bluuebunny/crossref_metadata_2025 huggingface dataset:
Off-label Use of Drugs in Childhood Asthma
Authors: Cabral António J , Morais-Almeida Mário ,   Specialist in Paediatrics, Funchal Central Hospital, Madeira,   Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal,   Head of the Allergy Center, CUF Descobertas Hospital and CUF Infante Santo Hospital, Lisbon, Portugal,   CINTESIS – Center for Research in Health Technologies and Information Systems – Faculty of Medicine, University of Porto, Porto, Portugal
Published: October 2015

Asthma is among the most common illnesses in childhood and may require off-label drug use for adequate symptom control. Several studies have assessed that this use is common mainly due to a lack of clinical research. The leading concerns are the increased risk of adverse drug reactions and prescription errors. However, off-label prescriptions are not necessarily incorrect. The European Medicines Agency released the Paediatric Regulation to promote research in the medicines for children; yet, recent data suggest only a minor impact.
Advances in Chemotherapy Options for Head and Neck Cancer
Authors: Rodriguez Cristina P , Adelstein David J ,   Associate Staff Member,   Professor of Medicine, Solid Tumor Oncology Department, Cleveland Clinic Taussig Center
Published: October 2015

The role of chemotherapy in the management of head and neck squamous cell cancers continues to evolve. Concurrent chemotherapy and radiation represents a standard treatment option for organ preservation in larynx and hypopharynx squamous cell carcinomas, unresectable locally advanced head and neck cancer, nasopharyngeal cancer, and post-operative therapy of high-risk resected disease. Chemotherapeutic agents and their combinations have known activity in metastatic disease and are frequently used for palliation. Emerging therapeutic approaches have been fueled by the observed shift in the pattern of disease recurrence after definitive therapy and the development of molecular targeted agents with disease activity. The recognition of human papillomavirus-associated oropharyngeal squamous cell carcinoma as a distinct clinical entity among head and neck cancers will influence the design of future clinical investigation.
A Practical Clinical Approach to Adjuvant Therapy in Breast Cancer—An Update
Authors: Hines Stephanie L , Tan Winston , Moreno-Aspitia Alvaro , Roy Vivek , Vallow Laura A , McLaughlin Sarah A , Perez Edith A ,   Assistant Professor of Medicine,   Assistant Professor of Medicine,   Assistant Professor of Medicine,   Assistant Professor of Medicine,   Assistant Professor of Radiation Oncology,   Assistant Professor of Surgery,   Professor of Medicine, Mayo Clinic, Jacksonville
Published: October 2015

Adjuvant therapy for breast cancer has evolved to reflect the heterogeneous nature of the disease. Specific subtypes such as luminal, HER2- positive, and basal subtypes express different molecular markers that can be targeted by a variety of novel agents; therapy is tailored to the individual profile of each tumor. New risk-stratification models, including models based on a tumor’s genetic expression, enhance assessments of recurrence risk so that the potential toxicities of a particular regimen can be weighed against the potential benefit. More precise tailoring of adjuvant therapy may be possible in the future with advances in pharmaco-genetics, which will help to predict an individual’s response to various agents. Optimal adjuvant treatment of breast cancer involves tailoring therapy to the individual patient and tumor.
Psycho-education for Breast Cancer Patients and Survivors— A Powerful Tool for Healthcare Providers
Authors: Bober Sharon L , Varela Veronica Sanchez ,   Director, Sexual Health Program,   Psychology Research Fellow, Perini Family Survivors’ Center, Dana-Farber Cancer Institute
Published: October 2015

Due to increased early detection and improved treatments, the number of breast cancer survivors is steadily increasing. However, it is now clear that breast cancer patients and survivors frequently face a difficult set of challenges as a result of their treatment. Many of these challenges can also be enduring over time, such as sexual dysfunction and fertility-related distress, and continue to disrupt daily functioning and affect quality of life. It is imperative to assess quality of life changes both during and after breast cancer treatment—specifically, psychosocial adjustment, sexuality and fertility concerns, and lifestyle change—in order to help patients access appropriate education, support and resource materials. Fortunately, there has been an enormous increase in available resources to breast cancer patients and survivors in recent years. This article will outline current advances in patient education with regard to these challenges.
The Role of Imatinib Following Complete Resection of Primary Gastrointestinal Stromal Tumors
Authors: Eisenberg Burton L ,   Professor of Surgery, Section of Surgical Oncology, Dartmouth Medical School/Dartmouth-Hitchcock Medical Center
Published: October 2015

