Use of alemtuzumab and rituximab consolidation in CLL: Pros and cons

As new therapeutic approaches have improved responses and outcomes in the treatment of chronic lymphocytic leukemia (CLL), the scientific community focuses now on diagnostic procedures and definitions of response in CLL. The use of monoclonal antibodies in particular has made it possible to treat CLL more effectively. The success of these new therapeutic tools can be traced back to the eradication of detectable disease in a significant number of patients. Therefore, the evaluation of minimal residual disease has become an important end point within clinical trials. This article describes various methods of assessing minimal residual disease and presents data demonstrating that new therapeutic approaches can eliminate residual malignant cells at the highest levels of sensitivity currently available. Although initial evidence suggests that the use of alemtuzumab induces a survival benefit when used in the consolidation setting, important safety issues remain to be resolved before this approach can be introduced in routine practice.     

Multidisciplinary quality assurance and control in oncological trials: Perspectives from European Organisation for Research and Treatment of Cancer (EORTC)

Quality assurance (QA) programmes are one of the mainstays of clinical research and constitute the pillars on which European Organisation for Research Treatment of Cancer (EORTC) delivers multidisciplinary therapeutic progress. Changing practice treatments require solid evidence-based data, which can only be achieved if integral QA is part of the infrastructure sustaining research projects. Cancer treatment is a multimodality approach, which is often applied either in sequence and/or in combination. Each modality plays a key role in cancer control. The modalities by which QA is applied varies substantially within and across the disciplines. In addition, translational and diagnostic disciplines take an increasing role in the era of precision medicine. Building on the structuring effect of clinical research with fully integrated multidisciplinary QA programmes associated with the solutions addressing the chain of custody for biological material and data integrity as well as compliance ensure at the same time validity of clinical research output but also have a training effect on health care providers, who are more likely to apply such principles as routine. The principles of QA are therefore critical to be embedded in multidisciplinary infrastructure to guarantee therapeutic progress. These principles also provide the basis for the functioning of multidisciplinary tumour board. However, technical, operational and economic challenges which go with the implementation of such programmes require optimal know-how and the coordination of the multiple expertise and such efforts are best achieved through centralised infrastructure.     

The changing landscape of cancer care – the impact of psychosocial clinical practice guidelines

The International Psycho‐Oncology Society (IPOS) has championed the need for quality care to incorporate attention to the psychosocial concerns of cancer patients. Widespread international endorsement of distress as the ‘6th vital sign’ is a major step towards improving access to psychosocial care and reducing the isolation and stigma experienced by many affected by cancer. However, the integration of psychosocial care into routine clinical practice also requires active multidisciplinary engagement, and demonstration that evidence‐based psychosocial interventions are effective and feasible to deliver in practice. Clinical practice guidelines are valuable in this context. Typically, they provide a synthesis and evaluation of existing evidence, critically appraised by stakeholders and clinicians, presented in a way which allows for translation of research evidence into practice. Such guidelines are also tools for informing and educating those who do not have psychosocial expertise, potentially increasing the status of psycho‐oncology. This paper describes the background to the development of psychosocial clinical practice guidelines in Australia as a means of understanding the factors that can underpin the evolution of attitudes and integration of psychosocial care in oncology, and considers the current status of psychosocial care in Australia and internationally, including challenges for the future. Copyright © 2015 John Wiley & Sons, Ltd.     

A care pathway for patients with oesophageal cancer

A well-functioning care pathway for oesophageal cancer patients is particularly important in view of the need for a multidisciplinary approach and of the complex diagnostic procedures, extensive treatment, increasing volume of patients at fewer centres, and poor prognosis. Nevertheless, the literature regarding organization of care pathways for cancer patients is sparse. We therefore present our newly developed care pathway for oesophageal cancer patients, created to optimize the organization, coordination and supportive care. Based on scientific evidence, the pathway includes all relevant diagnostic examinations and therapeutic options, multidisciplinary team meetings, programmes for follow-up, rehabilitation and after-hospital care, and organized supportive care throughout the pathway, all led by a specialist nurse. The specialist nurse maintains continuous contacts with the patient and family throughout the care pathway. The experience and evaluation of our care pathway indicate that it works well in clinical practice, and that the role of the specialist nurse seems to be the key to the success, from the colleagues', hospital's and patients' point of view. This pathway has therefore been established at our hospital, and we can recommend well-organized and nurse-led care pathways for oesophageal cancer patients.     

