bluuebunny/crossref_metadata_2025 huggingface dataset:
A Focus on the Treatment of Anthracycline Extravasation and Tissue Protection
Authors: Langer Seppo W , Sehested Maxwell , Jensen Peter Buhl ,   Consultant Medical Oncologist, Department of Oncology,   Consultant Pathologist, Copenhagen University Hospital,   Consultant Medical Oncologist, Department of Oncology
Published: October 2015

Accidental extravasation of anthracycline-based chemotherapy is a complication that has been feared since the introduction of the anthracyclines more than 40 years ago. Tissue infiltration with vesicant drugs may lead to progressive necrosis and destruction of muscles, tendons, nerves, and joints, and may be associated with severe functional and cosmetic changes. During the last four decades, much effort has been made to prevent such accidents from happening. In addition, different surgical approaches and several non-pharmacolgical and pharmacological treatments have been used to counteract the devastating effects of the extravasation. Most treatment modalities have been empirically based, and only a few have undergone thorough evaluation. Recently, dexrazoxane was shown to be an effective and non-toxic acute treatment for anthracycline extravasation. It has since become a widely recommended treatment, and Totect® is currently the only approved drug for this indication.
Cisplatin plus Cetuximab in the Treatment of Recurrent and Persistent Cancers of the Cervix
Authors: Oliver Kate E , Farley John H ,   First Year Gynecologic Oncology Fellow, National Capital Consortium Uniformed Services Fellowship in Gynecologic Oncology, Walter Reed Army Medical Centre,   Associate Professor of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences
Published: October 2015

With the discovery of the human genome, new frontiers in the treatment of cancer include the development of targeted biologic therapies directed at tumor-specific antigens. Novel targeted molecular therapies provide more specific antitumor activity than traditional chemotherapeutic agents while simultaneously improving toxicity. Cetuximab is a recombinant monoclonal antibody directed at the epidermal growth factor receptor (EGFR). EGFR serves as the gatekeeper to the intracellular pathways responsible for angiogenesis, metastasis, cellular growth, and survival. EGFR overexpression has been demonstrated in several tumors, and its presence often confers worse prognosis and more aggressive tumor behavior. Recurrent and persistent cervical cancers have historically been treated with single-agent cisplatin. To date, this agent exhibits the greatest known single-agent activity against cervical tumors despite achieving low response rates of 17–38%. Molecular targeting of cervical cancers could provide enhancement of cisplatin activity. EGFR overexpression has been noted in cervical cancer, suggesting a possible role for targeted monoclonal antibody therapy in this setting.
Adolescent Psychopathology and Adult Health Behaviors in Long-term Survivors of Childhood Cancer
Authors: Harder Lana L , Krull Kevin R ,   Pediatric Neuropsychologist, Children’s Medical Center of Dallas, and Assistant Professor, University of Texas Southwestern Medical School,   Associate Member, Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital
Published: October 2015

As rates of childhood cancer survival increase and survivors reach adulthood, research aims to understand the unique ongoing difficulties for this burgeoning population. Survivors are at heightened risk for late effects associated with cancer and its treatment including those related to physical health, psychological wellbeing (i.e. cognitive and emotional functioning), and social outcomes (e.g. education, employment). Additionally, survivors are at greater risk for maladaptive health-related behaviors (e.g. tobacco use, excessive sun exposure, physical inactivity), which serve to amplify risk for late effects and secondary cancers. While risk associated with a medical history significant for childhood cancer is a stable factor, those associated with health-related behaviors are fortunately modifiable. Research efforts have yielded important findings linking cognitive and emotional difficulties with maladaptive health behaviors, which are detailed in this review. Such findings afford opportunity for targeted prevention and intervention programs to improve outcomes for survivors; however, limited research has evaluated interventions to address maladaptive health behaviors in pediatric cancer survivors and further investigation is warranted. The importance of long-term multidisciplinary follow-up is emphasized and associated challenges are discussed.
Breakthrough Pain in Cancer Patients— Pharmacologic Symptomatic Treatment
Authors: Pappagallo Marco ,   Professor, Department of Anesthesiology, Mount Sinai School of Medicine
Published: October 2015

Breakthrough pain is experienced by many cancer patients who are being treated with opioids for the management of chronic persistent pain. There is currently no ‘gold standard’ approach for the pharmacologic symptomatic treatment of breakthrough pain but proposed strategies include the implementation of primary therapies (e.g. chemotherapy, radiotherapy, and surgery) for the underlying cause of the pain; optimization of scheduled analgesia; use of adjuvants; and specific supplemental analgesia for breakthrough pain (the most common pharmacologic strategy). Individualization of treatment is important and a combination of these strategies may be required. In this article, pharmacotherapeutic approaches to managing breakthrough pain are discussed, including different routes of administration and newer opioid formulations. In addition, the current guidelines for managing breakthrough pain are examined.
Platelet Activation Following Exposure to Anti-ABO Antibodies— An In Vitro Study
Authors: Refaai Majed A , Henrichs Kelly F , Spinelli Sherry L , Phipps Richard P , Masel Edward , Smith Brian H , Francis Charles W , Blumberg Neil ,   Assistant Professor,   Medical Technologist Specialist,   Research Associate Professor,   Dean’s Professor of Environmental Medicine, Oncology, Pediatrics, and Microbiology and Immunology,   Medical Technologist Specialist,   Medical Technologist Specialist,   Professor Emeritus, Department of Medicine, and Professor,   Professor, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center
Published: October 2015

