of Medicine, University of California, Los Angeles
Published: October 2015

Hepatocellular carcinoma (HCC) ranks third as a leading cause of cancer death worldwide and has steadily increased in incidence. Due to the asymptomatic nature of early HCC, most patients unfortunately present with advanced or unresectable tumour. While traditional cytotoxic agents have failed to demonstrate a clear survival benefit, the development of newer, molecular targeted therapies has shown promising results in the management of HCC. Notably, sorafenib, an oral multikinase inhibitor, has proven its efficacy in two randomised phase III studies and is currently the only approved systemic therapy in HCC. While the overall survival benefit for patients on sorafenib is modest, it has highlighted the unmet medical need of patients with advanced HCC. Currently, there are several agents in development as both first-line and second-line therapies. Critical to their successful development will be the study designs and the selection of patients most likely to benefit taking into account the complex interplay between underlying liver disease/cirrhosis, cancer and outcomes. The recent failure of sunitinib, a promising oral multikinase inhibitor, because of a greater incidence of adverse events and failure to extend overall survival emphasises these points. This review highlights and summarises the evidence and ongoing challenges in the development of new molecular targeted therapy in HCC.
Future Role of the Gastroenterologist in Digestive Oncology — A European Perspective
Authors: Seufferlein Thomas , Schmiegel Wolff ,   Director, Department of Internal Medicine I, Martin Luther University Halle-Wittenberg,   Director, Medical Department, Knappschaftskrankenhaus, Ruhr-University Bochum
Published: October 2015

Like all other areas of medicine, gastroenterology is undergoing continuing evolution. During the past 20 years, many developments have substantially changed the way healthcare practitioners diagnose and treat patients with diseases of the gastrointestinal (GI) tract. A more recent development is the fact that gastroenterologists are increasingly involved in the diagnosis of GI cancers, as well as in their systemic treatment. This article highlights the opportunities and challenges of such a development for gastroenterology and its potential implications for the training of future specialists.
Dynamics of Human Papillomavirus and Cervical Cancer Screening
Authors: Schmeink Channa E , Massuger Leon FAG , Melchers Willem JG , Bekkers Ruud LM ,   Department of Obstetrics and Gynaecology,   Department of Medical Microbiology, Radboud University Nijmegen Medical Centre,   Department of Medical Microbiology, Radboud University Nijmegen Medical Centre,   Department of Obstetrics and Gynaecology
Published: October 2015

Primary screening based on detection of human papillomavirus (HPV) has proved to be more sensitive than cytology for the detection of high-grade cervical intraepithelial neoplasia (CIN). Self-sampling for specimen collection may also improve the participation rate, especially in the non-responder group. However, HPV is highly prevalent and therefore HPV detection has a lower specificity in cervical cancer screening than cytology. In addition to the clinically validated HPV test, HPV dynamics should be taken into account. It is important to identify women with a chronic productive infection likely to cause, or to already have caused, high-grade CIN or cervical carcinoma, and to limit overtreatment of women with a transient infection. Furthermore, the introduction of the HPV vaccine is likely to lower the incidence of CIN and cervical carcinoma, which will lower the positive predictive value of cervical cancer screening. This potential impact needs to be taken into account when planning for future screening guidelines.
Management of Metastatic Castration-resistant Prostate Cancer
Authors: Antonarakis Emmanuel S ,   Assistant Professor of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins
Published: October 2015

The management of men with metastatic castration-resistant prostate cancer (CRPC) has taken several leaps forwards in the last two years, with the demonstration of improved overall survival with three novel agents (sipuleucel-T, cabazitaxel and abiraterone acetate) and a significant delay in skeletal-related events observed with denosumab. The pipeline of systemic therapies in prostate cancer remains strong, as multiple agents with a diverse array of mechanisms of action are demonstrating preliminary signs of clinical benefit, leading to more definitive Phase III confirmatory trials. In this review, we will discuss the evolving landscape of treatment options for men with CRPC, with a particular focus on currently approved and emerging treatment options for these patients. Knowledge of these evolving standards will help to optimise delivery of care and long-term outcomes in men with advanced CRPC.
Review of Data for Monoclonal Antibody-purified Plasma-derived Factor IX
Authors: Morfini Massimo , Kreuz Wolfhart ,   Director, Agency for Haemophilia and Regional Reference Centre for Inherited Bleeding Disorders, Careggi University Hospital, Florence,   Associate Professor and Head, Comprehensive Care Centre for Haemophilia, Coagulation Disorders and Immunodeficiencies, Johann Wolfgang Goethe University Hospital, Frankfurt
Published: October 2015

