Science.gov

Sample records for advanced hematologic cancer

  1. Advances in hematology analyzers.

    PubMed

    DeNicola, Dennis B

    2011-05-01

    The complete blood count is one of the basic building blocks of the minimum database in veterinary medicine. Over the past 20 years, there has been a tremendous advancement in the technology of hematology analyzers and their availability to the general practitioner. There are 4 basic methodologies that can be used to generate data for a complete blood count: manual methods, quantitative buffy coat analysis, automated impedance analysis, and flow cytometric analysis. This article will review the principles of these methodologies, discuss some of their advantages and disadvantages, and describe some of the hematology analyzers that are available for the in-house veterinary laboratory. Copyright © 2011. Published by Elsevier Inc.

  2. Chemotherapy in Treating Patients With Refractory Advanced Solid Tumors or Hematologic Cancer

    ClinicalTrials.gov

    2013-06-20

    Bladder Cancer; Breast Cancer; Colorectal Cancer; Gastric Cancer; Head and Neck Cancer; Kidney Cancer; Leukemia; Lung Cancer; Melanoma (Skin); Ovarian Cancer; Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  3. DCB - Cancer Immunology, Hematology, and Etiology Research

    Cancer.gov

    Part of NCI’s Division of Cancer Biology’s research portfolio, studies supported include the characterization of basic mechanisms relevant to anti-tumor immune responses and hematologic malignancies.

  4. Advances in the treatment of hematologic malignancies using immunoconjugates

    PubMed Central

    Palanca-Wessels, Maria Corinna

    2014-01-01

    Monoclonal antibody therapy has revolutionized cancer treatment by significantly improving patient survival both in solid tumors and hematologic malignancies. Recent technological advances have increased the effectiveness of immunotherapy leading to its broader application in diverse treatment settings. Immunoconjugates (ICs) consist of a cytotoxic effector covalently linked to a monoclonal antibody that enables the targeted delivery of its therapeutic payload to tumors based on cell-surface receptor recognition. ICs are classified into 3 groups based on their effector type: immunotoxins (protein toxin), radioimmunoconjugates (radionuclide), and antibody drug conjugates (small-molecule drug). Optimization of each individual component of an IC (antibody, linker, and effector) is essential for therapeutic efficacy. Clinical trials have been conducted to investigate the effectiveness of ICs in hematologic malignancies both as monotherapy and in multiagent regimens in relapsed/refractory disease as well as frontline settings. These studies have yielded encouraging results particularly in lymphoma. ICs comprise an exciting group of therapeutics that promise to play an increasingly important role in the management of hematologic malignancies. PMID:24578502

  5. Drug Response and Resistance in Advanced NF-1-Associated Cancers

    DTIC Science & Technology

    2015-07-01

    hematologic improvement. Our controlled preclinical trials in Nf1 mutant mice stimulated clinical evaluation of MEK inhibitors for plexiform...spontaneously progress to AML (23). Shannon p. 3 Retroviral insertional mutagenesis (RIM) is a powerful strategy for generating hematologic cancers...executed preclinical trials in accurate mouse models of early stage and advanced hematologic cancers driven by Nf1 inactivation or oncogenic Kras

  6. Epigenetics in Cancer: A Hematological Perspective

    PubMed Central

    Stahl, Maximilian; Kim, Tae Kon; Zeidan, Amer M.; Prebet, Thomas

    2016-01-01

    For several decades, we have known that epigenetic regulation is disrupted in cancer. Recently, an increasing body of data suggests epigenetics might be an intersection of current cancer research trends: next generation sequencing, immunology, metabolomics, and cell aging. The new emphasis on epigenetics is also related to the increasing production of drugs capable of interfering with epigenetic mechanisms and able to trigger clinical responses in even advanced phase patients. In this review, we will use myeloid malignancies as proof of concept examples of how epigenetic mechanisms can trigger or promote oncogenesis. We will also show how epigenetic mechanisms are related to genetic aberrations, and how they affect other systems, like immune response. Finally, we will show how we can try to influence the fate of cancer cells with epigenetic therapy. PMID:27723796

  7. Cardiovascular and Hematological Medicine in 2013 - Advances and Insights.

    PubMed

    Mukherjee, Debabrata

    2012-12-11

    Welcome to the first issue of Cardiovascular & Hematological Agents in Medicinal Chemistry (CHAMC) for 2013. I hope everyone has had an enjoyable holiday season and I want to wish everyone a wonderful New Year. As you know, our journal (CHAMC) aims to cover the latest and outstanding developments in medicinal chemistry, rational drug design for the discovery of novel cardiovascular and hematological Agents and discusses such therapies in clinical practice. Each issue contains a series of timely in-depth reviews, original research articles and drug clinical trial studies written by leaders in the field covering a range of current topics in cardiovascular and hematological sciences. I feel that CHAMC is an essential journal for every medicinal chemist, clinician and healthcare provider who wishes to be kept informed and up-to-date with the latest and most important developments in cardiovascular and hematological drug discovery and their clinical uses. In the coming issues of the journal, we will discuss several important topics pertinent to chemists and clinicians in the cardiovascular and hematology fields such as curcumin and resveratrol as alternative medicinal agents against metabolic syndrome, interrelationship between chronic kidney disease and risk of cardiovascular diseases and effects of direct renin inhibitor, aliskiren, on arterial hypertension, chronic kidney disease and cardiovascular disease among others. The journal also delves into hot topics such as genetic testing and personalized medicine, use of literature-based discovery to identify novel therapeutic approaches, pharmacologic mechanism and clinical relevance of P2Y12 inhibitors and intracoronary injection of glycoprotein IIb/IIIa, abciximab, as adjuvant therapy in primary coronary intervention. Cardiovascular medicine and hematology are both very dynamic fields with rapid advances and we will continue to work to keep you up to date on new advances and therapies. I would also take this

  8. Femoral Resurfacing in Young Patients with Hematologic Cancer and Osteonecrosis

    PubMed Central

    Karimova, Evguenia J.; Rai, Shesh N.; Wu, Jianrong; Britton, Lunetha; Kaste, Sue C.

    2008-01-01

    Resurfacing hemiarthroplasties were performed to treat advanced osteonecrosis of 20 femoral heads in 14 patients (median age, 19.8 years; range, 15.1–27.4 years), treated for hematologic cancer in childhood or adolescence. Seven hips in five patients were revised to total hip arthroplasties (THA) because of pain; three of these showed radiographic loosening of the femoral head resurfacing component. The median time from resurfacing to revision was 2.4 years (range, 0.9–4.8 years). Marginal Cox-regression analysis, adjusting for correlations owing to bilateral involvement, showed positive association of revision-free survival of the prosthesis with patient’s age; time from resurfacing to the end of anticancer therapy, end of glucocorticosteroid therapy; percentage of joint space at the last radiograph; and size of the lesion has a negative association with revision-free survival. Because of this study’s exploratory nature, p values were not adjusted for the number of statistical comparisons. Among 14 patients, the probability of not requiring resurfacing prosthesis revision was 66% (SE, ±15%; 95% CI, 44%–100%) at 3 years. Osteonecrosis of the femoral head in young patients treated for hematologic cancer in childhood or adolescence poses a serious challenge to the orthopaedic surgeon. The data of this preliminary study suggest that in selected patients resurfacing hemiarthroplasty may delay the need for THA for 3–7 years. Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18679763

  9. Advanced mast cell disease: an Italian Hematological Multicenter experience.

    PubMed

    Pagano, Livio; Valentini, Caterina Giovanna; Caira, Morena; Rondoni, Michela; Van Lint, Maria Teresa; Candoni, Anna; Allione, Bernardino; Cattaneo, Chiara; Marbello, Laura; Caramatti, Cecilia; Pogliani, Enrico Maria; Iannitto, Emilio; Giona, Fiorina; Ferrara, Felicetto; Invernizzi, Rosangela; Fanci, Rosa; Lunghi, Monia; Fianchi, Luana; Sanpaolo, Grazia; Stefani, Pietro Maria; Pulsoni, Alessandro; Martinelli, Giovanni; Leone, Giuseppe; Musto, Pellegrino

    2008-12-01

    The aim of the study is to evaluate clinical features, treatments and outcome of patients with systemic mast cell disease (MCD) who arrived to the attention of hematologists. A retrospective study was conducted over 1995-2006 in patients admitted in 18 Italian hematological divisions. Twenty-four cases of advanced MCD were collected: 12 aggressive SM (50%), 8 mast cell leukemia (33%), 4 SM with associated clonal non-mast cell-lineage hematologic disease (17%). Spleen and liver were the principal extramedullary organ involved. The c-kit point mutation D816V was found in 13/18 patients in which molecular biology studies were performed (72%). Treatments were very heterogeneous: on the whole Imatinib was administered in 17 patients, alpha-Interferon in 8, 2-CdA in 3; 2 patients underwent allogeneic hematopoietic stem cell transplantation. The overall response rate to Imatinib, the most frequently employed drugs, was of 29%, registering one complete remission and four partial remission; all responsive patients did not present D816V c-kit mutation. Overall three patients (12%) died for progression of disease. We conclude that MCD is characterized by severe mediator-related symptoms but with a moderate mortality rate. D816V c-kit mutation is frequent and associated with resistance against Imatinib. Because of the rarity of these forms, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies.

  10. Advances in cellular technology in the hematology field: What have we learned so far?

    PubMed Central

    de Souza, Gustavo Torres; Maranduba, Claudinéia Pereira; de Souza, Camila Maurmann; do Amaral, Danielle Luciana Aurora Soares; da Guia, Francisco Carlos; Zanette, Rafaella de Souza Salomão; Rettore, João Vitor Paes; Rabelo, Natana Chaves; Nascimento, Lucas Mendes; Pinto, Ícaro França Navarro; Farani, Júlia Boechat; Neto, Abrahão Elias Hallack; Silva, Fernando de Sá; Maranduba, Carlos Magno da Costa; Atalla, Angelo

    2015-01-01

    Despite the advances in the hematology field, blood transfusion-related iatrogenesis is still a major issue to be considered during such procedures due to blood antigenic incompatibility. This places pluripotent stem cells as a possible ally in the production of more suitable blood products. The present review article aims to provide a comprehensive summary of the state-of-the-art concerning the differentiation of both embryonic stem cells and induced pluripotent stem cells to hematopoietic cell lines. Here, we review the most recently published protocols to achieve the production of blood cells for future application in hemotherapy, cancer therapy and basic research. PMID:25621110

  11. Epidemiology of venous thromboembolism in hematological cancers: The Scandinavian Thrombosis and Cancer (STAC) cohort.

    PubMed

    Gade, Inger Lise; Brækkan, Sigrid; Næss, Inger Anne; Hansen, John-Bjarne; Rosendaal, Frits; Cannegieter, Suzanne; Overvad, Kim; Jensvoll, Hilde; Hammerstrøm, Jens; Gran, Olga Vikhammer; Tjønneland, Anne; Kristensen, Søren Risom; Severinsen, Marianne Tang

    2017-09-05

    Venous thromboembolism (VTE) is an important cause of morbidity and mortality in cancer patients, however the risk of VTE differs according to cancer type. Hematological cancers have varying phenotypes. Incidence rates (IR) of VTE in different hematological cancer types have not been investigated in a cancer-exposed subset of the general population. In a population-based cohort, we estimated incidence rates of VTE among patients with six subtypes of hematological cancer and among age and sex matched reference subjects. During a mean follow-up of 4.8years, 30 objectively confirmed first-time symptomatic VTEs occurred among 838 subjects with hematological cancer. The IR of VTE was higher in all types of cancer except for indolent lymphoma but including chronic lymphocytic leukemia compared with reference subjects both during the first year after cancer diagnosis and 1-5years after diagnosis. IR of VTE for indolent lymphoma was not higher than controls. The IRs of VTE were increased in all types of hematological cancer (including chronic lymphocytic leukemia) compared with reference subjects except indolent lymphomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Nurses’ Health Study Contributions on the Epidemiology of Less Common Cancers: Endometrial, Ovarian, Pancreatic, and Hematologic

    PubMed Central

    Barnard, Mollie E.; Bertrand, Kimberly A.; Bao, Ying; Crous-Bou, Marta; Wolpin, Brian M.; De Vivo, Immaculata; Tworoger, Shelley S.

    2016-01-01

    Objectives. To review the contributions of the Nurses’ Health Study (NHS) to epidemiologic knowledge of endometrial, ovarian, pancreatic, and hematologic cancers. Methods. We reviewed selected NHS publications from 1976 to 2016, including publications from consortia and other pooled studies. Results. NHS studies on less common cancers have identified novel risk factors, such as a reduced risk of endometrial cancer in women of advanced age at last birth, and have clarified or prospectively confirmed previously reported associations, including an inverse association between tubal ligation and ovarian cancer. Through biomarker research, the NHS has furthered understanding of the pathogenesis of rare cancers, such as the role of altered metabolism in pancreatic cancer risk and survival. NHS investigations have also demonstrated the importance of the timing of exposure, such as the finding of a positive association of early life body fatness, but not of usual adult body mass index, with non-Hodgkin lymphoma risk. Conclusions. Evidence from the NHS has informed prevention strategies and contributed to improved survival from less common but often lethal malignancies, including endometrial, ovarian, pancreatic, and hematologic cancers. PMID:27459458

  13. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers.

    PubMed

    LaBelle, James L; Katz, Samuel G; Bird, Gregory H; Gavathiotis, Evripidis; Stewart, Michelle L; Lawrence, Chelsea; Fisher, Jill K; Godes, Marina; Pitter, Kenneth; Kung, Andrew L; Walensky, Loren D

    2012-06-01

    Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2-interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence-specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death.

  14. A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers

    PubMed Central

    LaBelle, James L.; Katz, Samuel G.; Bird, Gregory H.; Gavathiotis, Evripidis; Stewart, Michelle L.; Lawrence, Chelsea; Fisher, Jill K.; Godes, Marina; Pitter, Kenneth; Kung, Andrew L.; Walensky, Loren D.

    2012-01-01

    Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2–interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence–specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death. PMID:22622039

  15. Histone Deacetylase Inhibitors: Advancing Therapeutic Strategies in Hematological and Solid Malignancies

    PubMed Central

    Ellis, Leigh; Pili, Roberto

    2010-01-01

    Advancement in the understanding of cancer development in recent years has identified epigenetic abnormalities as a common factor in both tumorigenesis and refractory disease. One such event is the dysregulation of histone deacetylases (HDACs) in both hematological and solid tumors, and has consequently resulted in the development of HDAC inhibitors (HDACI) to overcome this. HDACI exhibit pleiotropic biological effects including inhibition of angiogenesis and the induction of autophagy and apoptosis. Although HDACI exhibit modest results as single agents in preclinical and clinical data, they often fall short, and therefore HDACI are most promising in combinational strategies with either standard treatments or with other experimental chemotherapies and targeted therapies. This review will discuss the induction of autophagy and apoptosis and the inhibition of angiogenesis by HDACI, and also pre-clinical and clinical combination strategies using these agents. PMID:21151768

  16. Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments.

    PubMed

    Horne, Gillian A; Copland, Mhairi

    2017-05-01

    Self-renewal is considered a defining property of stem cells. Self-renewal is essential in embryogenesis and normal tissue repair and homeostasis. However, in cancer, self-renewal pathways, e.g. WNT, NOTCH, Hedgehog and BMP, frequently become de-regulated in stem cells, or more mature progenitor cells acquire self-renewal properties, resulting in abnormal tissue growth and tumorigenesis. Areas covered: This review considers the conserved embryonic self-renewal pathways, including WNT, NOTCH, Hedgehog and BMP. The article describes recent advances in our understanding of these pathways in leukemia and, more specifically, leukemia stem cells (LSC), how these pathways cross-talk and interact with the LSC microenvironment, and discusses the clinical implications and potential therapeutic strategies, both in preclinical and in clinical trials for hematological malignancies. Expert opinion: The conserved embryonic self-renewal pathways are frequently de-regulated in cancer stem cells (CSC), including LSCs. There is significant cross-talk between self-renewal pathways, and their downstream targets, and the microenvironment. Effective targeting of these pathways is challenging due to cross-talk, and importantly, because these pathways are important for normal stem cells as well as CSC, adverse effects on normal tissues may mean a therapeutic window cannot be identified. Nonetheless, several agents targeting these pathways are currently in clinical trials in hematological malignancies.

  17. Nutritional status among pediatric cancer patients: a comparison between hematological malignancies and solid tumors.

    PubMed

    Tah, Pei Chien; Nik Shanita, Safii; Poh, Bee Koon

    2012-10-01

    This study aimed to compare the nutritional status of pediatric patients with hematological malignancies and solid tumors. A total of 74 pediatric cancer patients were assessed for anthropometric status, biochemical profiles, and dietary intake. The prevalence of undernutrition was higher among patients with solid tumors as reflected in their lower dietary intakes of energy and nutrients compared with patients with hematological malignancies. Adequate dietary intake is important for pediatric cancer patients, but nurses need to pay more attention to the diets of patients with solid tumors as compared with those with hematological malignancies. © 2012, Wiley Periodicals, Inc.

  18. TET proteins and 5-methylcytosine oxidation in hematological cancers

    PubMed Central

    An, Jungeun; Pastor, William A.; Ko, Myunggon; Rao, Anjana

    2015-01-01

    Summary DNA methylation has pivotal regulatory roles in mammalian development, retrotransposon silencing, genomic imprinting and X-chromosome inactivation. Cancer cells display highly dysregulated DNA methylation profiles characterized by global hypomethylation in conjunction with hypermethylation of promoter CpG islands (CGIs) that presumably lead to genome instability and aberrant expression of tumor suppressor genes or oncogenes. The recent discovery of Ten-Eleven-Translocation (TET) family dioxygenases that oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in DNA has led to profound progress in understanding the mechanism underlying DNA demethylation. Among the three TET genes, TET2 recurrently undergoes inactivating mutations in a wide range of myeloid and lymphoid malignancies. TET2 functions as a bona fide tumor suppressor particularly in the pathogenesis of myeloid malignancies resembling chronic myelomoncytic leukemia (CMML) and myelodysplastic syndromes (MDS) in human. Here we review diverse functions of TET proteins and the novel epigenetic marks that they generate in DNA methylation/demethylation dynamics and normal and malignant hematopoietic differentiation. The impact of TET2 inactivation in hematopoiesis and various mechanisms modulating the expression or activity of TET proteins are also discussed. Furthermore, we also present evidence that TET2 and TET3 collaborate to suppress aberrant hematopoiesis and hematopoietic transformation. A detailed understanding of the normal and pathological functions of TET proteins may provide new avenues to develop novel epigenetic therapies for treating hematological malignancies. PMID:25510268

  19. Dyspnea during Advanced Cancer

    MedlinePlus

    ... important in planning treatment. Treatment may be to control signs and symptoms of pleural effusion and improve quality of life. A malignant pleural effusion often occurs in cancer that is advanced , cannot be removed by surgery , or continues to ...

  20. Well-directed inclusion of hematology in African national cancer control plans.

    PubMed

    Weaver, Meaghann; Yao, Atteby J J; Renner, Lorna; Harif, Mhamed; Lam, Catherine G

    2017-07-01

    In the context of a convergent call for noncommunicable disease integration in the global agenda, recognizing cross-cutting needs and opportunities in national strategies across disease fields with shared priorities in low- and middle-income settings can enhance sustainable development approaches. We reviewed publicly available cancer control plans in Africa to evaluate for inclusion of hematology needs and shared service priorities. Pediatric data remain sparse in cancer control plans. While continental Africa represents incredible diversity, recognizing shared priorities and opportunity for collaboration between oncology and hematology services and across age groups may guide prioritized cancer control efforts and reduce programmatic redundancies in resource-limited settings. © 2017 Wiley Periodicals, Inc.

  1. Advances in colon cancer.

    PubMed

    Levin, Mark

    2003-06-01

    From May 29 to June 5, 2003, the American Society of Clinical Oncology held its 39th Annual Meeting in Chicago, Illinois, U.S.A. The meeting was devoted to the presentation of advances in clinical sciences, diagnosis, prevention and management of malignant disorders, and brings together investigators, clinicians, policy makers and other professionals interested in the science and impact of cancer worldwide. This report will be presented in two parts, the first focusing of colon cancer, and the second on breast cancer will be published in the next issue of Drug News & Perspectives.

  2. Coping with Advanced Cancer

    MedlinePlus

    ... of palliative care Coping with your feelings and getting support Advanced planning How to talk with friends and family about your cancer Looking for meaning in your life The booklet is meant to provide you with information and ways you can still have a control of your ...

  3. Pemetrexed in advanced colorectal cancer.

    PubMed

    Louvet, Christophe; de Gramont, Aimery

    2004-11-01

    Pemetrexed (Alimta) shows single-agent activity in advanced colorectal cancer. In two phase II studies in which patients received pemetrexed at 600 mg/m2 or 500 mg/m2 as first-line treatment for metastatic disease, objective response rates were 15.4% and 17.2%. These trials were conducted prior to supplementation with folic acid and vitamin B12, which markedly decreased the frequency of hematologic toxicities of pemetrexed; routine supplementation is now included in all clinical trials of the agent. The marked improvement in toxicity and tolerance with vitamin supplementation suggests the need to reexamine optimal dosing in pemetrexed combination schedules. In a National Surgical Adjuvant Breast and Bowel Project phase II trial in 54 patients with previously untreated advanced colorectal cancer, pemetrexed at 500 mg/m2 plus oxaliplatin (Eloxatin) at 120 mg/m2 every 21 days with folic acid/vitamin B12 supplementation resulted in an objective response of 23%. Three additionalpatients (5.6%) had unconfirmed partial response (partial response at one visit), and 27 patients (50%) had stable disease. Median progression-free survival was 5.3 months and median duration of response was 5.7 months; median overall survival was approximately 11.05 months. Grade 3/4 neutropenia was observed in only 17% of patients and treatment was well tolerated. A phase I/II study is under way to identify and assess the optimal combination of pemetrexed/irinotecan in second-line treatment of advanced colorectal cancer. Planned studies include a phase I study examining the combination of pemetrexed and oxaliplatin given every 2 weeks as first-line treatment, and a phase I/II trial to identify the optimal pemetrexed/ oxaliplatin dose in a 21-day schedule and to compare pemetrexed/ oxaliplatin with FOLFOX4 in first-line treatment of metastatic disease. All of these trials include vitamin supplementation. A phase III trial comparing the every-3-week pemetrexed/oxaliplatin regimen with FOLFOX4 as

  4. Body fat composition impacts the hematologic toxicities and pharmacokinetics of doxorubicin in Asian breast cancer patients.

    PubMed

    Wong, A L; Seng, K Y; Ong, E M; Wang, L Z; Oscar, H; Cordero, M T; Copones, R; Fan, L; Tan, S H; Goh, B C; Lee, S C

    2014-02-01

    Body surface area (BSA)-based dosing leads to wide inter-individual variations in drug pharmacokinetics and pharmacodynamics, whereas body composition has been shown to be a more robust determinant of efficacy and toxicity of certain chemotherapeutic agents. We correlated various parameters of body composition with doxorubicin pharmacokinetics and hematologic toxicities in Asian patients with locally advanced or metastatic breast cancer. Our analysis included 84 patients from two studies who received pre- or post-operative single-agent doxorubicin; pharmacokinetic parameters were available for 44 patients. Body composition parameters were derived from CT cross-sectional images and population pharmacokinetic analysis was conducted using mixed-effects modeling. Higher intra-abdominal fat volume and fat ratio (intra-abdominal:total abdominal fat volume) correlated with greater incidence of grade 4 leukopenia on cycle 1 day 15 (mean intra-abdominal fat volume: 97.4 ± 46.5 cm(3) vs 63.4 ± 30.9 cm(3), p = 0.014; mean fat ratio: 0.43 ± 0.11 vs 0.33 ± 0.09, p = 0.012, grade 4 vs grade 0-3 leukopenia). On subset analysis, this relationship was maintained even in underweight patients. Concordantly, there were positive correlations between doxorubicin AUC and intra-abdominal fat volume as well as total abdominal fat volume (r (2) = 0.324 and 0.262, respectively, all p < 0.001). BSA and muscle volume did not predict for doxorubicin pharmacokinetics or toxicities. High-intra-abdominal fat volume but not BSA predicted for greater doxorubicin exposure and hematologic toxicities, suggesting that body composition is superior to BSA in determining doxorubicin pharmacokinetics and pharmacodynamics. Body composition has an emerging role in chemotherapy dose determination.

  5. The risk of melanoma and hematologic cancers in patients with psoriasis.

    PubMed

    Reddy, Shivani P; Martires, Kathryn; Wu, Jashin J

    2017-04-01

    The risk of melanoma and hematologic cancers in patients with psoriasis is controversial. We sought to assess the risk of melanoma and hematologic cancers in patients with psoriasis, and the association with different treatments. We used case-control and retrospective cohort designs to determine melanoma or hematologic cancer risk in patients with psoriasis. Risk with treatment type was assessed using Fisher exact test. Patients with psoriasis had 1.53 times greater risk of developing a malignancy compared with patients without psoriasis (P < .01). There were no significant differences in malignancy risk among patients treated with topicals, phototherapy, systemics, or biologic agents. Patients with psoriasis and malignancy did not have significantly worse survival than patients without psoriasis. It is possible that patients developed malignancy subsequent to the follow-up time included in the study. Patients with psoriasis may experience an elevated risk of melanoma and hematologic cancers, compared with the general population. The risk is not increased by systemic or biologic psoriasis therapies. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  6. Alterations in the ribosomal machinery in cancer and hematologic disorders

    PubMed Central

    2012-01-01

    Ribosomes are essential components of the protein translation machinery and are composed of more than 80 unique large and small ribosomal proteins. Recent studies show that in addition to their roles in protein translation, ribosomal proteins are also involved in extra-ribosomal functions of DNA repair, apoptosis and cellular homeostasis. Consequently, alterations in the synthesis or functioning of ribosomal proteins can lead to various hematologic disorders. These include congenital anemias such as Diamond Blackfan anemia and Shwachman Diamond syndrome; both of which are associated with mutations in various ribosomal genes. Acquired uniallelic deletion of RPS14 gene has also been shown to lead to the 5q syndrome, a distinct subset of MDS associated with macrocytic anemia. Recent evidence shows that specific ribosomal proteins are overexpressed in liver, colon, prostate and other tumors. Ribosomal protein overexpression can promote tumorigenesis by interactions with the p53 tumor suppressor pathway and also by direct effects on various oncogenes. These data point to a broad role of ribosome protein alterations in hematologic and oncologic diseases. PMID:22709827

  7. Engagement of Patients With Advanced Cancer

    ClinicalTrials.gov

    2016-11-15

    End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

  8. Causes of death due to hematological and non-hematological cancers in 57 US patients with type 1 Gaucher Disease who were never treated with enzyme replacement therapy.

    PubMed

    Weinreb, Neal J; Lee, Robert E

    2013-01-01

    Patients with type 1 Gaucher disease (GD1) have increased risk of developing myeloma, other hematological cancers, hepatocellular carcinoma, and other solid tumors. Patient awareness of the GD1-cancer association causes anxiety and fear. Little is known about cancer as a cause of death in GD1, especially in patients never treated with GD1-specific therapies. Consequently, the effect of treatment on cancer mortality in GD1 patients is difficult to evaluate. In this review, starting with a population of 184 GD1 cases never treated, we annotate and analyze the causes of death of 57 GD1 patients who died of cancer. The proportional mortality ratio (PMR) for all malignancies in patients with GD1 is 1.57 (p = 0.0002), but it is much higher for myeloma (PMR = 9.66) and other hematological cancers, hepatocellular carcinoma, and kidney cancer (PMR = ≍4). However, deaths from colorectal and pancreatic cancers were not more frequent than expected, and deaths from lung, breast, gynecological, and prostate cancer occurred less than anticipated. Herein, we discuss whether GD1 is truly a hereditary cancer syndrome and the problem of comorbidities and cancer risk assessment, and we speculate as to whether the variability in death by cancer type might be attributable to biochemical sequelae of tumor cell and macrophage/stromal cell GBA1 mutation affecting signals for metastasis, the process most closely associated with cancer mortality.

  9. Hedgehog signaling in cancer stem cells: a focus on hematological cancers

    PubMed Central

    Campbell, Victoria; Copland, Mhairi

    2015-01-01

    The stem cell paradigm was first demonstrated in hematopoietic stem cells. Whilst classically it was cytokines and chemokines which were believed to control stem cell fate, more recently it has become apparent that the stem cell niche and highly conserved embryonic pathways play a key role in governing stem cell behavior. One of these pathways, the hedgehog signaling pathway, found in all organisms, is vitally important in embryogenesis, performing the function of patterning through early stages of development, and in adulthood, through the control of somatic stem cell numbers. In addition to these roles in health however, it has been found to be deregulated in a number of solid and hematological malignancies, components of the hedgehog pathway being associated with a poor prognosis. Further, these components represent viable therapeutic targets, with inhibition from a drug development perspective being readily achieved, making the hedgehog pathway an attractive potential therapeutic target. However, although the concept of cancer stem cells is well established, how these cells arise and the factors which influence their behavior are not yet fully understood. The role of the hedgehog signaling pathway and its potential as a therapeutic target in hematological malignancies is the focus of this review. PMID:25691811

  10. Clinical trials of dendritic cell-based cancer vaccines in hematologic malignancies

    PubMed Central

    Pyzer, Athalia R; Avigan, David E; Rosenblatt, Jacalyn

    2015-01-01

    The potential for the immune system to target hematological malignancies is demonstrated in the allogeneic transplant setting, where durable responses can be achieved. However, allogeneic transplantation is associated with significant morbidity and mortality related to graft versus host disease. Cancer immunotherapy has the capacity to direct a specific cytotoxic immune response against cancer cells, particularly residual cancer cells, in order to reduce the likelihood of disease relapse in a more targeted and tolerated manner. Ex vivo dendritic cells can be primed in various ways to present tumor associated antigen to the immune system, in the context of co-stimulatory molecules, eliciting a tumor specific cytotoxic response in patients. Several approaches to prime dendritic cells and overcome the immunosuppressive microenvironment have been evaluated in pre-clinical and early clinical trials with promising results. In this review, we summarize the clinical data evaluating dendritic cell based vaccines for the treatment of hematological malignancies. PMID:25625926

  11. Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort.

    PubMed

    Teras, Lauren R; Diver, W Ryan; Turner, Michelle C; Krewski, Daniel; Sahar, Liora; Ward, Elizabeth; Gapstur, Susan M

    2016-07-01

    Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer. The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148Bq/m(3)) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74Bq/m(3)) radon levels (HR=1.63, 95% CI:1.23-2.18), and there was evidence of a dose-response relationship (HRcontinuous=1.38, 95% CI:1.15-1.65 per 100Bq/m(3); p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Stem Cell Transplantation in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2012-05-31

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous/Nonmalignant Condition; Small Intestine Cancer

  13. Phase I Clinical, Pharmacokinetic, and Pharmacodynamic Study of the Akt-Inhibitor Triciribine Phosphate Monohydrate in Patients with Advanced Hematologic Malignancies

    PubMed Central

    Sampath, Deepa; Malik, Asifa; Plunkett, William; Nowak, Billie; Williams, Betsy; Burton, Michelle; Verstovsek, Srdan; Faderl, Stefan; Garcia-Manero, Guillermo; List, Alan F.; Sebti, Said; Kantarjian, Hagop M.; Ravandi, Farhad; Lancet, Jeffrey E.

    2013-01-01

    Akt, a serine/threonine protein kinase, is constitutively phosphorylated and hyperactivated in multiple cancers, including acute myeloid leukemia. High levels are linked to poor survival and inferior responses to chemotherapy, making Akt inhibition an attractive therapeutic target. In this phase I/II study of TCN-PM, a small-molecule Akt inhibitor, TCN-PM therapy was well tolerated in patients with advanced hematological malignancies, and reduced levels of phosphorylation of Akt and its substrate Bad were shown, consistent with inhibition of this survival pathway and induction of cell death. Further investigation of TCN-PM alone or in combination in patients with high Akt levels is warranted. PMID:23993427

  14. Complementary and alternative medicine use in patients with hematological cancers in Malaysia.

    PubMed

    Gan, G G; Leong, Y C; Bee, P C; Chin, E; Teh, A K H

    2015-08-01

    Complementary and alternative medicine (CAM) is often used by cancer patients, but not many studies had been published on the prevalence of CAM use in patients with hematological cancers. This study aims to determine the prevalence of CAM and type of CAM used in this group of patients in a multiracial and multicultural country. This is a cross-sectional survey carried out in two hospitals in Malaysia. Patients with underlying hematological cancers were asked to complete the questionnaires on CAM and the Hospital Anxiety and Depression Scale. A total of 245 patients participated. The prevalence of CAM use was 70.2 %. The most common types of CAM used are biological-based therapies (90.2 %) and mind-body interventions (42 %). Vitamin and diet supplements (68.6 %) and folk/herb remedies (58 %) are the most common biological-based therapies used. There is no significant association of CAM use with age, gender, education level, and household income. Female patients are more likely to use more than one CAM therapies. The most common reason reported for CAM use was to boost immunity (57 %) and cure (24 %). Majority of patients (65 %) felt CAM was effective, and 60 % did not inform their physicians regarding CAM usage. In view of the high prevalence of CAM use in patients with hematological cancers, it is important that the physicians play an active role in seeking information from patients and to monitor possible drug-vitamin-herbal interactions.

  15. Hope Herth Index (HHI): a validation study in Italian patients with solid and hematological malignancies on active cancer treatment.

    PubMed

    Ripamonti, Carla Ida; Buonaccorso, Loredana; Maruelli, Alice; Bandieri, Elena; Boldini, Stefania; Pessi, Maria Adelaide; Chiesi, Francesca; Miccinesi, Guido

    2012-01-01

    Although hope is a widely used term, the experience of hope in patients with chronic or even life-threatening diseases is often disregarded due to the scarcity of carefully designed and validated assessment tools. The aim of this study was to validate the Hope Herth Index (HHI) questionnaire in the Italian population of patients with solid or hematological malignancies during active cancer treatment. After the translation procedures, the psychometric properties of the Italian version of HHI were evaluated in 266 patients with non-advanced cancer cared for in four different settings. Summative scores ranged from 12-48, with a higher score denoting greater hope. Confirmative factorial analysis was performed to assess dimensionality. The test-retest reliability was assessed by means of the Lin concordance coefficient (two weeks' interval, 80 patients). Concurrent validity was assessed through the following questionnaires: Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp), Edmonton Symptom Assessment Scale (ESAS), and System Belief Inventory (SBI-15R). A total of 266 patients were enrolled. Confirmative factor analysis did not confirm the original three-factor solution, whereas a one-factor solution did perform well. Cronbach's alpha was 0.84 and the test-retest reliability was 0.64 (95% CI 0.51; 0.76). Large convergence was found with spiritual well-being as measured by the FACIT-Sp (0.69) and with anxiety-depression as measured by the HADS (inverse correlation: -0.51). Physical symptoms and religiousness were only slightly correlated, as expected. The Italian version of HHI is a valid and reliable assessment tool - useful to initiate conversation with someone who is troubled but finds it difficult to talk - in patients with either solid or hematological malignancies on active cancer treatment during the non-advanced stages of the disease.

  16. Recent Advances in Endometrial Cancer

    PubMed Central

    Tran, Arthur-Quan; Gehrig, Paola

    2017-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer. PMID:28184290

  17. Bloodstream infections in patients with hematological malignancies: which is more fatal – cancer or resistant pathogens?

    PubMed Central

    Gedik, Habip; Şimşek, Funda; Kantürk, Arzu; Yildirmak, Taner; Arica, Deniz; Aydin, Demet; Demirel, Naciye; Yokuş, Osman

    2014-01-01

    Background The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies. Methods In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward. Results During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in the second study year. In 13 of 18 cases (72%) with bloodstream yeast infections, previous azole exposure was recorded. Candida parapsilosis, C. glabrata, and C. albicans isolates were resistant to voriconazole and fluconazole. Conclusion BSIs that occur during febrile neutropenic episodes in hematology patients due to Gram-negative bacteria should be treated initially with non-carbapenem-based antipseudomonal therapy taking into consideration antimicrobial stewardship. Non-azole antifungal drugs, including caspofungin and liposomal amphotericin B, should be preferred as empirical antifungal therapy in the events of possible

  18. Childhood hematologic cancer and residential proximity to oil and gas development

    PubMed Central

    McKenzie, Lisa M.; Allshouse, William B.; Byers, Tim E.; Bedrick, Edward J.; Serdar, Berrin; Adgate, John L.

    2017-01-01

    Background Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Methods Participants were 0–24 years old, living in rural Colorado, and diagnosed with cancer between 2001–2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Findings Overall, ALL cases 0–24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5–24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0–4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Conclusion Because oil and gas development has potential to expose a large population

  19. Advanced Cancer Detection Center

    DTIC Science & Technology

    2000-10-01

    flSttfiferrces ReferentHistory Alternative Medicine Alternative and Complementary/Integrative Nutritional Therapies in Cancer Prevention and Treatment ...to meet a clear and compelling need to respond to Florida’s "cancer epidemic." Building a major cancer research and treatment center at the... Medicine . This Department includes all the basic science faculty recruited by the Cancer Center and will be the academic home for a new interdisciplinary

  20. Next-generation sequencing: advances and applications in cancer diagnosis

    PubMed Central

    Serratì, Simona; De Summa, Simona; Pilato, Brunella; Petriella, Daniela; Lacalamita, Rosanna; Tommasi, Stefania; Pinto, Rosamaria

    2016-01-01

    Technological advances have led to the introduction of next-generation sequencing (NGS) platforms in cancer investigation. NGS allows massive parallel sequencing that affords maximal tumor genomic assessment. NGS approaches are different, and concern DNA and RNA analysis. DNA sequencing includes whole-genome, whole-exome, and targeted sequencing, which focuses on a selection of genes of interest for a specific disease. RNA sequencing facilitates the detection of alternative gene-spliced transcripts, posttranscriptional modifications, gene fusion, mutations/single-nucleotide polymorphisms, small and long noncoding RNAs, and changes in gene expression. Most applications are in the cancer research field, but lately NGS technology has been revolutionizing cancer molecular diagnostics, due to the many advantages it offers compared to traditional methods. There is greater knowledge on solid cancer diagnostics, and recent interest has been shown also in the field of hematologic cancer. In this review, we report the latest data on NGS diagnostic/predictive clinical applications in solid and hematologic cancers. Moreover, since the amount of NGS data produced is very large and their interpretation is very complex, we briefly discuss two bioinformatic aspects, variant-calling accuracy and copy-number variation detection, which are gaining a lot of importance in cancer-diagnostic assessment. PMID:27980425

  1. Confirmation of the Reported Association of Clonal Chromosomal Mosaicism with an Increased Risk of Incident Hematologic Cancer

    PubMed Central

    Crane, Paul K.; Weston, Noah; Ehrlich, Kelly; Newton, Katherine M.; Wallace, Robert; Bookman, Ebony; Harrison, Tabitha; Aragaki, Aaron; Crosslin, David R.; Wang, Sophia S.; Reiner, Alex P.; Jackson, Rebecca D.; Peters, Ulrike; Larson, Eric B.; Jarvik, Gail P.; Carlson, Christopher S.

    2013-01-01

    Chromosomal abnormalities provide clinical utility in the diagnosis and treatment of hematologic malignancies, and may be predictive of malignant transformation in individuals without apparent clinical presentation of a hematologic cancer. In an effort to confirm previous reports of an association between clonal mosaicism and incident hematologic cancer, we applied the anomDetectBAF algorithm to call chromosomal anomalies in genotype data from previously conducted Genome Wide Association Studies (GWAS). The genotypes were initially collected from DNA derived from peripheral blood of 12,176 participants in the Group Health electronic Medical Records and Genomics study (eMERGE) and the Women’s Health Initiative (WHI). We detected clonal mosaicism in 169 individuals (1.4%) and large clonal mosaic events (>2 mb) in 117 (1.0%) individuals. Though only 9.5% of clonal mosaic carriers had an incident diagnosis of hematologic cancer (multiple myeloma, myelodysplastic syndrome, lymphoma, or leukemia), the carriers had a 5.5-fold increased risk (95% CI: 3.3–9.3; p-value = 7.5×10−11) of developing these cancers subsequently. Carriers of large mosaic anomalies showed particularly pronounced risk of subsequent leukemia (HR = 19.2, 95% CI: 8.9–41.6; p-value = 7.3×10−14). Thus we independently confirm the association between detectable clonal mosaicism and hematologic cancer found previously in two recent publications. PMID:23533652

  2. Advanced Cancer Detection Center

    DTIC Science & Technology

    1999-05-25

    Establish a center to expand cancer screening and education programs; find cancers in the population early enough to make a difference in morbidity and mortality; research and implement high quality, high technology, and cost effective communication delivery methods via telemedicine and teleconferencing; and implement basic science investigations of early genetic and biochemical transformations related to cancer that can be detected early in the disease process.

  3. Cancer Screening Among Patients With Advanced Cancer

    PubMed Central

    Sima, Camelia S.; Panageas, Katherine S.; Schrag, Deborah

    2013-01-01

    Context Cancer screening has been integrated into routine primary care but does not benefit patients with limited life expectancy. Objective To evaluate the extent to which patients with advanced cancer continue to be screened for new cancers. Design, Setting, and Participants Utilization of cancer screening procedures (mammography, Papanicolaou test, prostate-specific antigen [PSA], and lower gastrointestinal [GI] endoscopy) was assessed in 87 736 fee-for-service Medicare enrollees aged 65 years or older diagnosed with advanced lung, colorectal, pancreatic, gastroesophageal, or breast cancer between 1998 and 2005, and reported to one of the Surveillance, Epidemiology, and End Results (SEER) tumor registries. Participants were followed up until death or December 31, 2007, whichever came first. A group of 87 307 Medicare enrollees without cancer were individually matched by age, sex, race, and SEER registry to patients with cancer and observed over the same period to evaluate screening rates in context. Demographic and clinical characteristics associated with screening were also investigated. Main Outcome Measure For each cancer screening test, utilization rates were defined as the percentage of patients who were screened following the diagnosis of an incurable cancer. Results Among women following advanced cancer diagnosis compared with controls, at least 1 screening mammogram was received by 8.9% (95% confidence interval [CI], 8.6%-9.1%) vs 22.0% (95% CI, 21.7%-22.5%); Papanicolaou test screening was received by 5.8% (95% CI, 5.6%-6.1%) vs 12.5% (95% CI, 12.2%-12.8%). Among men following advanced cancer diagnosis compared with controls, PSA test was received by 15.0% (95% CI, 14.7%-15.3%) vs 27.2% (95% CI, 26.8%-27.6%). For all patients following advanced diagnosis compared with controls, lower GI endoscopy was received by 1.7% (95% CI, 1.6%-1.8%) vs 4.7% (95% CI, 4.6%-4.9%). Screening was more frequent among patients with a recent history of screening (16.2% [95

  4. Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

    2011-03-01

    Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving {>=}10 and 20 Gy (V{sub 10} and V{sub 20}) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V{sub 10} (regression coefficient ({beta}) = -0.060, p = 0.009) and V{sub 20} ({beta} = -0.044, p = 0.010). In the combined cohort, the (adjusted) {beta} estimates for log (white blood cell) vs. V{sub 10} and V{sub 20} were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V{sub 10} {>=} 95% were more likely to experience Grade {>=}3 leukopenia (68.8% vs. 24.6%, p < 0.001) than were patients with V{sub 20} > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V{sub 10} < 95% and V{sub 20} < 76% may reduce HT.

  5. Normal tissue complication probability modeling of acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy.

    PubMed

    Rose, Brent S; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M; Mundt, Arno J; Roeske, John C; Mell, Loren K

    2011-03-01

    To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving≥10 and 20 Gy (V10 and V20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V10 (regression coefficient (β)=-0.060, p=0.009) and V20 (β=-0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V10 and V20 were as follows: -0.022 (p=0.025) and -0.021 (p=0.002), respectively. Patients with V10≥95% were more likely to experience Grade≥3 leukopenia (68.8% vs. 24.6%, p<0.001) than were patients with V20>76% (57.7% vs. 21.8%, p=0.001). These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V10<95% and V20<76% may reduce HT. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. NORMAL TISSUE COMPLICATION PROBABILITY MODELING OF ACUTE HEMATOLOGIC TOXICITY IN CERVICAL CANCER PATIENTS TREATED WITH CHEMORADIOTHERAPY

    PubMed Central

    Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

    2009-01-01

    PURPOSE To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy (CRT), and to develop a normal tissue complication probability (NTCP) model for HT. METHODS AND MATERIALS We tested associations between hematologic nadirs during CRT and the volume of BM receiving ≥ 10 and 20 Gy (V10 and V20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with 37 identically treated patients from a prior study, forming a cohort of 81 patients for NTCP analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. RESULTS In the validation cohort, significant negative correlations were observed between white blood cell count (WBC) nadir and V10 (regression coefficient (β)=−0.060, p=0.009) and V20 (β=−0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log(WBC) vs. V10 and V20 were: −0.022 (p=0.025) and −0.021 (p=0.002), respectively. Patients with V10 ≥ 95% were more likely to experience grade ≥ 3 leukopenia (68.8% vs. 24.6%, p<0.001) as were patients with V20 > 76% (57.7% vs. 21.8%, p=0.001). CONCLUSIONS These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V10 < 95% and V20 < 76% may reduce HT. PMID:20400238

  7. Advanced Cancer Detection Center

    DTIC Science & Technology

    2007-10-01

    Cancer Treatment Affecting the Central Nervous System (HLMCC 0707) • Melatonin and sleep hygiene for the treatment of insomnia following cancer...Determinants of Diabetes in the Young. (PI: Jeffrey Krischer, Ph.D.) Moffitt Community Clinical Oncology Program Research Base (PI: Jeffrey Krischer

  8. Advances in Cancer Immunotherapy in Solid Tumors

    PubMed Central

    Menon, Smitha; Shin, Sarah; Dy, Grace

    2016-01-01

    Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field. PMID:27886124

  9. [Nutritional status in patients first hospital admissions service hematology National Cancer Institute].