Since platelets possess A and B antigen, mismatched ABO platelets could, theoretically, become activated or hypofunctional by exposure to anti-A or anti-B antibodies found in transfused or recipient plasma. Following normal baseline platelet aggregation to adenosine diphosphate (ADP), platelets from normal donors of different blood types were incubated at 37°C for 10 minutes with 50μl of normal saline (NS), O plasma, or AB plasma. Aggregation was then induced with ADP. No significant changes from baseline were seen in platelet aggregation studies following incubation with NS. However, platelet aggregations of type A and type B platelets were significantly inhibited when incubated with O plasma (mean of 41 and 22%, respectively). Our findings indicate that mediators in group O plasma, very likely anti-A and anti-B antibodies, cause impaired platelet aggregation of ABO non-identical platelets.
Intraoperative Considerations in Sentinel Lymph Node Biopsy for Breast Cancer
Authors: Chagpar Anees B ,   Director, The Breast Center, Smilow Cancer Hospital, Yale-New Haven and Associate Professor, Department of Surgery Yale University School of Medicine
Published: October 2015

Sentinel lymph node (SLN) biopsy has revolutionized breast cancer management and has been generally accepted as a mainstay in lymph node evaluation for breast cancer patients. Still, there are many controversies that surround both the surgical technique involved and how the SLNs should be evaluated intraoperatively. The ramifications of isolated tumor cells and micrometastases and the need for axillary node dissection in all SLN-positive patients remain subjects of debate. This article reviews the literature with regard to these issues and presents the current state of the science of SLN biopsy.
Diagnosis of Metastatic Breast Cancer—A Case Report Using Molecular Cancer Classification
Authors: Gandhi Yogesh , Gandhi Sunil ,   Intern,   Hematologist and Oncologist, Cancer and Blood Disease Center, Lecanto, Florida
Published: October 2015

An accurate cancer diagnosis is critical as it can direct the use of site-directed, and potentially more effective, treatment options for specific types of cancer. A differential or uncertain diagnosis could prevent cancer patients from receiving optimal treatment, thus affecting their overall prognosis. Advances in molecular technology have led to the development of molecular cancer classifiers that can direct or confirm the diagnosis of metastatic cancers which would otherwise be considered uncertain or unknown. This case report describes the role of molecular diagnostics in the evaluation of a patient with a large pancreatic mass and a history of breast cancer. Results from a 92-gene molecular profiling assay (CancerTYPE ID®) predicted that this new mass was breast cancer. This diagnosis allowed for effective treatment and complete response in this patient.
Percutaneous Instrumentation of Pathologic Vertebral Fractures
Authors: Clarke Michelle J , Yassari Reza , Sciubba Daniel M , Rose Peter , Dekutoski Mark B ,   Assistant Professor of Neurosurgery, Department of Neurologic Surgery, Mayo Clinic,   Assistant Professor, Department of Neurosurgery, Albert Einstein College of Medicine,   Assistant Professor of Neurosurgery, Oncology and Orthopaedic Surgery, Department of Neurosurgery, Johns Hopkins University School of Medicine,   Assistant Professor of Orthopaedics, Department of Orthopaedics and Department of Pediatric and Adolescent Medicine, Mayo Clinic,   Assistant Professor of Orthopaedics, Department of Orthopaedics and Department of Pediatric and Adolescent Medicine, Mayo Clinic
Published: October 2015

Vertebral metastatic disease leading to pathologic compression fractures is becoming increasingly common as patients with cancer are surviving for longer. Pathologic compression fractures severely limit quality of life; pain is nearly universal, and neurologic deficits are also common. Traditional treatment options have been limited to non-operative modalities, cement augmentation, or large circumferential decompressive procedures. Percutaneous spinal fixation provides another less invasive option, and can be used as a stand-alone procedure or in conjunction with open or minimally invasive decompression. This procedure may improve the quality of life of patients who would be deemed poor surgical candidates due to short life expectancy or medical comorbidities precluding major surgery.
Cabazitaxel in the Management of Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel-based Chemotherapy
Authors: Heidenreich Axel , Pfister David ,   Chairman and Director,   Head Urologist, Conservative Uro-oncology, Department of Urology, RWTH Aachen University
Published: October 2015

Docetaxel is the guideline-recommended first-line chemotherapy in men with castration-resistant prostate cancer (CRPC). Despite its proven survival benefit, however, all patients will experience disease progression after a mean interval of six to eight months. Recently, the US Food and Drug Administration approved cabazitaxel and abiraterone acetate as effective second-line treatment options in this clinical scenario. Compared with mitoxantrone, cabazitaxel improves progression-free survival, overall survival, time to prostate surface antigen (PSA) progression, and time to metastatic progression. On the other hand, cabazitaxel is associated with a significantly higher frequency of grade 3/4 hematotoxic and gastrointestinal side effects than mitoxantrone. In experienced hands, and with the use of proactive therapeutic measures (weekly monitoring, adequate patient counselling, appropriate application of the guidelines on management and prophylaxis of neutropenia and diarrhea), all side effects can be handled easily without harming the patient, as has been shown recently by the analysis of the results of the German and European compassionate use programs. Cabazitaxel is one of the key components in the management of disease progression after docetaxel, and might be of benefit in men with high metastatic burden, rapid PSA doubling time, and minimal side effects during first-line docetaxel therapy.
Carfilzomib—A Selective Proteasome Inhibitor for the Treatment of Relapsed and/or Refractory Multiple Myeloma
Authors: Siegel David S , Vij Ravi , Niesvizky Ruben ,   Chief, Division of Multiple Myeloma, John Theurer Cancer Center, Hackensack University, Hackensack, New Jersey,   Associate Professor of Medicine, Washington University School of Medicine, St Louis, Missouri,   Director, Multiple Myeloma Center and Associate Professor of Medicine, Departments of Medicine and Hematology/Oncology, Weill Cornell Medical College, New York, NY, US
Published: October 2015