Haemophilia B is attributed to a mutation in the gene that produces coagulation factor IX (FIX), resulting in FIX deficiency. Treatment of haemophilia B currently consists of replacing the deficient FIX by intravenous administration of exogenous FIX. There are two major treatment strategies: prophylactic FIX administration (to prevent recurrent bleeding episodes in patients), and on-demand FIX administration (to control existing bleeding in patients when it occurs). Prothrombin complex concentrates (PCCs), which were initially used to treat haemophilia B patients, have been available for approximately 40 years. However, PCCs have been largely replaced by highly purified plasma-derived FIX and recombinant FIX, which have benefited from improvements in purification and viral inactivation, reduction or elimination methods. Monoclonal antibody-purified plasma-derived FIX (MAb pd-FIX) has been extensively evaluated in clinical trials and has proved to be safe and efficacious for surgical prophylaxis and for on-demand and prophylactic treatment in previously untreated and previously treated patients. While intermittent dosing is the conventional method of administration, MAb pd-FIX is also suitable for continuous intravenous infusion; this dosing method has been shown to result in normal haemostasis in patients with haemophilia B. This article reviews the data available for MAb pd-FIX.
Update on the Management of Febrile Neutropenia
Authors: Natarajan Shiva K , Narayan Shruthi , Liu Yin John A ,   Clinical Research Fellow,   Specialist Registrar,   Consultant Haematologist, Department of Haematology, Manchester Royal Infirmary
Published: October 2015

Febrile neutropenia (FN) is a potentially life-threatening complication of chemotherapy. Supportive measures and diagnostic tools in the management of FN are constantly evolving. Recent evidence has validated the need for risk stratification. With the increasing use of dose-intense chemotherapy and evidence to show the detrimental effects of dose delay in the outcomes of cancer treatment, strategies, including the use of colony-stimulating factors and biosimilars to prevent FN, are being developed. This review is an update on the management of FN in adults undergoing chemotherapy.
Fifty Years of Progress Against Cancer — The European Organisation for Research and Treatment of Cancer Celebrates its Achievements
Authors: Bean John , Lacombe Denis , Meunier Françoise ,   Medical Science Writer,   Director,   Director General, European Organisation for Research and Treatment of Cancer
Published: October 2015

For 50 years, the European Organisation for Research and Treatment of Cancer (EORTC) has conducted and coordinated pan-European cancer clinical research and large-scale clinical trials in Europe, and many standard cancer treatments are a direct consequence of these trials. The EORTC was a pioneer in promoting multidisciplinary cancer research and is one of Europes leading players in facilitating the passage of experimental discoveries into novel treatments for patients with cancer. In this paper, the authors present a general overview of some of the achievements that have changed medical practice in cancer treatment with particular regard to new and improved chemotherapy and multi-modal treatment, the use of imaging and diagnostics, and the development of guidelines for optimising treatment and patient quality of life.
Inflammatory Breast Cancer — Does the Confirmation of Dermal Lymphatic Invasion Predict the Worst Outcome?
Authors: Tomasevic Zorica , Kolarevic Daniela ,   Director, Daily Chemotherapy Hospital, Institute for Oncology and Radiology of Serbia,   Oncologist, Daily Chemotherapy Hospital, Institute for Oncology and Radiology of Serbia
Published: October 2015

Inflammatory breast carcinoma (IBC) is a rare but aggressive breast cancer (BC) subtype. General prognosis is poor with higher incidence of axillary node involvement and metastatic disease at presentation (~30 %) as compared with common BC (~10 %). The typical IBC is characterised by rapid onset of localised or generalised skin redness, involving at least one-third of the breast, warmth and usually presence of skin oedema (peau dorange), often without an underlying tumour mass. This clinical presentation of skin inflammation is a consequence of pathological plugging of the dermal lymphatic of the breast with tumour emboli. Dermal lymphatic invasion (DLI), although not mandatory for IBC diagnosis, is one of the hallmarks of this malignancy and can be proven in up to 7580 % of IBCs. Surprisingly, there are very few data regarding whether the presence of DLI independently contributes to IBC prognosis as compared with IBC without DLI.
Concurrent Chemoradiation in Inoperable, Locally Advanced Non-small Cell Lung Cancer — Comparison of Efficacy and Toxicity in the Elderly
Authors: Collen Christine , Schallier Denis , Ridder Mark De ,   Resident Radiation Oncologist, Department of Radiation Oncology,   Senior Medical Oncologist, Department of Medical Oncology,   Head of Radiation Oncology Department, UZ Brussel, Vrije Universiteit Brussel
Published: October 2015