    PubMed

    Baltazar Luna, E; Omaña Guzmán, L I; Ortiz Hernández, L; Ñamendis-Silva, S A; De Nicola Delfin, L

    2013-01-01

    To determine the nutritional status of patients admitted to hospital for the first time the hematology service and who have not received treatment for cancer, to know if the nutritional status assessed by the EGS-GP and serum albumin related mortality of patients A longitudinal, prospective, analytical. EGS-Through GP assessed the nutritional status of patients, we used SPSS 19.0 for data analysis. Evaluaron 119 patients, 52.1% female and 47.9% male. The most common diagnosis was non-Hodgkin lymphoma in 43.7%. According to the EGS-GP 50.4% of patients had some degree of malnutrition or was at risk of suffering of which: 31.1% had moderate and 19.3% had severe malnutrition. The 49.6% of patients had an adequate nutritional status. 30.3% of the patients who died, 37% had severe malnutrition and 50% severe decrease in albumin concentration. The prevalence of malnutrition in hematological patients treated at the National Cancer Institute of Mexico that have not received medical treatment was high. There is an association between nutritional status and mortality in this patient group. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  10. Advanced Prostate Cancer

    MedlinePlus

    ... if it has spread to: • Bones • Lungs • Liver • Brain • Lymph nodes outside the pelvis • Other organs You may be diagnosed with metastatic prostate cancer when you are first diagnosed, after having completed ...

  11. Body Image Discomfort of Adolescent and Young Adult Hematologic Cancer Survivors.

    PubMed

    Zucchetti, Giulia; Bellini, Simona; Bertolotti, Marina; Bona, Francesca; Biasin, Eleonora; Bertorello, Nicoletta; Tirtei, Elisa; Fagioli, Franca

    2017-01-23

    This study focuses on body image discomfort (BID) of 50 adolescent and young adult (AYA) hematologic cancer survivors (age range 15-23; 52% males). The study results were obtained through data from a self-report questionnaire: the Body Uneasiness Test. Findings differed according to gender: a greater proportion of females were in the Risk category of impaired body image than males (χ(2) = 5.258, p < 0.05). No significant body image differences were found according to the type of diagnosis or to the length of survival. To manage survivors' BIDs and to improve their quality of life, assessing BID in AYA cancer survivors is important for identifying those who might be in need of additional supportive care or a program.

  12. [Therapeutic advances in breast cancer].

    PubMed

    Pestalozzi, B C

    2006-04-01

    The treatment of breast cancer has made significant improvements during the past ten years. For early breast cancer with a clinically negative axilla sentinel node biopsy has become the preferred approach. For endocrine therapy of postmenopausal patients the selective aromatase inhibitors have become standard in metastatic as well as in early breast cancer. Trastuzumab (Herceptin) plays an important role in the treatment of HER2-positive breast cancer in the metastatic and since 2005 also in the adjuvant setting. When chemotherapy is used to treat metastatic breast cancer drug combinations are superior to monotherapy only in terms of response rates. By contrast, in the adjuvant setting combination drug therapy is the standard. New methods of tissue analysis including expression patterns of mRNA and proteins are promising research strategies to further advance the field.

  13. Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

    ClinicalTrials.gov

    2017-09-05

    Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

  14. Advances in cancer immunology and cancer immunotherapy.

    PubMed

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models.

  15. Recent Advances in Management of Laryngeal Cancer

    PubMed Central

    2004-01-01

    Laryngeal cancers account for approximately 1.5% (1~2%) of the total cancers in Korea, and 30% of all head and neck cancers, not including thyroid cancer. Early laryngeal cancer is treated by operation, including transoral laser excision or radiotherapy. Advanced laryngeal cancer has been treated with mutilating operations, such as a total laryngectomy. However, a laryngeal preserving approach, which can improve the quality of life, has recently been tried with advanced laryngeal cancer. PMID:20396561

  16. The role of residence near hazardous waste sites containing benzene in the development of hematologic cancers in upstate New York.

    PubMed

    Boberg, Erik; Lessner, Lawrence; Carpenter, David O

    2011-12-01

    Epidemiologic studies suggest an association between environmental exposure to benzene and hematologic cancers, but the relationship is not firmly established. The aim of this study was to assess the potential association between residence near hazardous waste sites containing benzene and hospitalization discharge rates for persons having hematologic cancers. We determined the number of hospital discharges of people with hematologic cancers in New York State except for New York City for the years 1993 to 2008.Descriptive statistics and negative binomial regression models were used to compare the rates of hospitalization of residents in zip codes containing hazardous waste sites containing benzene to the rates of discharges from residents in zip codes without waste sites. When adjusting for potential confounders we found a 15% increase in the rate of hospitalization for chronic lymphatic leukemia (CLL) [rate ratio (RR): 1.15; 95% confidence interval (CI): 1.00-1.33], a 22% increase in the rate of discharges for total leukemia (RR: 1.22; 95% CI: 1.04-1.43) and a 17% increase in the rate of discharges for total lymphoma (RR: 1.17; 95% CI: 1.02-1.35) in the benzene exposed sites. We found greater effects of exposure in African Americans compared to Caucasians, females compared to males and people with higher socioeconomic status (SES) compared to those with lower SES for several of the diseases studied. After controlling for major confounders we found statistically significant increases in discharge rates for several hematologic cancers in persons residing in zip codes containing benzene waste sites. These results provide additional support for a relationship between environmental exposure to benzene and risk of hematologic cancers.

  17. The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies.

    PubMed

    Chon, Hae J; Bae, Kyoung J; Lee, Yura; Kim, Jiyeon

    2015-01-01

    The casein kinase 2 (CK2) protein kinase is a pro-survival kinase and therapeutic target in treatment of various human cancers. CK2 overexpression has been demonstrated in hematological malignancies, including chronic lymphocytic leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and multiple myeloma. CX-4945, also known as Silmitasertib, is an orally administered, highly specific, ATP-competitive inhibitor of CK2. CX-4945 induces cytotoxicity and apoptosis and is currently being evaluated in clinical trials for treatment of many cancer types. In the past 2 years, the focus on the therapeutic potential of CX-4945 has shifted from solid tumors to hematological malignancies. CX-4945 exerts anti-proliferative effects in hematological tumors by downregulating CK2 expression and suppressing activation of CK2-mediated PI3K/Akt/mTOR signaling pathways. Furthermore, combination of CX-4945 with other inhibitors yielded synergistic effects in cell death induction. These new findings demonstrate that CK2 overexpression contributes to blood cancer cell survival and resistance to chemotherapy. Combinatorial use of CX-4945 is a promising therapeutic tool for treatment of hematological malignancies.

  18. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies

    PubMed Central

    Choudary, Iqra; Barr, Paul M.; Friedberg, Jonathan

    2015-01-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential. PMID:26622997

  19. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies.

    PubMed

    Choudary, Iqra; Barr, Paul M; Friedberg, Jonathan

    2015-12-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential.

  20. Hematologic Toxicity in RTOG 0418: A Phase 2 Study of Postoperative IMRT for Gynecologic Cancer

    SciTech Connect

    Klopp, Ann H.; Moughan, Jennifer; Portelance, Lorraine; Miller, Brigitte E.; Salehpour, Mohammad R.; Hildebrandt, Evangeline; Nuanjing, Jenny; D'Souza, David; Souhami, Luis; Small, William; Gaur, Rakesh; Jhingran, Anuja

    2013-05-01

    Purpose: Intensity modulated radiation therapy (IMRT), compared with conventional 4-field treatment, can reduce the volume of bone marrow irradiated. Pelvic bone marrow sparing has produced a clinically significant reduction in hematologic toxicity (HT). This analysis investigated HT in Radiation Therapy Oncology Group (RTOG) 0418, a prospective study to test the feasibility of delivering postoperative IMRT for cervical and endometrial cancer in a multiinstitutional setting. Methods and Materials: Patients in the RTOG 0418 study were treated with postoperative IMRT to 50.4 Gy to the pelvic lymphatics and vagina. Endometrial cancer patients received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin (40 mg/m{sup 2}). Pelvic bone marrow was defined within the treatment field by using a computed tomography density-based autocontouring algorithm. The volume of bone marrow receiving 10, 20, 30, and 40 Gy and the median dose to bone marrow were correlated with HT, graded by Common Terminology Criteria for Adverse Events, version 3.0, criteria. Results: Eighty-three patients were eligible for analysis (43 with endometrial cancer and 40 with cervical cancer). Patients with cervical cancer treated with weekly cisplatin and pelvic IMRT had grades 1-5 HT (23%, 33%, 25%, 0%, and 0% of patients, respectively). Among patients with cervical cancer, 83% received 5 or more cycles of cisplatin, and 90% received at least 4 cycles of cisplatin. The median percentage volume of bone marrow receiving 10, 20, 30, and 40 Gy in all 83 patients, respectively, was 96%, 84%, 61%, and 37%. Among cervical cancer patients with a V40 >37%, 75% had grade 2 or higher HT compared with 40% of patients with a V40 less than or equal to 37% (P =.025). Cervical cancer patients with a median bone marrow dose of >34.2 Gy also had higher rates of grade ≥2 HT than did those with a dose of ≤34.2 Gy (74% vs 43%, P=.049). Conclusions: Pelvic IMRT with weekly cisplatin is

  1. Impact of Bone Marrow Radiation Dose on Acute Hematologic Toxicity in Cervical Cancer: Principal Component Analysis on High Dimensional Data

    SciTech Connect

    Yun Liang; Messer, Karen; Rose, Brent S.; Lewis, John H.; Jiang, Steve B.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2010-11-01

    Purpose: To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods and Materials: The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results: We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R{sup 2}, 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions: We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing.

  2. Impact of bone marrow radiation dose on acute hematologic toxicity in cervical cancer: principal component analysis on high dimensional data.

    PubMed

    Liang, Yun; Messer, Karen; Rose, Brent S; Lewis, John H; Jiang, Steve B; Yashar, Catheryn M; Mundt, Arno J; Mell, Loren K

    2010-11-01

    To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. The study included 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count nadir during treatment was used as the indicator for acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template, followed by dose remapping using deformable image registration, resulting in a dose array. Principal component (PC) analysis was applied to the dose array, and the significant eigenvectors were identified by linear regression on the PCs. The coefficients for PC regression and significant eigenvectors were represented in three dimensions to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. We identified five PCs associated with acute hematologic toxicity. PC analysis regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R(2), 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Childhood cancer survivorship educational resources in North American pediatric hematology/oncology fellowship training programs: a survey study.

    PubMed

    Nathan, Paul C; Schiffman, Joshua D; Huang, Sujuan; Landier, Wendy; Bhatia, Smita; Eshelman-Kent, Debra; Wright, Jennifer; Oeffinger, Kevin C; Hudson, Melissa M

    2011-12-15

    Childhood cancer survivors require life-long care by clinicians with an understanding of the specific risks arising from the prior cancer and its therapy. We surveyed North American pediatric hematology/oncology training programs to evaluate their resources and capacity for educating medical trainees about survivorship. An Internet survey was sent to training program directors and long-term follow-up clinic (LTFU) directors at the 56 US and Canadian centers with pediatric hematology/oncology fellowship programs. Perceptions regarding barriers to and optimal methods of delivering survivorship education were compared among training program and LTFU clinic directors. Responses were received from 45/56 institutions of which 37/45 (82%) programs require that pediatric hematology/oncology fellows complete a mandatory rotation focused on survivorship. The rotation is 4 weeks or less in 21 programs. Most (36/45; 80%) offer didactic lectures on survivorship as part of their training curriculum, and these are considered mandatory for pediatric hematology/oncology fellows at 26/36 (72.2%). Only 10 programs (22%) provide training to medical specialty trainees other than pediatric hematology/oncology fellows. Respondents identified lack of time for trainees to spend learning about late effects as the most significant barrier to providing survivorship teaching. LTFU clinic directors were more likely than training program directors to identify lack of interest in survivorship among trainees and survivorship not being a formal or expected part of the fellowship training program as barriers. The results of this survey highlight the need to establish standard training requirements to promote the achievement of basic survivorship competencies by pediatric hematology/oncology fellows. Copyright © 2011 Wiley Periodicals, Inc.

  4. Hematologic disorders of fish.

    PubMed

    Clauss, Tonya M; Dove, Alistair D M; Arnold, Jill E

    2008-09-01

    Hematology can be a useful tool for monitoring health status, detecting illness, and following the progress of disease and response to therapy. Despite advances in fish medicine in recent years, interpretation of fish hematology often is hampered by a lack of meaningful reference values and the bewildering diversity of fish species. A multitude of intrinsic and extrinsic factors cause normal and abnormal variation in hematologic data. This article provides an overview of some of the hematologic abnormalities in fish induced by infectious agents and environmental, husbandry, and nutritional issues.

  5. Hematologic malignancies in South Africa 2000-2006: analysis of data reported to the National Cancer Registry.

    PubMed

    Schonfeld, Sara J; Erdmann, Friederike; Wiggill, Tracey; Singh, Elvira; Kellett, Patricia; Babb, Chantal; Schüz, Joachim

    2016-04-01

    Little is known about the incidence patterns of hematologic malignancies in Sub-Saharan Africa, including South Africa. We estimated incidence rates of pathology-confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and 2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender-specific age-standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20-50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set-up of the NCR (pathology-based) could lead to some degree of under-ascertainment in all groups. This is the first country-wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer-related health care. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy

    PubMed Central

    2013-01-01

    Introduction Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center. Methods This was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent. Results We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm3 (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1–1133 mg/L; minimum concentration, 0.47–37.65 mg/L; volume of distribution, 0.08–0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42–27.25 L/h (mean, 9.93 L/h); half-life (t1/2), 0.55–2.65 h (mean, 1.38 h); and area under the curve, 115.12–827.16 mg · h/L. Conclusion Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1/2 and decreased CL. PMID:24286231

  7. Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy.

    PubMed

    Álvarez, José C; Cuervo, Sonia I; Garzón, Javier R; Gómez, Julio C; Díaz, Jorge Augusto; Silva, Edelberto; Sánchez, Ricardo; Cortés, Jorge A

    2013-11-28

    Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center. This was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent. We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm³ (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1-1133 mg/L; minimum concentration, 0.47-37.65 mg/L; volume of distribution, 0.08-0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42-27.25 L/h (mean, 9.93 L/h); half-life (t(1/2)), 0.55-2.65 h (mean, 1.38 h); and area under the curve, 115.12-827.16 mg · h/L. Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1(/2) and decreased CL.

  8. One-unit versus two-unit cord-blood transplantation for hematologic cancers.

    PubMed

    Wagner, John E; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R; Wall, Donna A; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R; Walters, Mark; Horowitz, Mary M; Kurtzberg, Joanne

    2014-10-30

    Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the

  9. Rationing cancer care: a survey among the members of the german society of hematology and oncology.

    PubMed

    Krause, Stefan W; Schildmann, Jan; Lotze, Christian; Winkler, Eva C

    2013-06-01

    Rising costs of cancer care and the growing burden of cancer in a world of finite resources seem to make rationing in oncology inevitable. Information is currently lacking about oncologists' strategies in responding to resource constraints and the prevalence of withholding costly treatments. An online survey was offered via e-mail to physician members of the German Society of Hematology and Oncology. Those actively practicing were asked to complete an online questionnaire asking how limited resources were currently affecting their clinical practice. Two-thirds of 345 participating oncologists reported withholding costly treatments in at least some instances. Regarding their rationale, 70% stated that evidence for costly intervention was not convincing enough, and 59% said that they rationed approved treatments because of an unfavorable cost/benefit calculation. Only 29% reported being explicit about their rationing decision if the patient did not know or inquire about the respective intervention. Withholding expensive procedures from individual patients was widespread among the respondents. Oncologists withheld treatments not only if they perceived the scientific evidence to be questionable but also if they perceived reimbursement prospects or the cost/benefit ratio to be unfavorable, a behavior that could be called rationing. Currently this mostly refers to costly procedures with limited additional benefits. Although this result may be interpreted as indicating that oncologists assume responsibility for spending the resources in a justified way, more transparency and an open discussion on cost-effectiveness and the just allocation of costly treatments is needed.

  10. The presence of wild type p53 in hematological cancers improves the efficacy of combinational therapy targeting metabolism.

    PubMed

    Allende-Vega, Nerea; Krzywinska, Ewelina; Orecchioni, Stefania; Lopez-Royuela, Nuria; Reggiani, Francesca; Talarico, Giovanna; Rossi, Jean-François; Rossignol, Rodrigue; Hicheri, Yosr; Cartron, Guillaume; Bertolini, Francesco; Villalba, Martin

    2015-08-07

    Manipulation of metabolic pathways in hematological cancers has therapeutic potential. Here, we determined the molecular mechanism of action of the metabolic modulator dichloroacetate (DCA) in leukemic cells. We found that DCA induces the AMP-activated protein kinase (AMPK)/p53 pathway with increased efficacy in tumors expressing wild type (wt p53). Clinically relevant, low concentrations of doxorubicin synergize in vitro and in vivo with DCA to further enhance p53 activation and to block tumor progression. Leukemia cell lines and primary leukemic cells containing mutant p53 are resistant to the above-described combination approach. However, DCA synergized with the Hsp90 inhibitor 17-AAG to specifically eliminate these cells. Our studies strongly indicate that depending on the p53 status, different combination therapies would provide better treatment with decreased side effects in hematological cancers.

  11. Identification of Anti-tumor Cells Carrying Natural Killer (NK) Cell Antigens in Patients With Hematological Cancers.

    PubMed

    Krzywinska, Ewelina; Allende-Vega, Nerea; Cornillon, Amelie; Vo, Dang-Nghiem; Cayrefourcq, Laure; Panabieres, Catherine; Vilches, Carlos; Déchanet-Merville, Julie; Hicheri, Yosr; Rossi, Jean-François; Cartron, Guillaume; Villalba, Martin

    2015-10-01

    Natural killer (NK) cells, a cytotoxic lymphocyte lineage, are able to kill tumor cells in vitro and in mouse models. However, whether these cells display an anti-tumor activity in cancer patients has not been demonstrated. Here we have addressed this issue in patients with several hematological cancers. We found a population of highly activated CD56(dim)CD16(+) NK cells that have recently degranulated, evidence of killing activity, and it is absent in healthy donors. A high percentage of these cells expressed natural killer cell p46-related protein (NKp46), natural-killer group 2, member D (NKG2D) and killer inhibitory receptors (KIRs) and a low percentage expressed NKG2A and CD94. They are also characterized by a high metabolic activity and active proliferation. Notably, we found that activated NK cells from hematological cancer patients have non-NK tumor cell antigens on their surface, evidence of trogocytosis during tumor cell killing. Finally, we found that these activated NK cells are distinguished by their CD45RA(+)RO(+) phenotype, as opposed to non-activated cells in patients or in healthy donors displaying a CD45RA(+)RO(-) phenotype similar to naïve T cells. In summary, we show that CD45RA(+)RO(+) cells, which resemble a unique NK population, have recognized tumor cells and degranulate in patients with hematological neoplasias.

  12. Identification of Anti-tumor Cells Carrying Natural Killer (NK) Cell Antigens in Patients With Hematological Cancers

    PubMed Central

    Krzywinska, Ewelina; Allende-Vega, Nerea; Cornillon, Amelie; Vo, Dang-Nghiem; Cayrefourcq, Laure; Panabieres, Catherine; Vilches, Carlos; Déchanet-Merville, Julie; Hicheri, Yosr; Rossi, Jean-François; Cartron, Guillaume; Villalba, Martin

    2015-01-01

    Natural killer (NK) cells, a cytotoxic lymphocyte lineage, are able to kill tumor cells in vitro and in mouse models. However, whether these cells display an anti-tumor activity in cancer patients has not been demonstrated. Here we have addressed this issue in patients with several hematological cancers. We found a population of highly activated CD56dimCD16+ NK cells that have recently degranulated, evidence of killing activity, and it is absent in healthy donors. A high percentage of these cells expressed natural killer cell p46-related protein (NKp46), natural-killer group 2, member D (NKG2D) and killer inhibitory receptors (KIRs) and a low percentage expressed NKG2A and CD94. They are also characterized by a high metabolic activity and active proliferation. Notably, we found that activated NK cells from hematological cancer patients have non-NK tumor cell antigens on their surface, evidence of trogocytosis during tumor cell killing. Finally, we found that these activated NK cells are distinguished by their CD45RA+RO+ phenotype, as opposed to non-activated cells in patients or in healthy donors displaying a CD45RA+RO− phenotype similar to naïve T cells. In summary, we show that CD45RA+RO+ cells, which resemble a unique NK population, have recognized tumor cells and degranulate in patients with hematological neoplasias. PMID:26629531

  13. Correlation between bone marrow dose volumes and acute hematological toxicity in postoperative gynecological cancer patients

    PubMed Central

    Li, Qian; Jiang, Ming-Hua; Chen, Jing; Liu, Wei; Zhu, Bi-Qing; Lu, E-Mei

    2016-01-01

    Objective: To identify the association between radiation dose volume and acute hematological toxicity (HT) in postoperative gynecological cancer patients receiving whole pelvic radiotherapy (RT) or intensity-modulated RT (IMRT), a principal component regression model was used to calculate HT. Methods: Women (n=100) receiving with or without chemotherapy RT were retrospectively analyzed, 52 of whom received chemotherapy (paclitaxel and nedaplatin). The pelvis and lumbar vertebrae, defined as the prolong-pelvic bone marrow, were divided into the (1) combined ilium, ischium and pubis and the (2) lumbar vertebrae and the sacrum. The V5-V40 of subsides was calculated. The complete blood counts were recorded weekly. The principal component analysis was performed on volumes which generated the principal components (PCs), followed by using a logistic regression model. Results: Forty-seven patients presented with grade 2-3 HT during RT. Chemotherapy increased the incidence of HT compared with RT alone (70.21% vs. 29.79%; p=0.001). Fifty-three patients with persistent HT developed more serious HT at an earlier stage of RT. The chemotherapy cycles and three PCs associated with grade 2-3 HT was identified to form the resulting principal logistic regression model. Conclusion: A new method to calculate the NTCP was achieved by PCs logistic regression. PMID:28083062

  14. Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers

    PubMed Central

    Muralidharan, Sujatha; Sasi, Sharath P.; Zuriaga, Maria A.; Hirschi, Karen K.; Porada, Christopher D.; Coleman, Matthew A.; Walsh, Kenneth X.; Yan, Xinhua; Goukassian, David A.

    2015-01-01

    Exposure of individuals to ionizing radiation (IR), as in the case of astronauts exploring space or radiotherapy cancer patients, increases their risk of developing secondary cancers and other health-related problems. Bone marrow (BM), the site in the body where hematopoietic stem cell (HSC) self-renewal and differentiation to mature blood cells occurs, is extremely sensitive to low-dose IR, including irradiation by high-charge and high-energy particles. Low-dose IR induces DNA damage and persistent oxidative stress in the BM hematopoietic cells. Inefficient DNA repair processes in HSC and early hematopoietic progenitors can lead to an accumulation of mutations whereas long-lasting oxidative stress can impair hematopoiesis itself, thereby causing long-term damage to hematopoietic cells in the BM niche. We report here that low-dose 1H- and 56Fe-IR significantly decreased the hematopoietic early and late multipotent progenitor (E- and L-MPP, respectively) cell numbers in mouse BM over a period of up to 10 months after exposure. Both 1H- and 56Fe-IR increased the expression of pluripotent stem cell markers Sox2, Nanog, and Oct4 in L-MPPs and 10 months post-IR exposure. We postulate that low doses of 1H- and 56Fe-IR may induce endogenous cellular reprogramming of BM hematopoietic progenitor cells to assume a more primitive pluripotent phenotype and that IR-induced oxidative DNA damage may lead to mutations in these BM progenitors. This could then be propagated to successive cell lineages. Persistent impairment of BM progenitor cell populations can disrupt hematopoietic homeostasis and lead to hematologic disorders, and these findings warrant further mechanistic studies into the effects of low-dose IR on the functional capacity of BM-derived hematopoietic cells including their self-renewal and pluripotency. PMID:26528440

  15. Ionizing Particle Radiation as a Modulator of Endogenous Bone Marrow Cell Reprogramming: Implications for Hematological Cancers.

    PubMed

    Muralidharan, Sujatha; Sasi, Sharath P; Zuriaga, Maria A; Hirschi, Karen K; Porada, Christopher D; Coleman, Matthew A; Walsh, Kenneth X; Yan, Xinhua; Goukassian, David A

    2015-01-01

    Exposure of individuals to ionizing radiation (IR), as in the case of astronauts exploring space or radiotherapy cancer patients, increases their risk of developing secondary cancers and other health-related problems. Bone marrow (BM), the site in the body where hematopoietic stem cell (HSC) self-renewal and differentiation to mature blood cells occurs, is extremely sensitive to low-dose IR, including irradiation by high-charge and high-energy particles. Low-dose IR induces DNA damage and persistent oxidative stress in the BM hematopoietic cells. Inefficient DNA repair processes in HSC and early hematopoietic progenitors can lead to an accumulation of mutations whereas long-lasting oxidative stress can impair hematopoiesis itself, thereby causing long-term damage to hematopoietic cells in the BM niche. We report here that low-dose (1)H- and (56)Fe-IR significantly decreased the hematopoietic early and late multipotent progenitor (E- and L-MPP, respectively) cell numbers in mouse BM over a period of up to 10 months after exposure. Both (1)H- and (56)Fe-IR increased the expression of pluripotent stem cell markers Sox2, Nanog, and Oct4 in L-MPPs and 10 months post-IR exposure. We postulate that low doses of (1)H- and (56)Fe-IR may induce endogenous cellular reprogramming of BM hematopoietic progenitor cells to assume a more primitive pluripotent phenotype and that IR-induced oxidative DNA damage may lead to mutations in these BM progenitors. This could then be propagated to successive cell lineages. Persistent impairment of BM progenitor cell populations can disrupt hematopoietic homeostasis and lead to hematologic disorders, and these findings warrant further mechanistic studies into the effects of low-dose IR on the functional capacity of BM-derived hematopoietic cells including their self-renewal and pluripotency.

  16. Advancing Public Health in Cancer - Annual Plan

    Cancer.gov

    Cancer is the leading cause of death from disease among Americans under 85. Learn how NCI advances public health by conducting research to improve the delivery of quality cancer prevention, screening, and treatment to all Americans.

  17. Genetically Engineered Immunotherapy for Advanced Cancer

    Cancer.gov

    In this trial, doctors will collect T lymphocytes from patients with advanced mesothelin-expressing cancer and genetically engineer them to recognize mesothelin. The gene-engineered cells will be multiplied and infused into the patient to fight the cancer

  18. Hematology Glossary

    MedlinePlus

    ... Navigation Account Navigation Main Content American Society of Hematology ASH Store ASH Job Center ASH Apps Share ... Links Advocacy Toolkit Home For Patients Blood Basics Hematology Glossary Jump To: A acute: refers to a ...

  19. Patient dignity inventory (PDI) questionnaire: the validation study in Italian patients with solid and hematological cancers on active oncological treatments.

    PubMed

    Ripamonti, Carla Ida; Buonaccorso, Loredana; Maruelli, Alice; Bandieri, Elena; Pessi, M Adelaide; Boldini, Stefania; Primi, Caterina; Miccinesi, Guido

    2012-01-01

    In Oncology, little is known about dignity-related distress and the issues that influence the sense of dignity for patients. We validated the Patient Dignity Inventory (PDI) questionnaire in Italian patients on oncological active treatments. After the translation procedures, the PDI was administered to 266 patients along with other questionnaires to assess the psychometric properties of the Italian version of PDI. Factor structure was tested by both explorative and confirmatory factor analyses. Concurrent validity was tested through convergent and divergent validity with validated questionnaires inquiring about physical and psychological symptoms, and religiosity. The test/retest reliability was assessed through the concordance coefficient of Linn (two-week interval, 80 patients). The explorative analysis suggested one factor only loading highly on all the 25 items (>.45) and explaining the 48% variance; confirmative analysis and Cronbach alpha (0.96) confirmed the adequacy of the one-factor model. In the 2-week test-retest study, a concordance coefficient of 0.73 (95% CI, 0.64-0.83) was found. High correlations of problems with dignity were found with both physical and psychological symptoms (0.52 and 0.64 rho coefficient, respectively), and a moderate inverse correlation with spiritual well being (-.40). The dignity construct, as measured by PDI, proved to be orthogonal to that of religiosity (-.02). The Italian version of PDI is a valid and reliable tool to evaluate the dignity related-distress in out-patients with solid and hematological cancers, on active oncological treatments, in non advanced stages of the disease.

  20. Common symptoms in advanced cancer.

    PubMed

    Lagman, Ruth L; Davis, Mellar P; LeGrand, Susan B; Walsh, Declan

    2005-04-01

    The key points of this article are anorexia and cachexia are: A major cause of cancer deaths. Several drugs are available to treat anorexia and cachexia. Dyspnea in cancer usually is caused by several factors. Treatment consists of reversing underlying causes, empiric bronchodilators, cortico-steroids--and in the terminally ill patients-opioids, benzodiazepines,and chlorpromazine. Delirium is associated with advanced cancer. Empiric treatment with neuroleptics while evaluating for reversible causes is a reasonable approach to management. Nausea and vomiting are caused by extra-abdominal factors (drugs,electrolyte abnormalities, central nervous system metastases) or intra-abdominal factors (gastroparesis, ileus, gastric outlet obstruction, bowel obstruction). The pattern of nausea and vomiting differs depending upon whether the cause is extra- or intra-abdominal. Reversible causes should be sought and empiric metoclopramide or haloperidol should be initiated. Fatigue may be caused by anemia, depression, endocrine abnormalities,or electrolyte disturbances that should be treated before using empiric methylphenidate. Constipation should be treated with laxatives and stool softeners. Both should start with the first opioid dose.

  1. Cancer-related Fatigue in Patients with Advanced Cancer Treated with Autonomic Nerve Pharmacopuncture.

    PubMed

    Park, Ji-hye; Jeon, Hyung-jun; Kang, Hwi-joong; Jeong, In-Sook; Cho, Chong-kwan; Yoo, Hwa-seung

    2015-06-01

    The purpose of this study was to observe the effects of autonomic nerve pharmacopuncture (ANP) treatment on cancer-related fatigue (CRF) in patients with advanced cancer. This observational case study was conducted at the East West Cancer Center of Daejeon University's Dunsan Korean Medical Hospital. Two patients were observed. One patient was diagnosed with left thymic cancer metastatic to the left pleura. The other patient had terminal-stage cervical cancer with iliac bone and lumbar 5 metastases. We injected mountain ginseng pharmacopuncture (MGP) into acupoints alongside the spine (Hua-Tuo-Jia-Ji-Xue, EX B2). We examined the patients for CRF using the Korean version of the Revised Piper Fatigue Scale (RPFS-K), which is a self-assessment tool. The scores on the RPFS-K for both patients tended to decrease during the treatment. Laboratory findings, including hematological changes, were also checked. Liver and renal function tests showed that the treatment was safe. Although further large-population studies are necessary, this case study suggests that ANP has a favorable effect on CRF in patients with advanced cancer.

  2. Molecular and clinical profiles of syndecan-1 in solid and hematological cancer for prognosis and precision medicine

    PubMed Central

    Akl, Mohamed R.; Nagpal, Poonam; Ayoub, Nehad M.; Prabhu, Sathyen A.; Gliksman, Matthew; Tai, Betty; Hatipoglu, Ahmet; Goy, Andre; Suh, K. Stephen

    2015-01-01

    Syndecan-1 (SDC1, CD138) is a key cell surface adhesion molecule essential for maintaining cell morphology and interaction with the surrounding microenvironment. Deregulation of SDC1 contributes to cancer progression by promoting cell proliferation, metastasis, invasion and angiogenesis, and is associated with relapse through chemoresistance. SDC1 expression level is also associated with responses to chemotherapy and with prognosis in multiple solid and hematological cancers, including multiple myeloma and Hodgkin lymphoma. At the tissue level, the expression levels of SDC1 and the released extracellular domain of SDC1 correlate with tumor malignancy, phenotype, and metastatic potential for both solid and hematological tumors in a tissue-specific manner. The SDC1 expression profile varies among cancer types, but the differential expression signatures between normal and cancer cells in epithelial and stromal compartments are directly associated with aggressiveness of tumors and patient's clinical outcome and survival. Therefore, relevant biomarkers of SDC signaling may be useful for selecting patients that would most likely respond to a particular therapy at the time of diagnosis or perhaps for predicting relapse. In addition, the reciprocal expression signature of SDC between tumor epithelial and stromal compartments may have synergistic value for patient selection and the prediction of clinical outcome. PMID:26293675

  3. Aminoglutethimide in advanced breast cancer.

    PubMed

    Ceci, G; Passalacqua, R; Bisagni, G; Bella, M; Cocconi, G

    1985-10-31

    From July 1980 to June 1983, 61 postmenopausal women with progressive metastatic breast cancer were treated with aminoglutethimide, 250 mg 4 times daily, plus cortisone acetate, 25 mg twice daily. Of 51 evaluable patients, an objective remission was observed in 22 (43%) (partial remission in 19, complete in 3), stable disease in 14 (27%), and progressive disease in 15 (30%). The median duration of response was 60 weeks (range 12+; 94+). The response rate was higher when the dominant disease site was soft tissue (50%) or bone (56%) rather than viscera (29%). Side effects were common but usually slight and transient. Somnolence (69%), dizziness (41%), nausea (35%) and skin rash (27%) were the most frequent. Serum levels of gamma-GT, alkaline phosphatase and total cholesterol rose during aminoglutethimide treatment, whereas levels of uric acid and indirect bilirubin decreased. Aminoglutethimide plus cortisone acetate appears to be an active and relatively safe treatment in advanced breast cancer and may be recommended as second-line endocrine treatment.

  4. [Chemoradiotherapy for locally advanced cervical cancer].

    PubMed

    Bazaeva, I Ia; Gorbunova, V A; Kravets, O A; Khokhlova, S V; Limareva, S V; Panov, V O; Strel'tsova, O N; Tarachkova, E V

    2014-01-01

    Cervical cancer takes second place in morbidity and third place in mortality from gynecological cancer. Advanced stages among newly diagnosed cases is still large. The "gold standard" of treatment for locally advanced cervical cancer is chemoradiotherapy with cisplatin that results in a lower risk of death. Improvement of radiotherapy methods allowed to bring optimal dose to the primary tumor with the inclusion of regional metastasis areas with less risk of damage to surrounding healthy tissue and organs. The search for alternative combinations of cytostatics, modes of drug administration, adjuvant chemotherapy after chemoradiotherapy showed an increase in survival of patients with locally advanced cervical cancer.

  5. Advances in Hereditary Colorectal and Pancreatic Cancers.

    PubMed

    Underhill, Meghan L; Germansky, Katharine A; Yurgelun, Matthew B

    2016-07-01

    Innovations in genetic medicine have led to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer. This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer. This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of new genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed. Given the availability of new diagnostic, risk-reducing, and therapeutic strategies that exist for patients with hereditary risk of colorectal or pancreatic cancer, it is imperative that clinicians be vigilant about evaluating patients for hereditary cancer syndromes. Continuing to advance genetics research in hereditary gastrointestinal cancers will allow for more progress to be made in personalized medicine and prevention. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  6. Advances in cancer research. Volume 54

    SciTech Connect

    Vande Woude, G.F. ); Klein, G. )

    1990-01-01

    This book contains articles pertaining to Advances in Cancer Research. Included are the following groups: (1) The Role of DNA Methylation in Cancer, (2) Genetic and Epigenetic Losses of Heterozygosity in Cancer Predisposition and Progression, (3) Genetic and Molecular Studies of Cellular Immortalization.

  7. [Treatment of advanced gastric cancer with oxaliplatin plus 5-fluorouracil/ leucovorin (FOLFOX-4 chemotherapy)].

    PubMed

    Garrido, Marcelo; Melgoza, Geraldine; Galindo, Héctor; Madrid, Jorge; Sánchez, César; Nervi, Bruno; Alvarez, Manuel; Orellana, Eric

    2007-11-01

    Chemotherapy improves survival in advanced gastric cancer. However the most active combinations have a high level of toxicity that limits their use. To assess the response, toxicity and survival of patients with advanced gastric cancer, treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4 chemotherapy). Patients with stage IV gastric cancer, according to the American Joint Committee on Cancer or with relapsed disease and functional capacity 0-2 of the South West Oncology Group, were included. FOLFOX-4 chemotherapy was used as first or second line treatment. The response to treatment and survival were assessed. Between 2003 and 2006, 29 patients (median age 52.5 years, 69% males) were treated. FOLFOX-4 was given as first line treatment in 65% patients and as second line in 35%. There was a complete response in 4.6%, partial response in 68%, stable disease in 20.6% and progression in 6.8%. Toxicity was observed in 51% of patients, that was hematological and non hematological grade 3/4 in 14%. Median survival was 12.5 months. FOLFOX-4 chemotherapy was active in advanced gastric cancer and had a low level of toxicity.

  8. Chemotherapy for advanced gastric cancer.

    PubMed

    Wagner, Anna Dorothea; Syn, Nicholas Lx; Moehler, Markus; Grothe, Wilfried; Yong, Wei Peng; Tai, Bee-Choo; Ho, Jingshan; Unverzagt, Susanne

    2017-08-29

    Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen. To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs). We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer. Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is

  9. Exploring correlations between positive psychological resources and symptoms of psychological distress among hematological cancer patients: a cross-sectional study.

    PubMed

    Wang, Zi-Yue; Liu, Li; Shi, Meng; Wang, Lie

    2016-07-01

    Hematological cancer patients experience high levels of psychological distress during diagnoses and intensive treatments. The aim of the present study is to explore the effects of positive psychological resources on depressive and anxiety symptoms in hematological cancer patients. This survey was conducted in a hospital during the period from July 2013 to April 2014. A total of 300 inpatients were recruited and finally 227 of them completed the questionnaires. Questionnaires included demographic and clinical variables, the Center for Epidemiologic Studies Depression Scale, the Self-Rating Anxiety Scale, the Life Orientation Scale-Revised, the General Perceived Self-Efficacy Scale, and the Resilience Scale-14. Results showed that the prevalence of depressive and anxiety symptoms was 66.1 and 45.8%, respectively. Both optimism (β = -.479, p < .001) and resilience (β = -.174, p < .05) were negatively associated with depressive symptoms, and optimism (β = -.393, p < .001) was negatively associated with anxiety symptoms. However, resilience (β = -.133, p > .05) was not significantly associated with anxiety symptoms, and self-efficacy was not significantly associated with depressive (β = -.032, p > .05) or anxiety symptoms (β = -.055, p > .05). The results suggest that hematological cancer patients who possess high levels of positive psychological resources may have fewer symptoms of psychological distress. The findings indicate that enhancing positive psychological resources can be considered in developing intervention strategies for decreasing depressive and anxiety symptoms.

  10. Healing environments in cancer treatment and care. Relations of space and practice in hematological cancer treatment.

    PubMed

    Høybye, Mette Terp

    2013-02-01

    Given the growing attention to the importance of design in shaping healing hospital environments this study extends the understanding of healing environments, beyond causal links between environmental exposure and health outcome by elucidating how environments and practices interrelate. The study was conducted as an ethnographic fieldwork from March 2011 to September 2011 at the Department of Haematology at Odense University Hospital, Denmark, systematically using participant observation and interviews as research strategies. It included 20 patients, four of who were followed closely over an extended time period. Through thematic analysis five key concepts emerged about the social dynamics of hospital environments: practices of self; creating personal space; social recognition; negotiating space; and ambiguity of space and care. Through these concepts, the study demonstrates how the hospital environment is a flow of relations between space and practice that changes and challenges a structural idea of design and healing. Patients' sense of healing changes with the experience of progression in treatment and the capacity of the hospital space to incite an experience of homeliness and care. Furthermore, cancer patients continuously challenge the use and limits of space by individual objects and practices of privacy and home. Healing environments are complex relations between practices, space and care, where recognition of the individual patient's needs, values and experiences is key to developing the environment to support the patient quality of life. The present study holds implications for practice to inform design of future hospital environments for cancer treatment. The study points to the importance for being attentive to the need for flexible spaces in hospitals that recognize the dynamics of healing, by providing individualized care, relating to the particular and changing needs of patients supporting their potential and their challenged condition with the best

  11. A no-prophylaxis platelet-transfusion strategy for hematologic cancers.

    PubMed

    Stanworth, Simon J; Estcourt, Lise J; Powter, Gillian; Kahan, Brennan C; Dyer, Claire; Choo, Louise; Bakrania, Lekha; Llewelyn, Charlotte; Littlewood, Timothy; Soutar, Richard; Norfolk, Derek; Copplestone, Adrian; Smith, Neil; Kerr, Paul; Jones, Gail; Raj, Kavita; Westerman, David A; Szer, Jeffrey; Jackson, Nicholas; Bardy, Peter G; Plews, Dianne; Lyons, Simon; Bielby, Linley; Wood, Erica M; Murphy, Michael F

    2013-05-09

    The effectiveness of platelet transfusions to prevent bleeding in patients with hematologic cancers remains unclear. This trial assessed whether a policy of not giving prophylactic platelet transfusions was as effective and safe as a policy of providing prophylaxis. We conducted this randomized, open-label, noninferiority trial at 14 centers in the United Kingdom and Australia. Patients were randomly assigned to receive, or not to receive, prophylactic platelet transfusions when morning platelet counts were less than 10×10(9) per liter. Eligible patients were persons 16 years of age or older who were receiving chemotherapy or undergoing stem-cell transplantation and who had or were expected to have thrombocytopenia. The primary end point was bleeding of World Health Organization (WHO) grade 2, 3, or 4 up to 30 days after randomization. A total of 600 patients (301 in the no-prophylaxis group and 299 in the prophylaxis group) underwent randomization between 2006 and 2011. Bleeding of WHO grade 2, 3, or 4 occurred in 151 of 300 patients (50%) in the no-prophylaxis group, as compared with 128 of 298 (43%) in the prophylaxis group (adjusted difference in proportions, 8.4 percentage points; 90% confidence interval, 1.7 to 15.2; P=0.06 for noninferiority). Patients in the no-prophylaxis group had more days with bleeding and a shorter time to the first bleeding episode than did patients in the prophylaxis group. Platelet use was markedly reduced in the no-prophylaxis group. A prespecified subgroup analysis identified similar rates of bleeding in the two study groups among patients undergoing autologous stem-cell transplantation. The results of our study support the need for the continued use of prophylaxis with platelet transfusion and show the benefit of such prophylaxis for reducing bleeding, as compared with no prophylaxis. A significant number of patients had bleeding despite prophylaxis. (Funded by the National Health Service Blood and Transplant Research and

  12. Correlates of meeting the combined and independent aerobic and strength exercise guidelines in hematologic cancer survivors.

    PubMed

    Vallerand, James R; Rhodes, Ryan E; Walker, Gordon J; Courneya, Kerry S

    2017-03-28

    Most previous research on the correlates of physical activity has examined the aerobic or strength exercise guidelines separately. Such an approach does not allow an examination of the correlates of meeting the combined guidelines versus a single guideline, or one guideline versus the other. Here, we report the prevalence and correlates of meeting the combined and independent exercise guidelines in hematologic cancer survivors (HCS). In a population-based, cross-sectional survey of 606 HCS from Alberta, Canada using a mailed questionnaire, we obtained separate assessments of aerobic and strength exercise behaviors, as well as separate assessments for motivations, regulations, and reflective processes using the multi-process action control framework (M-PAC). Overall, 22% of HCS met the combined exercise guideline, 22% met aerobic-only, 10% met strength-only, and 46% met neither exercise guideline. HCS were more likely to meet the combined guideline over the aerobic-only guideline if they had no children living at home, and over both the aerobic and strength-only guidelines if they had completed university. As hypothesized, those meeting the combined guideline also had a more favorable strength-specific M-PAC profile (i.e., motivations, regulations, and reflective processes) than those meeting the aerobic-only guideline, and a more favorable aerobic-specific M-PAC profile than those meeting the strength-only guideline. Interestingly and unexpectedly, HCS meeting the combined guidelines also reported significantly greater aerobic-specific perceived control, planning, and obligation/regret than those meeting the aerobic-only guideline, and greater strength-specific perceived control, planning, and obligation/regret than those meeting the strength-only guideline. Few HCS are meeting the combined exercise guidelines. M-PAC based variables are strong correlates of meeting the combined guidelines compared to aerobic or strength only guidelines. Strategies to help HCS meet

  13. Interleukin-12 in Treating Patients With Hematologic Cancers or Solid Tumors

    ClinicalTrials.gov

    2014-09-09

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  14. Neonatal hematology.

    PubMed

    Diaz-Miron, Jose; Miller, Jacob; Vogel, Adam M

    2013-11-01

    Neonatal hematology is a complex and dynamic process in the pediatric population. Surgeons frequently encounter hematologic issues regarding hemostasis, inflammation, and wound healing. This publication provides a surgeon-directed review of hematopoiesis in the newborn, as well as an overview of the current understanding of their hemostatic profile under normal and pathologic conditions. © 2013 Published by Elsevier Inc.

  15. Targeted therapies in advanced differentiated thyroid cancer.

    PubMed

    Carneiro, Raquel M; Carneiro, Benedito A; Agulnik, Mark; Kopp, Peter A; Giles, Francis J

    2015-09-01

    Differentiated thyroid cancer is the most common endocrine malignancy, and its incidence has been rising rapidly over the past 10 years. Although most patients with this disease have an excellent prognosis, a subset develops a more aggressive disease phenotype refractory to conventional therapies. Until recently, there was no effective therapy for these patients. With increasing knowledge of the molecular pathogenesis of thyroid cancer, novel targeted therapies are being developed for this group of patients. Sorafenib and lenvatinib, small-molecule multikinase inhibitors, were approved for the treatment of progressive, symptomatic, radioactive iodine refractory, advanced differentiated thyroid cancer in 2013 and 2015, respectively. This represents a major innovation in the therapy of patients with advanced thyroid cancer. However, these therapies still have many limitations and further research needs to be pursued with the ultimate goal of providing safe and effective personalized therapy for patients with advanced thyroid cancer.

  16. Nanotechnology applications in hematological malignancies (Review)

    PubMed Central

    SAMIR, AHMED; ELGAMAL, BASMA M; GABR, HALA; SABAAWY, HATEM E

    2015-01-01

    A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up. PMID:26134389

  17. Novel agents for advanced pancreatic cancer

    PubMed Central

    Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

    2015-01-01

    Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

  18. Precision medicine for advanced prostate cancer.

    PubMed

    Mullane, Stephanie A; Van Allen, Eliezer M

    2016-05-01

    Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

  19. Precision medicine for advanced prostate cancer

    PubMed Central

    Mullane, Stephanie A.; Van Allen, Eliezer M.

    2016-01-01

    Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

  20. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  1. Integrated Molecular Profiling in Advanced Cancers Trial

    ClinicalTrials.gov

    2016-08-19

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  2. Management of Locally Advanced Pancreatic Cancer.