Preoperative Systemic Chemotherapy and Pathologic Assessment of Response

Preoperative systemic (neoadjuvant) chemotherapy is both routine therapeutic modality for locally advanced breast cancer and a translational research model to identify biomarkers that predict treatment response. It is imperative that pathologic response be strongly prognostic in order to optimize the clinical and scientific information that can be gained from neoadjuvant clinical trials. Dichotomization of response as pathologic complete response (pCR) or residual disease (RD) is overly simplistic for these objectives, particularly because residual disease (RD) after neoadjuvant treatment includes a broad range of actual responses from near-pCR to frank resistance. More effective or prolonged neoadjuvant treatments should reduce the extent of RD in many patients, possibly blurring the prognostic distinction between pCR and RD. On the other hand, it should be possible to identify patients with resistant disease in order to develop predictive tests for this adverse outcome. Our research group recently proposed to measure residual cancer burden (RCB) as a continuous variable derived from the primary tumor dimensions, cellularity of the tumor bed, and axillary nodal burden. Each component contributes meaningful pathologic information and can be obtained using routine pathologic materials and methods of interpretation that could easily be implemented in routine diagnostic practice.     

Biologie moléculaire dans le diagnostic des tumeurs des tissus mous et de l’os et apport au pronostic des sarcomes

Soft tissue and bone sarcoma are heterogeneous group of malignancies. They represent a diagnostic challenge due to their rarity, the large number of entities and the ongoing evolution of knowledge for a decade. Moreover, their accurate classification impact over treatment options. Simple and recurrent genetic alterations, such as mutation, amplification, and translocation can be identified in half the sarcomas and serve as new diagnostic markers. In this review we focus on the efficacy of molecular biology on diagnostic pathology of soft tissue and bone tumors in daily routine practice. The role of molecular genetics in the assessment of prognosis and the impact of molecular analysis on the therapeutic decision are also discussed.     

Radiobiology of systemic radiation therapy

Although systemic radionuclide therapy (SRT) is effective as a palliative therapy in patients with metastatic cancer, there has been limited success in expanding patterns of utilization and in bringing novel systemic radiotherapeutic agents to routine clinical use. Although there are many factors that contribute to this situation, we hypothesize that a better understanding of the radiobiology and mechanism of action of SRT will facilitate the development of future compounds and the future designs of prospective clinical trials. If these trials can be rationalized to the biological basis of the therapy, it is likely that the long-term outcome would be enhanced therapeutic efficacy. In this review, we provide perspectives of the current state of low-dose-rate (LDR) radiation research and offer linkages where appropriate with current clinical knowledge. These include the recently described phenomena of low-dose hyper-radiosensitivity-increased radioresistance (LDH-IRR), adaptive responses, and biological bystander effects. Each of these areas require a major reconsideration of existing models for radiation action and an understanding of how this knowledge will integrate into the evolution of clinical SRT practice. Validation of a role in vivo for both LDH-IRR and biological bystander effects in SRT would greatly impact the way we would assess therapeutic response to SRT, the design of clinical trials of novel SRT radiopharmaceuticals, and risk estimates for both therapeutic and diagnostic radiopharmaceuticals. We believe that the current state of research in LDR effects offers a major opportunity to the nuclear medicine community to address the basic science of clinical SRT practice, to use this new knowledge to expand the use and roles of SRT, and to facilitate the introduction of new therapeutic radiopharmaceuticals.     

What can oncologists learn from HIV?

Developments in HIV-related medicine have significant implications for the practice of oncology. Although HIV is a relatively new discipline within medicine, the identification and therapeutic targeting of HIV has been rapid. Furthermore, political lobbying has sculpted scientific research and patient care. Rational drug design has reduced morbidity and mortality to such an extent that the development of predictive surrogate endpoints has been necessary to enable randomised assessments of new protocols to continue. These studies now include the routine detection of resistance to tailor specific therapies to the patient. The involvement of affected communities in dynamically modelled studies have shown the efficacy of new, preventive strategies and debates about such approaches have improved the standard of care. In this review, we discuss what oncologists can learn from the HIV epidemic.     