Multiple myeloma (MM) is a plasma cell malignancy characterized by overproduction of monoclonal immunoglobulins, hypercalcemia, renal injury, anemia, and osteolytic lesions. Despite markedly improved clinical outcomes since the introduction of first-generation immunomodulatory drugs and proteasome inhibitors, survival is very short in patients who relapse and are refractory to these therapies. Carfilzomib is a selective proteasome inhibitor currently being developed for the treatment of MM. In clinical studies, carfilzomib has achieved durable responses in relapsed and/or refractory MM and demonstrated acceptable tolerability with minimal peripheral neuropathy and no evidence of cumulative toxicity. Herein we summarize the key clinical data for single-agent carfilzomib in the relapsed and/or refractory disease setting and provide an overview of the current clinical development of the drug, both as monotherapy and in combinations.
Effects of Denosumab versus Zoledronic Acid in Patients with Castration-Resistant Prostate Cancer and Bone Metastases
Authors: Shore Neal , Goessl Carsten ,   Director and Certified Physician Investigator, Carolina Urologic Research Center, South Carolina, US,   Clinical Research Medical Director, Amgen Inc, California, US
Published: October 2015

Progression of castration-resistant prostate cancer often leads to bone metastases, increasing the risk of skeletal-related events (SREs). The use of antiresorptive therapies such as denosumab, a human monoclonal antibody and zoledronic acid (ZA), a bisphosphonate, reduces bone destruction by inhibiting osteoclast function and survival. In 2002, ZA was approved for the prevention of skeletal complications in patients with bone disease from myeloma or bone metastases from solid tumors including prostate cancer. Recently, efficacy analysis demonstrated superiority of denosumab to ZA for the prevention or delay of SREs in 1,901 patients with prostate cancer and bone metastases, significantly delaying the time to first SRE and time to first and subsequent SRE compared to ZA. Decreases in bone turnover markers were greater with denosumab, mirroring the reduction in SREs. The reported incidence of adverse events were similar between denosumab and ZA. Advanced prostate cancer patients require long-term disease management where maintenance of overall bone health is an essential component of a comprehensive treatment program.
Castrate-resistant Prostate Cancer—Recent Advances in Therapy and Future Perspectives
Authors: Koletsky Alan J ,   Affiliate Assistant Professor of Clinical Biomedical Science, Charles E Schmidt College of Medicine, Florida Atlantic University, FL, US.
Published: October 2015

For many years, few therapeutic options were available for the treatment of advanced prostate cancer. Recent advances in our understanding of the molecular biology of prostate cancer, particularly in the transition to castrate resistant disease, have led to the development of more potent and selective endocrine therapies. In addition, elucidation of the many factors in the bone microenvironment that promote the development and subsequent progression of skeletal metastases has led to the discovery of new bone-targeting agents that can delay the onset of skeletal related events and improve quality of life and survival. This review will highlight recently approved novel agents as well as others currently under investigation for the treatment of castrate-resistant prostate cancer (CRPC).
Hormone Therapy plus mTOR Inhibitors in the Treatment of Endometrial Carcinoma
Authors: Stringer Erica M , Fleming Gini F ,   University of Chicago Medical Center, Chicago, IL, US.,   University of Chicago Medical Center, Chicago, IL, US.
Published: October 2015

Hormonal therapies such as progestins have only modest activity in the treatment of advanced endometrial cancer. Mechanisms of resistance to progestin therapy are not well understood. However, activation of the PI3K/AKT/mTOR pathway has been associated with resistance to hormonal therapy and alterations in components of the PI3K/AKT/mTOR pathway, including inactivating mutations in PTEN, activating mutations in PIK3CA, and mutations in PIK3R1, are very common in endometrial carcinomas. mTOR inhibitors, including temsirolimus, everolimus, and ridaforolimus, are also known to be active against endometrial cancer, and interest has been stimulated in combinations of hormonal treatment with mTOR inhibitors, as both therapies have single-agent activity, and it is hypothesized that mTOR inhibition would enhance sensitivity to hormonal therapy.
Prognostic Implications of Cytogenetic Features in Myelodysplastic Syndromes
Authors: Belli Carolina B , Bestach Yesica , Kornblihtt Laura , Larripa Irene B ,   Laboratory of Hematological Genetics, Institute of Experimental Medicine (IMEX-CONICET)/National Academy of Medicine (ANM), Buenos Aires,   Assistant Researcher,   Laboratory of Hematological Genetics, Institute of Experimental Medicine (IMEX-CONICET)/National Academy of Medicine (ANM), Buenos Aires,   Doctoral Fellow,   Division of Hematology, Clinic Hospital, ‘J de San Martín’, University of Buenos Aires, Buenos Aires,   Hematologist,   Laboratory of Hematological Genetics, Institute of Experimental Medicine (IMEX-CONICET)/National Academy of Medicine (ANM), Buenos Aires,   Department of Genetics, Institute of Hematological Research (IIHEMA)/ANM, Buenos Aires, # = on behalf of the Argentine MDS Study Group, Argentine Society of Hematology, Argentine.,   Superior Researcher.
Published: October 2015