Gastrointestinal stromal tumor (GIST) is a life-threatening disease, for which surgery is the standard of care. However, surgical resection of the primary tumor is associated with a high rate of recurrence and a low five-year overall survival (OS) rate. The introduction of the KIT protein kinase-targeted therapy imatinib mesylate has enhanced treatment options. It has demonstrated improvements in progression-free survival and OS in patients with unresectable and/or metastatic malignant GISTs. Based on this efficacy, imatinib has been evaluated as an adjuvant option in KIT-positive primary GIST patients who have undergone complete gross resection. Early data indicate that one-year adjuvant therapy with imatinib 400mg/day can prolong recurrence-free survival (RFS) in these patients. Preliminary data also indicate potential benefits of a higher imatinib dose (800mg/day) and a longer duration of adjuvant imatinib therapy. Currently, imatinib, at a recommended dose of 400mg/day, is approved by the US Food and Drug Administration (FDA) as an adjuvant therapy in adult patients who have undergone complete gross resection of KIT-positive GIST.
The Clinical Value of Radioembolization in the Treatment of Inoperable Liver Cancer
Authors: Moreno-Luna Laura E , Andrews James C , Roberts Lewis R ,   Professor, University of Guadalajara,   Professor of Radiology, and Consultant, Division of Vascular and Interventional Radiology, Department of Radiology,   Associate Professor of Medicine, and Consultant, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic Rochester
Published: October 2015

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. HCC-related mortality is high because most cases are diagnosed at an advanced stage. HCCs are relatively resistant to radiation and the liver is unable to tolerate the radiation doses required to achieve tumoricidal effects by standard external-beam radiation. Focal radiation techniques employing a 3D approach have been shown to safely permit higher levels of radiation to targeted regions within the liver. Delivery of therapy through hepatic artery branches preferentially affects HCC tumors and spares the surrounding liver parenchyma. Selective targeting of radionuclides to tumors has been shown to achieve high radiation dose ratios. Transarterial radionuclide therapies have been developed with the objective of achieving selective intra-arterial delivery of radiotherapy, including radioactive iodine-131 (131I), rhenium-188 (188Re), yttrium-90 (90Y) (resin or glass microspheres), and others. These treatments have been used to treat HCC via a selective transarterial approach as an alternative to TACE. Portal vein thrombosis (PVT) is a relative contraindication to transarterial chemoembolization (TACE); in contrast, high specific activity radiomicrospheres do not occlude a significant portion of the hepatic arterial vascular bed and can therefore be used in patients with PVT. The devices, toxicities, and results with use of the available radioembolic devices are reviewed in this article.
Advances in Treatment Options for Patients with Pancreatic Cancer
Authors: Harris Carole , Goldstein David ,   Medical Oncology Registrar, St George Hospital,   Conjoint Clinical Professor, Department of Medical Oncology, Prince of Wales Hospital
Published: October 2015

Pancreatic carcinoma continues to be a problematic malignancy characterized by poor long-term survival, late diagnosis, and resistance to systemic therapy. Nevertheless, meaningful advances in treatment have occurred. These include the use of gemcitabine chemotherapy alone and in combination, the identification of active second-line therapy, and the emergence of epidermal growth factor receptor (EGFR)-targeted therapy as a new avenue for investigation. The role of radiation in locally advanced disease is promising and will be tested in the phase III setting. Adjuvant therapy has made an important impact on survival and will need to be enhanced with studies of emerging agents. The future will depend on new direction from emerging advances in basic biology.
Is There an Optimal First-line Regimen for Advanced Ovarian Cancer? Variations on a Theme
Authors: Hoskins Paul J ,   Medical Oncologist, British Columbia Cancer Agency, and Clinical Professor, University of British Columbia
Published: October 2015

Maximal surgical debulking plus platin-based chemotherapy is the standard of care. Most oncologists would use carboplatin plus paclitaxel. However, other equally valid options would include carboplatin plus docetaxel, single-agent carboplatin, or a combined intraperitoneal/ intravenous platin–paclitaxel regimen (for the subset with stage III disease and less than 1cm disease left after primary debulking). Failed strategies include adding a third cytotoxic, autologous bone marrow transplant, immune modulation using anti-CA 125 antibody or interferon, intraperitoneal radiolabeled antibody, modulating multidrug resistance with a cyclosporine analogue, and, finally, matrix metalloproteinase inhibition. The jury is still out with regard to maintenance paclitaxel. Dose-dense therapy, as with breast cancer, appears to have promise.
Laparoscopic Radical Hysterectomy for Early-stage Cervical Cancer
Authors: King Erin R , Ramirez Pedro T ,   Resident, Department of Obstetrics and Gynecology, University of Virginia,   Associate Professor, Department of Gynecologic Oncology, MD Anderson Cancer Center
Published: October 2015

Total laparoscopic radical hysterectomy (TLRH) for early-stage cervical cancer is a safe and feasible procedure. The advantages over abdominal radical hysterectomy (ARH) include shorter operating times, less blood loss, lower transfusion rates, and a shorter hospital stay. Robotic radical hysterectomy (RRH) offers an alternate minimally invasive approach to performing radical hysterectomy. Robotic surgery provides improved depth perception, a greater range of motion of surgical instruments, decreased tremor, and improved ergonomics compared with laparoscopic surgery.
Chemotherapy-induced Oral Mucositis
Authors: Sadasivan Raj ,   Medical Director, Hope Cancer Institute
Published: October 2015