    PubMed

    Martin, Robert C G

    2016-12-01

    The diagnosis for locally advanced pancreatic cancer is based on high-quality cross-sectional imaging, which shows tumor invasion into the celiac/superior mesenteric arteries and/or superior mesenteric/portal venous system that is not reconstructable. The optimal management of these patients is evolving quickly with the advent of newer chemotherapeutics, radiation, and nonthermal ablation modalities. This article presents the current status of initial chemotherapy, surgical therapy, ablative therapy, and radiation therapy for patients with nonmetastatic locally advanced unresectable pancreatic cancer. Surgical resection offers the best chance of long-term disease control and the only chance for cure for patients with nonmetastatic exocrine pancreatic cancer.

  3. Nivolumab, anti-programmed death-1 (PD-1) monoclonal antibody immunotherapy: Role in advanced cancers.

    PubMed

    Rajan, Arun; Kim, Chul; Heery, Christopher R; Guha, Udayan; Gulley, James L

    2016-09-01

    The development of immune checkpoint inhibitors has altered the landscape of treatment of advanced cancers. These drugs are well tolerated and have shown clinical activity against a wide variety of solid tumors and hematological malignancies. The durability of response is particularly impressive when compared to other forms of systemic therapy. Nivolumab (Opdivo) is an IgG4 antibody that causes immune checkpoint blockade by diminishing inhibitory signaling through the programmed death receptor-1 pathway. It is approved for treatment of recurrent non-small cell lung cancer, melanoma, and renal cell carcinoma. Efforts to identify biomarkers of response to nivolumab are ongoing. Clinical trials are also being conducted to determine the benefits of combining nivolumab with other forms of treatment including chemotherapy, molecular-targeted therapy, radiation therapy, and other forms of immune therapy. This review outlines the clinical trials that have led to the emergence of nivolumab as a treatment option for patients with advanced cancers.

  4. Recent developments in advanced urothelial cancer.

    PubMed

    Chee, Karen Giselle; Cambio, Angelo; Lara, Primo N

    2005-09-01

    Metastatic or unresectable urothelial cancer of the urinary bladder has traditionally been treated with systemic chemotherapy, which is most often platinum-based. The long-term survival data and the associated toxicities from this form of therapy have spurred continuing interest in finding novel treatment options for this malignancy. Recently, trials of new chemotherapy combinations, many incorporating platinum analogs or deleting platinum entirely, have been reported. None has yet been shown to be superior to cisplatin-based regimens. In addition, recent advances in imaging and laboratory technologies have provided new avenues to understand urothelial cancer behavior and prognosis. These advances provide optimism for improvements in the diagnosis, staging, and ultimately, selection of therapy for patients with urothelial cancer. This review will summarize recent developments (circa 2004) in the diagnosis and management of advanced bladder cancer.

  5. Advances in personalized cancer immunotherapy.

    PubMed

    Kakimi, Kazuhiro; Karasaki, Takahiro; Matsushita, Hirokazu; Sugie, Tomoharu

    2017-01-01

    There are currently three major approaches to T cell-based cancer immunotherapy, namely, active vaccination, adoptive cell transfer therapy and immune checkpoint blockade. Recently, this latter approach has demonstrated remarkable clinical benefits, putting cancer immunotherapy under the spotlight. Better understanding of the dynamics of anti-tumor immune responses (the "Cancer-Immunity Cycle") is crucial for the further development of this form of treatment. Tumors employ multiple strategies to escape from anti-tumor immunity, some of which result from the selection of cancer cells with immunosuppressive activity by the process of cancer immunoediting. Apart from this selective process, anti-tumor immune responses can also be inhibited in multiple different ways which vary from patient to patient. This implies that cancer immunotherapy must be personalized to (1) identify the rate-limiting steps in any given patient, (2) identify and combine strategies to overcome these hurdles, and (3) proceed with the next round of the "Cancer-Immunity Cycle". Cancer cells have genetic alterations which can provide the immune system with targets by which to recognize and eradicate the tumor. Mutated proteins expressed exclusively in cancer cells and recognizable by the immune system are known as neoantigens. The development of next-generation sequencing technology has made it possible to determine the genetic landscape of human cancer and facilitated the utilization of genomic information to identify such candidate neoantigens in individual cancers. Future immunotherapies will need to be personalized in terms of the identification of both patient-specific immunosuppressive mechanisms and target neoantigens.

  6. Non-steroidal anti-inflammatory drugs induce severe hematologic toxicities in lung cancer patients receiving pemetrexed plus carboplatin: A retrospective cohort study

    PubMed Central

    Ishida, Yuri; Takechi, Kenshi; Katayama, Hitoshi; Ito, Ryoji; Yakushijin, Yoshihiro; Moriguchi, Toshihide; Tanaka, Mamoru; Tanaka, Akihiro; Araki, Hiroaki

    2017-01-01

    Purpose As the major toxicity induced by pemetrexed plus carboplatin is severe hematologic toxicities, the aim of this study was to determine the risk factors for severe hematologic toxicities in lung cancer patients. Methods We retrospectively investigated data from lung cancer patients who had received pemetrexed plus carboplatin, with or without bevacizumab. This observational study was carried out at Ehime University Hospital using electronic medical records dating from July 2009 to March 2015. Severe hematologic toxicities were defined as grade 3 or 4, according to the Common Terminology Criteria for Adverse Events, version 4.0. Results Forty-two patients were included in the study. The incidence of grade 3 or 4 hematologic toxicities during the first cycle of chemotherapy and during all cycles was 19.0% and 16.1%, respectively. Multivariate time-depend generalized estimating equations logistic regression analysis revealed that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted odds ratio (OR): 8.32, 95% confidence interval (CI): 1.27–54.38; p = 0.03), whereas creatinine clearance of <45 mL/min was not significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted OR: 0.91, 95% CI: 0.25–3.34; p = 0.88). Conclusions The results suggest that severe hematologic toxicities in patients receiving carboplatin-based pemetrexed may be significantly induced by the inhibition of renal tubular pemetrexed secretion through drug–drug interactions between NSAIDs and pemetrexed rather than through glomerular filtration of pemetrexed, even with moderate to sufficient renal function. PMID:28158216

  7. Advances in Breast Cancer Therapy

    DTIC Science & Technology

    2010-06-01

    will be scheduled in Q3 2010 Agustin Garcia, MD University of Southern California / Norris Comprehensive Cancer Center 1441 Eastlake Avenue Los...A 6 6 Agustin Garcia, MD USC / Norris Comprehensive Cancer Center • Q3 Approval by DoD Expected • June -- December Accrual Anticipated at 12

  8. Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2017-09-14

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia in Remission; Hematopoietic Cell Transplantation Recipient; JAK2 Gene Mutation; Loss of Chromosome 17p; Mantle Cell Lymphoma; Minimal Residual Disease; Myelodysplastic Syndrome; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; RAS Family Gene Mutation; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hematologic Malignancy; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome; TP53 Gene Mutation

  9. Palbociclib for Advanced Breast Cancer

    Cancer.gov

    An interim analysis of the PALOMA3 trial shows that women with hormone receptor-positive metastatic breast cancer who received palbociclib plus fulvestrant had longer progression-free survival rates than women who received a placebo plus fulvestrant.

  10. The microfluidic multitrap nanophysiometer for hematologic cancer cell characterization reveals temporal sensitivity of the calcein-AM efflux assay.

    PubMed

    Byrd, Thomas F; Hoang, Loi T; Kim, Eric G; Pfister, Matthew E; Werner, Erik M; Arndt, Stephen E; Chamberlain, Jeffrey W; Hughey, Jacob J; Nguyen, Bao A; Schneibel, Erik J; Wertz, Laura L; Whitfield, Jonathan S; Wikswo, John P; Seale, Kevin T

    2014-05-30

    Cytometric studies utilizing flow cytometry or multi-well culture plate fluorometry are often limited by a deficit in temporal resolution and a lack of single cell consideration. Unfortunately, many cellular processes, including signaling, motility, and molecular transport, occur transiently over relatively short periods of time and at different magnitudes between cells. Here we demonstrate the multitrap nanophysiometer (MTNP), a low-volume microfluidic platform housing an array of cell traps, as an effective tool that can be used to study individual unattached cells over time with precise control over the intercellular microenvironment. We show how the MTNP platform can be used for hematologic cancer cell characterization by measuring single T cell levels of CRAC channel modulation, non-translational motility, and ABC-transporter inhibition via a calcein-AM efflux assay. The transporter data indicate that Jurkat T cells exposed to indomethacin continue to accumulate fluorescent calcein for over 60 minutes after calcein-AM is removed from the extracellular space.

  11. Radiation Therapy and Late Mortality From Second Sarcoma, Carcinoma, and Hematological Malignancies After a Solid Cancer in Childhood

    SciTech Connect

    Tukenova, Markhaba; Guibout, Catherine; Hawkins, Mike; Quiniou, Eric; Mousannif, Abddedahir; Pacquement, Helene; Winter, David; Bridier, Andre; Lefkopoulos, Dimitri; Oberlin, Odile; Diallo, Ibrahima; Vathaire, Florent de

    2011-06-01

    Purpose: To compare patterns of long-term deaths due to secondary carcinomas, sarcomas, and hematological malignancies occurring after childhood cancer in a cohort of patients followed over a median of 28 years. Methods and Materials: The study included 4,230 patients treated at eight institutions, who were at least 5-year survivors of a first cancer, representing 105,670 person-years of observation. Complete clinical, chemotherapeutic, and radiotherapeutic data were recorded, and the integral radiation dose was estimated for 2,701 of the 2,948 patients who had received radiotherapy. The integral dose was estimated for the volume inside the beam edges. The causes of death obtained from death certificates were validated. Results: In total, 134 events were due to second malignant neoplasm(s) (SMN). We found that the standardized mortality ratio decreased with increasing follow-up for second carcinomas and sarcomas, whereas the absolute excess risk (AER) increased for a second carcinoma but decreased for second sarcomas. There was no clear variation in SMN and AER for hematological malignancies. We found a significant dose-response relationship between the radiation dose received and the mortality rate due to a second sarcoma and carcinoma. The risk of death due to carcinoma and sarcoma as SMN was 5.2-fold and 12.5-fold higher, respectively, in patients who had received a radiation dose exceeding 150 joules. Conclusions: Among patients who had received radiotherapy, only those having received the highest integral radiation dose actually had a higher risk of dying of a second carcinoma or sarcoma.

  12. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization

    PubMed Central

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A.; de Haas, Masja; de Vooght, Karen M.K.; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C.V.; Hudig, Francisca; van der Bom, Johanna G.

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19–0.68) and 0.30 (range 0.12–0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09–0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16–0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization. PMID:27634204

  13. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization.

    PubMed

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A; de Haas, Masja; de Vooght, Karen M K; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C V; Hudig, Francisca; van der Bom, Johanna G

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19-0.68) and 0.30 (range 0.12-0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09-0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16-0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization.

  14. Photodynamic Cancer Therapy - Recent Advances

    SciTech Connect

    Abrahamse, Heidi

    2011-09-22

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  15. Radiation or chemoradiation: initial utility study of selected therapy for local advanced stadium cervical cancer

    NASA Astrophysics Data System (ADS)

    Pramitasari, D. A.; Gondhowiardjo, S.; Nuranna, L.

    2017-08-01

    This study aimed to compare radiation only or chemo radiation treatment of local advanced cervical cancers by examining the initial response of tumors and acute side effects. An initial assessment employed value based medicine (VBM) by obtaining utility values for both types of therapy. The incidences of acute lower gastrointestinal, genitourinary, and hematology side effects in patients undergoing chemoradiation did not differ significantly from those undergoing radiation alone. Utility values for patients who underwent radiation alone were higher compared to those who underwent chemoradiation. It was concluded that the complete response of patients who underwent chemoradiation did not differ significantly from those who underwent radiation alone.

  16. Strategies for advancing cancer nanomedicine

    NASA Astrophysics Data System (ADS)

    Chauhan, Vikash P.; Jain, Rakesh K.

    2013-11-01

    Cancer nanomedicines approved so far minimize toxicity, but their efficacy is often limited by physiological barriers posed by the tumour microenvironment. Here, we discuss how these barriers can be overcome through innovative nanomedicine design and through creative manipulation of the tumour microenvironment.

  17. Advances in Breast Cancer Therapy

    DTIC Science & Technology

    2009-06-01

    Background Verified Anne Wallace, MD University of California San Diego/ Moores Cancer Center Clinical Trials Office 3855 Health Sciences Dr., MC...Requirements Received and Accepted • Contract Review at Site Pending • Federalwide Assurance Verified • Research Integrity Background Verified Agustin ...of Pittsburgh, University of California San Diego and University of Southern California). The process has taken more than 3 months and comments

  18. Advanced endoscopic technologies for colorectal cancer screening.

    PubMed

    Obstein, Keith L; Valdastri, Pietro

    2013-01-28

    Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation.

  19. Advanced endoscopic technologies for colorectal cancer screening

    PubMed Central

    Obstein, Keith L; Valdastri, Pietro

    2013-01-01

    Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation. PMID:23382621

  20. Randomized controlled trial of care bundles with chlorhexidine dressing and advanced dressings to prevent catheter-related bloodstream infections in pediatric hematology-oncology patients.

    PubMed

    Gerçeker, Gülçin Özalp; Yardımcı, Figen; Aydınok, Yeşim

    2017-06-01

    To compare the effects of the care bundles including chlorhexidine dressing and advanced dressings on the catheter-related bloodstream infection (CRBSI) rates in pediatric hematology-oncology patients with central venous catheters (CVCs). Twenty-seven PHO patients were recruited to participate in a prospective, randomized study in Turkey. The researcher used care bundles with chlorhexidine dressing in the experimental group (n = 14), and care bundles with advanced dressings in the control group (n = 13). According to the study results, 28.6% of the patients in the experimental group had CRBSI, while this rate was 38.5% in the control group patients. The CRBSI rate in the experimental group was 3.9, and the control group had 4.4 per 1000 inpatient catheter days. There was no exit-site infection in the experimental group. However, the control group had 1.7 per 1000 inpatient catheter days. Even though there was no difference between the two groups in which the researcher implemented care bundles with chlorhexidine dressing and advanced dressings in terms of CRBSI development, there was reduction in the CRBSI rates thanks to the care bundle approach. It is possible to control the CRBSI rates using care bundles in pediatric hematology-oncology patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. THE IMPACT OF BONE MARROW RADIATION DOSE ON ACUTE HEMATOLOGIC TOXICITY IN CERVICAL CANCER: PRINCIPAL COMPONENT ANALYSIS ON HIGH DIMENSIONAL DATA

    PubMed Central

    Liang, Yun; Messer, Karen; Rose, Brent S.; Lewis, John H.; Jiang, Steve B.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2009-01-01

    Purpose To study the effects of increasing pelvic bone marrow (BM) radiation dose on acute hematologic toxicity in patients undergoing chemoradiotherapy, using a novel modeling approach to preserve the local spatial dose information. Methods The study includes 37 cervical cancer patients treated with concurrent weekly cisplatin and pelvic radiation therapy. The white blood cell count (WBC) nadir during treatment was used as the indicator of acute hematologic toxicity. Pelvic BM radiation dose distributions were standardized across patients by registering the pelvic BM volumes to a common template followed by dose remapping using deformable image registration, resulting in a dose array. Principal component analysis (PCA) was applied to the dose array and the significant eigenvectors were identified by linear regression on the principal components (PCs). The coefficients for PC regression and significant eigenvectors were represented in 3-D to identify critical BM subregions where dose accumulation is associated with hematologic toxicity. Results We identified five PCs associated with acute hematologic toxicity. PCA regression modeling explained a high proportion of the variation in acute hematologicity (adjusted R2 0.49). Three-dimensional rendering of a linear combination of the significant eigenvectors revealed patterns consistent with anatomical distributions of hematopoietically active BM. Conclusions We have developed a novel approach that preserves spatial dose information to model effects of radiation dose on toxicity, which may be useful in optimizing radiation techniques to avoid critical subregions of normal tissues. Further validation of this approach in a large cohort is ongoing. PMID:20472344

  2. Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

    PubMed Central

    Smith, J. Joshua; Garcia-Aguilar, Julio

    2015-01-01

    Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

  3. Candidemia in Cancer Patients: Focus Mainly on Hematological Malignancyand Hematopoietic Stem Cell Transplantation.

    PubMed

    Okinaka, Keiji

    2016-01-01

    Although many new antifungals have become commercially available since 2000, candidemia remains an important public health issue because of its poor prognosis. Some studies have suggested that early antifungal therapy is associated with decreased mortality; however, it is difficult to promptly diagnose candidemia because of the poor sensitivity of blood cultures. Thus, prophylaxis against Candida infection is recommended in patient groups in whom the risk of infection is high, such as allogeneic hematopoietic stem cell transplant recipients or those undergoing intensive remission-induction chemotherapy for acute leukemia. Non-Candida albicans candidemia is dominant among hematology patients, and the use of an echinocandin is recommended as the initial therapy. However, echinocandin-resistant Candida have been reported with increasing frequency, mainly in Candida glabrata. Several studies have reported that echinocandin resistance is associated with prior exposure to an echinocandin. Therefore, susceptibility testing is vital in treating severe or refractory candidemia, and the introduction of an antifungal stewardship program is recommended.

  4. Breast cancer. Part 3: advanced cancer and psychological implications.

    PubMed

    Harmer, Victoria

    This is the last article in this 3-part series on breast cancer. The previous two articles have outlined the principles behind breast awareness and breast health, detailing common benign breast diseases, types of breast cancer and staging, and treatment for breast cancer, including surgery, chemotherapy, radiotherapy and endocrine treatment. The series concludes by giving information on advanced disease, including when a patient presents late with a fungating breast lesion, or if the disease has metastasized from the breast to other organs. Lymphoedema is also described and discussed, and the latter half of this article discusses psychological implications of breast cancer, from diagnosis through the individual treatments.

  5. Recent advances in cancer therapeutics.

    PubMed

    Chessum, Nicola; Jones, Keith; Pasqua, Elisa; Tucker, Michael

    2015-01-01

    In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry.

  6. Reptile hematology.

    PubMed

    Sykes, John M; Klaphake, Eric

    2015-01-01

    The basic principles of hematology used in mammalian medicine can be applied to reptiles. The appearances of the blood cells are significantly different from those seen in most mammals, and vary with taxa and staining method used. Many causes for abnormalities of the reptilian hemogram are similar to those for mammals, although additional factors such as venipuncture site, season, hibernation status, captivity status, and environmental factors can also affect values, making interpretation of hematologic results challenging. Values in an individual should be compared with reference ranges specific to that species, gender, and environmental conditions when available.

  7. Reptile Hematology.

    PubMed

    Sykes, John M; Klaphake, Eric

    2015-09-01

    The basic principles of hematology used in mammalian medicine can be applied to reptiles. The appearances of the blood cells are significantly different from those seen in most mammals, and vary with taxa and staining method used. Many causes for abnormalities of the reptilian hemogram are similar to those for mammals, although additional factors such as venipuncture site, season, hibernation status, captivity status, and environmental factors can also affect values, making interpretation of hematologic results challenging. Values in an individual should be compared with reference ranges specific to that species, gender, and environmental conditions when available.

  8. Major Advances in the Treatment of Cancer

    PubMed Central

    Burney, Ikram A; Al-Moundhri, Mansour S

    2008-01-01

    The last few years have seen major advances in the management of cancers. Since it is not possible for the non-oncologist to keep abreast with the latest developments in the field of oncology, this review summarises the most significant advances in the area of treatment of various cancers over the past four years. In some areas, a paradigm shift has occurred setting new standards of care, for example, the use of targeted therapy (trastuzumab) in adjuvant treatment of breast cancer; the use of monoclonal antibodies (rituximab), with or without chemotherapy, in the treatment and maintenance of indolent lymphoma; the use of the tyrosine kinase inhibitor, imatinib, in the adjuvant setting in resected gastrointestinal stromal tumours. In other areas, new treatments have emerged, such as, the use of targeted therapies in hepatocellular carcinoma (sorafenib) and renal cell carcinoma (sunitinib, sorafenib, temsirolimus, bevacizumab). In some other cancers, the addition of targeted therapies has improved survival rates, for example, in colon cancer (bevacizumab, cetuximb, panitumumab), head and neck cancers (cetuximab), and pancreatic adenocarcinoma (erlotinib). In yet another group, new targeted therapies have emerged where resistance was previously observed with the existing targeted therapies, for example, breast cancer (lapatinib), chronic myeloid leukemia (dasatinib). Finally, the addition of chemotherapeutic agents has improved survival in some forms of cancer, for example, oxaliplatin in adjuvant treatment of colon cancer, temozolamide in glioblastoma multiforme, and adjuvant chemotherapy in non-small cell lung cancer. The information summarized here may provide useful for the busy physician needing an update in the field of oncology. PMID:21748051

  9. New Treatment in Advanced Thyroid Cancer

    PubMed Central

    Giuffrida, Dario; Prestifilippo, Angela; Scarfia, Alessia; Martino, Daniela; Marchisotta, Stefania

    2012-01-01

    Thyroid cancer is the most common endocrine tumor. Thyroidectomy, radioactive iodine, and TSH suppression represent the standard treatment for differentiated thyroid cancer. Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. In this paper, we reviewed the recent literature reports (pubmed, medline, EMBASE database, and abstracts published in meeting proceedings) on new treatments in advanced nonmedullary and medullary thyroid carcinomas. Studies of many tyrosine kinase inhibitors as well as antiangiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. We summarized both the results obtained and the toxic effects associated with these treatments reported in clinical trials. Reported data in this paper are encouraging, but further trials are necessary to obtain a more effective result in thyroid carcinoma treatment. PMID:23133451

  10. Ablation Strategies for Locally Advanced Pancreatic Cancer.

    PubMed

    Linecker, Michael; Pfammatter, Thomas; Kambakamba, Patryk; DeOliveira, Michelle L

    2016-01-01

    With the advent of novel and somewhat effective chemotherapy against pancreas cancer, several groups developed a new interest on locally advanced pancreatic cancer (LAPC). Unresectable tumors constitute up to 80% of pancreatic cancer (PC) at the time of diagnosis and are associated with a 5-year overall survival of less than 5%. To control those tumors locally, with perhaps improved patients survival, significant advances were made over the last 2 decades in the development of ablation methods including cryoablation, radiofrequency ablation, microwave ablation, high intensity focused ultrasound and irreversible electroporation (IRE). Many suggested a call for caution for possible severe or lethal complications in using such techniques on the pancreas. Most fears were on the heating or freezing of the pancreas, while non-thermal ablation (IRE) could offer safer approaches. The multimodal therapies along with high-resolution imaging guidance have created some enthusiasm toward ablation for LAPC. The impact of ablation techniques on primarily non-resectable PC remains, however, unclear.

  11. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

    When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)

  12. Donor Stem Cell Transplant or Donor White Blood Cell Infusions in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2017-09-25

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unusual Cancers of Childhood

  13. Recent advances in cancer chemoprevention.

    PubMed

    Lippman, S M; Hittelman, W N; Lotan, R; Pastorino, U; Hong, W K

    1991-02-01

    The CCPC 90 conference and workshop included presentations by basic scientists describing the key in vitro and in vivo model systems used to study epithelial carcinogenesis and its associated biochemical and molecular alterations. A major conference theme was the identification of markers identifying specific carcinogenic stages. Current work focuses on defining the biology of preneoplasia, the critical specific molecular events in multistep carcinogenesis, and the dynamic interplay between viral, behavioral, dietary, and genetic factors in human carcinogenesis. Studies of molecular epidemiology and genetic susceptibility are identifying new risk groups and contributing to preventive strategies. Another major theme of the conference was the concept of field carcinogenesis and the study of carcinogen-exposed tissue "at risk" for the development of cancer. A specific example discussed by several investigators was the issue of SPT development in head and neck and lung cancers. Novel studies of biologic markers for use in early detection and as intermediate end points were described. The latter application, if validated in human trials, may allow short-term screening of chemopreventive agents and determinations of optimal doses/schedules for phase III chemoprevention trials. These biomarker trials may serve as a bridge between preclinical work and full-scale randomized trials. The status of the major phase III clinical trials was presented. Major problems in chemoprevention trials include (1) selection of agents, doses, and schedules, (2) lack of pharmacologic and pharma quality control, (5) adherence (drop-out and drop-in), and (6) trial-specific feasibility/recruitment, issues.

  14. The diaryl oxazole PC-046 is a tubulin-binding agent with experimental anti-tumor efficacy in hematologic cancers.

    PubMed

    Landowski, Terry H; Samulitis, Betty K; Dorr, Robert T

    2013-12-01

    Microtubule targeting agents are among the most widely used chemotherapeutics for both solid and hematological malignancies. This study characterizes the diaryl-oxazole based anticancer agent PC-046, which was originally identified for development based on selective activity in deleted in pancreas cancer locus 4 (DPC4/SMAD4) deficient tumors. PC-046 has growth inhibitory activity in a variety of tumor types in vitro, and efficacy in SCID mice was shown in human tumor xenografts of MV-4-11 acute myeloid leukemia, MM.1S multiple myeloma, and DU-145 prostate cancer. Pharmacokinetic studies demonstrated relatively high oral bioavailability (71%) with distribution to both plasma and bone marrow. No myelosuppression was seen in non-tumor bearing SCID mice given a single dose just under the acute lethal dose. The COMPARE algorithm in the NCI-60 cell line panel demonstrated that PC-046 closely correlated to other known tubulin destabilizing agents (correlation coefficients ≈0.7 for vincristine and vinblastine). Mechanism of action studies showed cell cycle arrest in metaphase and inhibition of tubulin polymerization. Overall, these studies show that PC-046 is a synthetically-derived, small molecule microtubule destabilizing agent. Advantages over existing microtubule destabilizing agents include ease of synthesis, lack of MDR cross-resistance, good oral bioavailability and the lack of acute myelotoxicity.

  15. The Diaryl Oxazole PC-046 is a Tubulin-Binding Agent with Experimental Anti-Tumor Efficacy in Hematologic Cancers

    PubMed Central

    Landowski, Terry H.; Samulitis, Betty K.; Dorr, Robert T.

    2013-01-01

    Summary Microtubule targeting agents are among the most widely used chemotherapeutics for both solid and hematological malignancies. This study characterizes the diaryl-oxazole based anticancer agent PC-046, which was originally identified for development based on selective activity in deleted in pancreas cancer locus 4 (DPC4/SMAD4) deficient tumors. PC-046 has growth inhibitory activity in a variety of tumor types in vitro, and efficacy in SCID mice was shown in human tumor xenografts of MV-4-11 acute myeloid leukemia, MM.1S multiple myeloma, and DU-145 prostate cancer. Pharmacokinetic studies demonstrated relatively high oral bioavailability (71%) with distribution to both plasma and bone marrow. No myelosuppression was seen in non-tumor bearing SCID mice given a single dose just under the acute lethal dose. The COMPARE algorithm in the NCI-60 cell line panel demonstrated that PC-046 closely correlated to other known tubulin destabilizing agents (correlation coefficients ≈ 0.7 for vincristine and vinblastine). Mechanism of action studies showed cell cycle arrest in metaphase and inhibition of tubulin polymerization. Overall, these studies show that PC-046 is a synthetically-derived, small molecule microtubule destabilizing agent. Advantages over existing microtubule destabilizing agents include ease of synthesis, lack of MDR cross-resistance, good oral bioavailability and the lack of acute myelotoxicity. PMID:24037082

  16. Bevacizumab Treatment for Advanced Breast Cancer

    PubMed Central

    Guarneri, Valentina; Icli, Fikri; Johnston, Stephen; Khayat, David; Loibl, Sibylle; Martin, Miguel; Zielinski, Christoph; Conte, PierFranco; Hortobagyi, Gabriel N.

    2011-01-01

    Significant advances in the treatment of patients with breast cancer have been made in the past 10 years. The current systemic treatment of breast cancer is characterized by the discovery of multiple cancer targets leading to treatments that are more sophisticated and specific than conventional cytotoxic chemotherapy. Two classes of compounds that have helped improve clinical outcomes are small molecules and monoclonal antibodies targeting specific tyrosine kinase receptors. Many novel targets have been discovered, and parallel multiple approaches to anticancer therapy have recently emerged from the literature. One promising strategy is targeting the proangiogenic vascular endothelial growth factors (VEGFs), either by ligand sequestration (preventing VEGF receptor binding) or inhibiting downstream receptor signaling. Bevacizumab, a monoclonal antibody directed against VEGF, has been shown to improve the efficacy of taxanes in frontline treatment of patients with metastatic breast cancer. This review outlines the most promising breast cancer studies using bevacizumab combined with traditional cytotoxic agents in advanced breast cancer. In addition, we discuss the current indications reviewed by the Oncologic Drug Advisory Committee and define our vision of how the benefit of patient clinical trials should be measured. PMID:21976315

  17. Hematologic malignancies

    SciTech Connect

    Hoogstraten, B.

    1986-01-01

    The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

  18. Paradoxes in cancer patients' advance care planning.

    PubMed

    Lamont, E B; Siegler, M

    2000-01-01

    To determine the frequency of advance care planning (ACP) in hospitalized cancer patients and to assess their reactions to a proposed policy in which medical housestaff would offer to discuss ACP at the time of hospital admission. Structured interviews with 111 consecutively admitted cancer patients on the oncology inpatient service of a tertiary care medical center. We found that 69% (77/111) of patients had discussed their advance care preferences with someone, usually a family member, and 33% (37/111) had completed at least one formal advance directive (e.g., a living will or durable power of attorney for health care); 32% (36/111) had done both; and 30% (33/111) had done neither. However, only 9% (10/111) of patients reported having discussed their advance care preferences with their clinic oncologists and only 23% (23/101) of the remaining patients stated that they wished to do so. By contrast, 58% (64/110) of patients supported a policy in which medical housestaff would offer to discuss these advance care preferences as a part of the admission history. Our data suggest that while oncology inpatients frequently have ACPs that they discuss with family and/or document in formal advance directives, they rarely discuss or wish to discuss these ACPs with clinic oncologists. We also show that most of the reticent patients would nevertheless consider discussing the same ACPs with admitting housestaff on the day of hospital admission.

  19. A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

    ClinicalTrials.gov

    2017-01-23

    CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Marginal Zone B Cell Lymphoma); Any T-cell Malignancy; Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma; Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer; Colorectal Adenocarcinoma, Non-small Cell Lung Cancer); Burkett's Lymphoma; Primary Lymphoma of the Central Nervous System

  20. Afatinib in Advanced Refractory Urothelial Cancer

    ClinicalTrials.gov

    2017-03-06

    Distal Urethral Cancer; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Urethral Cancer; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Stage IV Urethral Cancer; Ureter Cancer

  1. Respiratory problems in advanced cancer.

    PubMed

    Ripamonti, Carla; Fusco, Flavio

    2002-04-01

    Respiratory problems are an important issue in the palliative care setting, not only from a diagnostic and therapeutic point of view but also from emotion-related aspects involving both the patients and their families and also caregivers. In this paper we consider some of the most common respiratory problems, such as dyspnea, infections, hemoptysis, hiccup. A review of the literature was performed with reference to the frequency, diagnosis and management of the above respiratory problems in patients in advanced and terminal stages of the disease. Particular emphasis was given to the importance of communication with the patients and their families, which is considered a crucial point in the care and the cure of such patients.

  2. Fertility issues in patients with hematologic malignancies.

    PubMed

    Loren, Alison W

    2015-01-01

    An essential component of a cancer patient's comprehensive care is addressing potential threats to his or her reproductive health. Providers should discuss the risk of infertility with newly diagnosed patients and offer the chance to consult with a reproductive specialist as early as possible. Standard fertility preservation options include embryo or oocyte cryopreservation for women and sperm banking for men; all options for pre-pubertal children are experimental. Patients with hematologic malignancies are a distinct population in whom standard options may present special challenges, and alternative management strategies are being explored. Unique approaches in hematologic malignancy patients include experimental techniques, such as hormonal therapy, referrals to reproductive specialists after cancer treatment, or discontinuation of tyrosine kinase inhibitor therapy in appropriate chronic myelogenous leukemia patients. Importantly, expedited communication between hematologists and reproductive specialists may greatly enhance the quality of care for these patients. Facilitation of referrals will both improve the quality-of-life and expand the prospect of parenthood in survivors. There are ample opportunities to advance the field of oncofertility through additional research, especially in hematologic malignancy patients.

  3. [The current situation of adolescents with cancer in pediatric hematology-oncology units in Spain. Results of a national survey].

    PubMed

    Lassaletta, A; Andión, M; Garrido-Colino, C; Gutierrez-Carrasco, I; Echebarria-Barona, A; Almazán, F; López-Ibor, B; Ortega-Acosta, M J

    2013-04-01

    Little attention was paid to adolescents with Cancer in Spain up to 2010. In 2011 an "Adolescents with Cancer Committee" was established by the Spanish Society of Pediatric Hemato-Oncology (SEHOP) to care for the needs of these patients. The aim of this national survey was to outline the present situation of adolescents with cancer in Spanish Pediatric Hemato-Oncology units. A web based survey assessed institutional management of adolescents with cancer. The survey was personally sent to one member of the staff of each Pediatric Hemato-Oncology unit in Spain. It included questions about epidemiology, management, psycho-social coverage, specific facilities, and follow up of these patients. A total of 40 institutions out of 41 responded to the survey (overall response rate 98%). Fifty-six percent of the institutions had patients over 14, but only 36% of the institutions treated patients up to 18 years old. Only 25.6% of the units have more than 40 new pediatric cases every year. The percentage of patients between 14 and 18 years of age is below 10% in most of the units (77%). In 30.8% and 48.7% of the institutions, pediatric hemato-oncologists treat adolescents with hematological and solid tumors, respectively. The rest of the patients are seen by adult oncologists. There is only one institution that has a physician specifically dedicated to adolescent patients, and only two units have a "teenager's room". Only 2 units have a psychologist specifically trained to treat adolescents with cancer. The survey shows that most adolescents with cancer in Spain between 14 and 18 years of age are treated by adult oncologists. Most pediatric institutions still do not have specific facilities and psychosocial support for adolescents. The SEHOP is working hard in order to improve the quality of cancer care, and the quality of survival of this population. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  4. PALLIATIVE CARE FOR PATIENTS WITH ADVANCED CANCER

    PubMed Central

    Gray, Alan; Ezzat, Adnan

    1997-01-01

    The increasing life expectancy in Saudi Arabia will be accompanied by an alteration of the patterns of disease similar to that in Western countries. One of these will be cancer, the second leading cause of death in the west at present, where 1:3 people develop cancer during their lifetime and 1:4 die of it. Cancer deaths are rarely easy. The distress particularly the pain it can cause is legendary. Palliative care is the care and study of patients with active progressive far advanced disease, where cure is impossible, the prognosis predictably short, and the focus of care is the patient's quality of life. A Palliative Care Program has been developed at KFSH&RC, since 1991. This has broadened the spectrum of health services available to cancer patients. Palliative care needs to be more widely available in the kingdom to relieve an important cause of human suffering. PMID:23008572

  5. Important drugs for cough in advanced cancer.

    PubMed

    Homsi, J; Walsh, D; Nelson, K A

    2001-11-01

    Cough is a defense mechanism that prevents the entry of noxious materials into the respiratory system and clears foreign materials and excess secretions from the lungs and respiratory tract. In advanced cancer, it is a common symptom that interferes with the patient's daily activity and quality of life. Empiric treatment with antitussive agents is often needed. Two classes of antitussive drugs are available: (1) centrally acting: (a) opioids and (b) non-opioids; (2) peripherally acting: (a) directly and (b) indirectly. Antitussive availability varies widely around the world. Many antitussives, such as benzonatate, codeine, hydrocodone, and dextromethorphan, were extensively studied in the acute and chronic cough settings and showed relatively high efficacy and safety profiles. Benzonatate, clobutinol, dihydrocodeine, hydrocodone, and levodropropizine were the only antitussives specifically studied in cancer and advanced cancer cough. They all have shown to be effective and safe in recommended daily dose for cough. In advanced cancer the patient's current medications, previous antitussive use, the availability of routes of administration, any history of drug abuse, the presence of other symptoms and other factors, all have a role in the selection of antitussives for prescription. A good knowledge of the pharmacokinetics, dosage, efficacy, and side effects of the available antitussives provides for better management.

  6. Responses to advanced cancer: Chinese-Australians.

    PubMed

    Chui, Ying-Yu; Donoghue, Judith; Chenoweth, Lynn

    2005-12-01

    This paper describes a study identifying the impact of key aspects of Chinese culture on the responses of mid-aged Chinese-Australians to their advanced cancer in order to make recommendations about their care within the health system. Studies conducted in the 1960s and 1970s focused on understanding people's psychological responses to their experiences of terminal illness, but the issue of culture was not addressed. In recent years, a few studies have been conducted with Chinese-Australians, but were limited to issues related to their information needs and the disclosure of a cancer diagnosis. There is a lack of understanding of the impact of Chinese culture on the experiences of these patients. A grounded theory approach was used to generate a substantive theory to explain how mid-aged Chinese-Australians respond to advancing cancer. Eleven participants were recruited and data were collected from face-to-face interviews, telephone contacts, observation and researcher field notes. Data generation occurred between 1997 and 1999. Four modes of response to advanced cancer were identified: acute crisis, combat, despondency and waiting for death. This paper deals particularly with the combat mode which incorporated five culturally specific strategies used by participants in their struggle against advanced cancer. These were traditional Chinese medicine, traditional Chinese beliefs on the use of food for health maintenance, qi gong (a form of exercise), feng shui (which involves paying attention to spatial organization) and the worship of ancestors and gods. Deeply entrenched within these responses is the influence of Chinese culture, rooted in the beliefs and practices of traditional Chinese medicine and the philosophy of harmony and balance of yin and yang and qi. Health care professionals need to be aware of the cultural practices and beliefs of the different ethnic groups for whom they care, and of the importance of accommodation to and negotiation about these

  7. EZH2 in normal hematopoiesis and hematological malignancies

    PubMed Central

    Herviou, Laurie; Cavalli, Giacomo; Cartron, Guillaume; Klein, Bernard; Moreaux, Jérôme

    2016-01-01

    Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2, inhibits gene expression through methylation on lysine 27 of histone H3. EZH2 regulates normal hematopoietic stem cell self-renewal and differentiation. EZH2 also controls normal B cell differentiation. EZH2 deregulation has been described in many cancer types including hematological malignancies. Specific small molecules have been recently developed to exploit the oncogenic addiction of tumor cells to EZH2. Their therapeutic potential is currently under evaluation. This review summarizes the roles of EZH2 in normal and pathologic hematological processes and recent advances in the development of EZH2 inhibitors for the personalized treatment of patients with hematological malignancies. PMID:26497210

  8. Locally advanced rectal cancer: management challenges

    PubMed Central

    Kokelaar, RF; Evans, MD; Davies, M; Harris, DA; Beynon, J

    2016-01-01

    Between 5% and 10% of patients with rectal cancer present with locally advanced rectal cancer (LARC), and 10% of rectal cancers recur after surgery, of which half are limited to locoregional disease only (locally recurrent rectal cancer). Exenterative surgery offers the best long-term outcomes for patients with LARC and locally recurrent rectal cancer so long as a complete (R0) resection is achieved. Accurate preoperative multimodal staging is crucial in assessing the potential operability of advanced rectal tumors, and resectability may be enhanced with neoadjuvant therapies. Unfortunately, surgical options are limited when the tumor involves the lateral pelvic sidewall or high sacrum due to the technical challenges of achieving histological clearance, and must be balanced against the high morbidity associated with resection of the bony pelvis and significant lymphovascular structures. This group of patients is usually treated palliatively and subsequently survival is poor, which has led surgeons to seek innovative new solutions, as well as revisit previously discarded radical approaches. A small number of centers are pioneering new techniques for resection of beyond-total mesorectal excision tumors, including en bloc resections of the sciatic notch and composite resections of the first two sacral vertebrae. Despite limited experience, these new techniques offer the potential for radical treatment of previously inoperable tumors. This narrative review sets out the challenges facing the management of LARCs and discusses evolving management options. PMID:27785074

  9. New advances in targeted gastric cancer treatment

    PubMed Central

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-01-01

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  10. Chemotherapeutic management of advanced ovarian cancer.

    PubMed

    Gordon, Alan N; Butler, Julie

    2003-08-01

    To review current treatment strategies for patients with advanced ovarian cancer. Factors for treatment selection are discussed. Research articles and textbooks. Research efforts continue to identify novel agents and/or combination therapies that can effect a cure or prolong survival. Several agents offer similar efficacy outcomes but vary in safety aspects and administration requirements. Numerous clinical trials have defined the efficacy and safety of chemotherapy in patients with ovarian cancer. Oncology nurses can prepare patients to make treatment decisions; educate them about treatment-related side effects; and develop an ongoing relationship as patient advocates to ensure quality of life.

  11. Hyperthermia for locally advanced breast cancer.

    PubMed

    Zagar, Timothy M; Oleson, James R; Vujaskovic, Zeljko; Dewhirst, Mark W; Craciunescu, Oana I; Blackwell, Kimberly L; Prosnitz, Leonard R; Jones, Ellen L

    2010-01-01

    Hyperthermia (HT) has a proven benefit for treating superficial malignancies, particularly chest wall recurrences of breast cancer. There has been less research utilising HT in patients with locally advanced breast cancer (LABC), but available data are promising. HT has been combined with chemotherapy and/or radiotherapy in the neoadjuvant, definitive and adjuvant setting, albeit in series with small numbers of patients. There is only one phase III trial that examines hyperthermia in LABC, also with relatively small numbers of patients. The goal of this review is to highlight important research utilising HT in patients with LABC as well as to suggest future directions for its use.

  12. Hyperthermia for locally advanced breast cancer

    PubMed Central

    Zagar, Timothy M.; Oleson, James R.; Vujaskovic, Zeljko; Dewhirst, Mark W.; Craciunescu, Oana I.; Blackwell, Kimberly L.; Prosnitz, Leonard R.; Jones, Ellen L.

    2010-01-01

    Hyperthermia (HT) has a proven benefit for treating superficial malignancies, particularly chest wall recurrences of breast cancer. There has been less research utilising HT in patients with locally advanced breast cancer (LABC), but available data are promising. HT has been combined with chemotherapy and/or radiotherapy in the neoadjuvant, definitive and adjuvant setting, albeit in series with small numbers of patients. There is only one phase III trial that examines hyperthermia in LABC, also with relatively small numbers of patients. The goal of this review is to highlight important research utilising HT in patients with LABC as well as to suggest future directions for its use. PMID:20849257

  13. Advances in the treatment of testicular cancer

    PubMed Central

    Margel, David; Lubin, Marc Alan; Baniel, Jack

    2015-01-01

    Germ cell tumors (GCT) are relatively uncommon, accounting for only 1% of male malignancies in the United States. It has become an important oncological disease for several reasons. It is the most common malignancy in young men 15-35 years old. GCTs are among a unique numbers of neoplasms where biochemical markers play a critical role. Finally, it is a model of curable cancer. In this review we discuss cancer epidemiology, genetics, and therapeutic principles. Recent advances in the management of stage I GCT and controversies in the management of post chemotherapy residual mass are presented. PMID:26816836

  14. Telomerase Activation in Hematological Malignancies

    PubMed Central

    Ropio, Joana; Merlio, Jean-Philippe; Soares, Paula; Chevret, Edith

    2016-01-01

    Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT) is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies. PMID:27618103

  15. [Which recent results in Oncology and Hematology will have an impact on our practices? The point of vue of Bulletin du Cancer editorial board].

    PubMed

    Vignot, Stéphane; André, Thierry; Gonçalves, Anthony; Guièze, Romain; Magné, Nicolas; Orbach, Daniel; Penel, Nicolas; Thariat, Juliette; Wislez, Marie; Bay, Jacques-Olivier

    2017-01-01

    Among the results presented at international congresses or published in scientific journals, which are those that have a real impact on daily practice? Every year, the editorial board of the Bulletin du Cancer proposes a selection of key data in oncology and hematology. The objective is to discuss results that change or reinforce the strategies in 2016 but also identify key information for our reflections in 2017.

  16. Management of dysphagia in advanced oropharyngeal cancer.

    PubMed

    Penner, Jamie L; McClement, Susan E; Sawatzky, Jo-Ann V

    2007-05-01

    Individuals with advanced oropharyngeal cancer often experience dysphagia as a result of their illness and its treatment. Research consistently demonstrates that dysphagia and difficulty with oral intake have many implications, including a negative impact on quality of life. Nurses are in a key position to provide support and initiate appropriate interventions for individuals with dysphagia. Using the Human Response to Illness model (Mitchell et al, 1991) as an organising framework, this paper presents a critical review of the empirical literature regarding dysphagia in individuals with advanced oropharyngeal cancer that will: i) provide the reader with a comprehensive understanding of dysphagia; ii) identify current gaps in our knowledge; and iii) establish the foundation for appropriate evidence-based interventions to optimise functioning and quality of life in this patient population.

  17. Predictive value of hematological markers of systemic inflammation for managing cervical cancer.

    PubMed

    Wang, Lin; Jia, Jing; Lin, Lu; Guo, Junying; Ye, Xingming; Zheng, Xiongwei; Chen, Ying

    2017-01-26

    The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and red cell distribution width (RDW) are markers of systemic inflammation with prognostic significance for cancers. The aim of the study was to investigate the predictive significance of pretreatment values of NLR, PLR, and RDW in cervical cancer. We retrospectively analyzed 515 patients with cancer. Median values of NLR and PLR were higher in patients with cancer compared with controls and were consistently elevated during tumor progression, while the RDW was uninformative. Increased NLR was associated with lymph node (LN) metastasis and depth of stromal infiltration, and increased PLR correlated only with LN metastasis. The pretreatment NLR or PLR value was a significant predictor of LN metastasis, which enhanced when NLR and PLR values were combined. Further, NLR and PLR were as effective as squamous cell carcinoma antigen (SCC-Ag) for predicting distant tumor metastasis. However, no prognostic significance of NLR or PLR was found in the patients with early cancer stages. Our study suggested that pretreatment values of NLR and PLR might be helpful to predict the presence of distant and LN metastasis in patients with cervical carcinoma, but not adequate prognostic factors for early stage patients.

  18. Avian Hematology.

    PubMed

    Jones, Michael P

    2015-09-01

    Avian veterinarians often rely heavily on the results of various diagnostic tests, including hematology results. As such, cellular identification and evaluation of the cellular response are invaluable tools that help veterinarians understand the health or condition of their patient, as well as to monitor severity and clinical progression of disease and response to treatment. Therefore, it is important to thoroughly understand how to identify and evaluate changes in the avian erythron and leukon, as well as to interpret normal and abnormal results.