Myelodysplastic Syndromes (MDS) are a heterogeneous group of hematologic diseases characterized by refractory cytopenia(s) and variable risk of leukemic progression. Cytogenetic analysis is important in day-to-day clinical practice helping to define subgroups of MDS patients who share similarities in the course of the disease. There are recurring aberrations affecting chromosomes 5, 7, 8, and 20. While all of them do not suggest a therapeutic approach, their presence has been considered as a risk indicator since the original international prognostic scoring system (IPSS) was published. The most recent cytogenetic stratifications tried to find the prognostic significance of less frequent alterations which have been longer included in the intermediate group. Moreover, monitoring of karyotype changes is suggested to evaluate cytogenetic response to treatments and the acquisition of new aberrations associated to an unfavorable outcome. This review focuses on different cytogenetic risk stratifications that have been published during the past 20 years and the molecular background of the most relevant chromosomal findings.
Personalized Medicine—Some Things To Consider
Authors: Pipas J Marc , Lewis Lionel D , Ernstoff Marc S , Tsongalis Gregory J ,   Department of Medicine  Section of Hematology/Oncology,   Section of Clinical Pharmacology, Department of Medicine,   Department of Medicine – Section of Hematology/Oncology,   Department of Pathology; Geisel School of Medicine at Dartmouth, Hanover; DartmouthHitchcock Medical Center and The Norris Cotton Cancer Center, Lebanon, New Hampshire
Published: October 2015

The promise of individualized therapy has resonated with scientists, healthcare providers, and patients since the inception of the Human Genome Project. The ability to use designer drugs, such as novel monoclonal antibodies and molecularly targeted tyrosine kinase inhibitors, has created a new hope in the management of the cancer patient by individualizing therapy based on the unique molecular mutations in the cancer and the patients germline DNA. The nuances of implementing germline and somatic genomic testing in a clinical setting are discussed and the future role of pharmacogenomics testing in personalized cancer treatment is examined.
Chemotherapy-induced Nausea and Vomiting—Where We Stand Now
Authors: Wickham Rita ,   Adjunct Faculty, Rush College of Nursing, Chicago, Illinois
Published: October 2015

Chemotherapy-induced nausea and vomiting (CINV) has been a major supportive care concern since the development of cisplatin, which was probably the major factor that drove antiemetic research. If strategies, particularly using combination antiemetic therapy, had not been developed and studied, cancer chemotherapy research would also likely to have been stymied. The past 30 years or more have seen our understanding of the physiology of vomiting grow from the understanding of the medullary brain structures we call the chemoreceptor trigger zone and the vomiting center, as well as the neurotransmitters located about that site. The current view of chemotherapy-induced vomiting is that two main pathways are involveda peripheral pathway from the gut to the vomiting center that is mediated by increased release of serotonin by enterochromaffin cells in the gastrointestinal tract mucosa that binds to vagal terminals terminating in the nucleus tractus solitarius, and a central pathway in the brain that involves substance P binding at neurokinin 1 receptors near the vomiting center. Development of antiemetics that target these specific receptors, plus the use of dexamethasone, has resulted in prevention of acute vomiting in 7080 % of patients receiving highly emetogenic chemotherapy. The scientific evidence resulting from this antiemetic research, along with clinical application knowledge, forms the basis of current chemotherapy antiemetic guidelines. Although these are useful to clinical practice, they do no replace clinical assessment and follow up of individual patients. Furthermore, about half of patients receiving moderately or highly emetogenic chemotherapy experience distressing delayed nausea, which can alter a patient’s life activities, cause debilitating physical consequences, and interfere with their ability and willingness to undergo chemotherapy.
Gallbladder Cancer—Current Management Options
Authors: Ejaz Aslam , Sachs Teviah , Kamel Ihab R , Pawlik Timothy M ,   Research Fellow in Surgical Oncology, Division of Surgical Oncology, Department of Surgery,   Clinical Fellow in Surgical Oncology, Division of Surgical Oncology, Department of Surgery,   Professor of Radiology, Department of Radiology,   Chief, Division of Surgical Oncology; Professor of Surgery and Oncology; John L Cameron Professor of Alimentary Tract Surgery, Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, US
Published: October 2015