Oral mucositis is one of the most common side effects cancer patients experience when undergoing chemotherapy. However, it is frequently under-reported and leads to high morbidity and complication rates. Advances in molecular biology have provided greater insight into the pathophysiology of this condition. Although there are no current treatments that completely resolve this painful condition, encouraging research developments indicate that a new, over-the-counter pH-balanced salt solution, reBalanceCa, shows promise.
The Neurogenic Component of Cutaneous Toxicities Induced by Chemotherapy—New Solutions
Authors: Chanez Jean-François ,   Head, Scientific Department, Evolife Laboratoires
Published: October 2015

Most chemotherapies cause cutaneous side effects. Docetaxel entered the therapeutic arsenal in the 1990s; while undeniably a sign of progress, it can also cause cutaneous side effects. Other chemotherapeutic drugs can induce secondary cutaneous effects, such as acneiform rash, hand–foot syndrome or mucositis. Hair loss, reversible or not, and nail disorders are also well-known deleterious effects encountered with several drugs used in oncology. Furthermore, the development of new targeted therapies is contributing to an increased frequency of these undesirable effects. New products that take into account the neurogenic phenomena implicated in the local inflammatory response to chemotherapy are required to offer new alternative care for various cutaneous and muco-cutaneous side effects.
Autologous Stem Cell Transplantation—An Important Step Toward Improving Survival in Multiple Myeloma
Authors: Gupta Ajay ,   Consultant, Medical Oncology, Max Cancer Center
Published: October 2015

Conventional chemotherapy has been used in the treatment of multiple myeloma; however, the development of autologous stem cell transplantation (ASCT) represented a major advance in the therapy. Complete response (CR) rates of 40–45% were seen and this translated into improvements in progression-free survival (PFS) and overall survival (OS) in some studies. As a result, ASCT is the standard of care in eligible patients and can be carried out with low treatment-related mortality. The introduction of newer agents such as thalidomide, lenalidomide, bortezomib, and liposomal doxorubicin into induction regimens has resulted in higher CR rates, very good partial response rates (VGPR), and improvements in the ease of administration. These drugs have also proved useful in patients with adverse cytogenetics. Recent trials suggest that this has translated into improvements in response rates post-ASCT. There is a suggestion that patients achieving CR/near-CR (nCR) or VGPR after induction therapy should be placed on maintenance and ASCT could then be used as a treatment strategy at relapse; however, all of these trends await confirmation from further trials. Tandem transplants have been used to augment the results obtained with ASCT and have demonstrated their utility in patients who achieved only a partial response or stable disease in response to the first transplant and patients with adverse cytogenetics. Incorporation of bortezomib along with melphalan into the conditioning regimen has also been tried. It is hoped that recent advances in therapy will contribute greatly to improved survival.
Survival of Patients Treated with High-dose Radiotherapy and Concurrent Chemotherapy for Unresectable Non-small-cell Lung Cancer
Authors: Schild Steven E , Ross Helen J ,   Professor of Oncology, and Chair, Department of Radiation Oncology,   Associate Professor of Medicine, and Thoracic Medical Oncologist, Department of Hematology/Oncology, Mayo Clinic
Published: October 2015

Radiotherapy (RT) has been used to treat cancers for 110 years. Today, megavoltage RT is delivered with very precise linear accelerators. Computed tomography and/or positron-emission tomography are used to define both tumor and normal tissue volumes. Powerful computers analyze these volumes in 3D space and design complex treatment plans. Over time, the ratio of dose administered to tumor compared with dose administered to the normal structures has increased, resulting in a better therapeutic index and improved survival. In the 1970s and 1980s, the five-year survival rate of unresectable non-small-cell lung carcinoma was 5% with standard RT alone. Adding chemotherapy before or after radiation improved the five-year survival to about 15%. More recently, concurrent chemotherapy and RT has achieved five-year survival rates of up to 29%. Pilot trials employing chemotherapy and higher-dose RT have resulted in still better local control and survival. A phase III trial of chemotherapy plus either standard-dose RT (60Gy/30) or high-dose RT (74Gy/37) is ongoing. New technology is providing ways to improve the therapeutic ratio and administer greater RT doses more safely.
Breakthrough Pain in Cancer Patients— Characteristics, Impact, and Assessment
Authors: Davis Mellar P ,   Professor of Medicine, Palliative Medicine, Department of Solid Tumor Oncology, Cleveland Clinic Lerner School of Medicine of Case Western Reserve University, and Supportive Oncology Services, Cleveland Clinic, Taussig Cancer Institute
Published: October 2015