  19. Avian hematology.

    PubMed

    Jones, Michael P

    2015-01-01

    Avian veterinarians often rely heavily on the results of various diagnostic tests, including hematology results. As such, cellular identification and evaluation of the cellular response are invaluable tools that help veterinarians understand the health or condition of their patient, as well as to monitor severity and clinical progression of disease and response to treatment. Therefore, it is important to thoroughly understand how to identify and evaluate changes in the avian erythron and leukon, as well as to interpret normal and abnormal results.

  20. The microfluidic multitrap nanophysiometer for hematologic cancer cell characterization reveals temporal sensitivity of the calcein-AM efflux assay

    PubMed Central

    Byrd IV, Thomas F.; Hoang, Loi T.; Kim, Eric G.; Pfister, Matthew E.; Werner, Erik M.; Arndt, Stephen E.; Chamberlain, Jeffrey W.; Hughey, Jacob J.; Nguyen, Bao A.; Schneibel, Erik J.; Wertz, Laura L.; Whitfield, Jonathan S.; Wikswo, John P.; Seale, Kevin T.

    2014-01-01

    Cytometric studies utilizing flow cytometry or multi-well culture plate fluorometry are often limited by a deficit in temporal resolution and a lack of single cell consideration. Unfortunately, many cellular processes, including signaling, motility, and molecular transport, occur transiently over relatively short periods of time and at different magnitudes between cells. Here we demonstrate the multitrap nanophysiometer (MTNP), a low-volume microfluidic platform housing an array of cell traps, as an effective tool that can be used to study individual unattached cells over time with precise control over the intercellular microenvironment. We show how the MTNP platform can be used for hematologic cancer cell characterization by measuring single T cell levels of CRAC channel modulation, non-translational motility, and ABC-transporter inhibition via a calcein-AM efflux assay. The transporter data indicate that Jurkat T cells exposed to indomethacin continue to accumulate fluorescent calcein for over 60 minutes after calcein-AM is removed from the extracellular space. PMID:24873950

  1. Intensity-modulated radiotherapy reduces gastrointestinal toxicity in locally advanced pancreas cancer

    PubMed Central

    Prasad, Shreya; Cambridge, Lajhem; Huguet, Florence; Chou, Joanne F.; Zhang, Zhigang; Wu, Abraham J.; O'Reilly, Eileen M.; Allen, Peter; Goodman, Karyn A.

    2016-01-01

    Purpose We compared gastrointestinal (GI) and hematologic toxicity in patients with locally advanced pancreas cancer (LAPC) undergoing definitive chemoradiation using intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3D-CRT) planning. Methods and Materials We retrospectively studied 205 patients with LAPC undergoing IMRT (n=134) and 3D-CRT (n=71) between 05/03 and 03/12. Patient, tumor, and treatment characteristics and acute GI/hematology toxicity according to Common Terminology Criteria for Adverse Events v3.0 were recorded. Multivariable logistic regression models were used to test association between acute grade 2+ GI and hematologic toxicity outcomes and predictors. Propensity score analysis for grade 2+ GI toxicity was performed to reduce bias for confounding variables: age, gender, radiation dose, field size, and chemotherapy type. Results Median follow-up time for survivors was 22 months, similar between groups. Median RT dose was significantly higher for IMRT vs. 3D-CRT (5600 cGy vs 5040 cGy, P<.001); concurrent chemotherapy was mainly gemcitabine (56%) or 5-fluorouracil (5-FU, 38%). Grade 2+ GI toxicity occurred in 34% (n=24) of 3D-CRT compared with 16% (n=21) of IMRT patients. Using propensity-score analysis, 3D-CRT had significantly higher grade 2+ GI toxicity (odds ratio, 1.26 [95%CI, 1.08-1.45], P=.001). Grade 2+ hematologic toxicity was similar between IMRT and 3D-CRT groups but was significantly greater in recipients of concurrent gemcitabine over 5-FU (62% vs 29%, P<.0001). Conclusions IMRT is associated with significant lower grade 2+ GI toxicity versus 3D-CRT for patients undergoing definitive chemoradiotherapy for LAPC. Since IMRT is better tolerated at higher doses and may allow further dose escalation, potentially improving local control for this aggressive disease. Further prospective studies of dose-escalated chemoradiation using IMRT are warranted. PMID:26577010

  2. Advances for Studying Clonal Evolution in Cancer

    PubMed Central

    Raphael, Benjamin J.; Chen, Feng; Wendl, Michael C.

    2013-01-01

    The “clonal evolution” model of cancer emerged and “evolved” amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other’s survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. PMID:23353056

  3. Investigation of the oral infections and manifestations seen in patients with advanced cancer.

    PubMed

    Xu, Lihua; Zhang, Hualin; Liu, Jinsong; Chen, Xiaowei

    2013-09-01

    A prospective, observational study was undertaken to investigate the epidemiology of oral infection among the patients with advanced malignancies, and to investigate the effects of therapy strategies and risk factors on the incidence of oral infection. The patients with advanced malignancies were enrolled into the study. The incidence of oral infection with different malignant tumor groups or different treatment methods and the diagnoses of oral infection were confirmed. Demographic data on age, gender, bed rest time, nutritional status, smoking habit and the presence of oral prosthesis were also recorded. Oral infection was prevalent in 46% (391/850) of all cancer patients, with the highest rate in oral and maxillofacial cancer group (67%), followed by Hematological malignancy group (58.6%) and other groups (ranging from 43.3% to 35.3%). Oral candidiasis, oral herpes simplex, and oral mucositis were the popular infectious diseases in the patients. Chemotherapy and radiotherapy, especially combined radio- and chemotherapy, resulted in more oral infections compared with palliative care and surgery. Poor nutritional status and oral prosthesis were identified as independent risk factors associated with oral infection. Oral infection is prevalent among advanced cancer patients and associated with therapy methods and risk factors. More oral health care should be carried out for the patients with advanced malignant tumor.

  4. Recent advances in the study of somatic mosaicism and diseases other than cancer.

    PubMed

    Erickson, Robert P

    2014-06-01

    Somatic mosaicism is well appreciated as a cause of cancer and, possibly, aging. Somatic mosaicism as the cause of other diseases is becoming more appreciated. It is especially important in the causation of deforming diseases (e.g., Proteus syndrome; Sturge-Weber syndrome) which are not inherited because early developmental expression is lethal. It also known to make an important contribution to neurological, dermatological, hematological and other diseases (and probably all diseases but many in which it is harder to detect). There have been exciting recent advances in the detection of somatic mosaicism. In particular, for many diseases of somatic overgrowth in which somatic mosaicism as the sole cause was predicted, the gene somatically mutated has been found. A limited number of pathways seem involved in these disorders, some of which are also implicated in cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Rehabilitation in advanced, progressive, recurrent cancer: a randomized controlled trial.

    PubMed

    Jones, Louise; Fitzgerald, Gail; Leurent, Baptiste; Round, Jeffrey; Eades, Jane; Davis, Sarah; Gishen, Faye; Holman, Amanda; Hopkins, Katherine; Tookman, Adrian

    2013-09-01

    Two million people across the U.K. are living with cancer, often experienced as a long-term condition. They may have unmet needs after active treatment. Rehabilitation aims to address these needs, maximize psychological and physical function, and enable minimum dependency regardless of life expectancy. We aimed to test, in a randomized controlled trial, the clinical and cost effectiveness of a rehabilitation intervention for patients with advanced, recurrent cancer. We conducted a two-arm, wait-list control, randomized trial of a complex rehabilitation intervention delivered by a hospice-based multidisciplinary team vs. usual care for active, progressive, recurrent hematological and breast malignancies, with a follow-up at three months. The primary outcome was the psychological subscale of the Supportive Care Needs Survey (SCNS). Secondary outcomes were other domains of the SCNS, psychological status, continuity of care, quality of life, and resource use. Forty-one participants were enrolled and 36 completed the trial. The primary outcome was significantly lower in the intervention arm (adjusted difference -16.8, 95% CI -28.34 to -5.3; P = 0.006). The SCNS physical and patient care subscales (-14.2, 95% CI -26.2 to -2.2; P = 0.02 and -7.4, 95% CI -13.7 to -1.1; P = 0.02, respectively) and self-reported health state (12.8, 95% CI 3.2 to 22.4; P = 0.01) also differed significantly. The incremental cost-effectiveness ratio was £19,390 per quality-adjusted life year. This intervention significantly reduced the unmet needs of cancer survivors and it is likely that it is cost-effective. Despite small numbers, the main effect size was robust. We recommend implementation alongside evaluation in wider clinical settings and patient populations. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  6. Development of farnesyltransferase inhibitors for clinical cancer therapy: focus on hematologic malignancies.

    PubMed

    Karp, Judith E; Lancet, Jeffrey E

    2007-09-01

    Farnesyltransferase inhibitors (FTIs) target and inhibit the peptide prenylating enzyme farnesyltransferase. This new class of signal transduction inhibitors is being tested clinically in diverse malignancies, with encouraging results in hematololgic malignancies and breast cancer in particuarl. Critical questions have yet to be answered, for example, optimal dose and schedule, disease subgroups most likely to respond, and appropriate combinations with standard cytotoxics and new biologics. Gene profiling studies of malignant target cells obtained during FTI clinical trials will help to identify patients who are likely to respond to FTIs and to develop mechanisms for overcoming FTI resistance. Clinical trials and correlative laboratory studies in progress and under development will define the optimal roles of FTIs in cancer patients.

  7. [Fever profile of febrile neutropenia in patients treated with cancer chemotherapy for hematological malignancies].

    PubMed

    Tamai, Yotaro; Imataki, Osamu; Kawakami, Kimihiro

    2010-05-01

    It is important to diagnose infectious events in cancer patients during chemotherapy. Since many of them have complications of febrile neutropenia (FN), determining its cause is critical for their treatment course. We analyzed all febrile events (>38.0 degrees C, single axillary temperature) in hospitalized cancer patients treated at Shizuoka Cancer Center over a period of 8 months. Based on the clinical presentation at the onset, we estimated the cause of fever and classified it as infection, tumor fever, immunologic reaction or unknown. Clinical presentations found at the onset of FN were categorized into 4 groups: (1) oral mucositis, and (2) respiratory, (3) gastrointestinal and (4) cutaneous findings. We detected 85 febrile episodes (median age 58, range 26 approximately 86; 37 males and 48 females). Neutropenia was observed (500/mL) in 52. 9% (45/85) of the patients and clinical symptoms were detected in 74.1% (63/85). In eleven of 18 infection-proven cases, we successfully predicted the infection focus at the onset of fever. Multivariate analysis revealed that initial high fever, antimicrobial prophylaxis, cutaneous findings and severe neutropenia were important influencing factors in predicting infectious disease during FN. Physical examination can support the diagnosis of the cause of fever in FN patients.

  8. Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications.

    PubMed

    Veeraraghavan, Jamunarani; Ma, Jiacheng; Hu, Yiheng; Wang, Xiao-Song

    2016-07-01

    Gene fusions have long been considered principally as the oncogenic events of hematologic malignancies, but have recently gained wide attention in solid tumors due to several milestone discoveries and the advancement of deep sequencing technologies. With the progress in deep sequencing studies of breast cancer transcriptomes and genomes, the discovery of recurrent and pathological gene fusions in breast cancer is on the focus. Recently, driven by new deep sequencing studies, several recurrent or pathological gene fusions have been identified in breast cancer, including ESR1-CCDC170, SEC16A-NOTCH1, SEC22B-NOTCH2, and ESR1-YAP1 etc. More important, most of these gene fusions are preferentially identified in the more aggressive breast cancers, such as luminal B, basal-like, or endocrine-resistant breast cancer, suggesting recurrent gene fusions as additional key driver events in these tumors other than the known drivers such as the estrogen receptor. In this paper, we have comprehensively summarized the newly identified recurrent or pathological gene fusion events in breast cancer, reviewed the contributions of new genomic and deep sequencing technologies to new fusion discovery and the integrative bioinformatics tools to analyze these data, highlighted the biological relevance and clinical implications of these fusion discoveries, and discussed future directions of gene fusion research in breast cancer.

  9. Investigating Genomic Mechanisms of Treatment Resistance in Castration Resistant Prostate Cancer

    DTIC Science & Technology

    2015-05-01

    Today Men with AR-V7 variant may benefit from taxanes for advanced prostate cancer. July 6th, 2015. Available at http://www.healio.com/ hematology ...San Francisco Fellowship Hematology /Onc ology 2009 - 2010 University of California, San Francisco Chief Fellow Hematology /Onc ology 2010...year, supervising fellows, residents and medical students. Prepared: September 25, 2015 23 Fellow, Hematology /Oncology, UCSF Medical Center: During

  10. Surgery for advanced epithelial ovarian cancer.

    PubMed

    Hacker, Neville F; Rao, Archana

    2017-05-01

    Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational. In recent years, there has been increasing use of neoadjuvant chemotherapy and interval cytoreductive surgery in patients with poor performance status, which is usually due to large volume ascites and/or large pleural effusions. Neoadjuvant chemotherapy reduces the post-operative morbidity, but if the tumour responds well to the chemotherapy, the inflammatory response makes the surgery more difficult. Post-operative morbidity is generally tolerable, but increases in older patients, and in those having multiple, aggressive surgical procedures, such as bowel resection or diaphragmatic stripping. Primary cytoreductive surgery should be regarded as the gold standard for most patients until a test is developed which would allow the prediction of platinum resistance pre-operatively. Copyright © 2016. Published by Elsevier Ltd.

  11. Synthesis and antiproliferative activity of α-branched α,β-unsaturated ketones in human hematological and solid cancer cell lines.

    PubMed

    Karpavičienė, Ieva; Valiulienė, Giedrė; Raškevičius, Vytautas; Lebedytė, Indrė; Brukštus, Algirdas; Kairys, Visvaldas; Navakauskienė, Rūta; Čikotienė, Inga

    2015-06-15

    A series of α-branched α,β-unsaturated ketones were prepared via boron trifluoride etherate mediated reaction between arylalkynes and carboxaldehydes. The evaluation of the antiproliferative activity over hematological (NB4) and solid cancer (A549, MCF-7) cell lines provided a structure-activity relationship. 5-Parameter QSAR equations were built which were able to explain 80%-92% of the variance in activity. The resulting selective lead compound showed IC50 value 0.6 μM against the hematological cell line and did not cause apoptosis, but blocked cell cycle in G0/G1. Moreover, it was demonstrated that this compound enhances and accelerates retinoic acid induced granulocytic differentiation. Copyright © 2015. Published by Elsevier Masson SAS.

  12. Novel imaging in advanced prostate cancer.

    PubMed

    Goldberg, Hanan; Hamilton, Robert J

    2017-09-01

    Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer and second leading cause of death in men. Imaging evaluation of PCa is challenging because of the prostate's deep pelvic location, its complex zonal anatomy and its multifocal nature. Novel imaging modalities are needed to improve detection, reassessment in biochemical relapse, and disease progression in advanced metastatic stages. Current imaging modalities have distinct strengths. However, all lack the ability to diagnose micrometastases, differentiate high from low-grade disease and diagnose advanced disease, especially at low prostate specific antigen values. There is a need to combine the existing imaging methods with concepts utilizing tumor biology to differentiate biologically aggressive from indolent tumors. PET imaging with novel tracers facilitate improved imaging of PCa, but also usher in new compounds that could be useful for directing treatment as well. Most tracers have limited sensitivity, with the exception of prostate-specific membrane antigen (PSMA)-targeting tracers, that offer relatively higher sensitivity and specificity. PSMA-PET appears promising in improving the imaging yield particularly in recurrent and advanced disease states. Incorporating PSMA-PET in these settings could open or prolong windows along the trajectory of the disease that could allow new treatments or more effective use of currently existing treatments. Prospective studies focusing on novel imaging enhancement and integration with therapeutic applications are needed.

  13. Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

    Cancer.gov

    Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

  14. Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy

    SciTech Connect

    Mell, Loren K. . E-mail: lmell@radonc.uchicago.edu; Kochanski, Joel D.; Roeske, John C.; Haslam, Josh J.; Mehta, Neil; Yamada, S. Diane; Hurteau, Jean A.; Collins, Yvonne C.; Lengyel, Ernst; Mundt, Arno J.

    2006-12-01

    Purpose: To identify dosimetric parameters associated with acute hematologic toxicity (HT) and chemotherapy delivery in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. Methods and Materials: We analyzed 37 cervical cancer patients receiving concurrent cisplatin (40 mg/m{sup 2}/wk) and intensity-modulated pelvic radiotherapy. Pelvic bone marrow (BM) was contoured for each patient and divided into three subsites: lumbosacral spine, ilium, and lower pelvis. The volume of each region receiving 10, 20, 30, and {>=}40 Gy (V{sub 1}, V{sub 2}, V{sub 3}, and V{sub 4}, respectively) was calculated. HT was graded according to Radiation Therapy Oncology Group system. Multivariate regression models were used to test associations between dosimetric parameters and HT and chemotherapy delivery. Results: Increased pelvic BM V{sub 1} (BM-V{sub 1}) was associated with an increased Grade 2 or worse leukopenia and neutropenia (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.24-3.53; p = 0.006; and OR, 1.41; 95% CI, 1.02-1.94; p = 0.037, respectively). Patients with BM-V{sub 1} {>=}90% had higher rates of Grade 2 or worse leukopenia and neutropenia than did patients with BM-V{sub 1} <90% (11.1% vs. 73.7%, p < 0.01; and 5.6% vs. 31.6%, p = 0.09) and were more likely to have chemotherapy held on univariate (16.7% vs. 47.4%, p = 0.08) and multivariate (OR, 32.2; 95% CI, 1.67-622; p = 0.02) analysis. No associations between HT and V{sub 3} and V{sub 4} were observed. Dosimetric parameters involving the lumbosacral spine and lower pelvis had stronger associations with HT than did those involving the ilium. Conclusion: The volume of pelvic BM receiving low-dose radiation is associated with HT and chemotherapy delivery in cervical cancer patients undergoing concurrent chemoradiotherapy.

  15. Understanding strength exercise intentions and behavior in hematologic cancer survivors: an analysis of the intention-behavior gap.

    PubMed

    Vallerand, James R; Rhodes, Ryan E; Walker, Gordon J; Courneya, Kerry S

    2016-12-01

    Strength exercise improves many health outcomes in cancer survivors but the prevalence and correlates of strength exercise have not been well-described. Moreover, no study has examined the critical intention-behavior gap for exercise in cancer survivors. The aims of this study are to quantify the intention-behavior gap for strength exercise in hematologic cancer survivors (HCS) and examine correlates of both intention formation and translation using the multi-process action control framework (M-PAC). A random sample of 2100 HCS in Alberta, Canada, were mailed a survey assessing strength exercise behavior, the M-PAC, and demographic/medical variables. Separate logistic regressions were used to analyze the relationships between the correlates and intention formation and translation. Surveys were completed by 606 HCS with 58 % (n = 353) intending to do strength exercise. HCS who were not retired (OR = 1.56, p = 0.001), were highly educated (OR = 1.32, p = 0.001), and had a favorable attitude (OR = 1.56, p < 0.001), descriptive norm (OR = 1.38, p = 0.006), injunctive norm (OR = 1.45, p = 0.004), and perceived control (OR = 1.38, p < 0.001), were more likely to form an exercise intention. Of those with an exercise intention, 51 % (n = 181) reported regular strength exercise. HCS with a detailed plan (OR = 1.86, p < 0.001), favorable attitude (OR = 1.68, p = 0.001), sense of obligation (OR = 1.38, p = 0.010), and self-regulated their affinity for competing activities (OR = 1.35, p = 0.012), were more likely to translate their intention into behavior. Just over half of HCS intended to do strength exercise and only half of intenders translated that intention into behavior. Interventions targeting both intention formation and translation may provide the best approach for increasing strength exercise in HCS.

  16. [Implementation of the unified model of presenting cancer diagnosis in Polish pediatric onco-hematology centers].

    PubMed

    Samardakiewicz, Marzena; Kowalczyk, Jerzy R; Mazurowa, Mieczysława; Budziński, Waldemar; Antonowicz, Małgorzata; Borysławska, Anna; Szweda, Elzbieta; Groth, Anna; Pyka, Małgorzata; Figurska, Martyna; Chybicka, Alicja; Rokicka-Milewska, Roma; Matysiak, Michał; Balwierz, Walentyna; Sońta-Jakimczyk, Danuta; Balcerska, Anna; Wachowiak, Jacek

    2004-01-01

    Presentation of full information related to diagnosis of children with cancer should be one of principles in pediatric oncology. Multidisciplinary approach to each newly diagnosed child and its parents contributes to improving this standard. The Polish Pediatric Leukemia and Lymphoma Group is engaged in these activities since 1998 and it resulted in implementation of several SIOP recommendations in most of Polish pediatric oncohematology centers. The unified model of presentation of diagnosis for a child, parents and family was of an importance and the efforts to introduce it in all cooperating centers was undertaken. Proposed model of informing consists of several steps. Procedure should be individually tailored according to natural history of the disease and characteristics of the family. The purpose of the study was to evaluate the informing procedure in 60 children with newly diagnosed neoplasmatic disease.

  17. Epigenetics Advancing Personalized Nanomedicine in Cancer Therapy

    PubMed Central

    Liu, Shujun

    2012-01-01

    Personalized medicine aims to deliver the right drug to a right patient at the right time. It offers unique opportunities to integrate new technologies and concepts to disease prognosis, diagnosis and therapeutics. While selective personalized therapies are conceptually impressive, the majority of cancer therapies have dismal outcome. Such therapeutic failure could result from no response, drug resistance, disease relapse or severe side effect from improper drug delivery. Nanomedicine, the application of nanotechnology in medicine, has a potential to advance the identification of diagnostic and prognostic biomarkers and the delivery of right drug to disease sites. Epigenetic aberrations dynamically contribute to cancer pathogenesis. Given the individualized traits of epigenetic biomarkers, epigenetic considerations would significantly refine personalized nanomedicine. This review aims to dissect the interface of personalized medicine with nanomedicine and epigenetics. I will outline the progress and highlight challenges and areas that can be further explored perfecting the personalized health care. PMID:22921595

  18. Parental hope for children with advanced cancer.

    PubMed

    Kamihara, Junne; Nyborn, Justin A; Olcese, Maura E; Nickerson, Taylor; Mack, Jennifer W

    2015-05-01

    Previous work suggests that parents of children with cancer can remain hopeful despite receiving prognostic information, but we know little about what hope means to such parents, or the extent to which parents can feel hopeful even while facing the child's impending death. We audiotaped conversations between clinicians and parents of 32 children with relapsed or refractory cancer, and then interviewed parents about their hopes and expectations for their child. Parent statements about prognosis in interviews mirrored those made by clinicians during discussions about the child's diagnosis with refractory or relapsed cancer. Clinicians used language referring to hope during these conversations but did not ask parents directly about their hopes. Parents expressed a range of hopes for their children, from hopes related to cure or treatment response, to quality of life, normalcy, and love and relationships for the child. For most parents, expectations about prognosis were not aligned with their hopes for the child; for example, many parents hoped for a cure and also reported that they did not believe cure was possible. Many parents were able to acknowledge this incongruence. Parents accurately conveyed the reality of their child's serious condition in the setting of advanced cancer, and yet maintained hope. Hopes were not limited to hope for cure/treatment response. Clinicians should be encouraged to engage in direct conversations about hope with parents as a means to elicit realistic hopes that can help to focus the most meaningful plans for the child and family. Copyright © 2015 by the American Academy of Pediatrics.

  19. Advances in Radiotherapy Management of Esophageal Cancer

    PubMed Central

    Verma, Vivek; Moreno, Amy C.; Lin, Steven H.

    2016-01-01

    Radiation therapy (RT) as part of multidisciplinary oncologic care has been marked by profound advancements over the past decades. As part of multimodality therapy for esophageal cancer (EC), a prime goal of RT is to minimize not only treatment toxicities, but also postoperative complications and hospitalizations. Herein, discussion commences with the historical approaches to treating EC, including seminal trials supporting multimodality therapy. Subsequently, the impact of RT techniques, including three-dimensional conformal RT, intensity-modulated RT, and proton beam therapy, is examined through available data. We further discuss existing data and the potential for further development in the future, with an appraisal of the future outlook of technological advancements of RT for EC. PMID:27775643

  20. Radiation Therapy for Locally Advanced Esophageal Cancer.

    PubMed

    Chun, Stephen G; Skinner, Heath D; Minsky, Bruce D

    2017-04-01

    The treatment of locally advanced esophageal cancer is controversial. For patients who are candidates for surgical resection, multiple prospective clinical trials have demonstrated the advantages of neoadjuvant chemoradiation. For patients who are medically inoperable, definitive chemoradiation is an alternative approach with survival rates comparable to trimodality therapy. Although trials of dose escalation are ongoing, the standard radiation dose remains 50.4 Gy. Modern radiotherapy techniques such as image-guided radiation therapy with motion management and intensity-modulated radiation therapy are strongly encouraged with a planning objective to maximize conformity to the intended target volume while reducing dose delivered to uninvolved normal tissues.

  1. Radiation therapy for advanced gastric cancer

    SciTech Connect

    Tsukiyama, I.; Akine, Y.; Kajiura, Y.; Ogino, T.; Yamashita, K.; Egawa, S.; Hijikata, J.; Kitagawa, T.

    1988-07-01

    A retrospective study of 75 patients with advanced inoperable gastric cancers, referred to the National Cancer Center Hospital between 1962 and 1982, was performed. According to the Borrmann classification based on X ray findings, Type 1 was found in 3 patients, Type 2 in 5, Type 3 in 40, and Type 4 in 15. Twelve patients could not be classified. The histological type was papillary adenocarcinoma in 7 patients, tubular adenocarcinoma in 23, mucinous carcinoma in 6, poorly differentiated adenocarcinoma in 14, signet ring cell carcinoma in 12 and others in 13. The site of remote metastasis in 19 patients was Virchow's lymph node in 8 patients, Douglas pouch in 3, liver and lung in 2 each and others in 4. All patients were treated by a either telecobalt 60 unit or a linear accelerator using 6 Mv photon and the total dose to primary lesion was 4000 cGy in 5 weeks to 7000 cGy in 8-9 weeks. Complete response (CR) was achieved in 6 patients or 8.0%, partial response (PR) in 46 or 61.3%, and no change (NC) in 23 or 30.7%. The response rate based on the sum of CR and PR was about 70%. The 50% survival period in months was 26.5, 7.3, and 3.2, respectively for patients with CR, PR, and NC. For the response of advanced gastric cancer to chemotherapy in the National Cancer Center Hospital, the combined use of UFT and Mitomycin C gave the highest rate, 46%. As for as local response is concerned, the response rate to radiation was 70%, a better result than that of chemotherapy alone.

  2. Nanotechnology applications in hematological malignancies (Review).

    PubMed

    Samir, Ahmed; Elgamal, Basma M; Gabr, Hala; Sabaawy, Hatem E

    2015-09-01

    A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up.

  3. Endoscopic palliation of advanced esophageal cancer

    PubMed Central

    Mocanu, A; Bârla, R; Hoara, P; Constantinoiu, S

    2015-01-01

    Esophageal cancer represents one of the most aggressive digestive tumors, with a survival rate at 5 years of only 10%. Globally, during the last three decades, there has been an increasing incidence of the esophageal cancer, approx. 400,000 new esophageal cancers being currently diagnosed annually. This represents the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. Taking into account the population’s global aging and thus, the increase in the number of patients who will not bear surgery, PCT and radiation, or the fact that they do not want it especially because of deficiencies and associated pathology, the endoscopic ablative techniques with palliation purposes represent the alternative. If we refer to the Western Europe countries and North America, we notice an increase of esophageal adenocarcinoma rate versus squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. For at least half of the patients with EC (esophageal cancer) there is no hope of healing because of the advanced regional malignant invasion (T3-4, N+, M+) with no chemo and radiotherapy response, poor preoperative patients’ conditions or systemic metastasis. The low life expectancy does not justify the risky medical procedures, the goal of the therapy consisting in the improvement of the quality of life by eliminating dysphagia (reestablishing oral feeding) which represents the most common complication of EC, the respiratory tract complication caused by eso-tracheal fistulas or by eliminating chest pain. To treat dysphagia, which is the main target of palliation, combined methods like endoscopic, chemo and radio-therapy, can be used, each one with indications, benefits and risks. Abbreviations: SEPS = self expanding plastic stent, SREMS = self expanding metal stent, EBRT = Endoscopic brachy radiotherapy, EUS = Ultra sound endoscopy, CT = Computer tomograph, UGE

  4. [Perception about the importance of feeding in a group of hematologic cancer patients].

    PubMed

    Rodríguez-Durán, D; Palma, S; Loria-Kohen, V; Villarino, M; Bermejo, L M; Gómez-Candela, C

    2012-01-01

    Oncohematologic patients usually present nutritional deficits associated with the disease, the treatments and side effects, etc. However, there are hardly any descriptive data about the dietary recommendations used and the patient's self-perception of its usefulness in their disease. To assess the self-perception of the nutritional importance in a group of oncohematologic patients. 111 oncohematologic patients self-reported a questionnaire containing items about socio-sanitary data and self-perception of the nutritional importance in their disease. The mean age was 40.0 ± 12.8 years (64.86% women). The most frequent diagnosis and treatment was lymphoma (83.78%) and chemotheraphy (92.80%). 75% considered "very important" relationship between oncohematologic disease and nutritional status. Only 54.1% received dietary advice. And 53.2% and 50.5% considered that the use of nutritional supplements improve quality of life and/or disease respectively. A significant percentage of patients had advanced stages of their disease. However, half the group had not received dietary advice despite high interest in receiving nutritional care. Therefore, the nutritional assessment and the personalized nutritional support implementation of the patient should be included in routine clinical practice.

  5. [Markers of prostate cancer stem cells: research advances].

    PubMed

    Wang, Shun-Qi; Huang, Sheng-Song

    2013-12-01

    Prostate cancer is one of the most seriously malignant diseases threatening men's health, and the mechanisms of its initiation and progression are not yet completely understood. Recent years have witnessed distinct advances in researches on prostate cancer stem cells in many aspects using different sources of materials, such as human prostate cancer tissues, human prostate cancer cell lines, and mouse models of prostate cancer. Prostate cancer stem cell study offers a new insight into the mechanisms of the initiation and progression of prostate cancer and contributes positively to its treatment. This article presents an overview on the prostate cancer stem cell markers utilized in the isolation and identification of prostate cancer stem cells.

  6. Relation between tumor FDG uptake and hematologic prognostic indicators in stage I lung cancer patients following curative resection

    PubMed Central

    Jeong, Eugene; Hyun, Seung Hyup; Moon, Seung Hwan; Cho, Young Seok; Kim, Byung-Tae; Lee, Kyung-Han

    2017-01-01

    Abstract Hematologic parameters of systemic inflammation are receiving attention as promising prognostic indicators in cancer patients. Here, we investigated the relation and compared the prognostic values of circulating blood cell-based parameters and tumor 18F-fluoro-2-deoxyglucose (FDG) uptake in patients with stage I nonsmall cell lung cancers (NSCLC). Subjects were 1034 patients with newly diagnosed stage I NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) followed by curative resection. Total white blood cell (WBC) count, absolute neutrophil, lymphocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were obtained. Tumor FDG uptake was measured as SUVmax. WBC, neutrophil and lymphocyte counts, and NLR demonstrated weak but significant correlation to tumor SUVmax. Using the upper quartile as cutoff, patients with high tumor SUVmax had significantly higher WBC, neutrophil and lymphocyte counts, and greater NLR. There were 144 recurrences (13.9%) over a median follow-up of 29.5 months. On Cox proportional hazards regression analysis, WBC count, tumor SUVmax, age, gender, smoking, cell type, and tumor stage were significant univariate prognostic factors. On multivariate analysis, high tumor SUVmax (HR = 2.22; 95% CI, 1.52–3.25; P < 0.001), tumor stage 1B (HR = 2.11; 95% CI, 1.47–3.01; P < 0.001), and old age (HR = 1.03; 95% CI, 1.01–1.05; P = 0.002) were significant independent predictors of poor survival. Finally, high tumor SUVmax remained a significant predictor of prognosis in both low and WBC count groups. Circulating blood counts showed significant correlation to tumor FDG uptake in early stage NSCLC. WBC count was a significant univariate variable, but tumor FDG uptake was a superior and independent predictor of outcome. Hence, tumor FDG uptake effectively stratified prognosis in patients with low as well as high WBC count. PMID:28151879

  7. Recent Advances in Understanding, Diagnosing, and Treating Ovarian Cancer

    PubMed Central

    Mills, Kathryn; Fuh, Katherine

    2017-01-01

    Ovarian cancer, a term that encompasses ovarian, fallopian, and peritoneal cancers, is the leading cause of gynecologic cancer mortality. To improve patient outcomes, the field is currently focused on defining the mechanisms of cancer formation and spread, early diagnosis and prevention, and developing novel therapeutic options. This review summarizes recent advances in these areas. PMID:28184293

  8. Dietary intake of advanced cancer patients.

    PubMed

    Walsh, T D; Bowman, K B; Jackson, G P

    1983-02-01

    A state registered dietitian assessed the voluntary dietary intake of 13 advanced cancer inpatients on one ward of St. Christopher's Hospice for five consecutive days. There were 11 females, two males; median age 74 years (range 56 to 83). Two patients died on the fourth day of the study. A partially individualised weighed technique was used. Standard sized scoops and spoons were used to serve the food in small, medium or large standard portions (depending on appetite) and were weighed as served. Individual plate waste (by weight) was subtracted to give estimated individual intake. Foods provided by visitors was not included. The median and range of individual mean daily intakes (estimated) were: energy 5760 (938-8945) kJ, 1376 (224-2137) kcal; protein 44 (11-86) g; fat 52 (9-93) g; carbohydrate 169 (21-194) g; calcium 748 (268-1457) mg; iron 4.8 (0.5-21.0) mg; dietary fibre 5.0 (0.5-21.0) g. Compared to recommended amounts, energy, iron and dietary fibre intakes were low; calcium intake was high. Nutritional status may affect prognosis and/or subjective well-being in advanced cancer. The value of nutritional supplementation and the role of appetite stimulants in improving nutritional status needs investigation.

  9. Chemotherapy for elderly patients with advanced cancer: A pilot study in Institute of Oncology Bucharest

    PubMed Central

    Grigorescu, Alexandru C.

    2015-01-01

    Objectives First objective was better understanding of the indications of chemotherapy in elderly with advanced cancer, tolerability and toxicity of chemotherapy in this age group. The second objective was to define current practice in chemotherapy for elderly people with advanced cancer for a selected group of patients treated in Institute of Oncology Bucharest (IOB). Materials and Methods The study makes a clinical analysis of medical records of 27 patients from the archive of Institute of Oncology Bucharest treated by the same doctor. Patients were selected according to: age ≥ 65 years, ECOG performance status 0–1, normal blood counts and blood biochemistry, histological confirmation of the diagnosis of cancer, patients should received at least 3 cycles of chemotherapy. We extract characteristics of the patients to see if they were a homogeneous group of patients and to compare them with data from the literature. Overall survival was calculated by the Kaplan Meyer curve. Results 295 patients more then 65 years were treated in our site in 2 years 2011, 2012. 93 patients received chemotherapy and only 27 patients were enrolled in this study following inclusion criteria. Common sites of cancer were lung and breast. The most used cytostatics for lung cancer was gemcitabine and carboplatine and cyclophosphamide, metotrexat and 5 fluorouracil for breast cancer. Toxicity was mild with the prevalence of hematologic toxicity. Overall survival without taking into account the type of cancer was 27.7 month. Conclusions For selected patients, chemotherapy was well tolerated and appears to prolong survival regardless of the location of cancer. The relatively small number of elderly patients who received chemotherapy is probably due to lack of compliance to treatment, the increased number of co-morbidities and evaluation of performance status only by the ECOG index known not to be good enough to establish the indication of chemotherapy. PMID:27847881

  10. Immune Modulation in Hematologic Malignancies

    PubMed Central

    Dhodapkar, Madhav V.; Dhodapkar, Kavita M.

    2015-01-01

    The therapeutic potential of the immune system in the context of hematologic malignancies has long been appreciated particularly due to the curative impact of allogeneic hematopoietic stem cell transplantation. The role of immune system in shaping the biology and evolution of these tumors is now well recognized. While the contribution of the immune system in anti-tumor effects of certain therapies such as immune-modulatory drugs and monoclonal antibodies active in hematologic malignancies is quite evident, the immune system has also been implicated in anti-tumor effects of other targeted therapies. The horizon of immune-based therapies in hematologic malignancies is rapidly expanding with promising results from immune-modulatory drugs, immune-checkpoint blockade and adoptive cellular therapies, including genetically-modified T cells. Hematologic malignancies present distinct issues (relative to solid tumors) for the application of immune therapies due to differences in cell of origin/developmental niche of tumor cells, and patterns of involvement such as common systemic involvement of secondary lymphoid tissues. This article discusses the rapidly changing landscape of immune modulation in hematologic malignancies and emphasizes areas wherein hematologic malignancies present distinct opportunities for immunologic approaches to prevent or treat cancer. PMID:26320065

  11. Quality of end-of-life care in patients with hematologic malignancies: a retrospective cohort study.

    PubMed

    Hui, David; Didwaniya, Neha; Vidal, Marieberta; Shin, Seong Hoon; Chisholm, Gary; Roquemore, Joyce; Bruera, Eduardo

    2014-05-15

    To the authors' knowledge, only limited data are available regarding the quality of end-of-life care for patients with hematologic malignancies. In this retrospective cohort study, the quality of end-of-life care was compared between patients with hematologic malignancies and those with solid tumors. All adult patients who died of advanced cancer between September 1, 2009 and February 28, 2010 while under the care of the study institution were included. The authors collected baseline demographics and end-of-life care indicators, including emergency room visits, hospitalization, intensive care unit admissions, and systemic cancer therapy use within the last 30 days of life. Of a total of 816 decedents, 113 (14%) had hematologic malignancies. In the last 30 days of life, patients with hematologic malignancies were more likely to have emergency room visits (54% vs 43%; P = .03), hospital admissions (81% vs 47%; P < .001), ≥ 2 hospital admissions (23% vs 10%; P < .001), > 14 days of hospitalization (38% vs 8%; P < .001), intensive care unit admissions (39% vs 8%; P < .001) and death (33% vs 4%; P < .001), chemotherapy use (43% vs 14%; P < .001), and targeted therapy use (34% vs 11%; P < .001) compared with patients with solid tumors. Patients with hematologic malignancies were also less likely to have palliative care unit admissions (8% vs 17%; P = .02). The composite score for aggressiveness of care (with 0 indicating the best and 6 indicating the worst) was significantly higher among patients with hematologic malignancies compared with those with solid tumors (median, 2 vs 0; P < .001). On multivariate analysis, hematologic malignancy was found to be a significant factor associated with aggressive end-of-life care (odds ratio, 6.6; 95% confidence interval, 4.1-10.7 [P < .001]). The results of the current study indicate that patients with hematologic malignancies received more aggressive care at the end of life. © 2014 American Cancer Society.

  12. Adjuvant chemotherapy for advanced endometrial cancer.

    PubMed

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  13. Neoadjuvant chemoradiation for advanced primary vulvar cancer.

    PubMed

    van Doorn, H C; Ansink, A; Verhaar-Langereis, M; Stalpers, L

    2006-07-19

    In advanced stage primary vulvar cancer, treatment is tailored to individual patient needs. Combined treatment modalities have been developed, using chemotherapy, radiotherapy and surgery. To determine whether the combined treatment strategy using concurrent neoadjuvant chemoradiation therapy followed by surgery is effective and safe in vulvar cancer patients with advanced primary disease. Main outcomes of interest were: types of surgical intervention following chemoradiation and survival, recurrence and complication rates. We searched the Cochrane Gynaecological Cancer Review Group Specialised Register. The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (PubMed), EMBASE, CANCERLIT, other databases and reference lists of articles. The latest search was conducted on 12 March 2005. Studies of curative treatment of patients with advanced, primary squamous cell carcinoma of the vulva were included. Treatment included concurrent radiotherapy and chemotherapy, followed by surgery. Twenty-eight abstracts and papers were selected either by the search strategy or by checking the cross references. Randomised controlled trials (RCTs) were not available. Five studies met the inclusion criteria. (Eifel 1995; Landoni 1996; Montana 2000; Moore 1998; Scheistroen 1993). Two authors (HCvD, MV-L) independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. Chemotherapy was given uniformly within each of the five selected studies. However, four different chemoradiation schedules were applied. Radiotherapy dose fractionation techniques, fields and target definitions varied. Skin toxicity was observed in nearly all patients. Wound breakdown, infection, lymphedema, lymphorrhea and lymphoceles were also common. Operability was achieved in 63 to 92% of cases in the four studies using 5FU and CDDP or 5FU and MMC. In contrast, only 20% of

  14. Palbociclib and Letrozole in Advanced Breast Cancer.

    PubMed

    Finn, Richard S; Martin, Miguel; Rugo, Hope S; Jones, Stephen; Im, Seock-Ah; Gelmon, Karen; Harbeck, Nadia; Lipatov, Oleg N; Walshe, Janice M; Moulder, Stacy; Gauthier, Eric; Lu, Dongrui R; Randolph, Sophia; Diéras, Véronique; Slamon, Dennis J

    2016-11-17

    Background A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication. Methods In this double-blind study, we randomly assigned, in a 2:1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety. Results The median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group. Conclusions Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib

  15. Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

    ClinicalTrials.gov

    2016-09-16

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Precancerous/Nonmalignant Condition

  16. Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases

    ClinicalTrials.gov

    2014-12-22

    Accelerated Phase of Disease; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndrome; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  17. Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies.

    PubMed

    Larson, R A; Geller, R B; Janisch, L; Milton, J; Grochow, L B; Ratain, M J

    1995-01-01

    Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. Prior studies in patients with refractory solid tumors have identified the dose-limiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The dose-limiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3-5 weeks. Apart from CNS toxicity, non-hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose

  18. Fatigue in advanced cancer: a prospective study.

    PubMed

    Hauser, Katherine; Walsh, Declan; Rybicki, Lisa A; Davis, Mellar P; Seyidova-Khoshknabi, Dilara

    2008-01-01

    Fatigue is a common advanced cancer symptom. Clinical features are not well known. The authors surveyed consecutive patients admitted to a palliative medicine program to identify clinical correlates of fatigue. Data collected included age, sex, performance status, primary site, prior chemotherapy/radiation therapy, and blood transfusions. Visual analogue scales assessed fatigue, quality of life, and ability to perform daily activities. Weight change was estimated. Laboratory results including lactate dehydrogenase and hemoglobin were recorded. Fatigue severity was associated with brain metastases, poor performance status, poor quality of life, and reduced ability to perform activities. Prior radiation therapy was associated with less severe fatigue. Age, sex, and hemoglobin level were not associated with fatigue. Fatigue was universal on referral. Brain metastases and poor quality of life independently predicted severity. Hemoglobin level did not predict fatigue. Further studies are necessary to define the clinical features and relationships of fatigue.

  19. Discussing and managing hematologic germ line variants.

    PubMed

    Kohlmann, Wendy; Schiffman, Joshua D

    2016-12-02

    With the introduction of genomic technologies, more hereditary cancer syndromes with hematologic malignancies are being described. Up to 10% of hematologic malignancies in children and adults may be the result of an underlying inherited genetic risk. Managing these patients with hereditary hematologic malignancies, including familial leukemia, remains a clinical challenge because there is little information about these relatively rare disorders. This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines.

  20. Discussing and managing hematologic germ line variants.

    PubMed

    Kohlmann, Wendy; Schiffman, Joshua D

    2016-11-24

    With the introduction of genomic technologies, more hereditary cancer syndromes with hematologic malignancies are being described. Up to 10% of hematologic malignancies in children and adults may be the result of an underlying inherited genetic risk. Managing these patients with hereditary hematologic malignancies, including familial leukemia, remains a clinical challenge because there is little information about these relatively rare disorders. This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines.

  1. Advancements in cancer therapy with alpha-emitters: a review.

    PubMed

    Imam, S K

    2001-09-01

    This synopsis attempts to shed light on the progresses made in the field of cancer therapy using alpha-particles. The rationale of selection of radionuclides focusing on comparison of alpha- and beta-emitters, the hurdles and their solutions, and recent developments are addressed. The efforts made in the field of alpha-radioimmunotherapy of hematologic malignancies are emphasized. A good deal of progress has been achieved in the past decade, and preclinical studies with a variety of radioimmunoconjugates with astatine and bismuth radioisotopes (At-211, Bi-212, and Bi-213) have generated encouraging results, providing an impetus for future clinical trials. The onset of early clinical trials with alpha-emitters will hopefully enable the cancer researchers to come up with extremely effective and highly specific "smart bombs" to target cancer cells.

  2. Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients.