Carcinoma of the gallbladder is an aggressive disease, often with a poor prognosis. Although the incidence has remained relatively stable over the past decade, an increase in laparoscopic cholecystectomy has resulted in a increase in cases detected at earlier stages offering an opportunity for better prognosis. Diagnostic techniques including ultrasound (US), endoscopic US (EUS), computed tomography (CT) with multiplanar reconstruction, magnetic resonance imaging (MRI), positron emission tomography (PET), and diagnostic laparoscopy have evolved. Surgical resection to negative microscopic margins with lymphadenectomy offers the only chance for long-term survival. Adjuvant chemotherapy and radiation may be indicated in a subset of patients, and data have suggested a beneficial effect on overall survival. A multidisciplinary approach is required for the optimal management of this complex disease.
A Review of Liposomal Daunorubicin in the Treatment of Acute Leukemia
Authors: Klein Kim , Kaspers Gertjan L ,   Medical Doctor,   Professor and Head of Department of Pediatric Oncology, VU Medical Centre, Amsterdam, The Netherlands
Published: October 2015

Liposomal forms of anthracyclines, such as liposomal daunorubicin (L-DNR), have been developed in order to reduce the dose-limiting toxicity, especially cardiotoxicity. Efficacy and reduced toxicity of L-DNR have been demonstrated in severalin vitroand small phase I/II clinical studies. This has led to three recent randomized controlled trials in which efficacy and toxicity of L-DNR in acute myeloid leukemia (AML) patients was evaluated. In elderly, poor-risk AML patients, free DNR was compared with higher doses of L-DNR. This study demonstrated similar complete remission (CR) rates without increasing cardiotoxicity. Overall survival (OS) was slightly better in the L-DNR-arm, but when accounting for risk profiles the OS in the L-DNR arm was significantly better. In pediatric AML, induction therapy with L-DNR was compared with induction with idarubicin. Results showed similar event-free survival (EFS) and OS rates, but less cardiotoxicity with L-DNR. Subgroup analysis demonstrated better results of EFS and OS in core-binding factor AML with L-DNR. Reinduction therapy (fludarabine, cytarabine, granulocyte-colony stimulating factor ± L-DNR) in pediatric relapsed/refractory AML demonstrated higher CR rates in the L-DNR-arm. EFS and OS rates did not significantly improve in the L-DNR arm, but subgroup-analysis showed better results of EFS and OS in core-binding factor AML. The role of L-DNR also seems promising in patients with poor risk, relapsed/refractory ALL, apparently leading to higher CR rates and OS compared with standard regimes. But it should be noted that reports are scarce and no randomized controlled trials have been performed. This article demonstrates that L-DNR improves early treatment response in relapsed AML patients, or equal early treatment response in newly diagnosed AML compared with other anthracyclines, with similar or reduced toxicity. Higher dosages of L-DNR can be administered, without increasing (cardio)toxicity. Nevertheless, prognosis in refractory/ relapsed leukemia remains poor and identifying new therapeutic targets remains necessaryas well as optimization of treatment schedules with conventional agents, including L-DNR.
Management of Castration Refractory Prostate Cancer in Senior Adults
Authors: Boyle Helen Jane , Droz Jean-Pierre ,   Consultant, Department of Medical Oncology, Centre Léon-Bérard, Lyon, France,   Emeritus Professor Medical Oncology, Lyon-Est School of Medicine, Claude-Bernard Lyon 1 University, Lyon, France
Published: October 2015

Metastatic prostate cancer is frequent in elderly patients. Initial treatment is based on hormone-deprivation treatment. Resistance however occurs and several treatments have been developed and approved for castration-resistant prostate cancer, such as chemotherapy (docetaxel, cabazitaxel), new hormonal treatments (abiraterone, enzalutamide), and bone-targeting agents. These drugs have been studied in large phase III trials, and seem safe and effective even in older men; however, only fit elderly patients were enrolled in the pivotal trials.
Triple Negative Breast Cancer Pathologic Diagnosis and Current Chemotherapy Treatment Options
Authors: Rapoport Bernardo L , Nayler Simon , Demetriou Georgia S , Moodley Shun D , Benn Carol A ,   Specialist Physician and Medical Oncologist, The Medical Oncology Center of Rosebank, Johannesburg, South Africa,   Specialist Histopathologist, Gritzman and Thatcher Inc. and Wits Donald Gordon Medical Center, Johannesburg, South Africa,   Specialist Physician and Medical Oncologist, Department of Internal Medicine Division of Medical Oncology, University of the Witwatersrand and Wits Donald Gordon Medical Center, Johannesburg, South Africa,   Specialist Physician and Medical Oncologist, University of the Witwatersrand and Wits Donald Gordon Medical Center, Johannesburg, South Africa,   Specialist Surgeon, Netcare Milpark Hospital Breast Centre and Helen Joseph Hospital, University of the Witwatersrand, Johannesburg, South Africa
Published: October 2015