Breakthrough pain (brief flares of severe pain superimposed on baseline pain) is a common problem in patients with cancer and is associated with significant physical, psychologic and economic burdens on patients and carers. The successful management of breakthrough pain is dependent on the accurate diagnosis and adequate assessment of the patient, which in turn leads to appropriate and effective treatment. It is clear that the impact of breakthrough pain on patients is wide ranging, affecting patient quality of life, decreasing physical functioning, and often leading to psychologic consequences, such as anxiety and depression. A structured and appropriate approach to the assessment and diagnosis of breakthrough pain needs to be comprehensive to identify all the areas of impact on a patient’s life. In this article, cancer breakthrough pain is defined and the different subtypes of breakthrough pain are explained. Assessment tools that are frequently used to appropriately assess the effects of breakthrough pain are discussed and treatment options after diagnosis are also outlined, with a focus on non-pharmacologic interventions.
Fertility and Cancer—Patient, Physician, and Institutional Barriers
Authors: Quinn Gwendolyn P , Vadaparampil Susan T ,   Associate Member, Moffitt Cancer Center and Research Institute,   Associate Member, Moffitt Cancer Center and Research Institute,   Associate Member, Moffitt Cancer Center and Research Institute
Published: October 2015

Loss of fertility is often a negative consequence of cancer treatments that include chemotherapy and radiation. Cancer survivors who experience infertility are at increased risk for emotional distress and reduced quality of life. Fertility preservation options are available for cancer patients of childbearing age. Many cancer patients are greatly concerned about the loss of fertility and are interested in fertility preservation. Most preservation options are available only prior to the initiation of cancer treatment. Communication within this limited time-frame concerning fertility loss and fertility preservation options for newly diagnosed cancer patients is imperative. There are considerable barriers at the patient, physician, and system level that impede discussion and pursuit of fertility preservation for the newly diagnosed cancer patient. Barriers to fertility preservation include lack of physician referral, need for patient education resources, and financial costs.
Clinical Utility of Comprehensive Microarray Testing in Early-stage Breast Cancer
Authors: Bender Richard A , Snoo Femke A de ,   Senior Vice President, Medical Affairs for Oncology, Caris Life Sciences, Inc.,   Director, Medical Affairs, Department of Medical Affairs, Agendia BV
Published: October 2015

Microarray gene expression profiling in the diagnostic setting offers the opportunity of reading out multiple profiles and genes from a single array. Several additional profiles have been added to the Agendia breast cancer suite called Symphony(TM), along with MammaPrint, a US Food and Drug Administration (FDA) cleared prognostic and predictive assay, by virtue of this technology. These additional profiles, TargetPrint, BluePrint, and TheraPrint, expand the clinical utility of the Symphony profile. They also demonstrate the versatility of gene expression profiling in the diagnostic setting, enabling the addition of many more clinically relevant profiles (such as drug response profiles) as experience grows.
Positron-emission Tomography Imaging in Breast Cancer
Authors: Eubank William B , Lee Jean H , Mankoff David A ,   Associate Professor of Radiology, Puget Sound VA Health Care System,   Assistant Professor of Radiology,   Professor of Radiology, University of Washington and Seattle Cancer Care Alliance
Published: October 2015

There are four major diagnostic tasks in breast cancer: detection and diagnosis; staging (locoregional and distant metastases); response to treatment (neoadjuvant and metastatic therapy); and characterization of the individual tumor for selection of the most appropriate therapy. The use of fluorodeoxyglucose (FDG) positron-emission tomography (PET) and PET–computed tomography (PET-CT) in all four of these tasks has been investigated. The aim of this article is to discuss the strengths and weaknesses of FDG PET with regard to each of these tasks. The diagnostic areas for which FDG PET appears most suited for clinical decision-making will be highlighted.
Molecular Monitoring of BCR-ABL Transcripts—Standardization Needed to Properly Use, and Further Investigate the Value of, a Critical Surrogate Marker for Success in Therapy of Chronic Myeloid Leukemia
Authors: Giles Francis J ,   Director, HRB Clinical Research Facility, National University of Ireland, Galway, and Professor of Cancer Therapeutics, National University of Ireland, Galway and Trinity College, Dublin
Published: October 2015