    PubMed

    Mercadante, Sebastiano; Aielli, Federica; Adile, Claudio; Ferrera, Patrizia; Valle, Alessandro; Fusco, Flavio; Caruselli, Amanda; Cartoni, Claudio; Massimo, Pizzuto; Masedu, Francesco; Valenti, Marco; Porzio, Giampiero

    2015-11-01

    Oral symptoms can be a sign of an underlying systemic condition and have a significant impact on quality of life, nutrition, and cost of care, while these lesions are often studied in the context of cancer treatment. However, information regarding oral symptoms in advanced cancer patients is poor. The aim of this multicenter study was to determine the prevalence and the characteristics of oral symptoms in a large population of advanced cancer patients. A consecutive sample of patients with advanced cancer for a period of 6 months was prospectively assessed for an observational study. At time of admission, the epidemiological characteristics, surgery-radiotherapy of head and neck, and oncologic treatments in the last month were recorded. The presence of mucositis, dry mouth, and dysphagia was assessed by clinical examination and patients' report and their intensity recorded. Patients were also asked whether they had limitation on nutrition of hydration due to the local condition. Six hundred sixty-nine patients were surveyed in the period taken into consideration. The mean age was 72.1 years (SD 12.3), and 342 patients were males. The primary tumors are listed in Table 1. The prevalence of mucositis was 22.3 %. The symptom relevantly reduced the ingestion of food or fluids and was statistically associated with the Karnofsky level and head and neck cancer. The prevalence of dry mouth was 40.4 %, with a mean intensity of 5.4 (SD 2.1). Several drugs were concomitantly given, particularly opioids (78 %), corticosteroids (75.3 %), and diuretics (70.2 %). Various and nonhomogeneous treatments were given for dry mouth, that was statistically associated with current or recent chemotherapy, and hematological tumors. The prevalence of dysphagia was 15.4 % with a mean intensity of 5.34 (SD 3). Dysphagia for liquids was observed in 52.4 % of cases. A high level of limitation for oral nutrition due to dysphagia was found, and in 53.4 % of patients, alternative routes to the oral

  3. Laparoscopic Cytoreduction for Primary Advanced Ovarian Cancer

    PubMed Central

    Hojat, Rod; Johnson, Jil; Fenton, Bradford

    2010-01-01

    Introduction: We evaluated the feasibility of laparoscopic cytoreduction for primary advanced ovarian cancer. Methods: All patients with presumed stage 3/4 primary ovarian cancer underwent attempted laparoscopic cytoreduction. All patients had CT evidence of omental metastasis and ascites. A 5-port (5-mm) transperitoneal approach was used. A bilateral salpingo-oophorectomy, supracervical hysterectomy, and omentectomy were performed with PlasmaKinetic (PK) cutting forceps. A laparoscopic 5-mm Argon-Beam Coagulator was used to coagulate tumor in the pelvis, abdominal peritoneum, intestinal mesentery, and diaphragm. Results: Nine of 11 cases (82%) were successfully de-bulked laparoscopically without conversion to laparotomy. Median operative time was 2.5 hours, and median blood loss was 275 mL. All tumors were debulked to <2 cm and 45% had no residual disease. Stages were 1–3B, 7–3C, and 1–4. Median length of stay was one day. Median VAS pain score was 4 (discomforting). Two of 11 patients (18%) had postoperative complications. Conclusion: Laparoscopic cytoreduction was successful and resulted in minimal morbidity. Because of our small sample size, additional studies are needed. PMID:20529532

  4. Laparoscopic cytoreduction for primary advanced ovarian cancer.

    PubMed

    Fanning, James; Hojat, Rod; Johnson, Jil; Fenton, Bradford

    2010-01-01

    We evaluated the feasibility of laparoscopic cytoreduction for primary advanced ovarian cancer. All patients with presumed stage 3/4 primary ovarian cancer underwent attempted laparoscopic cytoreduction. All patients had CT evidence of omental metastasis and ascites. A 5-port (5-mm) transperitoneal approach was used. A bilateral salpingo-oophorectomy, supracervical hysterectomy, and omentectomy were performed with PlasmaKinetic (PK) cutting forceps. A laparoscopic 5-mm Argon-Beam Coagulator was used to coagulate tumor in the pelvis, abdominal peritoneum, intestinal mesentery, and diaphragm. Nine of 11 cases (82%) were successfully debulked laparoscopically without conversion to laparotomy. Median operative time was 2.5 hours, and median blood loss was 275 mL. All tumors were debulked to <2 cm and 45% had no residual disease. Stages were 1-3B, 7-3C, and 1-4. Median length of stay was one day. Median VAS pain score was 4 (discomforting). Two of 11 patients (18%) had postoperative complications. Laparoscopic cytoreduction was successful and resulted in minimal morbidity. Because of our small sample size, additional studies are needed.

  5. Refining the UGT1A Haplotype Associated with Irinotecan-Induced Hematological Toxicity in Metastatic Colorectal Cancer Patients Treated with 5-Fluorouracil/Irinotecan-Based Regimens

    PubMed Central

    Lévesque, Éric; Bélanger, Anne-Sophie; Harvey, Mario; Couture, Félix; Jonker, Derek; Innocenti, Federico; Cecchin, Erica; Toffoli, Giuseppe

    2013-01-01

    Despite the importance of UDP-glucuronosyltransferase (UGT) 1A1*28 in irinotecan pharmacogenetics, our capability to predict drug-induced severe toxicity remains limited. We aimed at identifying novel genetic markers that would improve prediction of irinotecan toxicity and response in advanced colorectal cancer patients treated with folic acid (leucovorin), fluorouracil (5-FU), and irinotecan (camptosar)-based regimens. The relationships between UGT1A candidate markers across the gene (n = 21) and toxicity were prospectively evaluated in 167 patients. We included variants in the 3′untranscribed region (3′UTR) of the UGT1A locus, not studied in this context yet. These genetic markers were further investigated in 250 Italian FOLFIRI-treated patients. Several functional UGT1A variants, including UGT1A1*28, significantly influenced risk of severe hematologic toxicity. As previously reported in the Italian cohort, a 5-marker risk haplotype [haplotype II (HII); UGTs 1A9/1A7/1A1] was associated with severe neutropenia in our cohort [odds ratio (OR) = 2.43; P = 0.004]. The inclusion of a 3′UTR single-nucleotide polymorphism (SNP) permitted refinement of the previously defined HI, in which HIa was associated with the absence of severe neutropenia in combined cohorts (OR = 0.55; P = 0.038). Among all tested UGT1A variations and upon multivariate analyses, no UGT1A1 SNPs remained significant, whereas three SNPs located in the central region of UGT1A were linked to neutropenia grade 3–4. Haplotype analyses of these markers with the 3′UTR SNP allowed the identification of a protective HI (OR = 0.50; P = 0.048) and two risk haplotypes, HII and HIII, characterized by 2 and 3 unfavorable alleles, respectively, revealing a dosage effect (ORs of 2.15 and 5.28; P ≤ 0.030). Our results suggest that specific SNPs in UGT1A, other than UGT1A1*28, may influence irinotecan toxicity and should be considered to refine pharmacogenetic testing. PMID:23386248

  6. The psychosocial outcomes of individuals with hematological cancers: Are we doing enough high quality research, and what is it telling us?

    PubMed

    Bryant, Jamie; Mansfield, Elise; Hall, Alix; Waller, Amy; Boyes, Allison; Jayakody, Amanda; Dodd, Natalie; Sanson-Fisher, Rob

    2016-05-01

    This systematic review assessed the quantity and quality of research examining the psychosocial outcomes among hematological cancer patients. Studies were categorised as either measurement, descriptive or intervention. Intervention studies were further assessed according to Effective Practice and Organisation of Care (EPOC) methodological criteria. A total of 261 eligible papers were identified. The number of publications increased by 8.8% each year (95% CI=7.5-10.2%; p<0.0001). The majority of studies were descriptive (n=232; 89%), with few measurement (n=8; 3%) and intervention (n=21; 8%) studies identified. Ten intervention studies met EPOC design criteria, however only two interventions, one targeted at individuals with Hodgkin's or Non-Hodgkin's lymphoma and one targeted at individuals with leukaemia, lymphoma or myelomatosis were successful in improving patients' psychosocial outcomes. Despite an increasing volume of research examining psychosocial outcomes of hematological cancer patients, there is a need for robust measurement and methodologically rigorous intervention research in this area. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Radiation-Related Predictors of Hematologic Toxicity After Concurrent Chemoradiation for Cervical Cancer and Implications for Bone Marrow-Sparing Pelvic IMRT

    SciTech Connect

    Albuquerque, Kevin; Giangreco, David; Morrison, Courtney; Siddiqui, Mohammed; Sinacore, Jim; Potkul, Ronald; Roeske, John

    2011-03-15

    Purpose: To determine factors predictive for hematologic toxicity (HT) associated with concurrent chemoradiation for Stage II through IV cervical cancer. Methods and Materials: The medical records of 40 women receiving concurrent chemoradiation for cervical cancer were reviewed. Hematologic toxicity was defined by use of Common Terminology Criteria for Adverse Events (version 3.0). Variables predicting for HT including age, body mass index, transfusions, and bone marrow volumes irradiated were included in the data analysis. Results: Of the patients, 13 (32.5%) had Grade 0 or 1 HT and 27 (67.5%) had Grade 2 through 4 HT (HT2+). Multiple logistic regression analysis of potential predictors showed that only the volume of bone receiving 20 Gy (V20) for whole pelvic bone tended toward significance for predicting HT2+. A strong correlation was noted between HT2+ and V20 (r = 0.8, p < 0.0001). A partitioning analysis to predict HT2+ showed a cutoff value of 79.42% (approximately 80%) for V20 of whole pelvic bone. That is, if the V20 of the whole pelvis exceeds 80%, the risk of HT2+ developing increases by a factor (odds ratio) of 4.5 (95%, confidence interval, 1.08-18.69) (p < 0.05). Conclusions: We have shown a correlation between bone marrow volume radiated and development of HT. This has implications for use of pelvic intensity-modulated radiation therapy, which can potentially decrease the volume of bone marrow radiated.

  8. Targeted Approach to Overcoming Treatment Resistance in Advanced Prostate Cancer

    DTIC Science & Technology

    2013-07-01

    therapy -­‐resistant   prostate   cancer  cells  and  in  combination   therapy  (SOW...treatment resistance in advanced prostate cancer PRINCIPAL INVESTIGATOR: Dr. Karin Scarpinato CONTRACTING ORGANIZATION: Georgia Southern...SUPPLEMENTARY NOTES 14. ABSTRACT The purpose of this project is to determine if rescinnamine is effective against prostate cancer and

  9. Targeting notch signaling pathway in cancer: clinical development advances and challenges.

    PubMed

    Takebe, Naoko; Nguyen, Dat; Yang, Sherry X

    2014-02-01

    Notch signaling plays an important role in development and cell fate determination, and it is deregulated in human hematologic malignancies and solid tumors. This review includes a brief introduction of the relevant pathophysiology of Notch signaling pathway and primarily focuses on the clinical development of promising agents that either obstruct Notch receptor cleavages such as γ-secretase inhibitors (GSIs) or interfere with the Notch ligand-receptor interaction by monoclonal antibodies (mAbs). Antitumor activity by GSIs and mAbs administered as single agent in early phases of clinical trials has been observed in advanced or metastatic thyroid cancer, non-small cell lung cancer, intracranial tumors, sarcoma or desmoid tumors, colorectal cancer with neuroendocrine features, melanoma and ovarian cancer. A number of mechanism-based adverse events particularly gastrointestinal toxicities emerged and mitigation strategies are developed after testing multiple GSIs and Notch targeting mAbs. We also discuss pharmacodynamic biomarkers in conjunction with methods of assessment of the molecular target inhibition validation. Biomarkers of efficacy or benefit may be of importance for a successful development of this class of drugs.

  10. Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies

    PubMed Central

    Akl, Mohamed R.; Nagpal, Poonam; Ayoub, Nehad M.; Tai, Betty; Prabhu, Sathyen A.; Capac, Catherine M.; Gliksman, Matthew; Goy, Andre; Suh, K. Stephen

    2016-01-01

    Fibroblast growth factor (FGF) signaling is essential for normal and cancer biology. Mammalian FGF family members participate in multiple signaling pathways by binding to heparan sulfate and FGF receptors (FGFR) with varying affinities. FGF2 is the prototype member of the FGF family and interacts with its receptor to mediate receptor dimerization, phosphorylation, and activation of signaling pathways, such as Ras-MAPK and PI3K pathways. Excessive mitogenic signaling through the FGF/FGFR axis may induce carcinogenic effects by promoting cancer progression and increasing the angiogenic potential, which can lead to metastatic tumor phenotypes. Dysregulated FGF/FGFR signaling is associated with aggressive cancer phenotypes, enhanced chemotherapy resistance and poor clinical outcomes. In vitro experimental settings have indicated that extracellular FGF2 affects proliferation, drug sensitivity, and apoptosis of cancer cells. Therapeutically targeting FGF2 and FGFR has been extensively assessed in multiple preclinical studies and numerous drugs and treatment options have been tested in clinical trials. Diagnostic assays are used to quantify FGF2, FGFRs, and downstream signaling molecules to better select a target patient population for higher efficacy of cancer therapies. This review focuses on the prognostic significance of FGF2 in cancer with emphasis on therapeutic intervention strategies for solid and hematological malignancies. PMID:27007053

  11. Development of Personalized Cancer Therapy for Men with AdvancedProstate Cancer

    DTIC Science & Technology

    2016-10-01

    biosignatures. The projects under way are largely, but not exclusively focused on non-small cell lung cancer . Specific Aims: Same as above Role...AWARD NUMBERS: W81XWH-14-1-0555 TITLE: Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer PRINCIPAL INVESTIGATOR...21/2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER N/A Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer 5b. GRANT

  12. Correlation Between Radiation Dose to {sup 18}F-FDG-PET Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    SciTech Connect

    Rose, Brent S.; Liang Yun; Lau, Steven K.; Jensen, Lindsay G.; Yashar, Catheryn M.; Hoh, Carl K.; Mell, Loren K.

    2012-07-15

    Purpose: To test the hypothesis that radiation dose to {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG-PET)-defined active bone marrow (BM{sub ACT}) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Methods and Materials: The conditions of 26 women with cervical cancer who underwent {sup 18}F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM{sub ACT} was defined as the subregion of total bone marrow (BM{sub TOT}) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM{sub INACT}) was defined as BM{sub TOT} - BM{sub ACT}. Generalized linear modeling was used to test the correlation between BM{sub ACT} and BM{sub INACT} dose-volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). Results: Increased BM{sub ACT} mean dose was significantly associated with decreased log(WBC) nadir ({beta} = -0.04; 95% CI, -0.07to -0.01; p = 0.009), decreased log(ANC) nadir ({beta} = -0.05; 95% CI, -0.08 to -0.02; p = 0.006), decreased hemoglobin nadir ({beta} = -0.16; 95% CI, -0.27 to -0.05; p = 0.010), and decreased platelet nadir ({beta} = -6.16; 95% CI, -9.37 to -2.96; p < 0.001). By contrast, there was no association between BM{sub INACT} mean dose and log(WBC) nadir ({beta} = -0.01; 95% CI, -0.06 to 0.05; p = 0.84), log(ANC) nadir ({beta} = -0.03; 95% CI, -0.10 to 0.04; p = 0.40), hemoglobin nadir ({beta} = -0.09; 95% CI, -0.31 to 0.14; p = 0.452), or platelet nadir ({beta} = -3.47; 95% CI, -10.44 to 3.50; p = 0.339). Conclusions: Irradiation of BM subregions with higher {sup 18}F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM{sub ACT} subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify

  13. Correlation between radiation dose to ¹⁸F-FDG-PET defined active bone marrow subregions and acute hematologic toxicity in cervical cancer patients treated with chemoradiotherapy.

    PubMed

    Rose, Brent S; Liang, Yun; Lau, Steven K; Jensen, Lindsay G; Yashar, Catheryn M; Hoh, Carl K; Mell, Loren K

    2012-07-15

    To test the hypothesis that radiation dose to (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET)-defined active bone marrow (BM(ACT)) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. The conditions of 26 women with cervical cancer who underwent (18)F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM(ACT) was defined as the subregion of total bone marrow (BM(TOT)) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM(INACT)) was defined as BM(TOT) - BM(ACT). Generalized linear modeling was used to test the correlation between BM(ACT) and BM(INACT) dose-volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). Increased BM(ACT) mean dose was significantly associated with decreased log(WBC) nadir (β = -0.04; 95% CI, -0.07 to -0.01; p = 0.009), decreased log(ANC) nadir (β = -0.05; 95% CI, -0.08 to -0.02; p = 0.006), decreased hemoglobin nadir (β = -0.16; 95% CI, -0.27 to -0.05; p = 0.010), and decreased platelet nadir (β = -6.16; 95% CI, -9.37 to -2.96; p < 0.001). By contrast, there was no association between BM(INACT) mean dose and log(WBC) nadir (β = -0.01; 95% CI, -0.06 to 0.05; p = 0.84), log(ANC) nadir (β = -0.03; 95% CI, -0.10 to 0.04; p = 0.40), hemoglobin nadir (β = -0.09; 95% CI, -0.31 to 0.14; p = 0.452), or platelet nadir (β = -3.47; 95% CI, -10.44 to 3.50; p = 0.339). Irradiation of BM subregions with higher (18)F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM(ACT) subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify optimal SUV thresholds to define BM(ACT). Copyright © 2012 Elsevier Inc. All rights reserved.

  14. 3rd Pavia international symposium on advanced kidney cancer.

    PubMed

    Porta, Camillo; Bracarda, Sergio

    2012-02-01

    Kidney cancers' natural history has radically changed in the past few years, due to the development of novel targeted agents. Despite these improvements, several unanswered questions still remain on the table, regarding the best first-line treatment, the ideal sequence of treatments, the management of specific subgroups of patients (e.g., elderly patients or those with comorbidities) and the relevance of prognostic factors, among many others. To foster discussions among clinicians and investigators working in this field, and to exchange different viewpoints concerning the newest advances in kidney cancer pathogenesis and treatment, the 3rd Pavia International Symposium on Advanced Kidney cancer was held in Pavia (Italy) between 30 June and 1 July 2011. The aim of this report is to summarize the most significant advances in the different disciplines applied to advanced kidney cancer, which were presented and discussed during the meeting, and how these advances will be changing the perspective of patients with this disease.

  15. Major clinical research advances in gynecologic cancer in 2015

    PubMed Central

    2016-01-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review. PMID:27775259

  16. Major clinical research advances in gynecologic cancer in 2015.

    PubMed

    Suh, Dong Hoon; Kim, Miseon; Kim, Hak Jae; Lee, Kyung Hun; Kim, Jae Weon

    2016-11-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7-9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.

  17. Improving management of patients with advanced cancer

    PubMed Central

    Drudge-Coates, Lawrence

    2010-01-01

    Development of bone metastases in patients with advanced cancer is associated with skeletal-related events (SREs) such as pathologic fractures, spinal cord compression, the requirement for surgery or palliative radiotherapy to bone, and hypercalcemia of malignancy. Skeletal morbidity may reduce patient mobility, limit functional independence, and impair quality of life (QOL). Proactive management of new or worsening bone pain or motor impairment is crucial because of the potential for rapid progression of symptoms. Administration of bisphosphonate therapy as a monthly infusion to patients with bone metastases prevents or delays the onset and reduces the frequency of SREs and provides clinically meaningful improvements in bone pain and QOL. In addition to administration of therapy, the monthly infusion visit allows a dedicated team of healthcare professionals to regularly assess SREs, response to therapy, adverse events (AEs), QOL, and adherence to oral medications and supplements. The continuity of care that occurs during the monthly infusion visit provides oncology nurses with an opportunity to educate patients about effective strategies to manage SREs and AEs. In addition, regular interaction provides oncology nurses with an opportunity to recognize and proactively address subtle changes in the patients’ medical condition. Using a multidisciplinary medical team also eliminates barriers between the various healthcare professionals involved in patient management. Consequently, the monthly infusion visit can result in effective patient management and improved clinical outcomes in patients with malignant bone disease. PMID:21206517

  18. Randomized phase II trial of rubidazone and adriamycin in women with advanced breast cancer.

    PubMed

    Ingle, J N; Ahmann, D L; O'Fallon, J R; Bisel, H F; Rubin, J; Kvols, L K; Giuliani, E R

    1979-01-01

    Thirty-eight females with advanced breast cancer who had failed prior chemotherapy were entered in a randomized study of rubidazone (150 mg/m2 iv over 1 hour) versus Adriamycin (60 mg/m2 iv over 5 minutes), both given every 4 weeks. The two treatment groups each contained 19 patients and were similar with respect to age, menopausal status, dominant disease status, Eastern Cooperative Oncology Group performance score, and prior hormonal therapy and chemotherapy exposure. No regressions (complete or partial) were observed with rubidazone, but four (21%) patients achieved regressions (one complete and three partial) with Adriamycin. Considering all cycles, hematologic toxicity included leukopenia (wbc count nadir of less than 4000/mm3) in 88% of patients receiving rubidazone and in 89% of those receiving Adriamycin. Three of eight patients treated with Adriamycin after rubidazone failure achieved a regression. Rubidazone appears to be of little value in the treatment of patients with advanced breast cancer who have failed prior chemotherapy.

  19. Galectins in hematological malignancies.

    PubMed

    Giordano, Mirta; Croci, Diego O; Rabinovich, Gabriel A

    2013-07-01

    Galectins are a family of lectin molecules that have emerged as key players in inflammation and tumor progresssion by displaying intracellular and extracellular activities. This review describes the recent advances on the role of galectins in hematological neoplasms. Galectin-1 and galectin-3 are the best studied galectins in oncohematology. Increased expression of galectin-1 has been associated with tumor progression in Hodgkin's lymphoma and chronic lymphocytic leukemia, whereas galectin-3 plays a supporting role in chronic myelogenous leukemia and multiple myeloma. Functional studies have assigned a key role for galectin-1 as a negative regulator of T-cell immunity in Hodgkin's lymphoma and cutaneous T-cell lymphoma. Of therapeutic interest is the development of agents with the capacity to interfere with galectin functions. Current knowledge indicates a key role for galectins in hematological neoplasms by favoring the growth and survival of tumor cells and facilitating tumor immune escape. Intervention using specific galectin inhibitors is emerging as an attractive therapeutic option to alter the course of these malignancies.

  20. American Society of Hematology

    MedlinePlus

    ... Navigation Account Navigation Main Content American Society of Hematology ASH Store ASH Job Center ASH Apps Share ... youtube linkedin Research In This Section Agenda for Hematology Research Sickle Cell Priorities Lymphoma Roadmap Moonshot Initiative ...

  1. Population-Based Analysis of Hematologic Malignancy Referrals to a Comprehensive Cancer Center, Referrals for Blood and Marrow Transplantation, and Participation in Clinical Trial, Survey, and Biospecimen Research by Race.

    PubMed

    Clay, Alyssa; Peoples, Brittany; Zhang, Yali; Moysich, Kirsten; Ross, Levi; McCarthy, Philip; Hahn, Theresa

    2015-08-01

    Racial and ethnic disparities have been reported in clinical trial/research participation, utilization of autologous and allogeneic blood and marrow transplantation (BMT), and availability of allogeneic donors. We performed a population-based cohort study to investigate adult hematologic malignancy referrals to a US tertiary cancer center, utilization of BMT, and participation in clinical trial, survey, and biospecimen research by race. US Census Data and the New York State Public Access Cancer Epidemiology Database identified the racial distribution of the general population and new hematologic malignancy cases in the primary catchment area. From 2005 to 2011, 1106 patients aged 18 to 75 years were referred for BMT consultation; although the rate of BMT among hematologic malignancy referrals did not differ by race, the reasons for not receiving a BMT did. Participation in biospecimen research did not vary by race; however, African Americans and other minorities were significantly less likely to participate in survey research than European Americans. Although rates of hematologic malignancy referrals and use of BMT for minorities appear to be low (<10%), they closely reflect the race distribution of all hematologic malignancy cases and the western New York population. African Americans are equally likely as other races to participate in biospecimen banking, but further study is needed to understand reasons for lower participation in survey research. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Lactobacillus in Preventing Infection in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2017-02-02

    Breast Cancer; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  3. Crizotinib for Advanced Non-Small Cell Lung Cancer

    Cancer.gov

    A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

  4. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Cancer.gov

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  5. Bevacizumab improves survival for patients with advanced cervical cancer

    Cancer.gov

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  6. Blocking DNA Repair in Advanced BRCA-Mutated Cancer

    Cancer.gov

    In this trial, patients with relapsed or refractory advanced cancer and confirmed BRCA mutations who have not previously been treated with a PARP inhibitor will be given BMN 673 by mouth once a day in 28-day cycles.

  7. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  8. Epigenetics of hematopoiesis and hematological malignancies

    PubMed Central

    Hu, Deqing; Shilatifard, Ali

    2016-01-01

    Hematological malignancies comprise a diverse set of lymphoid and myeloid neoplasms in which normal hematopoiesis has gone awry and together account for ∼10% of all new cancer cases diagnosed in the United States in 2016. Recent intensive genomic sequencing of hematopoietic malignancies has identified recurrent mutations in genes that encode regulators of chromatin structure and function, highlighting the central role that aberrant epigenetic regulation plays in the pathogenesis of these neoplasms. Deciphering the molecular mechanisms for how alterations in epigenetic modifiers, specifically histone and DNA methylases and demethylases, drive hematopoietic cancer could provide new avenues for developing novel targeted epigenetic therapies for treating hematological malignancies. Just as past studies of blood cancers led to pioneering discoveries relevant to other cancers, determining the contribution of epigenetic modifiers in hematologic cancers could also have a broader impact on our understanding of the pathogenesis of solid tumors in which these factors are mutated. PMID:27798847

  9. Visual disturbances in advanced cancer patients: clinical observations.

    PubMed

    Saita, L; Polastri, D; De Conno, F

    1999-03-01

    Visual disturbances in advanced cancer patients are very rarely signaled, evaluated, or adequately treated. The main causes of sight disturbances are primary eye tumors, ocular metastases, and some paraneoplastic syndromes. Sight alteration can also be associated with asthenia, fatigue, anemia, and hypovitaminosis. These symptoms can be monocular or binocular, and their gravity and evolution can vary. Based on a survey of 156 patients, we estimate the prevalence of visual disturbances to be 12% in advanced cancer patients.

  10. Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

    DTIC Science & Technology

    2016-03-01

    Award Number: W81XWH-12-1-0323 TITLE: Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach PRINCIPAL... control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE March 2016 2. REPORT TYPE Final 3. DATES COVERED 4. TITLE AND...SUBTITLE Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

  11. End of life care in hematology: still a challenging concern.

    PubMed

    Niscola, Pasquale; Tendas, Andrea; Scaramucci, Laura; Giovannini, Marco

    2014-01-01

    The majority of patients with hematological malignancies (HM) may experience troublesome symptoms and complicating clinical syndromes throughout all phases of disease. Therefore, among the current concepts concerning the comprehensive management of hematological patients, palliative care should exert a more ever expanding role, in particular in the advanced phases of disease, as there are special clinical needs (such as blood transfusions and anti-infective treatments), presented by this peculiar category of cancer patients. However, reported experiences on advanced HM patients claimed a too intensive level of medical care during the last week of life for which the needs of future and collaborative researches in order to set a proper allocation of medical resources and the optimal end-of-life care in the hematologic setting are highly awaited. Indeed, the most important aspect of caring for these suffering patients is to ameliorate or restore their quality of life (QoL) though a highly humanized approach, whereas technological and pharmacological measures should be limited enough to control the symptoms burden and the several kinds of sufferance that may complicate the final phase of disease course.

  12. Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Advanced Ovarian Cancer Trialists Group.

    PubMed Central

    1991-01-01

    OBJECTIVES--To consider the role of platinum and the relative merits of single agent and combination chemotherapy in the treatment of advanced ovarian cancer. DESIGN--Formal quantitative overview using updated individual patient data from all available randomised trials (published and unpublished). SUBJECTS--8139 patients (6408 deaths) included in 45 different trials. RESULTS--No firm conclusions could be reached. Nevertheless, the results suggest that in terms of survival immediate platinum based treatment was better than non-platinum regimens (overall relative risk 0.93; 95% confidence interval 0.83 to 1.05); platinum in combination was better than single agent platinum when used in the same dose (overall relative risk 0.85; 0.72 to 1.00); and cisplatin and carboplatin were equally effective (overall relative risk 1.05; 0.94 to 1.18). CONCLUSIONS--In the past, randomised clinical trials of chemotherapy in advanced ovarian cancer have been much too small to detect the degree of benefit which this overview suggests is realistic for currently available chemotherapeutic regimens. Hence a new trial comparing cisplatin, doxorubicin, and cyclophosphamide (CAP) with carboplatin has been launched and plans to accrue 2000 patients. PMID:1834291

  13. Major clinical research advances in gynecologic cancer in 2014.

    PubMed

    Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

    2015-04-01

    In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

  14. Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high-risk hematologic patients with cancer with febrile neutropenia.

    PubMed

    Bucaneve, Giampaolo; Micozzi, Alessandra; Picardi, Marco; Ballanti, Stelvio; Cascavilla, Nicola; Salutari, Prassede; Specchia, Giorgina; Fanci, Rosa; Luppi, Mario; Cudillo, Laura; Cantaffa, Renato; Milone, Giuseppe; Bocchia, Monica; Martinelli, Giovanni; Offidani, Massimo; Chierichini, Anna; Fabbiano, Francesco; Quarta, Giovanni; Primon, Valeria; Martino, Bruno; Manna, Annunziata; Zuffa, Eliana; Ferrari, Antonella; Gentile, Giuseppe; Foà, Robin; Del Favero, Albano

    2014-05-10

    Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria. In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment. Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups. The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.

  15. Complementary and alternative therapies for advanced prostate cancer.

    PubMed

    Smith, M R

    2001-06-01

    This article reviews complementary and alternative therapies for advanced prostate cancer. This is not a comprehensive survey of nontraditional therapies for prostate cancer. Rather, this review focuses on alternative and complementary therapies with published studies to evaluate efficacy and safety. Three areas are addressed: alternative forms of hormonal therapy, management of side effects of hormonal therapy, and management of skeletal complications.

  16. Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

    DTIC Science & Technology

    2013-03-01

    target for therapy of prostate cancer , but approaches aimed at Ras itself, or its critical signaling pathways, which are required in normal tissues...Impact: Current therapies for prostate cancer are inadequate, and aberrant activation of Ras or Ras pathways are common. A novel therapeutic modality...to Advanced Prostate Cancer PRINCIPAL INVESTIGATOR: Douglas V. Faller, PhD, MD CONTRACTING ORGANIZATION: Trustees of Boston University

  17. Sipuleucel-T for the treatment of advanced prostate cancer.

    PubMed

    Frohlich, Mark W

    2012-06-01

    Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an immune response to prostate cancer that prolongs the overall survival of men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC). The clinical development program and key efficacy, safety, and immune response findings from the phase III studies are presented. The integration of sipuleucel-T into the treatment paradigm of advanced prostate cancer and future directions for research are discussed.

  18. Drug discovery in advanced prostate cancer: translating biology into therapy.

    PubMed

    Yap, Timothy A; Smith, Alan D; Ferraldeschi, Roberta; Al-Lazikani, Bissan; Workman, Paul; de Bono, Johann S

    2016-10-01

    Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs.

  19. Advances in the Management of Biliary Tract Cancers

    PubMed Central

    Ciombor, Kristen Keon; Goff, Laura Williams

    2013-01-01

    Biliary tract cancers (BTC), though uncommon, are highly fatal malignancies, and current treatments fail to cure or control the majority of tumors. Given the complexity of the anatomy and often aggressive nature of the disease, multidisciplinary treatment, including palliation, is often required. However, systemic therapy with cytotoxics and/or targeted agents are routinely the mainstay of treatment for patients with advanced biliary tract cancers, and new targets and agents provide hope for this disease. This article focuses on recent advances in the management of biliary tract cancers, with a special focus on the molecular basis for current therapeutic investigation in this disease. PMID:23416860

  20. Advances of Cancer Therapy by Nanotechnology

    PubMed Central

    Wang, Xu; Wang, Yiqing; Chen, Zhuo Georgia

    2009-01-01

    Recent developments in nanotechnology offer researchers opportunities to significantly transform cancer therapeutics. This technology has enabled the manipulation of the biological and physicochemical properties of nanomaterials to facilitate more efficient drug targeting and delivery. Clinical investigations suggest that therapeutic nanoparticles can enhance efficacy and reduced side effects compared with conventional cancer therapeutic drugs. Encouraged by rapid and promising progress in cancer nanotechnology, researchers continue to develop novel and efficacious nanoparticles for drug delivery. The use of therapeutic nanoparticles as unique drug delivery systems will be a significant addition to current cancer therapeutics. PMID:19688065

  1. Pyroxamide in Treating Patients With Advanced Cancer

    ClinicalTrials.gov

    2013-06-04

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  2. Barriers to cure for children with cancer in India and strategies to improve outcomes: a report by the Indian Pediatric Hematology Oncology Group.

    PubMed

    Yadav, Satya Prakash; Rastogi, Neha; Kharya, Gaurav; Misra, Ruchira; Ramzan, Mohammed; Katewa, Satyendra; Dua, Vikas; Bhat, Sunil; Kellie, Stewart J; Howard, Scott C

    2014-04-01

    The survival of children with cancer in India is inferior to that of children in high-income countries. The Indian Pediatric Hematology Oncology Group (IPHOG) held a series of online meetings via www.Cure4kids.org to identify barriers to cure and develop strategies to improve outcomes. Five major hurdles were identified: delayed diagnosis, abandonment, sepsis, lack of co-operative groups, and relapse. Development of regional networks like IPHOG has allowed rapid identification of local causes of treatment failure for children with cancer in India and identification of strategies likely to improve care and outcomes in the participating centers. Next steps will include interventions to raise community awareness of childhood cancer, promote early diagnosis and referral, and reduce abandonment and toxic death at each center. Starting of fellowship programs in pediatric hemato-oncology, short training programs for pediatricians, publishing outcome data, formation of parent and patient support groups, choosing the right and effective treatment protocol, and setting up of bone marrow transplant services are some of the effective steps taken in the last decade, which needs to be supported further.

  3. Effects on cancer patients of leukapheresis with the continuous-flow blood cell separator. I. Hematologic and immunologic parameters in vivo.

    PubMed

    Waldman, S R; Roth, J A; Silverstein, M; Veltman, L L; Pilch, Y H

    1975-12-01

    A study was undertaken to investigate the hematologic and in vivo immunologic effects of leukapheresis of from 2 X 10(9) to 1.6 X 10(10) peripheral blood lymphocytes from 9 cancer patients and 13 normal donors on the blood cell separator. The same parameters were measured in 10 individuals who did not undergo leukapheresis and 4 individuals who underwent sham leukapheresis. Studies were performed immediately prior to and following leukapheresis and at 4 hours, 1 day, 3 days, and 7 days following leukapheresis. There was a transient decline in blood lymphocyte pool (BLP) of the normal donors which returned to preleukapheresis values within 72 hours. Six of 13 normal donors and 2 of 9 cancer patients had a fall in blood lymphocyte count which was below the lower limit of the range of change in control donors immediately following leukapheresis, but all returned to control range within 24 hours. Five cancer patients had increases in lymphocyte count. DNCB reactivity and delayed cutaneous hypersensitivity reactions to common recall antigens were performed 2 weeks before, immediately before, and after leukapheresis, at 7 days and at 4 to 6 weeks following leukapheresis. There were no differences in skin test reactivity between groups. No clinical exacerbations of malignant disease occurred which might be construed to be due to leukapheresis.

  4. Advancing Breast Cancer Survivorship among African American Women

    PubMed Central

    Coughlin, Steven S.; Yoo, Wonsuk; Whitehead, Mary S.; Smith, Selina A.

    2015-01-01

    Purpose Advances have occurred in breast cancer survivorship but, for many African American women, challenges and gaps in relevant information remain. Methods This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African American women. Results For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. Conclusions There is a need for a better understanding of breast cancer survivorship among African American women. Additional evaluations of interventions for improving the quality of life and survival of African American breast cancer survivors are desirable. PMID:26303657

  5. Advancing breast cancer survivorship among African-American women.

    PubMed

    Coughlin, Steven S; Yoo, Wonsuk; Whitehead, Mary S; Smith, Selina A

    2015-09-01

    Advances have occurred in breast cancer survivorship but, for many African-American women, challenges and gaps in relevant information remain. This article identifies opportunities to address disparities in breast cancer survival and quality of life, and thereby to increase breast cancer survivorship among African-American women. For breast cancer survivors, common side effects, lasting for long periods after cancer treatment, include fatigue, loss of strength, difficulty sleeping, and sexual dysfunction. For addressing physical and mental health concerns, a variety of interventions have been evaluated, including exercise and weight training, dietary interventions, yoga and mindfulness-based stress reduction, and support groups or group therapy. Obesity has been associated with breast cancer recurrence and poorer survival. Relative to white survivors, African-American breast cancer survivors are more likely to be obese and less likely to engage in physical activity, although exercise improves overall quality of life and cancer-related fatigue. Considerable information exists about the effectiveness of such interventions for alleviating distress and improving quality of life among breast cancer survivors, but few studies have focused specifically on African-American women with a breast cancer diagnosis. Studies have identified a number of personal factors that are associated with resilience, increased quality of life, and positive adaptation to a breast cancer diagnosis. There is a need for a better understanding of breast cancer survivorship among African-American women. Additional evaluations of interventions for improving the quality of life and survival of African-American breast cancer survivors are desirable.

  6. Localization of thymidine phosphorylase in advanced gastric and colorectal cancer.

    PubMed

    Kobayashi, Michiya; Okamoto, Ken; Akimori, Toyokazu; Tochika, Naoshige; Yoshimoto, Tadashi; Okabayashi, Takehiro; Sugimoto, Takeki; Araki, Keijiro

    2004-01-01

    Thymidine phosphorylase (TP) is known to be more concentrated in human cancer tissues than in adjacent normal tissue based on findings using enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. However, the ultrastructural localization of TP in cancer tissues has not previously been demonstrated. We investigated the localization of TP in gastric cancer and colorectal cancer tissue by ELISA, immunohistochemistry, and immunoelectron microscopy. Between April 1997 and May 2000, we obtained surgically resected specimens from 42, 46, and 36 cases of advanced gastric, colon, and rectal cancer, respectively. ELISA demonstrated that the TP level was higher in cancer tissues than in adjacent normal tissue. Immunohistochemically, cancer cells were positive for the enzyme in some cases. However, in a number of cases immunopositive inflammatory cells were also present in cancerous tissues. At the electron microscope level, TP was diffusely distributed in the cytoplasm of cancer cells and in the mitochondria of the neutrophil in gastric cancer tissue. In rectal cancer tissues, cytoplasmic granules in macrophages in cancer tissues were immunoreactive for the TP. These findings suggest that TP is produced by macrophages and exists in neutrophils and cancer cells.

  7. Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer.

    PubMed

    Lee, K-W; Park, S R; Oh, D-Y; Park, Y-I; Khosravan, R; Lin, X; Lee, S-Y; Roh, E-J; Valota, O; Lechuga, M J; Bang, Y-J

    2013-12-01

    We evaluated the maximum tolerated dose (MTD) and safety of sunitinib plus capecitabine/cisplatin (XP) or capecitabine/oxaliplatin (XELOX) in Korean patients with advanced gastric cancer (GC). Sunitinib (37.5 or 25 mg/day) was administered on a 2-week-on/1-week-off schedule with chemotherapy. Assessments included dose-limiting toxicity (DLT), safety, pharmacokinetics, and antitumor activity. Twenty-eight patients received sunitinib/XP; 48 received sunitinib/XELOX. The MTDs were: sunitinib 25 mg/day, cisplatin 80 mg/m(2), and capecitabine 1,000 mg/m(2); sunitinib 37.5 mg/day, oxaliplatin 110 mg/m(2), and capecitabine 800 mg/m(2); and sunitinib 25 mg/day, oxaliplatin 110 mg/m(2), and capecitabine 1,000 mg/m(2). DLTs at the MTDs comprised grade (G) 4 febrile neutropenia plus G3 diarrhea (n = 1; sunitinib/XP), dose delays due to hematologic toxicity (n = 2; both sunitinib/XP), G3 bleeding (menorrhagia; n = 1; sunitinib/XELOX), and G3 increased alanine aminotransferase levels (n = 1; sunitinib/XELOX). There was a high frequency of G3/4 hematologic adverse events observed with both treatment regimens, particularly with sunitinib/XP. Frequent non-hematologic, G3/4 adverse events were nausea, stomatitis, and hypophosphatemia with sunitinib/XP and hypophosphatemia and pulmonary embolism with sunitinib/XELOX. No drug-drug interactions were apparent. At the MTDs, median progression-free survival was 6.4 months and 5.5-8.0 months for sunitinib/XP and sunitinib/XELOX, respectively; and the objective response rate was 46.7% and 43.5-45.5% for sunitinib/XP and sunitinib/XELOX, respectively. At the MTD, sunitinib/XELOX had an acceptable safety profile in patients with advanced GC.

  8. Lung Cancer Clinical Trials: Advances in Immunotherapy

    Cancer.gov

    New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.

  9. Recent advances in lung cancer biology

    SciTech Connect

    Lechner, J.

    1995-12-31

    This paper provides an overview of carcinogenesis, especially as related to lung cancers. Various growth factors and their mutated forms as oncogenes are discussed with respect to gene location and their role in the oncogenic process. Finally the data is related to lung cancer induction in uranium miners and exposure to radon.

  10. Targeting protein-protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies?

    PubMed Central

    Cierpicki, Tomasz; Grembecka, Jolanta

    2015-01-01

    Summary Over the past several years, there has been an increasing research effort focused on inhibition of protein-protein interactions (PPIs) to develop novel therapeutic approaches for cancer, including hematologic malignancies. These efforts have led to development of small molecule inhibitors of PPIs, some of which already advanced to the stage of clinical trials while others are at different stages of pre-clinical optimization, emphasizing PPIs as an emerging and attractive class of drug targets. Here, we review several examples of recently developed inhibitors of protein-protein interactions highly relevant to hematologic cancers. We address the existing skepticism about feasibility of targeting PPIs and emphasize potential therapeutic benefit from blocking PPIs in hematologic malignancies. We then use these examples to discuss the approaches for successful identification of PPI inhibitors and provide analysis of the protein-protein interfaces, with the goal to address ‘druggability’ of new PPIs relevant to hematology. We discuss lessons learned to improve the success of targeting new protein-protein interactions and evaluate prospects and limits of the research in this field. We conclude that not all PPIs are equally tractable for blocking by small molecules, and detailed analysis of PPI interfaces is critical for selection of those with the highest chance of success. Together, our analysis uncovers patterns that should help to advance drug discovery in hematologic malignancies by successful targeting of new protein-protein interactions. PMID:25510283

  11. Current advances in T-cell-based cancer immunotherapy.

    PubMed

    Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

    2014-01-01

    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

  12. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  13. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    PubMed

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

  14. Cancer and Radiation Therapy: Current Advances and Future Directions

    PubMed Central

    Baskar, Rajamanickam; Lee, Kuo Ann; Yeo, Richard; Yeoh, Kheng-Wei

    2012-01-01

    In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed. PMID:22408567

  15. Survival outcomes and toxicity of intraoperative intraperitoneal chemotherapy in advanced epithelial ovarian cancer

    PubMed Central

    Yoon, Ji-Young; Koo, Yu-Jin; Kim, Mi-Jung; Kim, Tae-Jin; Lim, Kyung-Taek

    2014-01-01

    Objective To assess the effect of single-dose cisplatin intraperitoneally administered during cytoreductive surgery in advanced epithelial ovarian cancer. Methods Data from patients who underwent surgical management followed by intravenous (IV) chemotherapy for stage III epithelial ovarian cancer from 2003 to 2012 were retrospectively reviewed. Subjects were divided into intraperitoneal (IP) and no-intraperitoneal (NIP) groups according to the administration of IP cisplatin 100 mg during the staging surgery. Clinical results such as survival outcomes and chemotherapeutic toxicity were compared between the two groups. Results Thirty-seven patients in the IP group and 26 in the NIP group were identified. There were no significant differences between the two groups in basic characteristics such as age, histology, and surgical procedures. After the surgery with or without IP chemotherapy, there was no difference in the rate of either hematologic or gastrointestinal toxicity or in the rate of incompletion of following IV chemotherapy. Tumor recurrence occurred in 67.6% (25 patients) of IP group and 57.7% (15 patients) of NIP group (P=0.423) during the mean follow-up period of 37 months. The 3-year disease free-survival rate was 39.9% in the IP group and 35.8% in the NIP group, and the relative risk of recurrence was 0.864 (95% confidence interval, 0.447-1.673; P=0.665) in the IP group as compared with the NIP group. Conclusion IP chemotherapy with single-dose cisplatin during cytoreductive surgery is safe and feasible with little chemotherapeutic toxicity in advanced epithelial ovarian cancer, but no distinct improvement in survival could be demonstrated in the present study. PMID:25469337

  16. Artificial intelligence in hematology.

    PubMed

    Zini, Gina

    2005-10-01

    Artificial intelligence (AI) is a computer based science which aims to simulate human brain faculties using a computational system. A brief history of this new science goes from the creation of the first artificial neuron in 1943 to the first artificial neural network application to genetic algorithms. The potential for a similar technology in medicine has immediately been identified by scientists and researchers. The possibility to store and process all medical knowledge has made this technology very attractive to assist or even surpass clinicians in reaching a diagnosis. Applications of AI in medicine include devices applied to clinical diagnosis in neurology and cardiopulmonary diseases, as well as the use of expert or knowledge-based systems in routine clinical use for diagnosis, therapeutic management and for prognostic evaluation. Biological applications include genome sequencing or DNA gene expression microarrays, modeling gene networks, analysis and clustering of gene expression data, pattern recognition in DNA and proteins, protein structure prediction. In the field of hematology the first devices based on AI have been applied to the routine laboratory data management. New tools concern the differential diagnosis in specific diseases such as anemias, thalassemias and leukemias, based on neural networks trained with data from peripheral blood analysis. A revolution in cancer diagnosis, including the diagnosis of hematological malignancies, has been the introduction of the first microarray based and bioinformatic approach for molecular diagnosis: a systematic approach based on the monitoring of simultaneous expression of thousands of genes using DNA microarray, independently of previous biological knowledge, analysed using AI devices. Using gene profiling, the traditional diagnostic pathways move from clinical to molecular based diagnostic systems.

  17. Increased rates of advanced thyroid cancer in California.

    PubMed

    Harari, Avital; Singh, Rasnik K

    2016-03-01

    We have noted an unusually high rate of advanced thyroid cancers presenting from across California. We examined the rates of thyroid cancer presentation throughout California for potential geographic clustering. A total of 26,983 patients with a new diagnosis of thyroid cancer (1999-2008) were abstracted from the California Cancer Registry and the Office of Statewide Health Planning and Development registry. Percentages of advanced thyroid cancer rates were calculated within each county (defined as those with distant metastatic stage; regional and/or distant metastatic stage [RM]) as well as those with well-differentiated thyroid cancer diagnosed before age 30. National averages were taken from Surveillance, Epidemiology, and End Results (SEER) data. There was no obvious clustering of advanced cases within certain regions in California; however, on average, the entire state of California had significantly higher rates of distant metastatic thyroid cancer (6.73%) and RM (34.92%) than the national SEER averages (4%, 29%, respectively, P < 0.001). Of the 47 California counties, 20 had significantly higher percentages of distant metastatic thyroid cancer than the national SEER average (range, 6%-13% versus 4%, P < 0.05), and 20 had a higher percentage of RM than the national SEER average (range, 35%-48% versus 29%, P < 0.05). Two California counties had higher rates of young patients with well-differentiated thyroid cancer (range, 14.29%-17.9%) than the national SEER average (12%). California exhibits more advanced thyroid cancers than the national SEER population average. Further studies are warranted to better understand etiologies for these disparities, which may include environmental impacts and/or delays in diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Conceptualizing prognostic awareness in advanced cancer: a systematic review.

    PubMed

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2014-09-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients' understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness.