Triple negative breast cancer (TNBC) comprises 12–20 % of all breast cancers and are a heterogeneous group of tumors, both clinically and pathologically. These cancers are characterized by the lack of expression of the hormone receptors estrogen receptor (ER) and progesterone receptor (PR), combined with the lack of either overexpression or amplification of the human epidermal growth factor receptor-2(HER2)gene. Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay of treatment of this disease in the neoadjuvant, adjuvant, and metastatic setting. The lack of predictive markers in identifying potential targets for the treatment of TNBC has left a gap in directed therapy in these patients. Platinum agents have seen renewed interest in TNBC based on an increasing body of preclinical and clinical data suggesting encouraging activity. However, comparisons between chemotherapy regimens are mostly retrospective in nature and the best agents or drug combinations for TNBC have not been established in prospective randomized trials. Numerous studies have now shown that TNBC has significantly higher pathologic complete response (pCR) rates compared with hormone receptor positive breast cancer when treated with neoadjuvant chemotherapy, and pCR correlates well with better outcomes for these patients. Patients with TNBC account for a larger number of deaths in the setting of metastatic breast cancer. There is no preferred treatment for the first-line metastatic setting. Although individual agents are recommended, given the often aggressive nature of TNBC and the presence of extensive visceral disease, the use of a combination of drugs, rather than a single agent, is often advocated. This review article will outline the pathologic diagnosis of TNBC and the treatment options available to these patients in the neoadjuvant, adjuvant, and metastatic setting, including an assessment of future directions of treatment.
Combination of Hormone Therapy and Radiotherapy in Treatment of Locally Advanced Prostate Cancer—Recent Developments and Update
Authors: Huang Roger YC , Catton Charles N , Warde Padraig R ,   Radiation Oncology Fellow, Department of Radiation Oncology, Princess Margaret Hospital/University Health Network,   Professor, Department of Radiation Oncology, University of Toronto; Radiation Oncologist, Department of Radiation Oncology, Princess Margaret Hospital/University Health Network,   Professor, Department of Radiation Oncology, University of Toronto; Radiation Oncologist, Princess Margaret Hospital/University Health Network; Provincial Head, Radiation Treatment Program Cancer Care Ontario, Canada
Published: October 2015

Prostate cancer is the sixth leading cause of cancer death among men worldwide. Risk stratification is used to facilitate the selection of optimal treatment approach; however, there is a lack of consensus in the prostate cancer risk-stratification systems. Furthermore, the term ‘locally advanced’ is often misused with high-risk disease. This poses problems when interpreting clinical trials and evaluating treatment outcomes. As a result the patients studied in clinical trials represent a heterogeneous population. The current standard care for locally advanced prostate cancer is a combination of radiotherapy (RT) and androgen deprivation therapy (ADT) and this is supported by several large randomized clinical trials. Long-term ADT is recommended but the optimal duration remains to be better defined. The use of newer and more potent hormonal agents appears to be promising, at least in the setting of metastatic castration-resistant disease, but their role in locally advanced disease remains undefined. This article will summarize the available literature concerning the recent development of hormone therapy in reference to locally advanced prostate cancer. As for the future, individualization of treatment and personalized cancer care is the trend. The availability and the use of improved cellular and/or molecular markers to better risk stratify prostate cancer patients will allow us to select the most effective therapy to enhance the overall outcome.
Systemic Treatment for Gastrointestinal Stromal Tumor—A State of Art
Authors: Feng Xiaolan , Morris Don ,   Medical Oncology Fellow,   Associate Professor, Tom Baker Cancer Center, Cancer Control, Alberta Health Services, Calgary, Alberta, Canada
Published: October 2015

The availability of the tyrosine kinase inhibitor (TKI) small molecule imatinib has revolutionized the systemic treatment for gastrointestinal stromal tumor (GIST), historically one of the most chemoresistant solid malignancies. Prior to imatinib availability approximately 14 years ago, surgery was the only effective treatment modality. Imatinib is now accepted as the first-line systemic treatment for advanced GIST and subsequently has become the standard systemic treatment for GIST in the neoadjuvant and adjuvant settings. Sunitinib and regorafenib have been approved for second- and third-line treatments, respectively, for patients with advanced GIST progressing on imatinib. The dramatic and continuing efficacy of TKIs targeting oncogenic driver pathways such as KIT, platelet-derived growth factor receptor alpha (PDGFR〈), and vascular epithelial growth factor receptors (VEGFs), in advanced GIST supports the utility of targeted therapy in oncogene addicted solid malignancies. Molecular mutational diagnostics has further defined subpopulations of responders. Although significant gains have been made in the treatment of GIST patients, future research is still warranted to help further improve clinical outcomes of patients with GIST.
State of the Art in Locally Advanced and Recurrent Non-metastatic Prostate Cancer
Authors: Vankayala Hema , Vaishampayan Ulka ,   Medical Oncologist, John D Dingell VA Medical Center, Wayne State University, Detroit,   Professor of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, US
Published: October 2015

Prostate cancer (PC) is the second leading cause of cancer-related death in men in the US. Biochemical relapse is a significant problem, due to the eventual progression to metastatic disease. It is also an opportunity to explore interventions that may have the potential to prevent or delay the occurrence of metastases. Multiple therapies with diverse mechanisms of action have become available for use in metastatic castrateresistant PC and are currently under active investigation in the non-metastatic disease state. The intent of this article is to discuss currently approved therapy in localized and locally advanced PC and to review the state of the art in clinical management within this disease state. We also discuss the novel agents and targets in development, especially for recurrent, non-metastatic PC.
Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome in 2014—Current Knowledge and Outcomes with Plasma Exchange
Authors: Farah Myriam , Hildebrand Ainslie M , Huang Susan , Dammas Hassnah , Clark William F ,   Assistant Professor of Medicine, Division of Nephrology, University of British Columbia, and Nephrology Consultant, St Paul’s Hospital, Vancouver, British Columbia,, Canada,   Senior Fellow, Kidney Clinical Research Unit, Lawson Research Institute, London Health Science Centre, London, Ontario, Canada,   Assistant Professor of Medicine, Schulich School of Medicine, Western University and Nephrology Consultant, London Health Science Centre, London, Ontario, Canada,   Renal Fellow, Schulich School of Medicine, Western University, Canada,   Professor of Medicine and Clinician Scientist, Program of Experimental Medicine, Western University, Canada and Consultant Nephrologist and Director of Apheresis, London Health Science Centre, London, Ontario, Canada
Published: October 2015