Targeted inhibition of the oncogenic function of the constitutively active BCR-ABL kinase with tyrosine kinase inhibitors is a highly effective and now standard therapeutic approach for patients with chronic myeloid leukemia. The early evaluation of response during the course of therapy is important for determining whether therapy is progressing according to expectations that correlate with optimal outcome. Therefore, frequent disease monitoring to assess treatment and to detect failure or suboptimal response is recommended. Current monitoring strategies incorporate hematological, cytogenetic, and molecular analysis, the latter involving the quantification of BCR-ABL transcripts in the blood. Molecular monitoring has been shown to be the most sensitive method available and has shown prognostic impact with regard to progression-free survival, but the use of diverse methods to quantify BCR-ABL levels has made it difficult to compare results between (and sometimes within) laboratories, with resulting implications for patient care. This article discusses the current approaches and challenges to BCR-ABL monitoring, summarizes some of the international efforts under way to standardize BCR-ABL analysis, and suggests potential alternative approaches to facilitating reproducible BCR-ABL monitoring results, such as a standardized US Food and Drug Administration-approved BCR-ABL testing kit.
Extracellular Hemoglobin Regulation of von Willebrand Factor Activity in Plasma of Patients with Sickle Cell Disease
Authors: Zhou Zhou , Guchhait Prasenjit ,   Post-doctoral Fellow,   Assistant Professor, Thrombosis Research Division, Cardiovascular Research Section, Department of Medicine, Baylor College of Medicine
Published: October 2015

Elevated levels of ultralarge (UL) von Willebrand factor (VWF) multimers in plasma play an important role in cell adhesion and vascular occlusion in sickle cell disease (SCD). Recently, we have shown that the binding of extracellular hemoglobin (ECHb) to the A2 domain of VWF significantly blocks VWF cleavage by the metalloprotease ADAMTS13in vitro. We speculated that on release from the inflamed endothelium, the VWF multimers maintain the UL structure in plasma if ECHb prevents their cleavage. We observed that a subpopulation of VWF multimers that are bound to ECHb (HbVWF), which accounted for about 14 % of the total VWF in the plasma of SCD patients. The plasma HbVWF level is parallely correlated with the ECHb and VWF-antigen levels. The HbVWF multimers are resistant to the metalloprotease ADAMTS13in vitroand are more adhesive to platelets and collagen compared with their Hb-free counterpart. Therefore, we speculate that the HbVWF, which are probably UL multimers, play an important role in tethering and stably adhering blood cells to the vascular endothelium and culminate in vascular occlusion/thrombosis/strokes in SCD patients. Thus, this article provides a new insight into the molecular pathophysiology of SCD.
Thalassemia as a Hypercoagulable State
Authors: Cappellini Maria D , Musallam Khaled M , Taher Ali T ,   Professor of Medicine, Department of Internal Medicine, Fondazione IRCCS “Ca’ Granda” Ospedale Policlinico, University of Milan,   Clinical Research Fellow,   Professor of Medicine, Department of Internal Medicine, Hematology–Oncology Division, American University of Beirut Medical Center
Published: October 2015

Although the life expectancy of thalassemia 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 thalassemia 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 thalassemia are highlighted, with a special focus on thalassemia intermedia, being the type with the highest incidence of thrombotic events as compared with other types of thalassemia. Clinical experience and available clues regarding optimal management are also discussed.
Ethical Dilemmas in Gynecologic Oncology—Practice Points for the Oncology Practitioner
Authors: Schlumbrecht Matthew P , Gallagher Colleen M ,   Chief Administrative Fellow, Department of Gynecologic Oncology and Reproductive Medicine,   Chief and Executive Director, Integrated Ethics in Cancer Care, Associate Professor, Critical Care, and Co-Director, Bioethics Initiative for Equity in Health Care and Research, The University of Texas MD Anderson Cancer Center
Published: October 2015

Gynecologic oncology is a unique field in which physicians frequently become engaged in, and manage, ethical dilemmas. Understanding the features of patients who receive ethics consults is crucial for maintaining continuity of care and identifying areas for physician education. A review of the MD Anderson Cancer Center clinical ethics database and institutional medical record was performed for gynecologic oncology patients receiving ethics consults from 1993 to 2008. Data abstracted included patient demographic and clinical information, clinical case types, and key underlying issues. Information on all gynecologic oncology patients seen during the study interval was also obtained to define a base population. Summary statistics were generated, and comparisons between consult and base populations were performed. Forty-one consults were conducted. Six (15.4 %) patients had established medical power of attorney, and seven (17.1 %) had a living will. The distribution of disease sites in consult patients was similar to the base population, except for gestational trophoblastic neoplasia, which was overrepresented (7.9 versus 0.8 %, p<0.0001). Compared with the base population, there was a greater proportion of consult patients who were African-American (33.3 versus 10.9 %, p<0.0001), had Medicaid (15.4 versus 4.8 %, p=0.002), or were self-pay (15.4 versus 5.4 %, p=0.009). The most common clinical ethics case types involved identifying levels of appropriate treatment. Common underlying issues included family dynamics and patient coping mechanisms. Ethics consultation provides a substantial resource in identifying relevant psychosocial issues experienced by gynecologic oncology patients, on which physician educational initiatives may be based.
Paradigm towards Tailored Therapies and Complete Responses in the Treatment of Metastatic Renal Cell Carcinoma
Authors: Fishman Mayer , Hutson Thomas , Agarwal Neeraj , Jonasch Eric ,   Medical Oncologist, Genitourinary Oncology Division, H Lee Moffitt Cancer Center and Research Institute,   Director, Genitourinary Program, Texas Oncology, PA, Baylor Charles A Sammons Cancer Center,   Assistant Professor, Division of Oncology, Department of Medicine and Huntsman Cancer Institute, University of Utah School of Medicine,   Associate Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Published: October 2015