  19. Conceptualizing prognostic awareness in advanced cancer: A systematic review

    PubMed Central

    Applebaum, Allison J; Kolva, Elissa A; Kulikowski, Julia R; Jacobs, Jordana D; DeRosa, Antonio; Lichtenthal, Wendy G; Olden, Megan E; Rosenfeld, Barry; Breitbart, William

    2015-01-01

    This systematic review synthesizes the complex literature on prognostic awareness in cancer. A total of 37 studies examining cancer patients’ understanding of their prognosis were included. Prognostic awareness definitions and assessment methods were inconsistent across studies. A surprisingly high percentage of patients (up to 75%) were unaware of their poor prognosis, and in several studies, even their cancer diagnosis (up to 96%), particularly in studies conducted outside of North America. This review highlights surprisingly low rates of prognostic awareness in patients with advanced cancer as well as discrepancies in prognostic awareness assessment, suggesting the need for empirically validated measures of prognostic awareness. PMID:24157936

  20. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  1. Radium-223 for Advanced Prostate Cancer

    Cancer.gov

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  2. Recent advances in personalized lung cancer medicine

    PubMed Central

    Okimoto, Ross A; Bivona, Trever G

    2014-01-01

    The identification of molecular subtypes of non-small-cell lung cancer has transformed the clinical management of this disease. This is best exemplified by the clinical success of targeting the EGFR or ALK with tyrosine kinase inhibitors in the front-line setting. Our ability to further improve patient outcomes with biomarker-based targeted therapies will depend on a more comprehensive genetic platform that can rationally interrogate the cancer genome of an individual patient. Novel technologies, including multiplex genotyping and next-generation sequencing are rapidly evolving and will soon challenge the oncologist with a wealth of genetic information for each patient. Although there are many barriers to overcome, the integration of these genetic platforms into clinical care has the potential to transform the management of lung cancer through improved molecular categorization, patient stratification, and drug development, thereby, improving clinical outcomes through personalized lung cancer medicine. PMID:25506379

  3. Sipuleucel-T: immunotherapy for advanced prostate cancer.

    PubMed

    Olson, Brian M; McNeel, Douglas G

    2011-05-03

    Prostate cancer continues to be one of the most serious afflictions of men of advanced age, remaining the most commonly diagnosed and second leading cause of cancer-related deaths in American men. The treatment options for patients with incurable metastatic, castrate-resistant disease have long focused on various chemotherapeutic approaches, which provide a slight survival benefit while being associated with potentially significant side effects. However, the recent approval of sipuleucel-T has given patients with advanced disease an additional treatment option that has demonstrated benefit without the side effects associated with chemotherapy. Sipuleucel-T is an antigen-presenting cell-based active immunotherapy that utilizes a patient's own immune cells, presumably to activate an antigen-specific immune response against tumor cells. This review focuses on the development and implementation of sipuleucel-T as a therapy for prostate cancer. Specifically, we present some of the issues associated with the management of advanced prostate cancer, the research and development that led to the approval of sipuleucel-T, how the approval of sipuleucel-T could change the clinical management of prostate cancer, and current and future areas of investigation that are being pursued with regard to sipuleucel-T and other treatments for advanced prostate cancer.

  4. Advanced gastric cancer: Current treatment landscape and future perspectives

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

    Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer. PMID:26937129

  5. Outcome and toxicity profiles in the treatment of locally advanced lung cancer with volumetric modulated arc therapy.

    PubMed

    Scorsetti, Marta; Navarria, Piera; De Rose, Fiorenza; Ascolese, AnnaMaria; Clerici, Elena; Franzese, Ciro; Lobefalo, Francesca; Reggiori, Giacomo; Mancosu, Pietro; Tomatis, Stefano; Fogliata, Antonella; Cozzi, Luca

    2014-11-01

    To report about the outcome of radiation treatment of advanced lung cancer patients with volumetric modulated arcs [RapidArc (RA)]. Seventy-five consecutive patients (all stages IIIA and IIIB) were treated with RA. Among them 71 % were men; 25.4 % presented unspecified non-small cell lung cancer, 41.3% adenocarcinoma and 33.3 % squamous cell carcinoma. Of them, 54.7 % received sequential chemotherapy while 45.3% were treated with concomitant regimen. Dose prescription ranged from 54 to 72 Gy. Analysis included survival, local control (LC) and toxicity profiles. Median follow-up was 21.2 months (range 6-75). One- two- and five-year actuarial LC was 91.9 ± 3.2, 79.5 ± 5.7 and 67.4 ± 9.5 %, respectively. Median survival was 19.0 ± 1.1 months. Actuarial survival at 1-2-5 years was 80.0 ± 4.6, 38.5 ± 5.9 and 15.2 ± 4.9 %, respectively. Acute toxicity of G2 was reported in 24, 25.3 and 4.0 % of patients for lung, esophageal and hematological profiles. A total of 2.7 % of patients reported G3 toxicity in the esophagus and 5.3 % of the patients experienced G3-G4 hematological toxicity. Significant differences were observed in all cases between concomitant and sequential chemotherapy regiments. Only 1.3 % (1 patient) showed G2 lung late toxicity. No significant correlation was found between toxicity and organ's irradiation levels. RA proved to be a safe and advantageous treatment modality for advanced lung cancer with results in line with expectations from earlier literature.

  6. Myofacial Trigger Points in Advanced Cancer Patients

    PubMed Central

    Hasuo, Hideaki; Ishihara, Tatsuhiko; Kanbara, Kenji; Fukunaga, Mikihiko

    2016-01-01

    Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation. We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points. PMID:26962285

  7. Neonatal hematologic disorders.

    PubMed

    Purves, Erica

    2005-01-01

    Neonatal hematology is a complex subspecialty of pediatric hematology, combining the unique aspects of the maternal/fetal relationship, the delicate balance of coagulation factors, and the distinctive physiologic conditions of the newborn period. The objective of this article is to briefly review specific hematologic disorders that commonly present in the newborn period. Alloimmune cytopenias, polycythemia, thrombosis and bleeding associated with vitamin K deficiency will be discussed through a focus on pathophysiology, signs and symptoms, current treatment strategies, and implications for nursing care.

  8. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-12-18

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  9. Association Between Bone Marrow Dosimetric Parameters and Acute Hematologic Toxicity in Anal Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Mell, Loren K. Schomas, David A.; Salama, Joseph K.; Devisetty, Kiran; Aydogan, Bulent; Miller, Robert C.; Jani, Ashesh B.; Kindler, Hedy L.; Roeske, John C.; Chmura, Steven J.

    2008-04-01

    Purpose: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V{sub 10} and PBM-V{sub 20}) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. Methods and Materials: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. Results: Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V{sub 5}, V{sub 10}, V{sub 15}, and V{sub 20} were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V{sub 10}, V{sub 15}, and V{sub 20} (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). Conclusion: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.

  10. Prospective phase I evaluation of radiation therapy, 5-fluorouracil, and levamisole in locally advanced gastrointestinal cancer.

    PubMed

    Martenson, J A; Schutt, A J; Grado, G L; Maples, W J; Marschke, R F

    1994-01-15

    A recent clinical trial in patients with resected node-positive colon cancer demonstrated a clear survival advantage for patients treated with adjuvant 5-fluorouracil and levamisole. This finding led to interest in development of a Phase III trial comparing 5-fluorouracil and levamisole with 5-fluorouracil, levamisole, and radiation therapy in colon cancer patients at high risk for local recurrence. A prospective evaluation of 5-fluorouracil, levamisole, and radiation therapy was undertaken with the goal of establishing a satisfactorily tolerated regimen. Fifteen patients were studied who had locally advanced or locally recurrent upper abdominal gastrointestinal cancer (11 patients) or large bowel cancer confined to the pelvis (4 patients). The tumor and regional lymph nodes received 45 Gy in 25 fractions. Patients with pelvic tumors subsequently were treated with a radiation boost of 5.4-9 Gy in 3-5 fractions. Systemic therapy consisted of 5-fluorouracil, 450 mg/m2, given intravenously for 3 consecutive days during the first and last weeks of radiation therapy. Levamisole, 50 mg, given orally 3 times daily was used for 3 consecutive days concurrent with initiation of radiation therapy and 5-fluorouracil, at the beginning of the third week of radiation therapy, and concurrent with the final 3-day course of 5-fluorouracil. Therapy was generally well tolerated. In two patients, > or = grade 3 nonhematologic toxicity developed and consisted of transient small bowel obstruction in one and severe nausea and vomiting related to levamisole administration in another. One patient experienced grade 3 hematologic toxicity with a leukocyte count nadir of 1,600 cells/microL. These results are similar to the toxicity profile reported elsewhere for radiation therapy and 5-fluorouracil. The addition of levamisole to radiation therapy and 5-fluorouracil does not appear to increase toxicity significantly.

  11. Current management of advanced and castration resistant prostate cancer.

    PubMed

    Gomella, Leonard G; Petrylak, Daniel P; Shayegan, Bobby

    2014-04-01

    Newer approaches to the management of advanced prostate cancer have rapidly evolved. While basic androgen deprivation remains as the first line in newly diagnosed hormone naïve metastatic prostate cancer, the agents used and strategies followed have undergone significant changes. Numerous new agents such as sipuleucel-T, abiraterone, enzalutamide, cabazitaxel and radium 223 have all been approved since 2010 to treat metastatic castration resistant prostate cancer (CRPC). New imaging techniques to detect advanced disease such as F-18 PET, 11 C-choline PET and other modalities are becoming available. The concepts of "bone health" and the management of side effects related to androgen deprivation therapy are also gaining attention as men are being treated with longer courses of androgen deprivation. Understanding the theory behind these new agents and management approaches while focusing on the practical clinical considerations are essential to improve outcomes in advanced prostate cancer. A review of the current state of the art in the management of advanced and castration resistant prostate cancer presented in this Canadian Journal of Urology International supplement was performed. Key findings are summarized and presented along with critical updates based on recent publications and meeting presentations. Key concepts identified in the management of advanced prostate cancer included the new understanding of prostate cancer based on translational discoveries, applications of various hormonally based strategies in advanced disease including traditional and recently approved agents. The use of new imaging modalities to identify metastatic disease, immunotherapy approaches and discussions of sequencing and which new agents are likely to be available in the future in the management of CRPC were identified. Bone targeted strategies are also addressed in the setting of androgen deprivation and metastatic disease. The management of men with advanced prostate cancer has

  12. Photodynamic Cancer Therapy—Recent Advances

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2011-09-01

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when "photoradiation therapy" was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  13. Nanovector-based therapies in advanced pancreatic cancer

    PubMed Central

    Tsai, Chang-Sung

    2011-01-01

    Systemic therapy for advanced pancreatic cancer has been largely disappointing owing to the unfavorable pharmacokinetic profile and poor penetration of current chemotherapeutic agents ,as well as the fragile patient population with compromised tolerance to toxic chemotherapies. Nanovectors can provide passive drug delivery through abnormal tumor neo-vasculature microanatomy or active targeting via binding to receptors or macromolecules associated with the tumor. In such a manner, nanovector-based therapy may not only modulate the pharmacokinetics and therapeutic index of chemotherapeutic agents but also provide new treatment options in patients with advanced pancreatic cancer. In this article, we present the rationale and currently available clinical results of nanovector-based therapies to highlight the potential use of this class of agent in patients with advanced pancreatic cancer. PMID:22811849

  14. Assessing spirituality and religiousness in advanced cancer patients.

    PubMed

    Mystakidou, Kyriaki; Tsilika, Eleni; Parpa, Efi; Smyrnioti, Marilena; Vlahos, Lambros

    The aim of this study was to translate the Spiritual Involvement and Beliefs Scale into the Greek language and validate its psychometric properties in a sample of advanced cancer patients treated in a palliative care unit. The scale was translated into Greek with the "forward-backward" procedure. It was administered twice, with a 3-day interval, to 82 patients with advanced cancer. Patients completed the Spiritual Involvement and Beliefs Scale and the Greek Hospital Anxiety and Depression Scale. The scale had an overall Cronbach alpha of 0.89. Overall test-retest reliability was satisfactory at P<.0005. Satisfactory construct validity was supported between the Spiritual Involvement and Beliefs Scale subscales and Hospital Anxiety and Depression subscales. Interscale and interitem correlations were found satisfactory at P<.0005. These results support that the Spiritual Involvement and Beliefs Scale is an instrument with satisfactory psychometric properties and is a valid research tool for spirituality in advanced cancer patients.

  15. Evolving treatment paradigms for locally advanced and metastatic prostate cancer.

    PubMed

    Dorff, Tanya B; Quek, Marcus L; Daneshmand, Siamak; Pinski, Jacek

    2006-11-01

    While men with early stage prostate cancer typically enjoy long-term survival after definitive management, for those who present with locally advanced or metastatic disease, survival is compromised. Multimodality therapy can prolong survival in these patients, with state-of-the-art options including intensity-modulated radiation or brachytherapy in conjunction with androgen ablation, adjuvant androgen ablation and/or chemotherapy with radical retropubic prostatectomy. In addition, novel biological therapies are being explored to target the unique molecular changes in prostate cancer cells and their interactions with the microenvironment. With these advances the outlook will undoubtedly improve, even for patients presenting with advanced disease. Careful application of these emerging therapies to a select group of prostate cancer patients most likely to obtain benefit from them is the challenge for urologists, medical oncologists and radiation oncologists for the future.

  16. Nanoparticles for Advanced Photodynamic Therapy of Cancer.

    PubMed

    Abrahamse, Heidi; Kruger, Cherie Ann; Kadanyo, Sania; Mishra, Ajay

    2017-09-21

    The world widespread rise in cancer incidence has caused an increase in the demand for effective and safe materials for treatment. One of the most prevalent forms of treatment for cancer is photodynamic therapy (PDT), which is seen as an alternative to radiotherapy, as well as chemotherapy. In more recent years, researchers are exploring new nanotechnology-based strategies to improve the effectiveness of PDT. The objective of this review is to explore the current trends and research findings associated with PDT and the development of nanotechnology as treatment modality for cancer. Nanotechnology commonly deals with nanomaterials, which are well defined by their reduced size (which is <100 nm), allowing these small nanostructured particles to have unique physical, chemical, and biological properties. The unique properties of nanomaterials attribute them to have enormous potential application in many interdisciplinary fields such as medicine, electronics, biomaterials, and so on. This mini-review presents a collection of important works published with focus of nanotechnology and cancer treatment by PDT. Despite significant efforts to develop nanosystems for efficient PDT cancer treatment, it remains a challenge to develop nanostructured drug delivery systems that combine targeted tumor recognition with effective production of reactive singlet oxygen under PDT irradiation.

  17. Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

    DTIC Science & Technology

    2016-10-01

    exclusively focused on non-small cell lung cancer . Specific Aims: Same as above Role: Investigator P50 CA140388-06A1 Title: Time Commitment: Supporting...AWARD NUMBERS: W81XWH-14-1-0554 TITLE: Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer PRINCIPAL INVESTIGATOR...Dr. Nora M. Navone (Initiating PI) RECIPIENT: The University of Texas MD Anderson Cancer Center Houston, TX 77030 REPORT DATE: TYPE OF

  18. Advanced prostate cancer: Every Voice Matters.

    PubMed

    Payne, Heather; Westcott, Gemma

    2015-01-01

    Heather Payne speaks to Gemma Westcott, Commissioning Editor: Heather Payne was appointed as a consultant in Clinical Oncology at University College Hospital (London, UK) in 1997. Following her training at St Mary's Hospital London Medical School and after qualifying, she spent time working in general medicine in both London and Haiti. Currently, she specializes in the management of urological malignancies, and is actively involved in clinical research as well as being the principal investigator in a number of international multicenter and local studies. She enjoys helping patients with quality of life and decision-making issues with regard to their treatment options. In addition, she is the chairman of the British Uro-oncology Group, and is a member of the Department of Health Prostate Cancer Advisory Group. Further to this, she is a trustee of the Prostate Cancer Research Centre and clinical lead for the National Prostate Cancer Audit.

  19. [Advances in measles virus for cancer therapy].

    PubMed

    Zhou, Duo; Zhao, Zheng-yan

    2015-07-01

    Oncolytic virotherapy is a novel cancer therapy. Vaccine-attenuated strains of measles virus(MV)is an ideal candidate for oncolytic virotherapy which has an excellent safety record. Vaccine-attenuated MV uses CD46 and Nectin-4 molecule as major entry receptors into cells. Vaccine-attenuated MV can selectively infect and kill a wide variety of cancer cells in vitro and in vivo. With the development of molecular cloning, scientists have successfully rescued cDNA of vaccine-attenuated MV and increased its oncolytic efficiency with molecular engineering techniques. Phase I clinical trials of virotherapy for ovarian cancer and multiple myeloma with vaccine-attenuated MV are underway. The preliminary results indicate the promising antitumor potential of vaccine-attenuated MV.

  20. Recent advances in the medical treatment of breast cancer

    PubMed Central

    Vorobiof, Daniel A.

    2016-01-01

    Over the past few decades, the systemic therapy of breast cancer (early and advanced) has changed considerably. For the past 40–50 years, and since the discovery and further therapeutic use of tamoxifen, a selective estrogen receptor modulator, breast cancer treatment has become the model for the development and success of tailored medical treatment. Much still needs to be done in improving outcomes for all patients with breast cancer, and especially for those who have advanced breast cancer, a challenging area for medical oncologists. Ongoing international clinical trials are currently evaluating new therapeutic approaches and identifying specific biological subsets that could determine a patient’s ability to respond to particular chemotherapeutic drugs. PMID:27990275

  1. Advances in molecular imaging for breast cancer detection and characterization

    PubMed Central

    2012-01-01

    Advances in our ability to assay molecular processes, including gene expression, protein expression, and molecular and cellular biochemistry, have fueled advances in our understanding of breast cancer biology and have led to the identification of new treatments for patients with breast cancer. The ability to measure biologic processes without perturbing them in vivo allows the opportunity to better characterize tumor biology and to assess how biologic and cytotoxic therapies alter critical pathways of tumor response and resistance. By accurately characterizing tumor properties and biologic processes, molecular imaging plays an increasing role in breast cancer science, clinical care in diagnosis and staging, assessment of therapeutic targets, and evaluation of responses to therapies. This review describes the current role and potential of molecular imaging modalities for detection and characterization of breast cancer and focuses primarily on radionuclide-based methods. PMID:22423895

  2. [New advances in hereditary colorectal cancer].

    PubMed

    Moreira, Leticia

    2015-09-01

    Colorectal cancer is the most frequent malignancy in both sexes in Spain. Between 20% and 25% of affected individuals have a family history of the disease, and 5% to 6% have a germ mutation, i.e. the disease develops in the context of a hereditary syndrome. The importance of identifying patients with hereditary syndromes predisposing them to colorectal cancer lies in the possibility of applying preventive measures, screening, and more appropriate management of both patients and their families. The present article outlines the most important studies presented at the congress of the American Gastroenterological Association. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  3. Emerging challenges of advanced squamous cell lung cancer

    PubMed Central

    Zhang, Yi-Chen; Zhou, Qing

    2016-01-01

    Squamous cell lung cancer (SQCLC) is an aggressive type of lung cancer and most are diagnosed at advanced stage. Patients with advanced SQCLC tend to be older, current or former smoker, with central type tumour located near large blood vessels and seldom with druggable genetic alternations. Consequently, progress of targeted therapy and antivascular agents available in lung adenocarcinoma could not be duplicated in this subset of patients. The treatment paradigms have long been dominant by cytotoxic agents and posed many therapeutic challenges. Until recent years, immune checkpoint inhibitors, other monoclonal antibodies and afatinib have been approved for treatment of advanced SQCLC, presenting a novel treatment landscape and initiating the era of precision medicine in this subset of patients. This review will summarise the recent treatment progresses in advanced SQCLC with a focus on checkpoint inhibitors of programmed cell death-1 receptor or its ligand, and discuss the emerging challenges in this new era. PMID:28255454

  4. New Insight into the Treatment of Advanced Differentiated Thyroid Cancer

    PubMed Central

    Safavi, Arash; Vijayasekaran, Aparna; Guerrero, Marlon A.

    2012-01-01

    The vast majority of patients with differentiated thyroid cancer (DTC) are treated successfully with surgery and radioactive iodine ablation, yet the treatment of advanced cases is frustrating and largely ineffective. Systemic treatment with conventional cytotoxic chemotherapy is basically ineffective in most patients with advanced DTC. However, a better understanding of the genetics and biologic basis of thyroid cancers has generated opportunities for innovative therapeutic modalities, resulting in several clinical trials. We aim to delineate the latest knowledge regarding the biologic characteristics of DTC and to describe the available data related to novel targeted therapies that have demonstrated clinical effectiveness. PMID:23326755

  5. Comprehensive Approaches to Managing Delirium in Patients with Advanced Cancer

    PubMed Central

    Kang, Jung Hun; Shin, Seong Hoon; Bruera, Eduardo

    2013-01-01

    Delirium is a frequently under-recognized complication in patients with advanced cancer. Uncontrolled delirium eventually leads to significant distress to patients and their families. However, delirium episodes can be reversed in half of these patients by eliminating precipitating factors and using appropriate interventions. The purpose of this narrative review is to discuss the most recent updates in the literature on the management of delirium in patients with advanced cancer. This article addresses the epidemiology, cause, pathophysiology, clinical characteristics, and assessment of delirium as well as various treatment options, including nonpharmacologic intervention and palliative sedation. PMID:22959227

  6. Immunotherapy and complexity: overcoming barriers to control of advanced cancer.

    PubMed

    Lage, Agustin

    2014-01-01

    Recent advances in fundamental immunology are changing paradigms for management of advanced cancer, now acknowledged as a chronic disease whose prevalence will increase, and one whose complexity makes it difficult to control. Immunotherapy is emerging as an alternative, with new monoclonal antibodies, therapeutic vaccines and deeper understanding of fundamental phenomena in the interaction between tumor and immune system. These novel insights concern mechanisms of programmed contraction of the immune response, characterization of molecular and cellular markers of immunosenescence, the dual role of inflammation, characterization of myeloid-derived suppressor cells and cancer stem cells, and the phenomena of immunogenic apoptosis and oncogene addiction. Additionally, new data drive a deeper understanding of four barriers to overcome in control of advanced cancer: the complexity of biological systems, tumor heterogeneity, tumor mutation rates, and human genome-environment mismatch. The new landscape points to six main strategies: manage advanced cancer as a chronic disease, find relevant molecular markers for patient stratification, develop a rationale for therapeutic combinations, target regulatory control loops in the immune system, expand mathematical modeling capacity, and evaluate complex health intervention packages in real-world conditions. These transitions in cancer immunotherapy research are illustrated in this paper through description of ongoing projects at Cuba's Molecular Immunology Center.

  7. Profile of olaparib in the treatment of advanced ovarian cancer.

    PubMed

    Chase, Dana M; Patel, Shreya; Shields, Kristin

    2016-01-01

    Olaparib is a poly(ADP-ribose) polymerase inhibitor that received accelerated approval from the US Food and Drug Administration as monotherapy for patients with germline BRCA mutations and ovarian cancer treated with three or more prior lines of chemotherapy. This article summarizes the mechanism of poly(ADP-ribose) polymerase inhibition, therapeutic profile and uses of olaparib, and current and ongoing literature pertaining to olaparib in advanced ovarian cancer.

  8. Advancement in treatment and diagnosis of pancreatic cancer with radiopharmaceuticals

    PubMed Central

    Xu, Yu-Ping; Yang, Min

    2016-01-01

    Pancreatic cancer (PC) is a major health problem. Conventional imaging modalities show limited accuracy for reliable assessment of the tumor. Recent researches suggest that molecular imaging techniques with tracers provide more biologically relevant information and are benefit for the diagnosis of the cancer. In addition, radiopharmaceuticals also play more important roles in treatment of the disease. This review summaries the advancement of the radiolabeled compounds in the theranostics of PC. PMID:26909131

  9. Systemic therapy for advanced pancreatic cancer: individualising cytotoxic therapy.

    PubMed

    Collins, Dearbhaile Catherine; Morris, Patrick Glyn

    2015-04-01

    Pancreatic cancer is an aggressive solid tumour associated with a high risk of local invasion and metastatic spread. In the absence of validated screening approaches, many patients present with advanced, incurable disease. Despite advances in treatment, the prognosis for patients with advanced pancreatic cancer remains poor. The benefits of surgical resection and radiation are unproven in this setting and, as patients generally present with distant metastases, systemic therapy forms the mainstay of treatment. The importance of selecting the optimal cytotoxic therapy remains to be critical to improving outcome and retaining quality of life. This review sets out to compare the current therapies available for advanced pancreatic cancer. This review examines the evolution of the systemic management of advanced pancreatic cancer, with a particular focus on the landmark Phase III trials identified from an extensive PubMed and Google scholar literature search. The article summarises the cytotoxic agents in use and the results of two decades of clinical trials to culminate in an almost doubling of survival in clinical trials. In the concluding expert opinion, the challenges interpreting and translating trial results into clinical practice are discussed, where patients are often older and of worse performance status. In the future, novel biomarkers might be used to tailor therapy.

  10. A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies.

    PubMed

    Graux, Carlos; Sonet, Anne; Maertens, Johan; Duyster, Justus; Greiner, Jochen; Chalandon, Yves; Martinelli, Giovanni; Hess, Dagmar; Heim, Dominik; Giles, Francis J; Kelly, Kevin R; Gianella-Borradori, Athos; Longerey, Blandine; Asatiani, Ekaterine; Rejeb, Narmyn; Ottmann, Oliver G

    2013-09-01

    A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28 mg/m(2)/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Advances in cancer research: Volume 47

    SciTech Connect

    Klein, G.; Weinhouse, S.

    1986-01-01

    This book contains eight chapters. Some of the titles are: Genetic Epidemiology of Familial Aggregation of Cancer; Terminal Transferase in Normal and Leukemic Cells; Malignant Metamorphosis: Developmental Genes as Culprits for Oncogenesis in Xiphophorus; and Transcription Activation by Viral and Cellular Oncogenes.

  12. [Circulating tumor cells and advanced prostate cancer].

    PubMed

    Murez, Thibaut; Droupy, Stéphane; Rebillard, Xavier; Alix-Panabieres, Catherine

    2012-07-01

    Despite development and widespread of PSA, current tools evaluating prostate cancer still give inconsistent or insufficiently relevant results. As encouraging data raised from circulating tumor cells detection in colon or breast cancer, they were evaluated as a surrogate prostate cancer biomarker. Tumor cells need to leave their surrounding primary environment and to survive in mesenchymal environment before they spill and metastasize. Basic research revealed several mutations required through a complex transition phenomenon, including dormancy steps. Circulating cells detection techniques are based on molecular and immunologic methods. Most of them need an enrichment step to improve sensibility and/or specificity. As of today, Veridex' CellSearch is the only FDA approved technique in the evaluation of castration resistant prostate cancer response to new drugs. Clinical research using other techniques highlighted the need for clinical endpoints, as there's no relevant tool and as techniques' target differ. Further studies are required to improve circulating tumors cells' staging and prognosis value. Cellular characterization may be the way to identify metastasis development potential more than the spillage burden. Those techniques still need improvements before they are included in daily practice decisional trees.

  13. Current advances in esophageal cancer proteomics.

    PubMed

    Uemura, Norihisa; Kondo, Tadashi

    2015-06-01

    We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics.

  14. Advances in cancer research. Volume 48

    SciTech Connect

    Klein, G.; Weinhouse, S.

    1987-01-01

    This book contains the following five selections: Oncotrophoblast Gene Expression: Placental Alkaline Phosphatase; Cellular Events during Hepatocarcinogenesis in Rats and the Questions of Premalignancy; Human Papillomaviruses and Genital Cancer; Herpes Simplex Type 2 Virus and Cervical Neoplasia; and Transforming Genes and Target Cells of Murine Spleen Focus-Forming Viruses.

  15. Integrative clinical genomics of advanced prostate cancer

    PubMed Central

    Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

    2015-01-01

    SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

  16. Irradiation of FDG-PET-Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Anal Cancer Patients Undergoing Chemoradiation.

    PubMed

    Rose, Brent S; Jee, Kyung-Wook; Niemierko, Andrzej; Murphy, Janet E; Blaszkowsky, Lawrence S; Allen, Jill N; Lee, Leslie K; Wang, Yingbing; Drapek, Lorraine C; Hong, Theodore S; Wo, Jennifer Y

    2016-03-15

    Irradiation of pelvic bone marrow (BM) has been correlated with hematologic toxicity (HT) in patients undergoing chemoradiation for anal cancer. We hypothesized that irradiation of hematologically active bone marrow (ABM) subregions defined by fluorodeoxyglucose (FDG) positron emission tomography (PET) is a principal cause of radiation-associated HT. The cohort included 45 patients with nonmetastatic anal cancer who underwent FDG-PET imaging prior to definitive chemoradiation with mitomycin-C and 5-fluorouracil. Total bone marrow (TBM) was defined as the external contour of the pelvic bones from the top of lumbar 5 (L5) to the bottom of the ischial tuberosity. Standardized uptake values (SUV) for all voxels within the TBM were quantified and normalized by comparison to normal liver SUV. Subvolumes of the TBM that exhibited the highest and lowest 50% of the SUVs were designated ABM50 and IBM50, respectively. The primary endpoint was the absolute neutrophil count (ANC) nadir during or within 2 weeks of completion of treatment. Multivariate linear modeling was used to analyze the correlation between the equivalent uniform doses (EUD) with an a value of 0.5, 1 (equivalent to mean dose), 3, 7, and 12 to the BM structures and the ANC. Mean ± SD ANC nadir was 0.77 × 10(9)/L (±0.66 × 10(9)/L). Grades 3 and 4 ANC toxicity occurred in 26.7% and 44.4% of patients, respectively. The EUD a parameter of 0.5 was optimal for all BM models indicating high radiation sensitivity. EUD of TBM and ABM50 and IBM50 were all significantly associated with ANC nadir. However, model performance for ABM50 was not superior to that of the TBM and IBM50 models. Irradiation of pelvic BM was associated with HT. However, FDG-PET-defined ABM models failed to improve model performance compared to the TBM model. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Trichomonas vaginalis infection and risk of advanced prostate cancer.

    PubMed

    Shui, Irene M; Kolb, Suzanne; Hanson, Christi; Sutcliffe, Siobhan; Rider, Jennifer R; Stanford, Janet L

    2016-05-01

    The epidemiologic evidence for an association of Trichomonas vaginalis (Tv) with overall prostate cancer is mixed, but some studies suggest Tv may increase risk of more aggressive disease. The aim of this study was to assess whether Tv serostatus is associated with advanced or fatal prostate cancer. A total of 146 men with advanced (metastatic or fatal) prostate cancer and 181 age-matched controls were selected from two prior population-based, case-control studies. Tv serostatus was determined with the same laboratory methods used in previous epidemiologic studies. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression to compare Tv serostatus in prostate cancer cases and controls adjusted for potential confounders. The seroprevalence of Tv in controls was 23%. Tv serostatus was not associated with an increased risk of metastatic or fatal prostate cancer (ORs < 1). Our study does not support an increased risk of advanced or fatal prostate cancer in men seropositive for Tv. © 2016 Wiley Periodicals, Inc.

  18. Medical Advances and Racial/ethnic Disparities in Cancer Survival

    PubMed Central

    Tehranifar, Parisa; Neugut, Alfred I.; Phelan, Jo C.; Link, Bruce G.; Liao, Yuyan; Desai, Manisha; Terry, Mary Beth

    2013-01-01

    BACKGROUND Although advances in early detection and treatment of cancer improve overall population survival, these advances may not benefit all population groups equally, and may heighten racial/ethnic (R/E) differences in survival. METHODS We identified cancer cases in the Surveillance, Epidemiology, and End Results program, who were ≥ 20 years and diagnosed with one invasive cancer in 1995–1999 (n=580,225). We used 5-year relative survival rates (5Y-RSR) to measure the degree to which mortality from each cancer is amenable to medical interventions (amenability index). We used Kaplan-Meier methods and Cox proportional hazards regression to estimate survival differences between each R/E minority group relative to whites, by the overall amenability index, and three levels of amenability (non-amenable, partly and mostly amenable cancers, corresponding to cancers with 5Y-RSR <40%, 40–69% and ≥ 70%, respectively), adjusting for gender, age, disease stage and county-level poverty concentration. RESULTS As amenability increased, R/E differences in cancer survival increased for African Americans, American Indians/Native Alaskans and Hispanics relative to whites. For example, the hazard rate ratios (95% confidence intervals) for African Americans vs. whites from non-amenable, partly amenable and mostly amenable cancers were 1.05 (1.03, 1.07), 1.38 (1.34,1.41), and 1.41 (1.37, 1.46), respectively. Asians/Pacific Islanders had similar or longer survival relative to whites across amenability levels; however, several subgroups experienced increasingly poorer survival with increasing amenability. CONCLUSIONS Cancer survival disparities for most R/E minority populations widen as cancers become more amenable to medical interventions. Efforts in developing cancer control measures must be coupled with specific strategies for reducing the expected disparities. PMID:19789367

  19. Music in Reducing Anxiety and Pain in Adult Patients Undergoing Bone Marrow Biopsy for Hematologic Cancers or Other Diseases

    ClinicalTrials.gov

    2017-01-18

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Psychosocial Effects of Cancer and Its Treatment

  20. Cediranib Maleate and Combination Chemotherapy in Treating Patients With Advanced Biliary Cancers

    ClinicalTrials.gov

    2017-02-10

    Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  1. Phase II trial to evaluate gemcitabine and etoposide for locally advanced or metastatic pancreatic cancer.

    PubMed

    Melnik, Marianne K; Webb, Craig P; Richardson, Patrick J; Luttenton, Charles R; Campbell, Alan D; Monroe, Thomas J; O'Rourke, Timothy J; Yost, Kathleen J; Szczepanek, Connie M; Bassett, Michelle R; Truszkowski, Kimberly J; Stein, Phyllis; Van Brocklin, Matthew W; Davis, Alan T; Bedolla, Gabriela; Vande Woude, George F; Koo, Han-Mo

    2010-08-01

    Prior studies suggest that tumor cell lines harboring RAS mutations display remarkable sensitivity to gemcitabine and etoposide. In a phase II clinical trial of patients with locally advanced or metastatic pancreatic cancer, we evaluated the response rate to a combination of these drugs. Forty chemo-naïve patients with nonresectable and histologically confirmed pancreatic cancer were accrued. Patients received gemcitabine 1,000 mg/m(2) (days 1 and 8) and etoposide 80 mg/m(2) (days 8, 9, and 10; 21-day cycle). The primary end point was radiological response rate. Secondary objectives were determination of overall survival, response duration (time to progression), quality of life, toxicity, and CA 19-9 biomarker response. In 35 evaluable patients, 10 exhibited a radiological partial response and 12 had stable disease in response to treatment. Twenty patients exhibited a >20% decrease in CA 19-9 biomarker levels. Median overall survival was 6.7 months for all patients (40) and 7.2 months for evaluable patients (35). Notably, four patients survived for longer than 1 year, with two patients surviving for more than 2 years. Median time to progression for evaluable patients was 3.1 months. The median overall survival for locally advanced patients was 8.8 months and 6.75 months for metastatic patients. One-year survival was 10% for all patients and 11.4% for evaluable patients. Quality of life improved in 12 patients and remained stable in 3 of the evaluable patients. The primary dose-limiting toxicities were hematologic toxicity and fatigue. These results show that the gemcitabine and etoposide combination is generally well-tolerated and exhibits a response rate similar to other published studies. (c) 2010 AACR.

  2. Recent Advances in Microwave Imaging for Breast Cancer Detection

    PubMed Central

    Kwon, Sollip

    2016-01-01

    Breast cancer is a disease that occurs most often in female cancer patients. Early detection can significantly reduce the mortality rate. Microwave breast imaging, which is noninvasive and harmless to human, offers a promising alternative method to mammography. This paper presents a review of recent advances in microwave imaging for breast cancer detection. We conclude by introducing new research on a microwave imaging system with time-domain measurement that achieves short measurement time and low system cost. In the time-domain measurement system, scan time would take less than 1 sec, and it does not require very expensive equipment such as VNA. PMID:28096808

  3. Recent advances in the field of anti-cancer immunotherapy

    PubMed Central

    Neves, Henrique; Kwok, Hang Fai

    2015-01-01

    Background The main goal of anti-cancer therapy is to specifically inhibit the malignant activity of cancer cells, while leaving healthy cells unaffected. As such, for every proposed therapy, it is important to keep in mind the therapeutic index — the ratio of the toxic dose over the therapeutic dose. The use of immunotherapy has allowed a means to both specifically block protein–protein interaction and deliver cytotoxic events to a tumor-specific antigen. Review scope It is the objective of this review to give an overview on current immunotherapy treatment for cancers using monoclonal antibodies. We demonstrate three exciting targets for immunotherapy, TNF-α Converting Enzyme (TACE), Cathepsin S and Urokinase Plasmogen Activator and go over the advances made with one of the most used monoclonal antibodies in cancer therapy, Rituximab; as well as Herceptin, which is used for breast cancer therapy. Furthermore, we touch on other venues of immunotherapy, such as adaptive cell transfer, the use of nucleic acids and the use of dendritic cells. Finally, we summarize some ongoing studies that spell tentative advancements for anti-cancer immunotherapy. General significance Immunotherapy is at the forefront of anti-cancer therapies, allying both a high degree of specificity to general high effectiveness and fewer side-effects. PMID:26673349

  4. Recent advances and future challenges in cancer immunotherapy.

    PubMed

    Okuyama, Namiko; Tamada, Koji; Tamura, Hideto

    Remarkable advances have been made in cancer immunotherapy. Recent treatment strategies, especially chimeric antigen receptor-T (CAR-T) cell therapy and immune checkpoint inhibitors, reportedly achieve higher objective responses and better survival rates than previous immunotherapies for patients with treatment-resistant malignancies, creating a paradigm shift in cancer treatment. Several clinical trials of cancer immunotherapy for patients with various malignancies are ongoing. However, those with certain malignancies, such as low-immunogenic cancers, cannot be successfully treated with T-cell immunotherapy, and subsets of immunotherapy-treated patients relapse, meaning that more effective immunotherapeutic strategies are needed for such patients. Furthermore, the safety, convenience, and cost of cancer immunotherapy need to be improved in the near future. Herein, we discuss recent advances and future challenges in cancer immunotherapy, i.e., the identification of neoantigens for the development of individualized immunotherapies, the development of new CAR-T cell therapies, including so-called armored CAR-T cells that can induce greater clinical effects and thereby achieve longer survival, the development of off-the-shelf treatment regimens using non-self cells or cell lines, and effective cancer immunotherapy combinations.

  5. Advances in treatment of colorectal cancer.

    PubMed

    McCafferty, Michael H

    2005-10-01

    The purpose of this review is to provide the practicing surgeon with an outline of several significant developments in colorectal cancer treatment that have affected the care of patients. This review is not intended to report on every important publication of the past few years nor is it intended to be encyclopedic. The author simply hopes to provide a useful reference for surgeons in their daily practice.

  6. Prostate cancer: 9. Treatment of advanced disease

    PubMed Central

    Gleave, M E; Bruchovsky, N; Moore, M J; Venner, P

    1999-01-01

    A 70-year-old man is referred to a urologist for recommendations on the management of metastatic prostate cancer. His cancer was diagnosed 5 years ago, and he underwent radical prostatectomy at that time. The tumour was confined to the prostate gland (Gleason score 7), and during surgery the lymph nodes were assessed as being clear of cancer. Before the surgery, the patient's prostate-specific antigen (PSA) level had been 8 ng/mL. After the prostatectomy, PSA was at first undetectable, but recently the PSA level rose to 2 ng/mL and then, at the most recent test, to 16 ng/mL. A bone scan was ordered to investigate back discomfort, which has been persistent but easily controlled with acetaminophen. Unfortunately, the bone scan shows several sites of metastatic disease. The man's medical history includes type 2 diabetes, which has developed during the past 3 years and which is controlled by diet, as well as asymptomatic hypertension, which is managed by means of a thiazide diuretic. The patient asks what treatments are available, what impact they are likely to have on his disease and what risks are associated with the therapies. PMID:9951446

  7. Advances in the understanding of cancer immunotherapy.

    PubMed

    Shore, Neal D

    2015-09-01

    The principal role of the immune system is to prevent and eradicate pathogens and infections. The key characteristics or features of an effective immune response include specificity, trafficking, antigen spread and durability (memory). The immune system is recognised to have a critical role in controlling cancer through a dynamic relationship with tumour cells. Normally, at the early stages of tumour development, the immune system is capable of eliminating tumour cells or keeping tumour growth abated; however, tumour cells may evolve multiple pathways over time to evade immune control. Immunotherapy may be viewed as a treatment designed to boost or restore the ability of the immune system to fight cancer, infections and other diseases. Immunotherapy manifests differently from traditional cancer treatments, eliciting delayed response kinetics and thus may be more effective in patients with lower tumour burden, in whom disease progression may be less rapid, thereby allowing ample time for the immunotherapy to evolve. Because immunotherapies may have a different mechanism of action from traditional cytotoxic or targeted biological agents, immunotherapy techniques have the potential to combine synergistically with traditional therapies.

  8. Advances and challenges in hereditary cancer pharmacogenetics.

    PubMed

    Cascorbi, Ingolf; Werk, Anneke Nina

    2017-01-01

    Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. Areas covered: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC). Moreover, the association between genetic variants of drug transporters with the clinical outcome is comprehensively discussed. Expert opinion: Precision therapy in the field of oncology is developing tremendously. There are a number of somatic tumor genetic markers that are indicative for treatment with anti-cancer drugs. By contrast, for some hereditary variants, recommendations have been developed. Although we have vast knowledge on the association between drug transporter variants and clinical outcome, the overall data is inconsistent and the predictability of the related phenotype is low. Further developments in research may lead to the discovery of rare, but functionally relevant single nucleotide polymorphisms and a better understanding of multiple genomic, epigenomic as well as phenotypic factors, contributing to drug response in malignancies.

  9. Hormonal therapy in advanced or recurrent endometrial cancer

    PubMed Central

    Kokka, Fani; Brockbank, Elly; Oram, David; Gallagher, Chris; Bryant, Andrew

    2014-01-01

    Background Endometrial cancer is a cancer of the lining of the womb and worldwide is the seventh most common cancer in women. Treatment with hormones is thought to be beneficial in patients with endometrial cancer. Objectives To assess the indications, effectiveness and safety of hormone therapy for advanced or recurrent epithelial endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE up to May 2009 and and CENTRAL (Issue 2, 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies, and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that studied hormonal therapy in adult women diagnosed with advanced or recurrent endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Comparisons were restricted to single-trial analyses so we did not synthesise data in meta-analyses. Main results We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively). Authors’ conclusions We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or

  10. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2017-03-08

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  11. Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

    ClinicalTrials.gov

    2016-02-11

    Fallopian Tube Cancer; Female Reproductive Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer

  12. Evolving Approaches to Patients with Advanced Differentiated Thyroid Cancer

    PubMed Central

    Sherman, Steven I.

    2013-01-01

    Advanced differentiated thyroid cancer (DTC), defined by clinical characteristics including gross extrathyroidal invasion, distant metastases, radioiodine (RAI) resistance, and avidity for 18-fluorodeoxyglucose (positron emission tomography-positive), is found in approximately 10–20% of patients with DTC. Standard therapy (surgery, RAI, TSH suppression with levothyroxine) is ineffective for many of these patients, as is standard chemotherapy. Our understanding of the molecular mechanisms leading to DTC and the transformation to advanced DTC has rapidly evolved over the past 15–20 years. Newer targeted therapy, specifically inhibitors of intracellular kinase signaling pathways, and cooperative multicenter clinical trials have dramatically changed the therapeutic landscape for patients with advanced DTC. In this review focusing on morbidities, molecules, and medicinals, we present a patient with advanced DTC, explore the genetics and molecular biology of advanced DTC, and review evolving therapies for these patients including multikinase inhibitors, selective kinase inhibitors, and combination therapies. PMID:23575762

  13. Annual Advances in Cancer Prevention Lecture | Division of Cancer Prevention

    Cancer.gov

    2017 Keynote Lecture Re-visiting the Causes of Cancer A special keynote lecture became part of the NCI Summer Curriculum in Cancer Prevention in 2000. This lecture will be held on Thursday, July 20, 2017 at 1:30pm at Masur Auditorium, Building 10, NIH Main Campus, Bethesda, MD. This year’s keynote speaker is Sir Richard Peto, Fellow of the  Royal Soceity (FRS) of London. |

  14. Afatinib Dimaleate and Capecitabine in Treating Patients With Advanced Refractory Solid Tumors, Pancreatic Cancer or Biliary Cancer

    ClinicalTrials.gov

    2017-08-04

    Advanced Malignant Solid Neoplasm; Bile Duct Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer

  15. Primary chemotherapy with gemcitabine, liposomal doxorubicin and docetaxel in patients with locally advanced breast cancer: results of a phase I trial.

    PubMed

    Schmid, Peter; Krocker, Jutta; Schulz, Carsten-Oliver; Michniewicz, Katarzyna; Dieing, Annette; Eggemann, Holm; Heilmann, Volker; Blohmer, Jens-Uwe; Sezer, Orhan; Elling, Dirk; Possinger, Kurt

    2005-01-01

    The primary objective was to determine the optimal doses for gemcitabine (prolonged infusion), liposomal doxorubicin (Myocet) and docetaxel as primary (neoadjuvant) chemotherapy for locally advanced breast cancer. Secondary objectives included evaluation of the safety and efficacy of the regimen. Patients (n=19) with histologically confirmed stage II or III breast cancer were treated with liposomal doxorubicin (50-60 mg/m2) and docetaxel (60-75 mg/m2) on day 1, and gemcitabine as 4-h infusion (350-400 mg/m2) on day 4. Treatment was repeated every 3 weeks for a maximum of 6 cycles. The maximum tolerated doses were gemcitabine 350 mg/m2, liposomal doxorubicin 60 mg/m2 and docetaxel 75 mg/m2. Dose-limiting toxicities were stomatitis, diarrhea and infection. The predominant hematologic toxicity was mild-to-moderate myelosuppression with grade 3/4 neutropenia in 20% of cycles. Non-hematologic toxicity was generally mild, with no grade 4 toxicities being observed. Predominant non-hematologic toxicity was stomatitis, which occurred in 95% of patients. Grade 3 toxicities were reported for stomatitis, nausea, diarrhea, infection and constipation. No cases of cardiac, renal, pulmonary or neurotoxicity were observed. The clinical response rate was 83% and histologically confirmed, clinically complete remissions occurred in two patients (11%). We conclude that the combination of gemcitabine (prolonged infusion), liposomal doxorubicin and docetaxel is safe and highly effective in patients with locally advanced breast cancer as defined by maximum tolerated doses. The evaluated schedule is suitable for phase II studies.

  16. [The illness experience of women in advanced uterine cancer].