Great progress has been made in our understanding of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome since Moschowitz first described this entity in 1925. This review provides a contemporary insight into the pathophysiology, diagnosis, and classification of these disorders in both adults and children. Lessons learned from major worldwide registry data and disease epidemics, including the 2011 German outbreak, are discussed with recommendations for management of specific clinical conditions based on available evidence, including the role of plasma exchange, rituximab, and eculizumab.
Current Status of Maintenance Therapy in Multiple Myeloma
Authors: Sevindik Omur , Kumar Shaji K ,   Fellow in Hematology, Department of Hematology, Dokuz Eylul University, Izmir, Turkey,   Professor of Medicine, Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, US
Published: October 2015

Despite the introduction of autologous hematopoietic stem cell transplant (AHSCT) and novel agents, myeloma is considered to be incurable. The majority of patients will have disease progression or relapse at some point after AHSCT or after the initial front-line therapy. The depth and duration of the response achieved after AHSCT or front-line therapy is closely related to the long-term outcomes. Trying to develop strategies in order to prevent or delay disease progression or relapse has resulted in the concepts of consolidation or maintenance. Initial maintenance attempts with single agent corticosteroids, interferon-〈, conventional chemotherapies, or a combination of these agents have shown a variably prolonged progression-free survival (PFS) but no benefit to overall survival (OS) with high toxicity rates. Maintenance approaches with a prolonged course of novel agents have improved PFS and OS to a certain degree with tolerable drug-related toxicities. Despite contradictory data, maintenance therapy with novel agents can be a reasonable approach for those patients who have failed to achieve at least very good partial response (VGPR) after AHSCT or front-line therapy, or for the patients presented with high-risk disease based on genetic abnormalities as well as other laboratory features. Here, we review the available data on the various maintenance strategies that have been evaluated in the setting of myeloma.
Chronic Myeloid Leukemia— What Else is there Beyond Protein Kinase Inhibitors?
Authors: Jabbour Elias ,   Associate Professor, Leukemia Department, MD Anderson Cancer Center, Houston, Texas, US
Published: October 2015

Chronic myeloid leukemia (CML) is induced by the BCR-ABL oncogene. The advent of BCR-ABL tyrosine kinase inhibitors (TKIs) has redefined treatment goals in CML starting with imatinib and followed by the newer TKI inhibitors including dasatinib, nilotinib, bosutinib, and ponatinib. However, a significant proportion of patients do not achieve a satisfactory response to TKIs and resistance remains an unmet need in the in the treatment of CML. Furthermore, disease eradication with TKIs may pose a significant challenge: minimal residual disease (MRD) remains detectable following treatment with these agents. Recently, several new molecular targets have been proposed in CML, and several drugs are in clinical development. Omacetaxine, a protein translation inhibitor, has shown the potential to substantially reduce MRD in animal models and has demonstrated clinical activity in phase II clinical trials regardless of patients’BCR-ABLT313I mutation status. The broad range of therapeutic effects associated with interferon may reduce resistance and relapse, and has resulted in a resurgence of interest in this therapy. In addition, several other therapeutic targets are currently undergoing clinical investigation.
PD-1 and PD-L1 Inhibitors in Advanced Non-small Cell Lung Cancer—Promising Agents and Evolving Questions
Authors: Sacher Adrian G , Gandhi Leena ,   Advanced Fellow in Thoracic Oncology,   Assistant Professor of Medicine Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute/Brigham and Womens Hospital and Harvard Medical School, Boston, Massachusetts, US
Published: October 2015

There exists increasing evidence that PD-1 and PD-L1 inhibitors may be effective in the treatment of non-small cell lung cancer (NSCLC) an unforeseen finding given the early failure of several immuno- and vaccine-based therapies in this field. This suggests that NSCLC is a more immunogenic tumor than initially appreciated and that it may manipulate various immune checkpoints in order to blunt a potential anti-tumor immune response. NSCLC has subsequently been shown to commonly overexpress PD-L1 as a means of suppressing such cell-mediated immune response through PD-1-mediated signaling. Numerous PD-1 and PD-L1 inhibitors are currently in development as well as various combinations of these inhibitors with chemotherapy, kinase inhibitors, and other immune checkpoint inhibitors. Although these treatments have demonstrated clinical activity in early phase clinical trials, reliable data on the impact of these agents on clinically meaningful endpoints in advanced NSCLC remains scarce. Important questions remain unanswered regarding the appropriate use of PD-L1 expression as a predictive biomarker for the use of these agents as well as the ability of the aforementioned drug combinations to achieve durable disease control.
Gastrointestinal Stromal Tumors (GIST)—Paving the Way for Modern Oncology—Epidemiology, Diagnosis, Treatment
Authors: Tsvetkova Elena , Marginean E Celia , Nessim Carolyn , Verma Shailendra ,   Medical Oncologist, Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada,   Associate Professor of Pathology, Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada,   Surgical Oncologist and Assistant Professor of Surgery, University of Ottawa; Clinician Investigator, Ottawa Hospital Research Institute, Ottawa General Hospital, Ontario, Canada,   Medical Oncologist, The Ottawa Hospital Cancer Centre and Associate Professor, Department of Medicine, University of Ottawa, Ontario, Canada
Published: October 2015