New diagnostic tools for neonatal sepsis: the role of a real-time polymerase chain reaction for the early detection and identification of bacterial and fungal species in blood samples

Early diagnosis and treatment of neonatal sepsis are essential to prevent severe and life threatening complications. Consequently, rapid diagnostic tests capable to differentiate infected from non-infected newborns have the potential to make a significant impact on neonatal care. A new real-time polymerase chain reaction (PCR; LightCycler SeptiFast test M GRADE) has been proposed in the routine assessment of neonatal sepsis for the detection and identification of bacterial and fungal DNA from microorganisms which cause approximately 90% of all blood stream infections. The LightCycler SeptiFast test can detect and identify simultaneously the 25 most important bacterial and fungal species causing bloodstream infections within few hours by using a small volume of a single whole blood sample. Real-time PCR can be easily incorporated into the hospital setting for term or near-term infants admitted to the neonatal intensive care unit for sepsis evaluation.     

Biomarkers in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is currently the third most frequent form of malignancy. The role of biomarkers in the diagnostic and therapeutic strategy of cancer is constantly expanding. Translational research is already changing paradigms in tumours encompassing from early diagnosis to precision medicine in advanced disease. Nomenclature for molecular subtypes of tumours is gradually gaining acceptance and there are growing expectations it will further go from the bench to the bedside. However, the clinical relevance of biomarkers in PDAC is still far behind the relevance of biomarkers in other solid tumours. This article is part of a wider project (GALLgo) involving over forty specialists devoted to the multidisciplinary management of PDAC which concluded in recommendations based on scientific evidence. The aim of the present article is to review the diagnostic, prognostic and predictive biomarkers, either in localised or advanced disease, which have been lately subjected to study and analysis and others currently available for PDAC in order to give strength-graded recommendations linked to quality of evidence that can be used as guidelines in routine clinical practice.     

Cancer networks

The complexity of legislation and the obstacle race run by all promoters in search of approval and funding for their projects could have greatly hindered the development of healthcare networks in France, or at least discouraged many promoter. Yet social and health professionals, along with certain healthcare service staff, considered these networks highly useful for decompartmentalising the French healthcare system. They would favour patient-oriented projects. It is not a surprise that the number of networks in the field of oncology is expanding rapidly, with more than 60 projects registered by public authorities by the end of 1999. Cancers are chronic diseases which often bring into play the patient's vital prognosis, as well as psychological and social consequences - sometimes dreadful - for patients and their relatives. Cancer patient management calls for a multidisciplinary approach in elaborating the therapeutic project and providing psychological support. Continuity and consistency of care require a partnership between different care providers from different specialities, with different medical practice and environments - hospital or home care, public or private practice. Though so much information has become available in the medical literature, quality of care demands that each healthcare professional keeps fully aware of the latest diagnostic or therapeutic findings and techniques in his/her field. Certain cancer networks have become a place where care providers and establishments can share methods and medical practice. Network promoters and members have thus been able to regain control over the functioning and the future of their profession. Patients have also obtained a place in decisions concerning their own health. Setting up healthcare networks will certainly shake up the tranquil system which the WHO has reported as the world's best health care system at the dawn of this century. However, this will also probably contribute to maintaining this excellence.     

Evidence-Based Decision Making as a Tool for Continuous Professional Development in the Medical Radiation Technologies