    PubMed

    Tae, Young-Sook; Cho, Moung-Ock; Hong, Yong-Hae

    2003-12-01

    This hermeneutical inquiry was aimed at understanding the experience of women with advanced uterine cancer and providing sociocultural data on hospice nursing for these Korean women. We adopted hermeneutic phenomenological approach of van Manen. The research question was "What do women with advanced uterine cancer experience in their life?". The data for this paper came from interviews with 11 participants between February, 2000 and May, 2001 and reviews of secondary text of essay and drama, poet, memorandum. Each informant was interviewed three or more times for 30 min.-2 hours. In the process of analysis we did reflective thinking and used line-by-line and highlighting analysis techniques. The substantial themes of illness experience of women in advanced uterine cancer were 'Endless suffering', 'In the midst of chaos and darkness,' 'on the wish of new possibility', 'finding new transformed self. Women with Advanced uterine cancer suffer with complex problems and wonder in the midst of chaos and darkness, but they find a new transformed self by the wish of new possibility and experience human becoming.

  17. Advances in pancreatic cancer research: moving towards early detection.

    PubMed

    He, Xiang-Yi; Yuan, Yao-Zong

    2014-08-28

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

  18. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  19. [Assessment and impact of intrathoracic disease in advanced ovarian cancer].

    PubMed

    Cohen-Mouly, S; Badia, A; Bats, A-S; Barthes, F; Bensaïd, C; Huchon, C; Riquet, M; Lécuru, F

    2010-05-01

    As seventy-five percent of patients with ovarian cancer are diagnosed at an advanced stage (FIGO stage III/IV), optimal surgery is then difficult to perform. The aim of our study is to assess the interest of thoracoscopy in the management of ovarian carcinoma with pleural effusion.

  20. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  1. Concurrent apatinib and local radiation therapy for advanced gastric cancer

    PubMed Central

    Zhang, Ming; Deng, Weiye; Cao, Xiaoci; Shi, Xiaoming; Zhao, Huanfen; Duan, Zheping; Lv, Bonan; Liu, Bin

    2017-01-01

    Abstract Rationale: Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. Patient concerns and Diagnoses: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. Interventions and Outcomes: The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. Lessons: Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer. PMID:28248891

  2. Economic impact of advanced pediatric cancer on families.

    PubMed

    Bona, Kira; Dussel, Veronica; Orellana, Liliana; Kang, Tammy; Geyer, Russ; Feudtner, Chris; Wolfe, Joanne

    2014-03-01

    Despite emerging evidence of substantial financial distress in families of children with complex illness, little is known about economic hardship in families of children with advanced cancer. To describe perceived financial hardship, work disruptions, income losses, and associated economic impact in families of children with advanced cancer stratified by federal poverty level (FPL). Cross-sectional survey of 86 parents of children with progressive, recurrent, or nonresponsive cancer at three children's hospitals. Seventy-one families with complete income data (82%) are included in this analysis. Parental work disruptions were prevalent across all income levels, with 67 (94%) families reporting some disruption. At least one parent quit a job because of the child's illness in 29 (42%) families. Nineteen (27%) families described their child's illness as a great economic hardship. Income losses because of work disruptions were substantial for all families; families at or below 200% FPL, however, were disproportionately affected. Six (50%) of the poorest families lost more than 40% of their annual income as compared with two (5%) of the wealthiest families (P = 0.006). As a result of income losses, nine (15%) previously nonpoor families fell from above to below 200% FPL. The economic impact of pediatric advanced cancer on families is significant at all income levels, although poorer families suffer disproportionate losses. Development of ameliorative intervention strategies is warranted. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  3. Multifunctional Nanotherapeutic System for Advanced Prostate Cancer

    DTIC Science & Technology

    2012-10-01

    delivery of eIF4E siRNA and DTX using dendrimer as a nanocarrier. To this end the objective of this study is to prepare, characterize and test the...multifunctional delivery system by conjugating DTX to dendrimer and complexing eIF4E siRNA to the resulting conjugate. The DTX- dendrimer conjugate...formed complex with siRNA at 20:1 ratio. The dendrimer - siRNA complex was taken up by the prostate cancer cells while the free siRNA was not taken up by

  4. Advanced medullary thyroid cancer: pathophysiology and management

    PubMed Central

    Ferreira, Carla Vaz; Siqueira, Débora Rodrigues; Ceolin, Lucieli; Maia, Ana Luiza

    2013-01-01

    Medullary thyroid carcinoma (MTC) is a rare malignant tumor originating from thyroid parafollicular C cells. This tumor accounts for 3%–4% of thyroid gland neoplasias. MTC may occur sporadically or be inherited. Hereditary MTC appears as part of the multiple endocrine neoplasia syndrome type 2A or 2B, or familial medullary thyroid cancer. Germ-line mutations of the RET proto-oncogene cause hereditary forms of cancer, whereas somatic mutations can be present in sporadic forms of the disease. The RET gene encodes a receptor tyrosine kinase involved in the activation of intracellular signaling pathways leading to proliferation, growth, differentiation, migration, and survival. Nowadays, early diagnosis of MTC followed by total thyroidectomy offers the only possibility of cure. Based on the knowledge of the pathogenic mechanisms of MTC, new drugs have been developed in an attempt to control metastatic disease. Of these, small-molecule tyrosine kinase inhibitors represent one of the most promising agents for MTC treatment, and clinical trials have shown encouraging results. Hopefully, the cumulative knowledge about the targets of action of these drugs and about the tyrosine kinase inhibitor-associated side effects will help in choosing the best therapeutic approach to enhance their benefits. PMID:23696715

  5. [Management of pregnant women with advanced cervical cancer].

    PubMed

    Vincens, C; Dupaigne, D; de Tayrac, R; Mares, P

    2008-04-01

    The purpose of this study is to update the management of pregnant women with advanced cervical cancer, thanks to a literature review indexed in Medline((R)) (from 1980 till 2006 using those keywords: advanced cervix cancer, neoadjuvant chemotherapy and pregnancy), ScienceDirect (from 1990 till 2006) and the French Encyclopédie Médico-Chirurgicale. It occurs that pregnancy is a privileged period to diagnose cervical cancer, particularly in early stages. We ought to beware of symptoms such as vaginal bleeding, which could be underestimated during pregnancy. Colposcopically selected biopsies are reference techniques to confirm the diagnostic. The assessment of extension includes an abdominal and pelvic MRI and echography and a radiography of the chest for locally advanced stages. The decision to interrupt pregnancy should be based on a collegial evaluation and depends on state and histology of disease, patient's desire for pregnancy, as well as gestational age and disease evolution. Cesarean is preferred to natural delivery even though survival rates are the same. The cesarean section prevents from short-term complications and recurrence on the episiotomy, but the hysterotomy type is controversial throughout literature. The prognosis of cervical cancer does not seem to be influenced by pregnancy. Management is the same, even though we have to adapt the treatment from the pregnancy state. No study could show the benefit and the safety of neoadjuvant chemotherapy during pregnancy, due to few cases, but it could be a solution with patients suffering from an advanced cancer and not willing to stop pregnancy. To conclude, the detection by cervical smears should be systematic during pregnancy. When cancer is diagnosed, cesarean section is the favourite way to deliver. Pregnancy does not modify disease's prognosis and the therapeutic choice depends on the stage of the disease.

  6. Pharmacotherapy options for advanced thyroid cancer: a systematic review.

    PubMed

    Lerch, Christian; Richter, Bernd

    2012-01-01

    Poor prognosis of anaplastic thyroid cancer and advanced disease in differentiated and medullary thyroid cancer, together with absence of effective therapeutic measures, has induced recent intensified basic and clinical research in this area. The aim of this article is to assess the effects of new drug treatment for advanced thyroid cancer. We searched MEDLINE and EMBASE until the end of September 2011 for relevant data. Further sources were reference lists of original publications and review articles. We included prospective studies that investigated drug interventions for advanced thyroid cancer published in any language. We did not include trials solely communicated as abstracts. For inclusion, studies had to report overall survival, progression-free survival or similar, or response outcomes. Data were extracted by one author and checked by the other. All tables are part of this publication. Because only non-comparative studies were included, we had to focus on descriptive analysis. Twenty-four studies with 715 patients were included; 18 studies investigated kinase inhibitors, the remainder various drugs. All studies reported response (only one complete response was observed; proportions of partial response were up to 49%). Median progression-free survival was about 12 months, ranging from 3.7 to 27.9 months. Adverse events (at least grade 3) of kinase inhibitors included hypertension, hand foot syndrome and diarrhoea (10%, 16% and 9%, respectively). Due to bias-prone data, any interpretation of newer pharmacotherapy options for advanced thyroid cancer is limited because only non-comparative studies could be included. Therefore, we strongly argue the need for adequate randomized controlled trials that should provide a better basis for therapeutic decision making in thyroid cancer.

  7. Palliative care in pediatric patients with hematologic malignancies.

    PubMed

    Humphrey, Lisa; Kang, Tammy I

    2015-01-01

    Children with advanced cancer, including those with hematologic malignancies, can benefit from interdisciplinary palliative care services. Palliative care includes management of distressing symptoms, attention to psychosocial and spiritual needs, and assistance with navigating complex medical decisions with the ultimate goal of maximizing the quality-of-life of the child and family. Palliative care is distinct from hospice care and can assist with the care of patients throughout the cancer continuum, irrespective of prognosis. While key healthcare organizations, including the Institute of Medicine, the American Academy of Pediatrics and the American Society of Clinical Oncology among many others endorse palliative care for children with advanced illness, barriers to integration of palliative care into cancer care still exist. Providing assistance with advance care planning, guiding patients and families through prognostic uncertainty, and managing transitions of care are also included in goals of palliative care involvement. For patients with advanced malignancy, legislation, included in the Patient Protection and Affordable Health Care Act allows patients and families more options as they make the difficult transition from disease directed therapy to care focused on comfort and quality-of-life.

  8. More U.S. Women Living Longer with Advanced Breast Cancer

    MedlinePlus

    ... html More U.S. Women Living Longer With Advanced Breast Cancer Better treatments, aging population may explain promising trend, ... women living with the most advanced stage of breast cancer has been rising since the 1990s, a new ...

  9. CAR T cell immunotherapy in hematology and beyond.

    PubMed

    Rossig, Claudia

    2017-09-18

    Chimeric T cell receptors (CARs) combine extracellular antigen recognition domains and T cell activation components in single molecules. CAR gene transfer thereby allows to generate T cells with engineered specificities. The translational development of CAR-based T cell therapies is most advanced in B cell cancers where CAR-engineered T cells against the B lineage antigen CD19 have generated impressive results in early clinical trials. CARs are now also explored as tools to eliminate autoreactive B cell clones and to engineer T cells with immunosuppressive function for preventing pathological auto- or alloresponses. With ongoing intensive preclinical investigation and the advent of simplified manufacturing techniques, CAR T cells are expected to enter clinical investigation in a broader variety of hematological and solid cancers and in autoimmune diseases in the near future. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

    PubMed

    Pérez-Herrero, Edgar; Fernández-Medarde, Alberto

    2015-06-01

    Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vascularization and, in time, acquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastatic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, such as the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic drugs, as well as the development of multidrug resistance, support the need to find new effective targeted treatments based on the changes in the molecular biology of the tumor cells. These novel targeted therapies, of increasing interest as evidenced by FDA-approved targeted cancer drugs in recent years, block biologic transduction pathways and/or specific cancer proteins to induce the death of cancer cells by means of apoptosis and stimulation of the immune system, or specifically deliver chemotherapeutic agents to cancer cells, minimizing the undesirable side effects. Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that

  11. American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer.

    PubMed

    Rizzo, J Douglas; Brouwers, Melissa; Hurley, Patricia; Seidenfeld, Jerome; Arcasoy, Murat O; Spivak, Jerry L; Bennett, Charles L; Bohlius, Julia; Evanchuk, Darren; Goode, Matthew J; Jakubowski, Ann A; Regan, David H; Somerfield, Mark R

    2010-11-18

    To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.

  12. American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer.

    PubMed

    Rizzo, J Douglas; Brouwers, Melissa; Hurley, Patricia; Seidenfeld, Jerome; Arcasoy, Murat O; Spivak, Jerry L; Bennett, Charles L; Bohlius, Julia; Evanchuk, Darren; Goode, Matthew J; Jakubowski, Ann A; Regan, David H; Somerfield, Mark R

    2010-11-20

    To update American Society of Clinical Oncology/American Society of Hematology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.

  13. Advances in the treatment of advanced oestrogen-receptor-positive breast cancer.

    PubMed

    Turner, Nicholas C; Neven, Patrick; Loibl, Sibylle; Andre, Fabrice

    2016-12-06

    Oestrogen-receptor-positive breast cancer is the most common subtype of breast cancer. Endocrine therapies that target the dependence of this subtype on the oestrogen receptor have substantial activity, yet the development of resistance to therapy is inevitable in advanced cancer. Major progress has been made in identifying the drivers of oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into major advances in the treatment of advanced breast cancer, with several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of mTOR and inhibitors of the cyclin-dependent kinases CDK4 and CDK6 substantially improve progression-free survival. A new wave of targeted therapies is being developed, including inhibitors of PI3K, AKT, and HER2, and a new generation of oestrogen-receptor degraders. Considerable challenges remain in patient selection, deciding on the most appropriate order in which to administer therapies, and establishing whether cross-resistance occurs between therapies.

  14. Advances and Implications in Nanotechnology for Lung Cancer Management.

    PubMed

    Sarkar, Sana; Osama, Khwaja; Jamal, Qazi Mohammad Sajid; Kamal, Mohammad Amjad; Sayeed, Usman; Khan, M Kalim A; Siddiqui, Mohd Haris; Akhtar, Salman

    2016-11-14

    Lung cancer is one of the most important chronic diseases in the field of respiratory medicine. Conventional treatment strategies for lung cancer include chemotherapy, surgery and radiation therapy. These current therapies lack specificity and are limited by undesirable toxicities in normal cells, as well as a high rate of recurrence.Nanotechnological intervention has greatly revolutionized the therapy of lung cancer by surmounting the current limitations in conventional therapies. Nanoparticles (NPs) achieve preferential accumulation in the tumor cells by employing two mechanisms: passive and active targeting. Several nanoscale drug delivery systems for lung cancer treatment are currently in clinical trials and few of them are already commercially available. Recently, the interest to develop pulmonary delivery system of nano-based drug formulations suitable for lung cancer has been also increased which have resulted in more effective and advanced treatment of Lung cancer. However, although nanotechnology based drug carriers for lung cancer treatment have established outstanding therapeutic potential at both preclinical and clinical Phases, but there are still many limitations to be solved. This review details the till date drug nanocarriers researches performed for lung cancer therapy.

  15. Advances in Lipidomics for Cancer Biomarkers Discovery

    PubMed Central

    Perrotti, Francesca; Rosa, Consuelo; Cicalini, Ilaria; Sacchetta, Paolo; Del Boccio, Piero; Genovesi, Domenico; Pieragostino, Damiana

    2016-01-01

    Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell–cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive lipids are mediators of a number of oncogenic processes. The current review gives a synopsis of a lipidomic approach in tumor characterization; we provide an overview on potential lipid biomarkers in the oncology field and on the principal lipidomic methodologies applied. The novel lipidomic biomarkers are reviewed in an effort to underline their role in diagnosis, in prognostic characterization and in prediction of therapeutic outcomes. A lipidomic investigation through mass spectrometry highlights new insights on molecular mechanisms underlying cancer disease. This new understanding will promote clinical applications in drug discovery and personalized therapy. PMID:27916803

  16. Annual Advances in Cancer Prevention Lecture | Division of Cancer Prevention

    Cancer.gov

    2015 Keynote Lecture HPV Vaccination: Preventing More with Less A special keynote lecture became part of the NCI summer Curriculum in Cancer Prevention in 2000. This lecture will be held on Thursday, July 23, 2015 at 3:00pm at Masur Auditorium, Building 10, NIH Main Campus, Bethesda, MD. This year’s keynote speaker is Dr. Douglas Lowy, NCI Acting Director. |

  17. Annual Advances in Cancer Prevention Lecture | Division of Cancer Prevention

    Cancer.gov

    2016 Keynote Lecture Polyvalent Vaccines Targeting Oncogenic Driver Pathways A special keynote lecture became part of the NCI Summer Curriculum in Cancer Prevention in 2000. This lecture will be held on Thursday, July 21, 2016 at 1:30pm at Masur Auditorium, Building 10, NIH Main Campus, Bethesda, MD. This year’s keynote speaker is Dr. Mary L. (Nora) Disis, MD. |

  18. Nanoparticles for cancer gene therapy: Recent advances, challenges, and strategies.

    PubMed

    Wang, Kui; Kievit, Forrest M; Zhang, Miqin

    2016-12-01

    Compared to conventional treatments, gene therapy offers a variety of advantages for cancer treatment including high potency and specificity, low off-target toxicity, and delivery of multiple genes that concurrently target cancer tumorigenesis, recurrence, and drug resistance. In the past decades, gene therapy has undergone remarkable progress, and is now poised to become a first line therapy for cancer. Among various gene delivery systems, nanoparticles have attracted much attention because of their desirable characteristics including low toxicity profiles, well-controlled and high gene delivery efficiency, and multi-functionalities. This review provides an overview on gene therapeutics and gene delivery technologies, and highlight recent advances, challenges and insights into the design and the utility of nanoparticles in gene therapy for cancer treatment.

  19. Physician allocation of Medicare resources for patients with advanced cancer.

    PubMed

    Rocke, Daniel J; Lee, Walter T; Beumer, Halton W; Taylor, Donald H; Schulz, Kristine; Thomas, Steven; Puscas, Liana

    2013-08-01

    Little is known about what patients and physicians value in end-of-life care, or how these groups would craft a health plan for those with advanced cancer. The study objective was to assess how otolaryngology, head and neck surgery (OHNS) physicians would structure a Medicare benefit plan for patients with advanced cancer, and to compare this with cancer patient and cancer patient caregiver preferences. OHNS physicians used an online version of a validated tool for assessing preferences for health plans in the setting of limited resources. These data were compared to cancer patient and caregiver preferences. OHNS physicians nationwide were assessed with comparison to similar data obtained in a separate study of cancer patients and their caregivers treated at Duke University Medical Center. Otolaryngology physicians (n=767) completed the online assessment and this was compared with data from 146 patients and 114 caregivers. OHNS physician allocations differed significantly in 14 of the 15 benefit categories when compared with patients and caregivers. Physicians elected more coverage in the Advice, Emotional Care, Palliative Care, and Treatment for Cancer benefit categories. Patients and their caregivers elected more coverage in the Cash, Complementary Care, Cosmetic Care, Dental and Vision, Drug Coverage, Home Improvement, House Calls, Nursing Facility, Other Medical Care, and Primary Care benefit categories. Otolaryngology physicians have significantly different values in end-of-life care than cancer patients and their caregivers. This information is important for efficient allocation of scarce Medicare resources and for effective end-of-life discussions, both of which are key for developing appropriate health policy.

  20. Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

    PubMed

    Chamberlin, Mary D; Bernhardt, Erica B; Miller, Todd W

    2016-11-01

    The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Improving Goals of Care Discussion in Advanced Cancer Patients

    ClinicalTrials.gov

    2016-12-20

    Primary Stage IV Hepatobiliary; Esophageal; Colorectal Cancer; Glioblastoma; Cancer of Stomach; Cancer of Pancreas; Melanoma; Head or Neck Cancer; Stage III; Stage IV; Lung Cancers; Pancreatic Cancers

  2. Germline genetic variants in ABCB1, ABCC1, and ALDH1A1 and risk of hematological and gastrointestinal toxicities in a SWOG Phase III trial S0221 for breast cancer

    PubMed Central

    Yao, Song; Sucheston, Lara E.; Zhao, Hua; Barlow, William E.; Zirpoli, Gary; Liu, Song; Moore, Halle C.F.; Budd, G. Thomas; Hershman, Dawn L.; Davis, Warren; Ciupak, Gregory L.; Stewart, James A.; Isaacs, Claudine; Hobday, Timothy J.; Salim, Muhammad; Hortobagyi, Gabriel N.; Gralow, Julie R.; Livingston, Robert B.; Albain, Kathy S.; Hayes, Daniel F.; Ambrosone, Christine B.

    2013-01-01

    Hematological and gastrointestinal toxicities are common among patients treated with cyclophosphamide and doxorubicin for breast cancer. To examine whether single nucleotide polymorphisms (SNPs) in key pharmacokinetic genes were associated with risk of hematological or gastrointestinal toxicity, we analyzed 78 SNPs in ABCB1, ABCC1 and ALDH1A1 in 882 breast cancer patients enrolled in the SWOG trial S0221 and treated with cyclophosphamide and doxorubicin. A two-SNP haplotype in ALDH1A1 was associated with an increased risk of grade 3 and 4 hematological toxicity (odds ratio [OR]=1.44, 95% confidence interval [CI]=1.16-1.78), which remained significant after correction for multiple comparisons. In addition, 4 SNPs in ABCC1 were associated with gastrointestinal toxicity. Our findings provide evidence that SNPs in pharmacokinetic genes may have an impact on the development of chemotherapy-related toxicities. This is a necessary first step towards building a clinical tool that will help assess risk of adverse outcomes prior to administration of chemotherapy. PMID:23999597

  3. Chemotherapy Resistance Mechanisms in Advanced Skin Cancer

    PubMed Central

    Kalal, Bhuvanesh Sukhlal; Upadhya, Dinesh; Pai, Vinitha Ramanath

    2017-01-01

    Melanoma is a most dangerous and deadly type of skin cancer, and considered intrinsically resistant to both radiotherapy and chemotherapy. It has become a major public health concern as the incidence of melanoma has been rising steadily over recent decades with a 5-year survival remaining less than 5%. Detection of the disease in early stage may be curable, but late stage metastatic disease that has spread to other organs has an extremely poor prognosis with a median survival of less than 10 months. Since metastatic melanoma is unresponsive to therapy that is currently available, research is now focused on different treatment strategies such as combinations of surgery, chemotherapy and radiotherapy. The molecular basis of resistance to chemotherapy seen in melanoma is multifactorial; defective drug transport system, altered apoptotic pathway, deregulation of apoptosis and/or changes in enzymatic systems that mediate cellular metabolic machinery. Understanding of alterations in molecular processes involved in drug resistance may help in developing new therapeutic approaches to treatment of malignant melanoma. PMID:28382191

  4. Recent advances in immunotherapy for hepatocellular cancer.

    PubMed

    Butterfield, Lisa H

    2007-02-10

    There is a continuing need for innovative, alternative therapies for hepatocellular carcinoma (HCC). Immunotherapy of cancer is attractive because of the exquisite specificity of the immune response. Activation of an HCC-specific response can be accomplished by strategies targeting tumour-associated antigens (for example: alpha fetoprotein (AFP)) or viral antigens in those patients infected with hepatitis B or C. Uncharacterised and mutated antigens can also be targeted with whole tumour cell or tumour lysate-based immunisation strategies. Viral vectors coding for genes which make the patient's tumour immunogenic can allow the immune system to naturally evolve specificity against immunogenic target antigens. Strategies which have been tested in human clinical trials include adoptive transfer of lymphocytes, cytokine injections, autologous tumour-pulsed dendritic cells (DC) as well as AFP-derived peptides in adjuvant and pulsed onto autologous DC. These trials, testing novel immune-based interventions in HCC subjects, have resulted in immunological responses and some have impacted recurrence and survival of HCC subjects.

  5. [Advances of molecular targeted therapy in squamous cell lung cancer].

    PubMed

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  6. Advances in PARP inhibitors for the treatment of breast cancer.

    PubMed

    Dizdar, Omer; Arslan, Cagatay; Altundag, Kadri

    2015-01-01

    Poly(ADP-Ribose) polymerases (PARPs) are one of the important components of base excision repair pathway for single strand DNA breaks. Currently accepted hypothesis for the mechanism of action for PARP inhibitors in tumors with homologous recombination deficiency is synthetic lethality, as the simultaneous blockage of both pathways prevents the tumor cells from repairing DNA damage. Other proposed mechanisms include PARP trapping, defective BRCA1 and POLQ recruitment to sites of DNA repair. Breast cancer subgroups with germline BRCA mutations or non-mutational functional defects in BRCA proteins exemplify potential targets for PARP inhibitors. Promising results have been achieved with PARP inhibitors in BRCA associated cancers, particularly in ovarian and breast cancer. Olaparib is the only PARP inhibitor approved by FDA in the treatment of patients with germline BRCA mutated advanced ovarian cancer pretreated with ≥3 prior lines of chemotherapy. In this article, we reviewed the current status of PARP inhibitors, completed and ongoing trials, safety and resistance issues in patients with breast cancer. PARP inhibitors show promise in cancers with BRCA mutation and in the treatment of sporadic cancers with defective homologous recombination. Predictors of response, strategies to overcome resistance, combination with other chemotherapies and targeted agents, optimum dose and schedule of administration should be investigated in future trials.

  7. Nursing care dependence in the experiences of advanced cancer inpatients.

    PubMed

    Piredda, Michela; Bartiromo, Chiara; Capuzzo, Maria Teresa; Matarese, Maria; De Marinis, Maria Grazia

    2016-02-01

    Increasing burden of cancer in Europe and socio-demographic trends imply that more cancer patients will face high levels of dependency. Care dependency is often perceived as a distressing experience by cancer patients who are concerned about becoming a burden to others. The experience of care dependence has been scarcely investigated in advanced cancer patients, especially in the hospital setting. This study aimed at describing advanced cancer patients' experiences of care dependence in hospital and of the factors perceived by them as contributing to decrease or increase this dependence. The study used a descriptive phenomenological approach based on Husserl's (1913) life world perspective. Data collection and analysis followed Giorgi's (1997) five basic methodological steps. Data were gathered by semi-structured interviews with thirteen advanced cancer adult inpatients of a teaching hospital. The interviews were audio-recorded and the recordings transcribed word for word. Three themes emerged: 'dependency discovers new meanings of life', 'active coping with dependency' and 'the care cures the dependent person'. The essential meaning of care dependency was the possibility to become aware of being a person as both an object and subject of care. Dependence appears as an experience with strong relational connotations, which enable patients to see differently their life, themselves, the world and others. Dependency is revealed as a natural experience, only partly in accordance with previous studies. Deeper insight into the meaning patients attach to care dependency can enable nurses to better meet the patient's needs, e.g. by improving caring relationships with patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Psychological distress in parents of children with advanced cancer.

    PubMed

    Rosenberg, Abby R; Dussel, Veronica; Kang, Tammy; Geyer, J Russel; Gerhardt, Cynthia A; Feudtner, Chris; Wolfe, Joanne

    2013-06-01

    Parent psychological distress can impact the well-being of childhood cancer patients and other children in the home. Recognizing and alleviating factors of parent distress may improve overall family survivorship experiences following childhood cancer. To describe the prevalence and factors of psychological distress (PD) among parents of children with advanced cancer. Cohort study embedded within a randomized clinical trial (Pediatric Quality of Life and Evaluation of Symptoms Technology [PediQUEST] study). Multicenter study conducted at 3 children's hospitals (Boston Children's Hospital, Children's Hospital of Philadelphia, and Seattle Children's Hospital). Parents of children with advanced (progressive, recurrent, or refractory) cancer. Parental PD, as measured by the Kessler-6 Psychological Distress Scale. Eighty-six of 104 parents completed the Survey About Caring for Children With Cancer (83% participation); 81 parents had complete Kessler-6 Psychological Distress Scale data. More than 50% of parents reported high PD and 16% met criteria for serious PD (compared with US prevalence of 2%-3%). Parent perceptions of prognosis, goals of therapy, child symptoms/suffering, and financial hardship were associated with PD. In multivariate analyses, average parent Kessler-6 Psychological Distress Scale scores were higher among parents who believed their child was suffering highly and who reported great economic hardship. Conversely, PD was significantly lower among parents whose prognostic understanding was aligned with concrete goals of care. Parenting a child with advanced cancer is strongly associated with high to severe levels of PD. Interventions aimed at aligning prognostic understanding with concrete care goals and easing child suffering and financial hardship may mitigate parental PD.

  9. Inverse correlation between body mass index and clinical outcomes in men with advanced castration-recurrent prostate cancer.

    PubMed

    Halabi, Susan; Ou, San-San; Vogelzang, Nicholas J; Small, Eric J

    2007-10-01

    Obesity has a variety of adverse health outcomes, but to the authors' knowledge, the effect of obesity on outcome in patients with advanced prostate cancer is not known. For this reason, the correlation between an elevated body mass index (BMI) and clinical outcomes in patients with metastatic, castration-recurrent prostate cancer (CRPC) was evaluated. A total of 1226 men with CRPC who were enrolled in 9 prospective clinical trials conducted by the Cancer and Leukemia Group B (CALGB) for the treatment of metastatic disease were considered. Eligible patients had progressive prostate cancer during androgen deprivation therapy (with documented castrate levels of testosterone); an Eastern Cooperative Oncology Group performance status of 0 to 2; and adequate hematologic, renal, and hepatic function. Patients were classified based on BMI as normal (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and mildly to severely obese (> or =30 kg/m(2)). Approximately 24% of the patients had a normal BMI, 43% were overweight, and 33% were mildly to severely obese. On multivariable analysis, BMI was found to be a statistically significant predictor of overall survival and prostate cancer-specific mortality. Compared with men with normal BMIs, the hazard ratios for death for overweight men and mildly to severely obese men were 0.80 (95% confidence interval [95% CI], 0.68-0.93; P = .001) and 0.80 (95% CI, 0.68-0.94; P = .010), respectively. In patients with metastatic CRPC, obesity (as defined by an elevated BMI) appears to have a protective effect against overall mortality and prostate cancer-specific mortality. Alternatively, a higher BMI may reflect different cancer biology (ie, the lack of cachexia-producing substances). Further studies to gain a more comprehensive understanding of the mechanisms behind these clinical observations are needed.

  10. Phase II Trial of Neoadjuvant Bevacizumab, Capecitabine, and Radiotherapy for Locally Advanced Rectal Cancer

    SciTech Connect

    Crane, Christopher H.; Eng, Cathy; Feig, Barry W.; Das, Prajnan; Skibber, John M.; Chang, George J.; Wolff, Robert A.; Krishnan, Sunil; Hamilton, Stanley; Janjan, Nora A.; Maru, Dipen M.; Ellis, Lee M.; Rodriguez-Bigas, Miguel A.

    2010-03-01

    Purpose: We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer. Methods: Between April 2004 and December 2007, 25 patients with clinically staged T3N1 (n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m{sup 2} orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later. Results: Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5-32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences. Conclusions: The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study.

  11. Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

    ClinicalTrials.gov

    2016-12-20

    Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

  12. The meaning of suffering in patients with advanced progressive cancer.

    PubMed

    Ellis, Jackie; Cobb, Mark; O'Connor, Tina; Dunn, Laurie; Irving, Greg; Lloyd-Williams, Mari

    2015-09-01

    There is a lack of research into suffering and what it means to the individual patient with advanced cancer and its importance in end of life care. To explore the concept of suffering and distress by eliciting what individual patients with advanced cancer perceived as suffering and how they utilised their own resources to manage suffering. A qualitative study design of focused narrative interviews analysed by thematic analysis was conducted with a heterogeneous sample of 49 palliative day care patients. For those patients who perceived they were suffering, this study revealed a wide spectrum of definitions which could be described within the following areas; the unavoidable and avoidable suffering, physical and emotional suffering, suffering as loss and finally transformation through suffering. These findings provide important insight that broadens and enriches our understanding into the concept of suffering and how patients utilise their resources, which may have important implications for end of life care. © The Author(s) 2015.

  13. The lived experience of people with progressive advanced cancer.

    PubMed

    Esteves, Amélia; Roxo, José; Saraiva, Maria da Conceição

    Cancer is a long-term, life-limiting condition, and its end-of-life stage is complex. This study aimed to understand the lived experience of patients with progressive advanced oncological disease. Seven women in an acute hospital in Portugal were interviewed and the results analysed using a phenomenological approach to understand their lived experience. The analysis indicated that lived experience of these patients has six essential constituents: information about one's own health; perception of the disease; emotional reactions; aid strategies by nurses; imitations imposed by the disease; and changes in life perspective. The experience of advanced progressive cancer is very powerful and complex. The authors believe that this study has contributed to the understanding of this situation, particularly in terms of helping to improve palliative care practices.

  14. Aesthetic engagements: "being" in everyday life with advanced cancer.

    PubMed

    la Cour, Karen; Hansen, Helle Ploug

    2012-03-01

    Living with advanced cancer can present an overwhelming challenge. It may impact the everyday life of the individual with respect to an array of psychological, physical, social, and existential issues. We focus on ways in which people with advanced cancer experience and use their engagement in daily activities when confronting nearing death. Through a phenomenological analysis based on Heidegger's thinking, we illuminate the complexities of "being toward death" and the human striving for authentic being through engagement in daily living. The main findings demonstrate how sensory experiences support being through an appreciation of everyday aesthetics. Furthermore, the making of material things was identified as a means to express the value of self and others in relation to the involved individual's past, present, and future.

  15. Recent advances in surgery for head and neck cancer.

    PubMed

    de Bree, Remco; Leemans, Charles René

    2010-05-01

    This paper reviews the advances in surgery in head and neck cancer patients. Sentinel node biopsy is a promising diagnostic technique to detect occult lymph node metastases, especially in oral carcinomas. Fludeoxyglucose-PET seems to be useful in detecting recurrent (laryngeal) carcinoma after radiotherapy. The role of fludeoxyglucose-PET to detect residual disease in the neck after radiotherapy with or without chemotherapy is not yet clear. The armamentarium of reconstructive surgery is still expanding. Endonasal endoscopic, robotic surgery and image-guided surgery are used as minimal invasive surgery in selected patients. Other advances include photodynamic therapy, ultrasonic surgery and mechanical sutures. New diagnostic techniques are used to avoid futile extensive surgery. Technical improvements have been made to treat head and neck cancer patients with minimal invasive surgery. Large prospective trials are needed to determine the indications for each technique.

  16. Resection versus other treatments for locally advanced pancreatic cancer.

    PubMed

    Gurusamy, Kurinchi Selvan; Kumar, Senthil; Davidson, Brian R; Fusai, Giuseppe

    2014-02-27

    Pancreatic cancer is an aggressive cancer. Resection of the cancer is the only treatment with the potential to achieve long-term survival. However, a third of patients with pancreatic cancer have locally advanced cancer involving adjacent structures such as blood vessels which are not usually removed because of fear of increased complications after surgery. Such patients often receive palliative treatment. Resection of the pancreas along with the involved vessels is an alternative to palliative treatment for patients with locally advanced pancreatic cancer. To compare the benefits and harms of surgical resection versus palliative treatment in patients with locally advanced pancreatic cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 12), MEDLINE, EMBASE, Science Citation Index Expanded, and trial registers until February 2014. We included randomised controlled trials comparing pancreatic resection versus palliative treatments for patients with locally advanced pancreatic cancer (irrespective of language or publication status). Two authors independently assessed trials for inclusion and independently extracted the data. We analysed the data with both the fixed-effect and random-effects models using Review Manager (RevMan). We calculated the hazard ratio (HR), risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on an intention-to-treat analysis. We identified two trials comparing pancreatic resection versus other treatments for patients with locally advanced pancreatic cancer. Ninety eight patients were randomised to pancreatic resection (n = 47) or palliative treatment (n = 51) in the two trials included in this review. Both trials were at high risk of bias. Both trials included patients who had locally advanced pancreatic cancer which involved the serosa anteriorly or retroperitoneum posteriorly or involved the blood vessels. Such pancreatic cancers would be considered

  17. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    PubMed Central

    Kwak, Yoo-Kang; Lee, Jong Hoon; Lee, Myung-Ah; Chun, Hoo-Geun; Kim, Dong-Goo; You, Young Kyoung; Hong, Tae-Ho

    2014-01-01

    Purpose Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Materials and Methods Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. Results With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Conclusion Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival. PMID:25061572

  18. Prognostic Tools in Patients With Advanced Cancer: A Systematic Review.

    PubMed

    Simmons, Claribel P L; McMillan, Donald C; McWilliams, Kerry; Sande, Tonje A; Fearon, Kenneth C; Tuck, Sharon; Fallon, Marie T; Laird, Barry J

    2017-05-01

    In 2005, the European Association for Palliative Care made recommendations for prognostic markers in advanced cancer. Since then, prognostic tools have been developed, evolved, and validated. The aim of this systematic review was to examine the progress in the development and validation of prognostic tools. Medline, Embase Classic and Embase were searched. Eligible studies met the following criteria: patients with incurable cancer, >18 years, original studies, population n ≥100, and published after 2003. Descriptive and quantitative statistical analyses were performed. Forty-nine studies were eligible, assessing seven prognostic tools across different care settings, primary cancer types, and statistically assessed survival prediction. The Palliative Performance Scale was the most studied (n = 21,082), comprising six parameters (six subjective), was externally validated, and predicted survival. The Palliative Prognostic Score composed of six parameters (four subjective and two objective), the Palliative Prognostic Index composed of nine parameters (nine subjective), and the Glasgow Prognostic Score composed of two parameters (two objective) and were all externally validated in more than 2000 patients with advanced cancer and predicted survival. Various prognostic tools have been validated but vary in their complexity, subjectivity, and therefore clinical utility. The Glasgow Prognostic Score would seem the most favorable as it uses only two parameters (both objective) and has prognostic value complementary to the gold standard measure, which is performance status. Further studies comparing all proved prognostic markers in a single cohort of patients with advanced cancer are needed to determine the optimal prognostic tool. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  19. Advancing cancer control research in an emerging news media environment.

    PubMed

    Smith, Katherine C; Niederdeppe, Jeff; Blake, Kelly D; Cappella, Joseph N

    2013-12-01

    Cancer is both highly feared and highly newsworthy, and there is a robust body of research documenting the content and effects of cancer news coverage on health behaviors and policy. Recent years have witnessed ongoing, transformative shifts in American journalism alongside rapid advances in communication technology and the public information environment. These changes create a pressing need to consider a new set of research questions, sampling strategies, measurement techniques, and theories of media effects to ensure continued relevance and adaptation of communication research to address critical cancer control concerns. This paper begins by briefly reviewing what we know about the role of cancer news in shaping cancer-related beliefs, attitudes, behaviors, and policies. We then outline challenges and opportunities, both theoretical and methodological, posed by the rapidly changing news media environment and the nature of audience engagement. We organize our discussion around three major shifts associated with the emerging news media environment as it relates to health communication: 1) speed and dynamism of news diffusion, 2) increased narrowcasting of media content for specialized audiences, and 3) broadened participation in shaping media content. In so doing, we articulate a set of questions for future theory and research, in an effort to catalyze innovative communication scholarship to improve cancer prevention and control.

  20. Recent Advances in Metabolic Profiling And Imaging of Prostate Cancer

    PubMed Central

    Thapar, Roopa; Titus, Mark A

    2015-01-01

    Cancer is a metabolic disease. Cancer cells, being highly proliferative, show significant alterations in metabolic pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino acid metabolism. Metabolites like peptides, nucleotides, products of glycolysis, the TCA cycle, fatty acids, and steroids can be an important read out of disease when characterized in biological samples such as tissues and body fluids like urine, serum, etc. The cancer metabolome has been studied since the 1960s by analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Current research is focused on the identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients and distinguish between benign and advanced metastatic forms of the disease. In this review, we discuss the current state of prostate cancer metabolomics, the biomarkers that show promise in distinguishing indolent from aggressive forms of the disease, the strengths and limitations of the analytical techniques being employed, and future applications of metabolomics in diagnostic imaging and personalized medicine of prostate cancer. PMID:25632377

  1. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.

  2. Navigating the evolving therapeutic landscape in advanced prostate cancer.

    PubMed

    Crawford, E David; Petrylak, Daniel; Sartor, Oliver

    2017-03-07

    Prostate cancer is the most common cause of cancer in men, with 137.9 new cases per 100,000 men per year. The overall 5-year survival rate for prostate cancer is very high. Up to 20% of men who undergo state-of-the art treatment for prostate cancer will develop castration-resistant prostate cancer (CRPC) within 5 years, with median survival for those with metastatic CRPC ranging from approximately 15 to 36 months in recent studies. With the advent of several new drugs in the past 5 years to treat CRPC, the challenge facing clinicians is how to best sequence or combine therapies or both to optimize outcomes. A better understanding of the disease process and the role of the androgen receptor as a target for both therapy and resistance have led to the consideration of biomarkers as an approach to aid in selecting the appropriate agent for a given patient as patients respond to or tolerate different drugs differently. Research to identify new prognostic biomarkers, which are associated with outcome measures, as well as predictive biomarkers, which predict response or resistance to therapy is ongoing. The treatment of advanced prostate cancer and the research related to biomarkers are discussed.

  3. Glucose Addiction in Cancer Therapy: Advances and Drawbacks.

    PubMed

    Granja, Sara; Pinheiro, Céline; Reis, Rui Manuel; Martinho, Olga; Baltazar, Fátima

    2015-01-01

    While normal differentiated cells primarily use mitochondrial respiration to generate the required energy for cellular processes, most cancer cells rely on glycolysis, even in sufficient oxygen conditions. This phenomenon is known as the "Warburg effect" or aerobic glycolysis and the metabolic reprogramming of cancer cells towards this altered energy metabolism is currently recognized as one of the "hallmarks of cancer". Aerobic glycolysis underlies the rapid growth of tumor cells, with high rates of glucose consumption and lactic acid production, leading to cellular acidosis. Metabolic reprogramming renders cancer cells dependent on specific metabolic enzymes or pathways that could be exploited in cancer therapy. The development of treatments that target tumor glucose metabolism is receiving renewed attention, with several drugs targeting metabolic pathways currently in clinical trials. The search for suitable targets, however, is limited by the high plasticity of the metabolic network that can induce compensatory routes. Deregulated glucose metabolism is a prominent feature associated with resistance to classical chemotherapy or oncogene-targeted therapies, strengthening the clinical potential of combining these therapies with glycolysis inhibitors. The aim of this review is to compare the advances of different therapeutic strategies targeting the glucose "addiction" of tumor cells, highlighting their potential as effective weapons against cancer. We further discuss recent evidence for the involvement of glucose metabolism as a compensatory response to the use of drugs that target different signaling pathways, where the combination with glycolysis inhibitors could prove extraordinarily useful.

  4. Molecular Targets of Isothiocyanates in Cancer: Recent Advances

    PubMed Central

    Gupta, Parul; Kim, Bonglee; Kim, Sung-Hoon; Srivastava, Sanjay K.

    2014-01-01

    Cancer is a multistep process resulting in uncontrolled cell division. It results from aberrant signaling pathways that lead to uninhibited cell division and growth. Various recent epidemiological studies have indicated that consumption of cruciferous vegetables such as garden cress, broccoli, etc., reduces the risk of cancer. Isothiocyanates (ITC) have been identified as major active constituents of cruciferous vegetables. ITCs occur in plants as glucosinolate and can readily be derived by hydrolysis. Numerous mechanistic studies have demonstrated the anti-cancer effects of ITCs in various cancer types. ITCs suppress tumor growth by generating reactive oxygen species or by inducing cycle arrest leading to apoptosis. Based on the exciting outcomes of pre-clinical studies, few ITCs have advanced to the clinical phase. Available data from pre-clinical as well as available clinical studies suggests ITCs to be one of the promising anti-cancer agents available from natural sources. This is an up-to-date exhaustive review on the preventive and therapeutic effects of ITCs in cancer. PMID:24510468

  5. Stereotactic Body Radiation Therapy Boost in Locally Advanced Pancreatic Cancer

    SciTech Connect

    Seo, Young Seok; Kim, Mi-Sook; Yoo, Sung Yul; Cho, Chul Koo; Yang, Kwang Mo; Yoo, Hyung Jun; Choi, Chul Won; Lee, Dong Han; Kim, Jin; Kim, Min Suk; Kang, Hye Jin; Kim, YoungHan

    2009-12-01

    Purpose: To investigate the clinical application of a stereotactic body radiation therapy (SBRT) boost in locally advanced pancreatic cancer patients with a focus on local efficacy and toxicity. Methods and Materials: We retrospectively reviewed 30 patients with locally advanced and nonmetastatic pancreatic cancer who had been treated between 2004 and 2006. Follow-up duration ranged from 4 to 41 months (median, 14.5 months). A total dose of 40 Gy was delivered in 20 fractions using a conventional three-field technique, and then a single fraction of 14, 15, 16, or 17 Gy SBRT was administered as a boost without a break. Twenty-one patients received chemotherapy. Overall and local progression-free survival were calculated and prognostic factors were evaluated. Results: One-year overall survival and local progression-free survival rates were 60.0% and 70.2%, respectively. One patient (3%) developed Grade 4 toxicity. Carbohydrate antigen 19-9 response was found to be an independent prognostic factor for survival. Conclusions: Our findings indicate that a SBRT boost provides a safe means of increasing radiation dose. Based on the results of this study, we recommend that a well controlled Phase II study be conducted on locally advanced pancreatic cancer.

  6. Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes

    SciTech Connect

    Tinkle, Christopher L.; Weinberg, Vivian; Chen, Lee-May; Littell, Ramey; Cunha, J. Adam M.; Sethi, Rajni A.; Chan, John K.; Hsu, I-Chow

    2015-08-01

    Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall

  7. High-Intensity Focused Ultrasound Treatment for Advanced Pancreatic Cancer

    PubMed Central

    Zhou, Yufeng

    2014-01-01

    Pancreatic cancer is under high mortality but has few effective treatment modalities. High-intensity focused ultrasound (HIFU) is becoming an emerging approach of noninvasively ablating solid tumor in clinics. A variety of solid tumors have been tried on thousands of patients in the last fifteen years with great success. The principle, mechanism, and clinical outcome of HIFU were introduced first. All 3022 clinical cases of HIFU treatment for the advanced pancreatic cancer alone or in combination with chemotherapy or radiotherapy in 241 published papers were reviewed and summarized for its efficacy, pain relief, clinical benefit rate, survival, Karnofsky performance scale (KPS) score, changes in tumor size, occurrence of echogenicity, serum level, diagnostic assessment of outcome, and associated complications. Immune response induced by HIFU ablation may become an effective way of cancer treatment. Comments for a better outcome and current challenges of HIFU technology are also covered. PMID:25053938

  8. Evidence-based approaches to other symptoms in advanced cancer.

    PubMed

    Dy, Sydney Morss; Apostol, Colleen C

    2010-01-01

    Dyspnea, nausea and vomiting, anorexia, fatigue, and sleep disturbances are common and distressing in advanced cancer. We updated previous systematic reviews of how these symptoms can be alleviated with targeted literature searches. The approach to these symptoms requires comprehensive symptom assessment; treating underlying causes when benefits exceed risks; prioritizing treatment, as patients usually have many symptoms; and addressing psychosocial and spiritual distress. For dyspnea, evidence supports systemic opioids and nonpharmacological treatments such as a fan. The strongest evidence supports metoclopramide for cancer-related nausea and octreotide for bowel obstruction. For anorexia, enteral or parenteral nutrition is indicated with obstruction and expected prognosis of at least 6 weeks. Evidence supports several drugs for appetite affecting quality of life. For fatigue, evidence supports psychosocial interventions and methylphenidate. For insomnia, evidence supports cognitive-behavioral therapy in cancer; no sleep agents have superior effectiveness.