Clinicians are faced with the challenge of treating increasing numbers of elderly patients with locally advanced non-small cell lung cancer (LA-NSCLC) and co-morbid conditions. The benefit of combined chemoradiation in the younger patient using the concurrent modality compared with the sequential administration of both modalities has been established in several randomised trials and recent meta-analyses. Because of the underrepresentation of elderly patients in clinical trials on concurrent chemoradiation (CCRT) in LA-NSCLC, treatment guidelines for this age group are not well established. The objective of this report is to summarise the data on efficacy and toxicity of CCRT in the elderly.
Surgery of the Primary Tumour in Stage IV Colorectal Cancer with Unresectable Metastases
Authors: Ayez Ninos , Alberda Wijnand J , Verheul Henk M , Burger Jacobus W , Wilt Johannes H de , Verhoef Cornelis ,   Division of Surgical Oncology, Erasmus MC University Medical Centre, Daniel den Hoed Cancer Centre, Rotterdam,   Division of Surgical Oncology, Erasmus MC University Medical Centre, Daniel den Hoed Cancer Centre, Rotterdam,   Division of Medical Oncology, VU University Medical Centre, Amsterdam,   Division of Surgical Oncology, Erasmus MC University Medical Centre, Daniel den Hoed Cancer Centre, Rotterdam,   Division of Surgical Oncology, Radboud University Medical Centre, Nijmegen,   Division of Surgical Oncology, Erasmus MC University Medical Centre, Daniel den Hoed Cancer Centre, Rotterdam
Published: October 2015

Since patients with incurable metastatic colorectal cancer (CRC) only have a relatively limited life expectancy, and resection of the primary tumour is accompanied by both morbidity and mortality, it is under debate whether resection of the primary tumour has an effect on survival or quality of life. The rationale behind the resection strategy is that prophylactic surgery prevents future complications. With current new chemotherapy regimens, a relatively low number of patients with metastatic CRC require surgery for their primary tumour. Many studies concerning the management of incurable stage IV CRC have been performed and most studies suggest a survival benefit for patients undergoing surgical resection of the primary tumour compared with those who received palliative treatment. However, in stage IV CRC with unresectable metastases, the role of a palliative resection of the primary tumour has never been assessed properly. Because randomised clinical trials are lacking, it is difficult to draw conclusions from the present literature.
VAL 201 — An Inhibitor of Androgen Receptor-associated Src and a Potential Treatment of Castration-resistant Prostate Cancer
Authors: Auricchio Ferdinando , Migliaccio Antimo ,   Professor, Department of General Pathology, II University of Naples,   Professor, Department of General Pathology, II University of Naples
Published: October 2015

Prostate cancer is the second leading cause of cancer death in men in the US. The initial treatment of metastatic prostate cancer is androgen deprivation (castration) therapy and this is achieved through either surgical or medical castration, however these therapies are also associated with undesirable side effects including impotence, tumour flare and loss of bone mass. Over time, nearly all patients with metastatic disease become resistant to androgen deprivation, progressing to castration-resistant prostate cancer (CRPC), and at this stage of the disease the prognosis is extremely poor (<50 % survival at two years). Currently there are few treatment options for CRPC. Only four have been found to extend survival and none are curative. Effective treatment of CRPC is a major unmet clinical need, and the identification of alternative therapeutic targets is an active focus of research. In this article we discuss the development of a new agent, Val 201 as a potential future treatment for CRPC. VAL 201 targets the association of androgen receptor with Src, a non-receptor tyrosine kinase signal-transduction protein that is important in tumour cell proliferation, and represents a novel and exciting approach for cancer chemotherapy.
Use of Bendamustine in Chronic Lymphocytic Leukaemia Patients with Co-morbidities
Authors: Leblond Véronique ,   Professor and Head, Haematology Department, Pitié Salpêtrière Hospital, Paris
Published: October 2015

Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia and mainly affects older patients. First-line treatments for 'fit' (go go) and 'unfit' (no go) CLL patients are well defined, in the form of fludarabinecyclophosphamiderituximab (FCR) combination chemoimmunotherapy and best supportive care, respectively. However, the majority of CLL patients fall between these two extremes (slow go patients), nevertheless the standard of care for these patients is not well defined. Recent data suggest that bendamustine chemotherapy may be a good option in this group. In a recent Phase III study, significant improvements in overall response rate, complete response and progression-free survival were reported with bendamustine compared with chlorambucil. Chlorambucil plus rituximab has been shown to induce high responses in elderly CLL patients with a relatively low complete response rate. Bendamustine plus rituximab, and reduced-dose fludarabine plus cyclophosphamide plus high-dose rituximab have demonstrated promising efficacy, but have not been evaluated in elderly CLL patients. Several trials are also ongoing evaluating novel cytostatic agents, combination chemotherapy and chemoimmunotherapy regimens in elderly patients.
A Review of Sleep Concerns in Paediatric Sickle Cell Disease
Authors: Daniel Lauren C , Barakat Lamia P ,   Postdoctoral Researcher, Division of Oncology, The Childrens Hospital of Philadelphia,   Postdoctoral Researcher, Division of Oncology, The Childrens Hospital of Philadelphia,   Director of Psychosocial Services and Associate Professor of Clinical Psychology, Department of Pediatrics, Perelman School of Medicine of the University of Pennsylvania
Published: October 2015

Children with sickle cell disease (SCD) are at an increased risk for sleep disorders as compared to healthy children, possibly because of disease processes, pain, minority status and living in an urban environment. Adequate sleep is an essential component of typical development, moodand- affect regulation and health maintenance, but more research is needed to understand the contribution of sleep to health outcomes in children with SCD. AS SCD is a chronic disease that can be affected by environmental, health, and behavioural factors, understanding the impact of the disease on sleep is important to maximise the quality of life in these children. If the disease causes poor sleep quality, then children may be at risk for a host of developmental and psychosocial problems, beyond those caused by SCD, as a result of inadequate sleep. Also, poor sleep may affect the disease course, thus exacerbating symptoms. Prevalent sleep disorders in this population are reviewed, including sleep-disordered breathing, periodic limb movements, restless legs syndrome and nocturnal enuresis. Also, the contribution of the disease symptoms pain, hypoxaemia, daytime tiredness and fatigue to disrupted sleep are examined. Finally, the effects of sociodemographic factors, such as poverty and minority status, are described, as these contextual factors significantly impact sleep across several chronic conditions in paediatrics. Frequent monitoring for sleep disruptions can be essential to improving health outcomes and quality of life in children with SCD.
Health Status Screening in Elderly Patients — Is this the Way Forward?
Authors: Kazmierska Joanna ,   Radiation Oncologist and Head, Radiotherapy Department II, Greater Poland Cancer Centre and Research Associate, Poznan University of Medical Sciences
Published: October 2015

The rapid ageing of the European population poses a challenge for healthcare systems. The incidence of cancers will rise as the number of adults aged 65 years and older increases. Moreover, the health status of individuals in this age group is diverse, and thus requires modern oncology to apply an individualised approach to treatment. There is a clear need to develop and validate health assessment tools enabling the identification of specific geriatric issues which might be overlooked by standard assessment methods. The Comprehensive Geriatric Assessment (CGA) is the gold standard for geronto-oncology assessment. However, the complexity of this test has stimulated a search for pre-screening methods able to identify individuals with the potential to gain most from full pre-treatment CGA. Such tools consist of specific tests to evaluate health status in the important functional, psychological, social and cognitive domains. The choice of which tests are best to use within the various screening tools is still a subject of debate. This paper presents a review of the most commonly used tests within various health status domains as well as of the most valuable screening tools.
NGR-hTNF plus Doxorubicin in Recurrent Ovarian Cancer
Authors: Lorusso Domenica , Malaguti Paola , Scambia Giovanni , Bordignon Claudio , Raspagliesi Francesco ,   Assistant Professor, Department of Gynaecologic Oncology, National Cancer Institute, Milan,   Assistant Professor, Department of Gynaecologic Oncology, Catholic University of Rome,   Professor, Department of Gynaecologic Oncology, Catholic University of Rome,   Founder, MolMed SpA, Milan and Professor of Haematology, University of San Raffaele,   Assistant Professor, University of San Raffaele, Italy
Published: October 2015