All components of contemporary health care practice must be supported by the best available evidence in order to maximize the potential for successful patient care. As in other disciplines, researched-based evidence is a major contributor to the development of contemporary clinical practice and decision making in the medical radiation technologies.However, in recent years a rapid proliferation of clinical studies and journal publications combined with a growing complexity of diagnostic imaging methods has made it difficult for practicing medical radiation technologists (MRT's) to remain current with the relevant clinical research. Because we rely on this clinical research evidence to determine the efficacy and applicability of new diagnostic tests and treatments, it is essential that we possess the skills for the effective procurement and interpretation of the scientific literature. For MRT's, barriers to this task may include lack of training in: defining good clinical questions, the optimal use the bibliographic databases and search engines used in accessing scientific research literature, and the appraisal and integration of acquired research evidence.Evidence-based decision making (EBDM) is a systematic process that enables the “conscientious, explicit, and judicious use of the current best evidence in making health care decisions.” 1 The development of this approach is derived in large part by the need to manage information overload. Such information is essential to the management of skyrocketing health care costs, ensuring the delivery of best diagnosis and treatment. When combined with clinical skills and judgments, patient values and expectations, the EBDM approach serves to maximize the potential for achieving successful patient care outcomes. Specifically, the implementation of EBDM has been shown to: close the gap between knowledge and practice, decrease variability in practice, and increase the use of best research evidence in practice thereby improving the level of clinical care provided by health care professionals. In this directed study article, we define the EBDM process as it pertains to medical radiation technologies.     

Update: the case for patient-specific dosimetry in radionuclide therapy

In this review of the literature and general practice in the use of radiopharmaceuticals for therapy, an argument is provided to demonstrate that the use of patient-individualized radiation dose assessment should become routine in these forms of therapy, as they are in other uses of radiation in therapy. Individual objections to patient-specific dosimetry will be raised and addressed, using findings presented in the literature. Such approaches are superior to the use of a fixed activity or activity per unit body weight approach in nuclear medicine therapy, which is current practice. It will be demonstrated that standardized and automated methods, with adjustment for patient-specific physical and biokinetic data, are of similar cost and difficulty to those used in other therapeutic modalities. Most importantly, the data show that careful use of patient-individualized dose calculations will produce calculated radiation dose estimates that correlate well with observed effects and that use of a dosimetry-based approach will result in better patient outcomes, improving the quality of medical care for patients and reducing costs for the institutions involved. The conclusion of this analysis is that the time has come for this reasonable paradigm to become routine practice.     

Effectiveness of complete diagnostic examination in clinical practice settings

BACKGROUND: Thorough follow-up of a positive fecal occult blood test (FOBT) result, or a complete diagnostic evaluation (CDE), is recommended as routine care on the basis of findings from colorectal cancer (CRC) screening trials. CDE involves either colonoscopy or the combination of flexible sigmoidoscopy and double contrast barium enema X-ray. However, little evidence outside clinical screening trial settings has been reported in the literature to support CDE performance. The focus of this study was to determine the impact of CDE in primary care practice settings. METHODS: We determined diagnostic outcomes for 461 adult patients with a positive FOBT result in 318 primary care practices in southeastern Pennsylvania and southern New Jersey. Sociodemographic data were collected and CDE status was ascertained for these patients. Polytomous logistic models were used to identify whether having CDE was associated with subsequently being diagnosed with lower gastrointestinal "neoplastic disease" or "other gastrointestinal disease" as compared to "normal findings. RESULTS: Patients who underwent CDE were significantly more likely to have a reported diagnosis of colorectal neoplasia than normal findings (adjusted odds ratio = 3.65, 95% confidence interval = 1.58-8.39, p = 0.02). CDE performance did not result in the differential diagnosis of other gastrointestinal disease. CONCLUSIONS: Patients with a positive screening FOBT who underwent CDE were more likely to be diagnosed with colorectal neoplasia than with less serious conditions or have normal findings. Results support the use of CDE in CRC screening.     

2016年版WHO淋巴瘤分类新进展及其应用

淋巴瘤分类从早期到2016年版世界卫生组织（WHO）分类经历了一系列变化。2016年版WHO淋巴瘤分类旨在提供最新的淋巴瘤诊断类型、更准确的诊断标准以及生物学与临床的相关性,从而推动淋巴瘤领域的基础研究,促进未来的治疗进展,为患者提供更好的服务。     

Methodology of research and practice for the third millennium: evidence-based medicine

In the past 10 years there have been significant scientific advances in biological sciences and health care. The growth in basic and translational research data to guide medical practice, which has an impact on health care costs has made it critical for clinicians to appraise and use published evidence for medical decisions. Evidence-based medicine should be strengthened and promoted to enhance the rationale and quality of medical care provided to our patients. Basic laboratory research and properly designed, relevant and timely prospective clinical trials should be strongly supported; patient participation must be increased to acquire more accurate information to develop innovative therapeutic strategies in oncology. New avenues in cancer detection and staging, as well as therapy, suggested by basic and translational laboratory research, must be vigorously pursued and adequately funded. Methodology for accurate cost accounting of medical care and cost-benefit studies needs further development. Technology assessment will substantially contribute to better utilization of scarce health care resources.     