In recent years, the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of targeted therapies. Multitargeted kinase inhibitors (such as sunitinib, sorafenib, pazopanib, and axitinib), the vascular endothelial growth factor inhibitor bevacizumab, and mammalian target of rapamycin inhibitors (such as everolimus and temsirolimus) have become the standard of care for the palliation of metastatic disease. Unfortunately, cumulative toxicities and the lack of marked benefits have prevented the combined use of most molecularly targeted agents. Selected patients with mRCC benefit from immunotherapy, as subsets of patients can experience long-term disease remission or complete response with high-dose interleukin-2. In order to optimize the value of immunotherapy, improvements in the selection of drugs and combinations with novel immunomodulatory agents must be pursued.
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, Radiation Oncology Department,   Senior Medical Oncologist, Medical Oncology Department,   Head, Radiation Oncology Department, University Hospital, Vrije University, Brussels
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 comorbid conditions. In the younger patient, the benefit of combined chemoradiation 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 article is to summarise the data on efficacy and toxicity of CCRT in the elderly.
Stereotactic Radiotherapy for Liver Metastases
Authors: Pocinho Rute , Roberge David ,   Radiation Oncology Resident, Department of Radiotherapy, Francisco Gentil Portuguese Oncology Institute of Lisbon,   Department Head, Radiation Oncology, Notre Dame Hospital, Montreal
Published: October 2015

Liver metastases are common in oncologic patients, causing substantial morbidity and mortality. Systemic therapy is now standard palliative treatment for most patients with liver metastases, often providing transient responses and increased overall survival. In selected oligometastatic patients, local treatment can lead to long disease-free intervals and even permanent disease control. Although surgery remains the gold standard of local treatments, most patients will not be appropriate surgical candidates. For these patients, alternate local treatments have been developed. Among these, stereotactic body radiotherapy (SBRT) presents an attractive non-invasive option for selected patients with limited hepatic involvement. This article reviews the development, indications, methods, and results of SBRT in the management of liver metastases.
Management Strategies for Elderly Patients with Diffuse Large B-Cell Lymphoma
Authors: Nastoupil Loretta J , Sinha Rajni , Flowers Christopher R ,   Fellow,   Assistant Professor,   Director, Lymphoma Program and Associate Professor, Department of Hematology and Oncology, Winship Cancer Institute
Published: October 2015

Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of lymphoma and most commonly presents in the sixth decade. Given the dramatic rise of the incidence of lymphoma since the late 1990s in patients who present over the age of 65, and the expected increase in the prevalence of DLBCL with the aging population, defining appropriately tailored modern therapy for elderly DLBCL patients is an increasingly important clinical concern. Moreover, age has been one of the most important adverse prognostic features, with numerous studies associating older age with inferior outcomes. Although it has been well established that B-cell diversity decreases with age, and that the loss of diversity can be associated with clonal expansion of B-cells, it remains unknown how this or other factors contribute to the pathogenesis and poor prognosis in elderly patients with DLBCL. Furthermore, elderly patients often have more comorbid illnesses, worse performance status, less hematologic reserve, and altered pharmacokinetics related to decreased metabolism and clearance of drugs. We examine the impact of these factors on therapeutic decision-making in patients with DLBCL and explore treatment alternatives for elderly individuals. Future research is needed not only to address treatment strategies but also to define the biologic heterogeneity between younger and older patients with DLBCL, so that more rational therapeutic approaches can be investigated.
The Role of Complete Blood Cell Count in Prognosis—Watch this Space!
Authors: Rochet Nicole M , Markovic Svetomir N , Porrata Luis F ,   MD/MS Student, Division of Hematology,   Professor of Medicine and Oncology, Department of Medical Oncology and Division of Hematology,   Assistant Professor, Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine, Rochester
Published: October 2015

Prognostic factors in cancer patients provide information about possible clinical outcomes and help classify patients into different risk groups. Treatment and clinical management decisions are often challenging, thus the availability of reliable and accessible prognostic markers is vital when designing treatment plans and discussing them with patients. This article discusses the prognostic value of the complete blood cell count components (i.e., white blood cell count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, hemoglobin level, and platelet count) in regard to clinical outcomes in patients with malignant disorders.
Time for a New Paradigm in the Treatment of Metastatic Melanoma
Authors: Wargo Jennifer , Gonzalez Rene , Amaria Rodabe ,   Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, US,   Melanoma Research Clinics, University of Colorado Denver, Colorado, US,   Melanoma Research Clinics, University of Colorado Denver, Colorado, US
Published: October 2015