Ovarian cancer is the most lethal gynaecological cancer. Despite surgery and first-line chemotherapy, tumours recur in 6070 % of cases and prognosis is poor. Several studies have indicated that the cytokine tumour necrosis factor (TNF) has antitumour activity when given systematically, but its high toxicity has limited its use. Peptides containing the aspargine-glycine-arginine motif (NGR peptides) selectively bind to the aminopeptidase N ligand CD13, which is overexpressed in the cells of tumour blood vessels. It has been found that the combination of an NGR peptide and human TNF (NGR-hTNF) has the ability to increase intratumoural doxorubicin distribution by altering the tumour vasculature. In this article, we describe the activity and toxicity profile of NGR-hTNF plus doxorubicin as a combination treatment for recurrent ovarian cancer.
Elacytarabine — A New Agent in the Treatment of Relapsed/Refractory Acute Myeloid Leukaemia
Authors: Vey Norbert ,   Professor, Head of Leukaemia Service, Department of Haematology, Paoli-Calmettes Institute, Marseille, France
Published: October 2015

The prognosis for patients with relapsed acute myeloid leukaemia (AML) is poor, and effective treatments for this patient group remain a substantially unmet clinical need. Elacytarabine is a promising new cytotoxic nucleoside agent made by an esterification reaction between cytarabine and elaidic acid, currently in development for use in the treatment of relapsed/refractory AML. Unlike cytarabine, cellular uptake of elacytarabine is independent of human equilibrative nucleoside transporter-1 (hENT-1) and results in prolonged intracellular retention of the active nucleoside. In addition, elacytarabine inhibits DNA synthesis for twice the duration seen with cytarabine and exhibits a different intracellular distribution. A Phase I trial in patients with AML identified a recommended dose of 2,000 mg/m²/day for five days and showed limited non-haematological side effects, liver toxicity being dose-limiting. Elacytarabine can be safely combined with idarubicin. A recent Phase II trial demonstrated an improved complete remission rate and overall survival with elacytarabine as a single agent in patients with advanced AML, as compared with a historical control group treated with second salvage therapy. Following these encouraging results, the results of an ongoing Phase III clinical trial comparing elacytarabine with the investigators choice of standard of care are awaited with interest.
Very Rare Tumours in Paediatric Age — From ‘Tumori Rari in Età Pediatrica’ to the European Cooperative Study Group for Paediatric Rare Tumours
Authors: Bisogno Gianni , Cecchetto Giovanni , Ferrari Andrea ,   Paediatric Consultant and Head, Solid Tumour Unit, Haematology/Oncology Division, Department of Paediatrics, University Hospital of Padua,   Associate Professor, Division of Paediatric Surgery, Department of Paediatrics, University Hospital of Padua,   Oncologist Consultant and Head, Outpatient Service, Paediatric Oncology Unit, National Tumour Institute, IRCCS, Milan, Italy
Published: October 2015

Very rare tumours (VRTs) in paediatric age are a heterogeneous group of cancers very rarely encountered in daily practice, even in large paediatric oncology centres. Some of them are typical of paediatric age, such as pleuropulmonary blastoma or pancreatoblastoma; others are typically found in adulthood, such as carcinomas and melanoma. With the objective of improving the research on, and management of, paediatric VRTs, a national study group was founded and the Tumori Rari in Età Pediatrica (Rare Tumours in Paediatric Age [TREP]) project was launched in Italy in 2000. For the purposes of this project, VRTs have been defined as any solid malignancy characterized by an annual incidence of <2 cases/million children and not considered in other clinical trials. From January 2000 to December 2011, 652 patients <18 years of age were registered in the TREP database. This article presents the experience gathered so far and underlines the need to develop international collaborations dedicated to paediatric VRTs. With this aim, national groups from Italy, Germany, France, Poland and the UK have created, in June 2008, a new collaborative group named European Cooperative Study Group for Paediatric Rare Tumours (EXPeRT).
Streamlining Workflows Across Multiple Cancer Centres with the MOSAIQ® Oncology Information System
Authors: Francis Laura ,   Global Product Marketing Manager, Business Software Systems, Elekta Ltd, Stockholm, Sweden
Published: October 2015

In the UK, The Christie NHS Foundation Trust provides a unique network of radiotherapy centres supported by the MOSAIQ® oncology information system, which serve a population of 3.2 million across Greater Manchester, Cheshire and beyond. The implementation of MOSAIQ has dramatically improved local patients access to radiation therapy services, allowing them to be treated closer to home.