Implementation and spread of interventions into the multilevel context of routine practice and policy: implications for the cancer care continuum

The promise of widespread implementation of efficacious interventions across the cancer continuum into routine practice and policy has yet to be realized. Multilevel influences, such as communities and families surrounding patients or health-care policies and organizations surrounding provider teams, may determine whether effective interventions are successfully implemented. Greater recognition of the importance of these influences in advancing (or hindering) the impact of single-level interventions has motivated the design and testing of multilevel interventions designed to address them. However, implementing research evidence from single- or multilevel interventions into sustainable routine practice and policy presents substantive challenges. Furthermore, relatively few multilevel interventions have been conducted along the cancer care continuum, and fewer still have been implemented, disseminated, or sustained in practice. The purpose of this chapter is, therefore, to illustrate and examine the concepts underlying the implementation and spread of multilevel interventions into routine practice and policy. We accomplish this goal by using a series of cancer and noncancer examples that have been successfully implemented and, in some cases, spread widely. Key concepts across these examples include the importance of phased implementation, recognizing the need for pilot testing, explicit engagement of key stakeholders within and between each intervention level; visible and consistent leadership and organizational support, including financial and human resources; better understanding of the policy context, fiscal climate, and incentives underlying implementation; explication of handoffs from researchers to accountable individuals within and across levels; ample integration of multilevel theories guiding implementation and evaluation; and strategies for long-term monitoring and sustainability.     

TCP and NTCP in preclinical and clinical research in Europe

European research in radiation oncology has a long and successful tradition. The aim of this research is to increase the therapeutic window of radiotherapy by increasing the tumor control probability (TCP) and/or by decreasing the normal tissue complication probability (NTCP). This paper summarizes the basic radiobiological concept underlying treatment optimization by TCP-NTCP data and discusses some of the limitations of currently used models. These are controversial in many aspects and cannot be recommended for clinical routine practice but should rather be considered as a research tool.     

Immunohistochimie et médecine personnalisée en oncologie pulmonaire: potentialités et limites

The concept of personalized or stratified medicine in thoracic oncology have led to the development of companion diagnostic testing in the laboratories in order to detect genomic alterations which can be targeted by therapeutic molecules. The use of these companion tests has to be associated with an optimized quality control with the aim of getting solid results before treatment administration to the patients. The great majority of these tests is based on molecular biology approach. However, since the commercial availability of different antibodies targeting genomic alterations which can be used in formalin fixed paraffin sections, an alternative method to the molecular approach is the immunohistochemistry (IHC). Some of these antibodies are or will be probably soon used in a daily routine practice (such as anti-ALK or anti-MET antibodies). Other antibodies have currently a more restricted use in thoracic oncology (such as anti-BRAF V600E, anti-ROS1 and mutation-specific anti-EGFR antibodies). In this review, we aim to detail the advantages and the limits of IHC method in thoracic oncology field for personalized medicine, in particular comparatively to the molecular biology technology. Moreover, we discuss the opportunity to provide accredited IHC tests in the context of stratified medicine for lung cancer patients.     

Neue Erkenntnisse und Strategien einer rationalen Diagnostik und Bildgebung bei prim?ren Lebertumoren

It is not uncommon for focal liver lesions and suspected tumor lesions to be found by imaging techniques during routine practice as incidental findings by applying specific surveillance strategies for risk patients. The evaluation of these lesions is of central importance for a further individual therapeutic approach. New insights, especially concerning hepatocellular carcinomas have led to a change of the previously performed methods of diagnostics and imaging, which will be presented in the following article.