Gastrointestinal stromal tumors (GIST) are relatively rare tumors arising in the gastrointestinal tract. Clinical presentations of GIST are related to the site of origin, tumor size, and presence of ulceration. Surgery followed by adjuvant treatment with the BCR-ABL tyrosine kinase inhibitor, imatinib, for 3 years, in high-risk tumors is the only curative modality. Neoadjuvant treatment with imatinib may be considered in the setting of locally advanced primary borderline resectable/unresectable disease. Treatment with imatinib in patients with metastatic or unresectable disease is associated with significant improvements in overall survival (OS) from 18 to 57 months. In patients with metastatic disease, those responding to imatinib therapy may be considered for surgery and this may be beneficial if resection of the primary and metastatic disease is feasible and if imatinib is continued post resection. Other locoregional treatments such as radiofrequency ablation (RFA) and hepatic artery embolization (HAE) with or without chemotherapy may achieve long-lasting disease control and may be considered in highly selected patients. In patients with primary or secondary resistance to imatinib, second-line treatment with sunitinib and third-line treatment with regorafenib is recommended. However, despite all of these advances, few patients with metastatic disease are cured and further trials of novel agents or combinations are required.
Gastrointestinal Stromal Tumors (GIST)—Paving the Way for Modern Oncology—Epidemiology, Diagnosis, Treatment
Authors: Tsvetkova Elena , Marginean E Celia , Nessim Carolyn , Verma Shailendra ,   Medical Oncologist, Department of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada,   Associate Professor of Pathology, Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada,   Surgical Oncologist and Assistant Professor of Surgery, Univeristy of Ottawa; Clinician Investigator, Ottawa Hospital Research Institute, Ottawa General Hospital, Ontario, Canada,   Medical Oncologist, The Ottawa Hospital Cancer Centre and Associate Professor, Department of Medicine, University of Ottawa, Ontario, Canada
Published: October 2015

Gastrointestinal stromal tumors (GIST) are relatively rare tumors arising in the gastrointestinal tract. Clinical presentations of GIST are related to the site of origin, tumor size, and presence of ulceration. Surgery followed by adjuvant treatment with the BCR-ABL tyrosine kinase inhibitor, imatinib, for 3 years, in high-risk tumors is the only curative modality. Neoadjuvant treatment with imatinib may be considered in the setting of locally advanced primary borderline resectable/unresectable disease. Treatment with imatinib in patients with metastatic or unresectable disease is associated with significant improvements in overall survival (OS) from 18 to 57 months. In patients with metastatic disease, those responding to imatinib therapy may be considered for surgery and this may be beneficial if resection of the primary and metastatic disease is feasible and if imatinib is continued post resection. Other locoregional treatments such as radiofrequency ablation (RFA) and hepatic artery embolization (HAE) with or without chemotherapy may achieve long-lasting disease control and may be considered in highly selected patients. In patients with primary or secondary resistance to imatinib, second-line treatment with sunitinib and third-line treatment with regorafenib is recommended. However, despite all of these advances, few patients with metastatic disease are cured and further trials of novel agents or combinations are required.
Fibrates - The Other Life-saving Lipid Drugs
Authors: Fazio Sergio
Published: October 2015

The main controversy in the area of lipid management today is related to the usefulness of �non-statin� agents to maximize cardiovascular risk reduction in particular patient types, such as those with diabetes and metabolic syndrome. Fibrate drugs, such as gemfibrozil (Lopid) and fenofibrate (TriCor), are undoubtedly the best tools to address the condition characterized by high triglycerides, low high-density lipoprotein (HDL), and small dense low-density lipoprotein (LDL) (atherogenic dyslipidemia), but the most recent guidelines from both the American Diabetes Association (ADA) and the National Cholesterol Education Panel continue to focus on LDL control as the target of therapy.
Triglyceride Management in Cardiovascular Risk Reduction
Authors: Miller Michael
Published: October 2015

Elevated triglycerides are now considered an independent risk factor for coronary heart disease (CHD), even apart from elevated low-density lipoprotein (LDL) cholesterol. While the primary lipid target for CHD risk management remains LDL cholesterol, the treatment of elevated triglycerides is now also recommended. Elevated triglycerides are believed to increase cardiovascular risk because certain triglyceride-rich lipoproteins, called remnant lipoproteins (partially degraded chylomicrons and very-low density lipoproteins (VLDL)), are atherogenic. Hypertri-glyceridemia, together with low levels of high-density lipoprotein (HDL) cholesterol and an increased prevalence of small, dense LDL particles, comprise a triad of lipid risk factors known as atherogenic dyslipidemia.The significance of hypertriglyceridemia as a cardiovascular risk factor is further highlighted by its inclusion as a component of the metabolic syndrome, a cluster of metabolic abnormalities, related to insulin resistance. The other criteria for metabolic syndrome include low HDL cholesterol, central obesity, elevated blood pressure, and abnormal fasting glucose. The metabolic syndrome is recognized as a major risk factor not only for premature CHD but also for type 2 diabetes mellitus.