Metastatic melanoma is a very common disease with an increasing incidence worldwide and is notoriously difficult to treat. The long-established treatments including dacarbazine and interleukin-2 have shown limited response rates and are associated with significant toxicities. More recently, treatments have been developed that decrease inhibition of T-cell action against melanomas. Among these, ipilimumab was recently approved for use in metastatic melanoma and has shown improved overall survival (OS) and progression-free survival rates (PFS). Another such treatment currently in development is the monoclonal antibody, anti-PD-1. This blocks PD-1 inhibition of T-cells and has shown promising response rates in early clinical trials. Another treatment approach is to use targeted therapies in patients with mutations in BRAF or CKIT signaling pathways and it is vital that the mutational status of these genes be determined in patients with metastatic melanoma to best determine effective therapeutic options. Vemurafenib was recently approved for metastatic melanoma and targets the BRAF V600E mutation which occurrs in about 50 % of cutaneous melanomas. Recent results from the ongoing Phase III BRIM-3 study comparing vemurafenib with dacarbazine showed that median 12-month OS rates and the risk of death were reduced with vemurafenib. Other BRAF inhibitors such as dabrafenib and MEK inhibitors such as trametinib are also in development. New treatments in ongoing clinical trials coupled with an improved biologic understanding are likely to improve responses and outcomes for patients with metastatic melanoma.
The Role of F18-fluorodeoxyglucose Positron Emission Tomography in the Management of Relapsed or Refractory Hodgkin’s Lymphoma
Authors: Cashen Amanda F ,   Assistant Professor of Medicine, Washington University School of Medicine, St Louis, Missouri, US
Published: October 2015

Positron emission tomography (PET) is widely used in the diagnosis and response assessment after first-line treatment of Hodgkin’s lymphoma (HL). For the approximately 30 % of patients who relapse or have refractory disease, PET can provide valuable prognostic information during second-line therapy, at the time of autologous stem cell transplant (ASCT). Retrospective studies performed over the past decade have consistently found a significant association between a positive PET scan after salvage chemotherapy for HL and progression-free and overall survival after ASCT. In fact, the predictive value of pre-transplant PET appears higher than that of more traditional clinical risk factors. Unfortunately, there is little data to recommend the best treatment course for patients who have a positive pre-ASCT PET, and few studies have addressed the role of PET in other relapsed/refractory HL settings.
Exercise Recommendations for Cancer-Related Fatigue, Cognitive Impairment, Sleep Problems, Depression, Pain, Anxiety, and Physical Dysfunction—A Review
Authors: Mustian Karen M , Sprod Lisa K , Janelsins Michelle , Peppone Luke J , Mohile Supriya ,   Assistant Professor and Director,   Research Assistant Professor,   Research Assistant Professor,   Research Assistant Professor,   Associate Professor, Physical Exercise, Activity and Kinesiology (PEAK) Laboratory, James P Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York, US
Published: October 2015

Cancer and its treatments produce a myriad of burdensome side effects and significantly impair quality of life (QoL). Exercise reduces side effects and improves QoL for cancer patients during treatment and recovery. Exercise prior to, during, and after completion of cancer treatments provides numerous beneficial outcomes. It represents an effective therapeutic intervention for preparing patients to successfully complete treatments, for reducing acute, chronic, and late side effects, and for improving QoL during and after treatments. This overview of exercise oncology and side effect management summarizes existing evidence-based exercise guidelines for cancer patients and survivors.
Recent Developments in Treatments for Metastatic Castration-resistant Prostate Cancer—A Mechanistic Perspective
Authors: Sonpavde Guru , Crawford E David ,   Oncologist, Comprehensive Cancer Center, Department of Medicine, Section of Medical Oncology, University of Alabama at Birmingham, Birmingham, Alabama, US,   Professor of Surgery/Urology/Radiation Oncology, Head of Urologic Oncology, E David Crawford Endowed Chair in Urologic Oncology, University of Colorado, Denver, Colorado, US
Published: October 2015

Over the past decade, the treatment landscape in metastatic castration-resistant prostate cancer (CRPC) has markedly changed, with the introduction of three new chemotherapeutic agents. The mechanism of CRPC is not fully understood, but it may result from multiple pathways, including a loss or androgen receptor (AR) specificity and increased downstream signalling activity that provide multiple targets for therapeutic agents. For some years, docetaxel was the mainstay of treatment in CRPC, but recently, cabazitaxel (a microtubule inhibitor), sipuleucel-T (a cancer vaccine), and abiraterone acetate (a CYP17 inhibitor) were approved for CRPC treatment. In Phase III clinical trials, these agents have shown significant improvements in survivalover mitoxantrone (for cabazitaxel) and over placebo (for sipuleucel-T and abiraterone acetate)and were well tolerated. There are also two treatments in late-stage development, MDV3100 (an oral AR antagonist) and radium-223 (an isotope that creates breaks in double-stranded DNA). These have also shown improvements in survival in Phase III trials; their regulatory approval is expected soon. The modes of actions of the existing and new drugs in CRPC are varied, but some are complementary and investigations of different combinations of these medications are much needed; they may enhance efficacy, further extend survival, and improve outcomes in this formerly untreatable disease.
Salvage Therapy for Prostate Cancer
Authors: Westesson Karin E , Stephenson Andrew J ,   Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, US.,   Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, US.
Published: October 2015

Biochemical recurrence after treatment of prostate cancer occurs in 3050 % of patients. Confirming that recurrence is localized to the pelvis is challenging as PSA is nonspecific and imaging modalities are imperfect in identifying location of recurrent disease. Salvage therapy after radical prostatectomy is limited to external beam radiotherapy and androgen-deprivation therapy. After radiotherapy, local salvage therapy consists of salvage radical prostatectomy, salvage brachytherapy, and salvage high-intensity ultrasound. Each treatment modality provides various rates of cure but with its own side-effect profile, prompting discussion between patient and clinician to determine appropriate treatment course. Local salvage therapy has the potential to be curative and disease control has been reported in a substantial number of select patients. However, the survival benefit of these therapies has yet to be definitively proved.
Sorafenib in Non-Small Cell Lung Cancer—Results of Clinical Trials
Authors: Mellema Wouter W , Smit Egbert F , Dingemans Anne-Marie C ,   Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands,   Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands,   Department of Pulmonary Diseases Pulmonary Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands.
Published: October 2015

Non-small lung cancer (NSCLC) patients with metastatic disease have a poor prognosis and platinum-based chemotherapy is the only treatment option in the majority of these patients. There is a great need for new targeted therapies in this complex and heterogeneous disease. Sorafenib is a multi-target tyrosine kinase inhibitor (TKI), which inhibits proteins involved in proliferation and angiogenesis and could be an attractive agent for patients with NSCLC. Sorafenib is studied in first- and second-line treatment as mono and combination therapy. In phase III trials, sorafenib failed to show improvement in survival as first-line treatment in addition to chemotherapy and as monotherapy in third or fourth line. Even detrimental effects were observed in patients with squamous histology. Still, a subgroup of patients derive long-term benefit from treatment with sorafenib. To identify these patients, biomarker studies have been conducted, but no predictive biomarker has yet been found. Combination therapy of sorafenib with other targeted agents is currently being studied.
Combination and Sequencing of Therapies for the Treatment of Metastatic Melanoma
Authors: Joseph Richard W , Sullivan Ryan J , Tarhini Ahmad A , Sherry Richard M ,   Department of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida, US,   Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, US,   Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh,   Tumor Immunology Section, Surgery Branch, National Cancer Institute, Bethesda, Maryland, US
Published: October 2015

Advances in molecular biology have lead to the development and approval of new treatments that improve survival for patients with metastatic melanoma. The limited duration of clinical response for targeted agents and the low overall response rate for immunotherapies illustrate that more work needs to be carried out. There are four Food and Drug Administration (FDA)-approved therapies for the treatment of metastatic melanoma. The optimal sequence of these therapies remains unclear with no prospective data to guide clinicians. It is also uncertain whether combining agents with different cell signaling properties or different immune mechanisms will provide therapeutic benefit to patients. Defining appropriate therapeutic sequences and or combinations may lead to improved treatment efficacy and is currently an area of active research. In this article we discuss recent advances in the treatment of metastatic melanoma and current treatment limitations. We summarize the limited clinical data on the sequencing and combination of therapies and discuss future therapeutic strategies.
Nab-Paclitaxel versus Docetaxel for the First-line Treatment of Metastatic Breast Cancer
Authors: Gradishar William J ,   Professor of Medicine, Hematology/Oncology, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, US.
Published: October 2015

Taxane-based treatment regimens are standard first-line therapies for metastatic breast cancer (MBC). The clinical benefit of solvent-based taxanes, including solvent-based paclitaxel and docetaxel, in MBC has been established in large randomized clinical trials. Docetaxel has demonstrated greater efficacy versus solvent-based paclitaxel in at least one trial, but both solvent-based paclitaxel and docetaxel are associated with undesirable dose-limiting toxicities, including neutropenia, sensory neuropathy, and hypersensitivity reactions.nab-Paclitaxel, an albuminbound form of paclitaxel, was developed to improve the therapeutic index of taxane treatment. This review summarizes preclinical experiments and clinical data from MBC trials comparingnab-paclitaxel with docetaxel. In preclinical studies,nab-paclitaxel more effectively suppressed tumor growth than docetaxel (80 versus 29 % inhibition) in breast cancer tumor xenograft models and was associated with less toxicity. Clinical studies confirmed these findings and reported a better therapeutic index with nab-paclitaxel than docetaxel. As such, the clinical experience withnab-paclitaxel supports its role as an important advance in the treatment of MBC with taxane-based regimens.