  9. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Li, Yi; Wang, Ji; Ma, Xiaowei; Tan, Li; Yan, Yanli; Xue, Chaofan; Hui, Beina; Liu, Rui; Ma, Hailin; Ren, Juan

    2016-01-01

    Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Different therapeutic reactions to neoadjuvant chemoradiotherapy affect the type of surgical techniques, hence calling for the need of much attention. Furthermore, many problems such as accurate staging before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and sensitivity prediction to preoperative radiotherapy need to be well settled. PMID:27489505

  10. Radiotherapy combined with surgery as treatment for advanced cervical cancer.

    PubMed

    Perches, R D; Lobaton, A T; Garcia, M C

    1983-12-01

    Experience obtained in a group of 44 patients with advanced cervical cancer is reported here. In this study, patients with residual cancer underwent laparotomy eight weeks after one or two different radiotherapy protocols. Sixty-eight percent of patients underwent radical surgery, 85% of patients pelvic exenterations, and 15% radical hysterectomies. In 27% of patients, no evidence of residual cancer was found in surgical specimens. Radical surgery was well tolerated, and one-third of patients were free of disease for one year or more. Control of disease was obtained in 50% of pelvic exenterations and in 60% of radical hysterectomies, regardless of prognosis, clinical stage or radiotherapy scheme. Although results show an improvement of up to 22% when comparing this to other more conventional treatments, we have concluded that we must obtain a wider experience in order to support our findings.

  11. Fast neutron irradiation for locally advanced pancreatic cancer

    SciTech Connect

    Smith, F.P.; Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-11-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials.

  12. Drugging Chromatin in Cancer: Recent Advances and Novel Approaches

    PubMed Central

    Cai, Sheng F.; Chen, Chun-Wei; Armstrong, Scott A.

    2015-01-01

    Chromatin regulatory mechanisms play a major role in the control of gene expression programs during normal development and are disrupted in specific disease states, particularly in cancer. Important mediators of chromatin regulatory processes can broadly be classified into writers, erasers, and readers of covalent chromatin modifications that modulate eukaryotic gene transcription and maintain the integrity of the genome. The reversibility and disease-specific nature of these chromatin states make these regulators attractive therapeutic targets. As such, there is an ever-increasing number of candidate therapies aimed at targeting cancer-associated chromatin states that are in various stages of preclinical and clinical development. In this review, we discuss recent advances that have been made in the rational therapeutic targeting of chromatin regulatory mechanisms and highlight certain cancers where there is a specific rationale to assess these therapeutic approaches. PMID:26590715

  13. Evaluation of rational extent lymphadenectomy for local advanced gastric cancer

    PubMed Central

    Liang, Han; Deng, Jingyu

    2016-01-01

    Based upon studies from randomized clinical trials, the extended (D2) lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Due to the limitation of low metastatic rate in para-aortic nodes (PAN) in JCOG9501, the clinical benefit of D2+ para-aortic nodal dissection (PAND) for patients with stage T4 and/or stage N3 disease, which is very common in China and other countries except Japan and Korea, cannot be determined. Furthermore, the role of splenectomy for complete resection of No.10 and No.11 nodes has been controversial, and however, the final results from the randomized trial of JCOG0110 have yet to be completed. Gastric cancer with the No.14 and No.13 lymph node metastasis is defined as M1 stage in the current version of the Japanese classification. We propose that D2+No.14v and +No.13 lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with apparent metastasis to the No.6 nodes or infiltrate to duodenum. The examined lymph node and extranodal metastasis are significantly associated with the survival of gastric cancer patients. PMID:27647967

  14. Locally advanced colon cancer with cutaneous invasion: case report.

    PubMed

    Tenreiro, Nádia; Ferreira, Cátia; Silva, Silvia; Marques, Rita; Ribeiro, Artur; Sousa, Paulo Jorge; Luís, Fernando Próspero

    2017-03-01

    Locally advanced colon cancer with direct abdominal wall and skin invasion is an extremely rare finding with most data being derived from case reports, historical autopsy-based or single-center retrospective studies. We present a unique case of a colon cancer with direct cutaneous invasion and colocutaneous fistulization. Eighty-six year old Caucasian female with multiple comorbidities, referred to Surgical Consultation due to ulcerated skin lesion in the abdomen. She had a long-standing large umbilical hernia but with no previous episodes of incarceration or occlusive symptoms. She denied any digestive or constitutional symptoms. Physical examination showed a large non-reducible umbilical hernia, with an associated painless firm mass within the hernia sac and cutaneous ulcerated growth. Colonoscopy revealed transverse colon cancer (endoscopic biopsy of the tumor and skin punch biopsy confirmed adenocarcinoma of the colon). Computed tomography showed a tumoral mass within the umbilical hernia, with cutaneous infiltration and enlarged regional lymph nodes. Rapid local progression led to colocutaneous fistula with total fecal diversion. We performed an extended right hemicolectomy with en bloc excision of the hernia sac and infiltrating cutaneous mass. In the current era of widespread use of screening colonoscopies, initial diagnosis of locally advanced colon cancer is decreasing. However, this unique case presented an opportunity to recall the advantages of multivisceral resections.

  15. hemaClass.org: Online One-By-One Microarray Normalization and Classification of Hematological Cancers for Precision Medicine

    PubMed Central

    Falgreen, Steffen; Ellern Bilgrau, Anders; Brøndum, Rasmus Froberg; Hjort Jakobsen, Lasse; Have, Jonas; Lindblad Nielsen, Kasper; El-Galaly, Tarec Christoffer; Bødker, Julie Støve; Schmitz, Alexander; H. Young, Ken; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

    2016-01-01

    Background Dozens of omics based cancer classification systems have been introduced with prognostic, diagnostic, and predictive capabilities. However, they often employ complex algorithms and are only applicable on whole cohorts of patients, making them difficult to apply in a personalized clinical setting. Results This prompted us to create hemaClass.org, an online web application providing an easy interface to one-by-one RMA normalization of microarrays and subsequent risk classifications of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin and chemotherapeutic sensitivity classes. Classification results for one-by-one array pre-processing with and without a laboratory specific RMA reference dataset were compared to cohort based classifiers in 4 publicly available datasets. Classifications showed high agreement between one-by-one and whole cohort pre-processsed data when a laboratory specific reference set was supplied. The website is essentially the R-package hemaClass accompanied by a Shiny web application. The well-documented package can be used to run the website locally or to use the developed methods programmatically. Conclusions The website and R-package is relevant for biological and clinical lymphoma researchers using affymetrix U-133 Plus 2 arrays, as it provides reliable and swift methods for calculation of disease subclasses. The proposed one-by-one pre-processing method is relevant for all researchers using microarrays. PMID:27701436

  16. Confocal microscopy of skin cancers: Translational advances toward clinical utility

    PubMed Central

    Rajadhyaksha, Milind

    2014-01-01

    Recent advances in translational research in and technology for confocal microscopy of skin cancers, toward clinical applications, are described. Advances in translational research are in diagnosis of melanoma in vivo, pre-operative mapping of lentigo maligna melanoma margins to guide surgery and intra-operative imaging of residual basal cell carcinomas to guide shave-biopsy. Advances in technology include mosaicing microscopy for detection of basal cell carcinomas in large areas of excised tissue, toward rapid pathology-at-the-bedside, and development of small, simple and low-cost line-scanning confocal microscopes for worldwide use in diverse primary healthcare settings. Current limitations and future opportunities and challenges for both clinicians and technologists are discussed. PMID:19964286

  17. Overcoming Drug Resistance and Treating Advanced Prostate Cancer

    PubMed Central

    Semenas, Julius; Allegrucci, Cinzia; Boorjian, Stephen A; Mongan, Nigel P; Persson, Jenny Liao

    2012-01-01

    Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens are available to eradicate the metastasis, and cancer-related death becomes inevitable. In 2012, it is estimated that there will be 28,170 PCa deaths in the United States. Thus, PCa bone metastasis-associated clinical complications and treatment resistance pose major clinical challenges. In this review, we will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa. We will address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis, and will further discuss why prostate cancer cells preferentially metastasize to the bone. Additionally, we will discuss novel roles of several key pathways, including angiogenesis and extracellular matrix remodeling in bone marrow and stem cell niches with their relationship to PCa bone metastasis and poor treatment response. We will evaluate how various chemotherapeutic drugs and radiation therapies may allow aggressive PCa cells to gain advantageous mutations leading to increased survival and rendering the cancer cells to become resistant to treatment. The novel concept relating several key survival and invasion signaling pathways to stem cell niches and treatment resistance will be reviewed. Lastly, we will provide an update of several recently developed novel drug candidates that target metastatic cancer microenvironments or niches, and discuss the advantages and significance provided by such therapeutic approaches in pursuit of overcoming drug resistance and treating advanced PCa. PMID:22746994

  18. Advancing Cancer Control Through Research and Cancer Registry Collaborations in the Caribbean

    PubMed Central

    Banydeen, Rishika; Rose, Angela M.C.; Martin, Damali; Aiken, William; Alexis, Cheryl; Andall-Brereton, Glennis; Ashing, Kimlin; Avery, J. Gordon; Avery, Penny; Deloumeaux, Jacqueline; Ekomaye, Natasha; Gabriel, Owen; Hassell, Trevor; Hughes, Lowell; Hutton, Maisha; Jyoti, Shravana Kumar; Layne, Penelope; Luce, Danièle; Patrick, Alan; Prussia, Patsy; Smith-Ravin, Juliette; Veronique-Baudin, Jacqueline; Blackman, Elizabeth; Roach, Veronica; Ragin, Camille

    2016-01-01

    Background Few national registries exist in the Caribbean, resulting in limited cancer statistics being available for the region. Therefore, estimates are frequently based on the extrapolation of mortality data submitted to the World Health Organization. Thus, regional cancer surveillance and research need promoting, and their synergy must be strengthened. However, differences between countries outweigh similarities, hampering registration and availability of data. Methods The African-Caribbean Cancer Consortium (AC3) is a broad-based resource for education, training, and research on all aspects of cancer in populations of African descent. The AC3 focuses on capacity building in cancer registration in the Caribbean through special topics, training sessions, and biannual meetings. We review the results from selected AC3 workshops, including an inventory of established cancer registries in the Caribbean region, current cancer surveillance statistics, and a review of data quality. We then describe the potential for cancer research surveillance activities and the role of policymakers. Results Twelve of 30 Caribbean nations have cancer registries. Four of these nations provide high-quality incidence data, thus covering 14.4% of the population; therefore, regional estimates are challenging. Existing research and registry collaborations must pave the way and are facilitated by organizations like the AC3. Conclusions Improved coverage for cancer registrations could help advance health policy through targeted research. Capacity building, resource optimization, collaboration, and communication between cancer surveillance and research teams are key to obtaining robust and complete data in the Caribbean. PMID:26678981

  19. Ixabepilone in Treating Patients With Advanced Urinary Tract Cancer

    ClinicalTrials.gov

    2013-01-23

    Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer

  20. On the Effect of Triplet or Doublet Chemotherapy in Advanced Gastric Cancer: Results From a National Cancer Registry.

    PubMed

    Carmona-Bayonas, Alberto; Jiménez-Fonseca, Paula; Lorenzo, Maria Luisa Sánchez; Ramchandani, Avinash; Martínez, Elena Asensio; Custodio, Ana; Garrido, Marcelo; Echavarría, Isabel; Cano, Juana María; Barreto, Jose Enrique Lorenzo; García, Teresa García; Manceñido, Felipe Álvarez; Lacalle, Alejandra; Cardona, Marta Ferrer; Mangas, Monserrat; Visa, Laura; Buxó, Elvira; Azkarate, Aitor; Díaz-Serrano, Asunción; Montes, Ana Fernández; Rivera, Fernando

    2016-11-01

    There is currently no consensus regarding first-line chemotherapy for patients with advanced gastric cancer (AGC) who are ineligible to receive trastuzumab. The objective of this study was to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. Patients with AGC treated with polychemotherapy without associating trastuzumab were included from 2008 through 2016. The effect of triplets versus doublets was compared using 3 methods: Cox proportional hazards regression, propensity score matching (PSM), and coarsened exact matching (CEM). A total of 970 patients were recruited (doublets: n=569; triplets: n=401). In the multivariate Cox model, the use of triplets was associated with better overall survival (OS), with a hazard ratio (HR) of 0.84 (95% CI, 0.72-0.98; P=.035). After PSM, the sample contained 340 pairs. A significant increase in OS, 11.14 months (95% CI, 9.60-12.68) versus 9.60 months (95% CI, 8.44-10.75), was seen in favor of triplets (HR, 0.77; 95% CI, 0.65-0.92; stratified log-rank test, P=.004). The effect appeared to be comparable for anthracycline-based (HR, 0.78; 95% CI, 0.64-0.94) or docetaxel-based triplets (HR, 0.78; 95% CI, 0.60-1.009). The trend was similar after applying the CEM algorithm, with an HR of 0.78 (95% CI, 0.63-0.97; P=.03). Triplet therapy was viable and relative dose intensities exceeded 85%, except for cisplatin in DCX (docetaxel, cisplatin, capecitabine). Triplets had more severe toxicity overall, especially hematologic, hepatic, and mucosal adverse events. With the limitations of a retrospective study that examines a heterogeneous set of chemotherapy regimens, we found that triplets are feasible in daily practice and are associated with a discreet benefit in efficacy at the expense of a moderate increase in toxicity. Copyright © 2016 by the National Comprehensive Cancer Network.

  1. Practical use of advanced mouse models for lung cancer.

    PubMed

    Safari, Roghaiyeh; Meuwissen, Ralph

    2015-01-01

    To date a variety of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) mouse models have been developed that mimic human lung cancer. Chemically induced or spontaneous lung cancer in susceptible inbred strains has been widely used, but the more recent genetically engineered somatic mouse models recapitulate much better the genotype-phenotype correlations found in human lung cancer. Additionally, improved orthotopic transplantation of primary human cancer tissue fragments or cells into lungs of immune-compromised mice can be valuable tools for preclinical research such as antitumor drug tests. Here we give a short overview of most somatic mouse models for lung cancer that are currently in use. We accompany each different model with a description of its practical use and application for all major lung tumor types, as well as the intratracheal injection or direct injection of fresh or freeze-thawed tumor cells or tumor cell lines into lung parenchyma of recipient mice. All here presented somatic mouse models are based on the ability to (in) activate specific alleles at a time, and in a tissue-specific cell type, of choice. This spatial-temporal controlled induction of genetic lesions allows the selective introduction of main genetic lesions in an adult mouse lung as found in human lung cancer. The resulting conditional somatic mouse models can be used as versatile powerful tools in basic lung cancer research and preclinical translational studies alike. These distinctively advanced lung cancer models permit us to investigate initiation (cell of origin) and progression of lung cancer, along with response and resistance to drug therapy. Cre/lox or FLP/frt recombinase-mediated methods are now well-used techniques to develop tissue-restricted lung cancer in mice with tumor-suppressor gene and/or oncogene (in)activation. Intranasal or intratracheal administration of engineered adenovirus-Cre or lentivirus-Cre has been optimized for introducing Cre

  2. Hematologic neoplasms: Dendritic cells vaccines in motion.

    PubMed

    Galati, Domenico; Zanotta, Serena

    2017-09-11

    Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a key role in cancer vaccination as potent antigen-presenting cells within the immune system. Cancer microenvironment can modulate DCs maturation resulting in their accumulation into functional states associated with a reduced antitumor immune response. In this regard, a successful cancer vaccine needs to mount a potent antitumor immune response able to overcome the immunosuppressive tumor milieu. As a consequence, DCs-based approaches are a safe and promising strategy for improving the therapeutic efficacy in hematological malignancies, particularly in combinations with additional treatments. This review summarizes the most significant evidence about the immunotherapeutic strategies performed to target hematologic neoplasms including the tumoral associated antigens (TAA) pulsed on DCs, whole tumor cell vaccines or leukemia-derived DCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

    PubMed

    Gillessen, S; Omlin, A; Attard, G; de Bono, J S; Efstathiou, E; Fizazi, K; Halabi, S; Nelson, P S; Sartor, O; Smith, M R; Soule, H R; Akaza, H; Beer, T M; Beltran, H; Chinnaiyan, A M; Daugaard, G; Davis, I D; De Santis, M; Drake, C G; Eeles, R A; Fanti, S; Gleave, M E; Heidenreich, A; Hussain, M; James, N D; Lecouvet, F E; Logothetis, C J; Mastris, K; Nilsson, S; Oh, W K; Olmos, D; Padhani, A R; Parker, C; Rubin, M A; Schalken, J A; Scher, H I; Sella, A; Shore, N D; Small, E J; Sternberg, C N; Suzuki, H; Sweeney, C J; Tannock, I F; Tombal, B

    2015-08-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  4. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

    PubMed Central

    Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.

    2015-01-01

    The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764

  5. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.

    PubMed

    Goetz, Matthew P; Toi, Masakazu; Campone, Mario; Sohn, Joohyuk; Paluch-Shimon, Shani; Huober, Jens; Park, In Hae; Trédan, Olivier; Chen, Shin-Cheh; Manso, Luis; Freedman, Orit C; Garnica Jaliffe, Georgina; Forrester, Tammy; Frenzel, Martin; Barriga, Susana; Smith, Ian C; Bourayou, Nawel; Di Leo, Angelo

    2017-10-02

    Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.

  6. Clinical trials update: Medical management of advanced breast cancer.

    PubMed

    Major, Maureen A

    2003-12-01

    Selection of treatment for metastatic breast cancer depends on several factors: the status of estrogen receptors or progesterone receptors on breast cancer cells and the expression levels of human epidermal growth factor receptor-2. The presence of estrogen or progesterone receptors typically indicates slower-growing tumors that may be amenable to hormonal manipulation, which provides significant disease control while offering a better toxicity profile than conventional chemotherapy. The understanding of hormonal therapies in patients with postmenopausal metastatic breast cancer has advanced greatly in the past several decades. Aromatase inhibitors, although used initially as second-line therapy, recently have proved to be as effective as tamoxifen, if not superior to it, as first-line therapy for metastatic breast cancer. New data also suggest that letrozole provides significantly better objective responses than anastrozole as second-line therapy. Exemestane, a steroidal aromatase inhibitor, is an effective third-line therapy. Fulvestrant, an estrogen receptor antagonist with no known agonist effect, provides a new option for hormonal therapy. For patients with metastatic breast cancer and overexpression of human epidermal growth factor receptor-2 on tumor cells, the monoclonal antibody trastuzumab is the preferred option, either in combination with paclitaxel as first-line treatment, or as a single agent for second-line therapy. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed, potentially extending patient survival rates and improving quality of life.

  7. Control of Advanced Cancer: The Road to Chronicity

    PubMed Central

    Lage, Agustin; Crombet, Tania

    2011-01-01

    Despite the recent trend toward a slight decrease in age-adjusted cancer mortality in some countries, crude mortality rates will continue to increase, driven by the demographic shift towards an aged population. Small molecules (small molecules and biologics) are not only a new therapeutic acquisition, but the tools of a more fundamental transition: the transformation of cancer from a rapidly fatal disease into a chronic condition. Antibodies and cancer vaccines can be used for a long time, even beyond progressive disease, and in aged patients, usually unfit for more aggressive conventional treatments. However, this transition to chronicity will require novel developmental guidelines adequate to this kind of drugs, for which optimal dose is not usually the maximal tolerated dose, pharmacokinetics does not define treatment schedule, and tumor shrinkage is not a good correlate of survival. The ongoing cancer immunotherapy program (including several monoclonal antibodies and therapeutic vaccines) at the Centre of Molecular Immunology can illustrate the issues to be addressed, both biological and social, along the path to transform advanced cancer into a chronic non-communicable disease compatible with years of quality life. PMID:21556173

  8. Advances in Genetic Testing for Hereditary Cancer Syndromes.

    PubMed

    Thomas, Ellen; Mohammed, Shehla

    2016-01-01

    The ability to identify genetic mutations causing an increased risk of cancer represents the first widespread example of personalised medicine, in which genetic information is used to inform patients of their cancer risks and direct an appropriate strategy to minimise those risks. Increasingly, an understanding of the genetic basis of many cancers also facilitates selection of the most effective therapeutic options. The technology underlying genetic testing has been revolutionised in the years since the completion of the Human Genome Project in 2001. This has advanced knowledge of the genetic factors underlying familial cancer risk, and has also improved genetic testing capacity allowing a larger number of patients to be tested for a constitutional cancer predisposition. To use these tests safely and effectively, they must be assessed for their ability to provide accurate and useful results, and be requested and interpreted by health professionals with an understanding of their strengths and limitations. Genetic testing is increasing in its scope and ambition with each year that passes, requiring a greater proportion of the healthcare workforce to acquire a working knowledge of genetics and genetic testing to manage their patients safely and sensitively.

  9. Perspectives of newly diagnosed advanced cancer patients receiving dignity therapy during cancer treatment.

    PubMed

    Dose, Ann Marie; Rhudy, Lori M

    2017-07-21

    Dignity therapy is a psychosocial intervention that has been used primarily at the end of life to improve quality of life and other patient outcomes, but many individuals are unable to complete it due to health decline and death. The purpose of this study was to identify what individuals with advanced pancreatic or lung cancer with limited life expectancy, undergoing active cancer treatment describe during the dignity therapy intervention as important to them when not immediately facing end of life. Twenty patients undergoing chemotherapy for advanced cancer participated in a dignity therapy intervention study. Initial interviews were analyzed using descriptive content analysis. Family provided the overall context and background for emerging themes of defining events, accomplishments, and God's plan, which led to lessons learned, and resulted in messages of hope. Interviews were often autobiographical in nature and contained much reminiscence, consistent with dignity therapy's intent. Few participants spoke about their cancer diagnoses during the interview. This study adds unique insight into the use of dignity therapy for those still receiving active cancer treatment, different from work by others in which it was offered only at end of life. As part of supportive care, clinicians need to validate the importance of family to those with advanced cancer and to provide opportunities for patients to share what they have learned throughout life and to impart messages of hope to those closest to them.

  10. Diagnostic hematology of reptiles.

    PubMed

    Stacy, Nicole I; Alleman, A Rick; Sayler, Katherine A

    2011-03-01

    The hematologic evaluation of reptiles is an indispensable diagnostic tool in exotic veterinary practice. The diversity of reptile species, their characteristic physiologic features, and effects of intrinsic and extrinsic factors present unique challenges for accurate interpretation of the hemogram. Combining the clinical presentation with hematologic findings provides valuable information in the diagnosis and monitoring of disease and helps guide the clinician toward therapy and further diagnostic testing. This article outlines the normal and pathologic morphology of blood cells of reptile species. The specific comparative aspects of reptiles are emphasized, and structural and functional abnormalities in the reptilian hemogram are described.

  11. Organ Preservation for Advanced Larynx Cancer: Issues and Outcomes.

    PubMed

    Forastiere, Arlene A; Weber, Randal S; Trotti, Andy

    2015-10-10

    To provide a review of the clinical data, controversies, and limitations that underpin current recommendations for approaches to larynx preservation for locally advanced larynx cancer requiring total laryngectomy. The key findings from pivotal randomized controlled trials are discussed, including quality of life, late effects, and function assessments. Trials investigating taxane inclusion in induction chemotherapy and trials of epidermal growth factor receptor inhibition for radiosensitization are put into perspective for larynx cancer. Controversies in the management of T4 primaries and the opportunities for conservation laryngeal surgery are reviewed. There are data from clinical trials to support induction chemotherapy, followed by radiotherapy (preferred approach in Europe) and concomitant cisplatin plus radiotherapy (preferred in North America) for nonsurgical preservation of the larynx. Treatment intensification by a sequential approach of induction, followed by concomitant treatment, is investigational. Transoral laryngeal microsurgery and transoral robotic partial laryngectomy have application in selected patients. The management of locally advanced larynx cancer is challenging and requires an experienced multidisciplinary team for initial evaluation, response assessment, and support during and after treatment to achieve optimal function, quality of life, and overall survival. Patient expectations, in addition to tumor extent, pretreatment laryngeal function, and coexisting chronic disease, are critical factors in selecting surgical or nonsurgical primary treatment. © 2015 by American Society of Clinical Oncology.

  12. Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances.

    PubMed

    Simpson, Guy R; Relph, Kate; Harrington, Kevin; Melcher, Alan; Pandha, Hardev

    2016-01-01

    Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors. Similarly to oncolytic viruses, the benefits of chemotherapeutic agents may be that they induce systemic antitumor immunity through the induction of immunogenic cell death of cancer cells. Combining these two treatment modalities has to date resulted in significant potential in vitro and in vivo synergies through various mechanisms without any apparent additional toxicities. Chemotherapy has been and will continue to be integral to the management of advanced cancers. This review therefore focuses on the potential for a number of common cytotoxic agents to be combined with clinically relevant oncolytic viruses. In many cases, this combined approach has already advanced to the clinical trial arena.

  13. Organ Preservation for Advanced Larynx Cancer: Issues and Outcomes

    PubMed Central

    Forastiere, Arlene A.; Weber, Randal S.; Trotti, Andy

    2015-01-01

    Purpose To provide a review of the clinical data, controversies, and limitations that underpin current recommendations for approaches to larynx preservation for locally advanced larynx cancer requiring total laryngectomy. Methods The key findings from pivotal randomized controlled trials are discussed, including quality of life, late effects, and function assessments. Trials investigating taxane inclusion in induction chemotherapy and trials of epidermal growth factor receptor inhibition for radiosensitization are put into perspective for larynx cancer. Controversies in the management of T4 primaries and the opportunities for conservation laryngeal surgery are reviewed. Results There are data from clinical trials to support induction chemotherapy, followed by radiotherapy (preferred approach in Europe) and concomitant cisplatin plus radiotherapy (preferred in North America) for nonsurgical preservation of the larynx. Treatment intensification by a sequential approach of induction, followed by concomitant treatment, is investigational. Transoral laryngeal microsurgery and transoral robotic partial laryngectomy have application in selected patients. Conclusion The management of locally advanced larynx cancer is challenging and requires an experienced multidisciplinary team for initial evaluation, response assessment, and support during and after treatment to achieve optimal function, quality of life, and overall survival. Patient expectations, in addition to tumor extent, pretreatment laryngeal function, and coexisting chronic disease, are critical factors in selecting surgical or nonsurgical primary treatment. PMID:26351339

  14. Advance Care Planning Does Not Adversely Affect Hope or Anxiety Among Patients With Advanced Cancer.

    PubMed

    Green, Michael J; Schubart, Jane R; Whitehead, Megan M; Farace, Elana; Lehman, Erik; Levi, Benjamin H

    2015-06-01

    Many physicians avoid advance care planning (ACP) discussions because they worry such conversations will lead to psychological distress. To investigate whether engaging in ACP using online planning tools adversely affects hope, hopelessness, or anxiety among patients with advanced cancer. Patients with advanced cancer and an estimated survival of two years or less (Intervention group) and a Control group were recruited at a tertiary care academic medical center (2007-2012) to engage in ACP using an online decision aid ("Making Your Wishes Known"). Pre/post and between-group comparisons were made, including hope (Herth Hope Index), hopelessness (Beck Hopelessness Scale), and anxiety (State Trait Anxiety Inventory). Secondary outcomes included ACP knowledge, self-determination, and satisfaction. A total of 200 individuals completed the study. After engaging in ACP, there was no decline in hope or increase in hopelessness in either the Control or Intervention group. Anxiety was likewise unchanged in the Control group but decreased slightly in the Intervention group. Knowledge of ACP (% correct answers) increased in both the groups, but more so in the Intervention group (13% increase vs. 4%; P<0.01). Self-determination increased slightly in both groups, and satisfaction with the ACP process was greater (P<0.01) in the Intervention than Control group. Engaging in ACP with online planning tools increases knowledge without diminishing hope, increasing hopelessness, or inducing anxiety in patients with advanced cancer. Physicians need not avoid ACP out of concern for adversely affecting patients' psychological well-being. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  15. Management of advanced pancreatic cancer in daily clinical practice.

    PubMed

    Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

    2016-01-01

    The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

  16. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  17. Cell Penetrating Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer

    DTIC Science & Technology

    2016-12-01

    Cancer REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average...Bispecific Antibodies for Targeting Oncogenic Transcription Factors in Advanced Prostate Cancer Michael Lilly, MD Richard Weisbart, MD Medical...0534, entitled Cell- penetrating bispecific antibodies for targeting oncogenic transcription factors in advanced prostate cancer . The research is a

  18. Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer

    ClinicalTrials.gov

    2015-09-30

    Breast Cancer; Chronic Myeloproliferative Disorders; Colorectal Cancer; Head and Neck Cancer; Leukemia; Lung Cancer; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic/Myeloproliferative Diseases; Prostate Cancer; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  19. Anticonvulsant drugs and hematological disease.

    PubMed

    Verrotti, A; Scaparrotta, A; Grosso, S; Chiarelli, F; Coppola, G

    2014-07-01

    Many antiepileptic drugs (AEDs) are associated with hematological disorders that range from mild thrombocytopenia or neutropenia to anemia, red cell aplasia, until bone marrow failure. Fortunately, potentially fatal hematological disorders such as aplastic anemia are very rare. This review investigates hematological effects associated with classic and newer AEDs: a PubMed search indexed for MEDLINE was undertaken to identify studies in adults, children and animals using the name of all anticonvulsant drugs combined with the terms "hematological disease" and "hematological abnormalities" as key words. The most common hematological alterations occur with older AEDs than newer. Indeed, careful hematological monitoring is needed especially using carbamazepine, phenytoin and valproic acid. The pathogenetic mechanisms are still unknown: they seem to be related to an immunological mechanism, but drugs pharmacokinetics and pharmacodynamics interactions may also play an important role. Further research is needed to assess the real pathogenetic mechanism at the basis of hematological complications caused by AEDs.

  20. Planned preoperative cisplatin and radiation therapy for locally advanced bladder cancer.

    PubMed

    Herr, H W; Yagoda, A; Batata, M; Sogani, P C; Whitmore, W F

    1983-12-15

    Cisplatin (DDP) is an active agent in the treatment of disseminated bladder cancer. In addition to its direct tumor cytotoxicity, recent animal and clinical data suggest synergism with radiation therapy (RT). Since improved survival with preoperative RT is largely restricted to bladder cancer patients in whom radiation-induced downstaging (P less than T) may be recognized, the authors administered DDP + RT preoperatively to patients with locally advanced (T3, T4) bladder tumors selected for cystectomy. The aim was to evaluate the feasibility of such a combination in relation to surgical and hematologic complications, the immediate effect on tumor downstaging, disease progression, and survival. Two thousand rad (400 rad X 5 days) was delivered to the whole pelvis, followed by cystectomy in 2 days. DDP (70 mg/m2) was given intravenously on day 2 of the RT. Twenty-four patients received preoperative DDP + RT and underwent attempted cystectomy; however, six patients were nonresectable owing to extensive pelvic disease, and an additional five patients had resectable pelvic lymph node metastases. Pelvic complications developed in 3 of 24 (12%) patients, but none required reoperation. No patient had a wound dehiscence. Transient myelosuppression was similar to that induced by 2000 rad preoperative RT alone. Tumor downstaging (P less than T) was seen in 9 of 24 (38%) patients, and in 5 (21%) patients, no tumor was found in the surgical specimen (P0). Distant metastases alone have been detected in 4 of 18 (22%) patients who had a cystectomy (all 4 had nodal metastases). Disease-free survival at a median follow-up of 22 months (range, 12-34 months) is 60% (14/24) for all patients (89% for P less than T and 40% for P greater than or equal to T patients) and 78% (14/18) for the resected patients. Combined preoperative DDP + RT proved to be a safe and feasible regimen which resulted in a possibly greater recognition of radioresponsive bladder tumors, and after cystectomy, an

  1. Cancer Pain Control for Advanced Cancer Patients by Using Autonomic Nerve Pharmacopuncture

    PubMed Central

    Kang, Hwi-joong; Yoon, Jung-won; Park, Ji-hye; Cho, Chong-kwan; Yoo, Hwa-seung

    2014-01-01

    Objectives: The purpose of this study is to report a case series of advanced cancer patients whose cancer pain was relieved by using autonomic nerve pharmacopuncture (ANP) treatment. ANP is a subcutaneous injection therapy of mountain ginseng pharmacopuncture (MGP) along the acupoints on the spine (Hua-Tuo-Jia-Ji-Xue; 0.5 cun lateral to the lower border of the spinous processes of vertebrae) to enhance the immune system and to balance autonomic nerve function. Methods: Patients with three different types of cancer (gastric cancer, lung cancer, colon cancer with distant metastases) with cancer pain were treated with ANP. 1 mL of MGP was injected into the bilateral Hua-Tuo-Jia-Ji-Xue on the T1-L5 sites (total 12 ─ 20 mL injection) of each patient’s dorsum by using the principle of symptom differentiation. During ANP treatment, the visual analogue scale (VAS) for pain was used to assess their levels of cancer pain; also, the dosage and the frequency of analgesic use were measured. Results: The cancer pain levels of all three patients improved with treatment using ANP. The VAS scores of the three patients decreased as the treatment progressed. The dosage and the frequency of analgesics also gradually decreased during the treatment period. Significantly, no related adverse events were found. Conclusion: ANP has shown benefit in controlling cancer pain for the three different types of cancer investigated in this study and in reducing the dosage and the frequency of analgesics. ANP is expected to be beneficial for reducing cancer pain and, thus, to be a promising new treatment for cancer pain. PMID:25780711

  2. Meta-analysis Exploring the Effectiveness of S-1-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

    PubMed

    Sun, Xin; Sun, Li; Zhang, Shu-Ling; Xiong, Zhi-Cheng; Ma, Jie-Tao; Han, Cheng-Bo

    2017-01-01

    S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

  3. Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea

    PubMed Central

    Gerber, David E.; Schiller, Joan H.

    2013-01-01

    Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting. PMID:23401441

  4. Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Mahadevan, Anand; Jain, Sanjay; Goldstein, Michael; Miksad, Rebecca; Pleskow, Douglas; Sawhney, Mandeep; Brennan, Darren M.D.; Callery, Mark; Vollmer, Charles

    2010-11-01

    Purpose: Patients with nonmetastatic locally advanced unresectable pancreatic cancer have a dismal prognosis. Conventional concurrent chemoradiotherapy requires 6 weeks of daily treatment and can be arduous. We explored the safety and effectiveness of a 3-day course of hypofractionated stereotactic body radiotherapy (SBRT) followed by gemcitabine in this population. Patients and Methods: A total of 36 patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with {>=}12 months of follow-up were included. They received three fractions of 8, 10, or 12 Gy (total dose, 24-36 Gy) of SBRT according to the tumor location in relation to the stomach and duodenum, using fiducial-based respiratory motion tracking on a robotic radiosurgery system. The patients were then offered gemcitabine for 6 months or until tolerance or disease progression. Results: With an overall median follow-up of 24 months (range, 12-33), the local control rate was 78%, the median overall survival time was 14.3 months, the median carbohydrate antigen 19-9-determined progression-free survival time was 7.9 months, and the median computed tomography-determined progression-free survival time was 9.6 months. Of the 36 patients, 28 (78%) eventually developed distant metastases. Six patients (17%) were free of progression at the last follow-up visit (range, 13-30 months) as determined by normalized tumor markers with stable computed tomography findings. Nine Grade 2 (25%) and five Grade 3 (14%) toxicities attributable to SBRT occurred. Conclusion: Hypofractionated SBRT can be delivered quickly and effectively in patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with acceptable side effects and minimal interference with gemcitabine chemotherapy.

  5. Locally advanced prostate cancer: current controversies and optimisation opportunities.

    PubMed

    Sridharan, S; Dal Pra, A; Catton, C; Bristow, R G; Warde, P

    2013-08-01

    Prostate cancer is the most common malignancy in men worldwide. The rate of patients presenting with locally advanced prostate cancer has declined in recent decades, mainly due to prostate-specific antigen screening, but the management of these patients still remains controversial. Current literature suggests that the standard of care for these patients is a combination approach with radiation therapy and androgen deprivation therapy. However, there remain many unresolved issues, including the role of dose-escalated radiation therapy, the additional benefit of surgery and the role of systemic therapy, both standard chemotherapeutic agents and novel agents. Furthermore, in the era of personalised medicine, additional research is needed to evaluate the role of biomarkers to better predict the risk of local and systemic relapse in this population.

  6. Advanced cell culture techniques for cancer drug discovery.

    PubMed

    Lovitt, Carrie J; Shelper, Todd B; Avery, Vicky M

    2014-05-30

    Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.

  7. Chemotherapy in advanced bladder cancer: current status and future

    PubMed Central

    2011-01-01

    Bladder cancer occurs in the majority of cases in males. It represents the seventh most common cancer and the ninth most common cause of cancer deaths for men. Transitional cell carcinoma is the most predominant histological type. Bladder cancer is highly chemosensitive. In metastatic setting, chemotherapy based on cisplatin should be considered as standard treatment of choice for patients with good performance status (0-1) and good renal function-glomerular filtration rate (GFR) > 60 mL/min. The standard treatment is based on cisplatin chemotherapy regimens type MVAC, HD-MVAC, gemcitabine plus cisplatin (GC) or dose dense GC. In unfit patients, carboplatin based regimes; gemcitabine plus carboplatin or methotrexate plus carboplatin plus vinblastine (MCAVI) are reasonable options. The role of targeted therapies when used alone, or in combination with chemotherapy, or in maintenance, was evaluated; targeting angiogenesis seem to be very promising. The purpose of this literature review is to highlight the role of chemotherapy in the management of advanced transitional cell carcinoma of the bladder. PMID:21906310

  8. [Satisfaction with immunotherapy in patients with advanced cancer].

    PubMed

    Moriyama, Yoshiaki; Fujisawa, Fumika; Kotani, Junko; Ohnishi, Masayuki; Watanabe, Toru

    2015-04-01

    Patient satisfaction with cancer immunotherapy, which is not covered by health insurance in Japan, was evaluated among 65 patients with advanced cancer who had received immunotherapy in our hospital for 2 years. Satisfaction measures were based on patients' expectations for medical care, cost, and staff services, and involved a questionnaire consisting of 25 items. Results of the questionnaire analysis showed that most patients, who expected much of antigen-specific vaccination such as dendritic cells (DC) pulsed tumor-associated antigens, were dissatisfied with the high cost of private immunotherapy(i. e., not covered by medical insurance), and were unable to perceive the effectiveness of the treatment because there was no quantitative analysis of killer T cells induced by immunotherapy. Therefore, it is critically important for us to confirm the safety and efficiency of cancer immunotherapy, before introducing medical insurance for cancer patients in Japan. In addition, the quantitative measurement of killer T cells induced by DC peptide vaccines should be considered, to meet patients' expectations.

  9. Locally advanced rectal cancer: The importance of a multidisciplinary approach

    PubMed Central

    Berardi, Rossana; Maccaroni, Elena; Onofri, Azzurra; Morgese, Francesca; Torniai, Mariangela; Tiberi, Michela; Ferrini, Consuelo; Cascinu, Stefano

    2014-01-01

    Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens. PMID:25516638

  10. Advanced Cell Culture Techniques for Cancer Drug Discovery

    PubMed Central

    Lovitt, Carrie J.; Shelper, Todd B.; Avery, Vicky M.

    2014-01-01

    Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor. PMID:24887773

  11. Recent advances in pancreatic cancer: biology, treatment, and prevention.

    PubMed

    Singh, Divya; Upadhyay, Ghanshyam; Srivastava, Rakesh K; Shankar, Sharmila

    2015-08-01

    Pancreatic cancer (PC) is the fourth leading cause of cancer-related death in United States. Efforts have been made towards the development of the viable solution for its treatment with constrained accomplishment because of its complex biology. It is well established that pancreatic cancer stem cells (CSCs), albeit present in a little count, contribute incredibly to PC initiation, progression, and metastasis. Customary chemo and radiotherapeutic alternatives, however, expands general survival, the related side effects are the significant concern. Amid the most recent decade, our insight about molecular and cellular pathways involved in PC and role of CSCs in its progression has increased enormously. Presently the focus is to target CSCs. The herbal products have gained much consideration recently as they, usually, sensitize CSCs to chemotherapy and target molecular signaling involved in various tumors including PC. Some planned studies have indicated promising results proposing that examinations in this course have a lot to offer for the treatment of PC. Although preclinical studies uncovered the importance of herbal products in attenuating pancreatic carcinoma, limited studies have been conducted to evaluate their role in clinics. The present review provides a new insight to recent advances in pancreatic cancer biology, treatment and current status of herbal products in its anticipation. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Locally advanced rectal cancer: the importance of a multidisciplinary approach.

    PubMed

    Berardi, Rossana; Maccaroni, Elena; Onofri, Azzurra; Morgese, Francesca; Torniai, Mariangela; Tiberi, Michela; Ferrini, Consuelo; Cascinu, Stefano

    2014-12-14

    Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.

  13. [Audit: medical record documentation among advanced cancer patients].

    PubMed

    Perceau, Elise; Chirac, Anne; Rhondali, Wadih; Ruer, Murielle; Chabloz, Claire; Filbet, Marilène

    2014-02-01

    Medical record documentation of cancer inpatients is a core component of continuity of care. The main goal of the study was an assessment of medical record documentation in a palliative care unit (PCU) using a targeted clinical audit based on deceased inpatients' charts. Stage 1 (2010): a clinical audit of medical record documentation assessed by a list of items (diagnosis, prognosis, treatment, power of attorney directive, advance directives). Stage 2 (2011): corrective measures. Stage 3 (2012): re-assessment with the same items' list after six month. Forty cases were investigated during stage 1 and 3. After the corrective measures, inpatient's medical record documentation was significantly improved, including for diagnosis (P = 0.01), diseases extension and treatment (P < 0.001). Our results highlighted the persistence of a weak rate of medical record documentation for advanced directives (P = 0.145).

  14. Hematologic Complications of Pregnancy

    PubMed Central

    Townsley, Danielle M.

    2013-01-01

    Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

  15. Targeted nanosystems: Advances in targeted dendrimers for cancer therapy

    PubMed Central

    Yang, Hu

    2015-01-01

    Dendrimers possess discrete highly compact nanostructures constituted of successive branched layers. Soon after the inception of dendrimers, recognition of their tunable structures and biologically favorable properties provoked a great enthusiasm in delving deeply into the utility of dendrimers for biomedical and pharmaceutical applications. One of the most important nanotechnology applications is the development of nanomedicines for targeted cancer therapies. Tremendous success in targeted therapies has been achieved with the use of dendrimer-based nanomedicines. This article provides a concise review on latest advances in the utility of dendrimers in immunotherapies and hormone therapies. PMID:26706410

  16. [Results of palliative treatment of advanced regional oropharyngeal cancer].

    PubMed

    Laskus, Z; Szutkowski, Z

    1998-01-01

    We present results of palliative radiotherapy in 76 oropharyngeal advanced cancer patients. We recommend, according to appreciated results of palliative treatment, the two high fractionation dose courses (so called split course) if the first application of high fractionation dose had resulted in partial remission. Conventional fractionation dose in the second part of split course of radiotherapy did not result in better effect in regression, better subjective feeling after radiotherapy and longer survival time in our material. Patients with poor presentation status (Zubrod 3) should be excluded from palliative radiotherapy.

  17. How people with advanced cancer manage changing eating habits.

    PubMed

    Hopkinson, Jane B

    2007-09-01

    This paper is a report of a study to explore the management of changing eating habits in people with advanced cancer. Internationally there is interest in supporting self-management as a way of helping people to live with illness. It is unknown if promoting self-management in people with cancer can lead to beneficial health outcomes. In order to develop and test interventions that promote self-management in cancer patients, it is first important to understand ways in which they can help themselves. A mixed-methods exploratory case study of the meaning, management and manifestations of weight loss and change in eating habits was conducted with 30 patients receiving palliative home care in England in 2003. Semi-structured interview data were analysed using both content and thematic approaches. Participants described a total of 141 different self-actions, each of which formed a component of up to four self-action strategies that were used to aid life with advanced cancer. The strategies were 'Taking control', 'Promoting self-worth', 'Relationship work', and 'Distraction'. Employing these strategies led to changes in thinking and behaviour that were motivated by a desire to sustain or enhance well-being. The pattern of self-action strategies adopted by each individual is theorized to be dependent on the personal and contextual resources available. Patients can and do find their own solutions to eating problems and nurses should support this self-action. The proposed theory of self-management of eating change provides an understanding that can inform the provision of this support.

  18. [Locally advanced prostate cancer: definition, prognosis and treatment].

    PubMed

    Plantade, Anne; Massard, Christophe; de Crevoisier, Renaud; Fizazi, Karim

    2007-07-01

    According to d'Amico's criteria, high-risk localized prostate cancer are defined either by an extracapsular extension (T3 or T4), either by a high Gleason score (> 7) or a PSA rate higher than 20 ng/ml. Pelvic lymph node involvement also corresponds to locally advanced prostate cancer. Statistical models called nomograms have been developed to predict the probability of prostate cancer recurrence and are also used to define locally advanced patients. Prostate MRI may help to detect an extracapsular extension or a seminal vesicles involvement but remains still discussed. A bone scan, an abdominal and pelvic CT scan have to be performed in order to detect metastases. A pelvic lymph node dissection is recommended in order to adapt the treatment of these patients. Standard treatment for high-risk localized prostate cancer without lymph node involvement is now well defined. The association of both local radiation and a long androgen deprivation (GnHR agonist) showed an overall survival benefit (more than 10%). The radiation dose of 74 Gy is recommended. Other questions are still debating : the optimal duration of the hormonotherapy , the use of the bicalutamide 150 mg instead of GnRH agonists, the optimal radiation dose. Radical prostatectomy is no more considered as a standard treatment for these patients. Since the use of chemotherapy for metastatic patients showed a benefit in overall survival, the place of chemotherapy as adjuvant or neo-adjuvant treatment is questionned in several randomized phase III studies. Sometimes high-risk disease is diagnosed after performance of a radical prostatectomy. A postoperative radiation may be performed in order to decrease clinical and biochemical progression. The use of bicalutamide 150 mg in this situation may have a positive impact too on progression free survival. In case of lymph node involvement, androgen deprivation is the standard treatment with an overall survival benefit. The place of local radiation therapy is still

  19. Symptom clusters and survival in Portuguese patients with advanced cancer.

    PubMed

    Barata, Pedro C; Cardoso, Alice; Custodio, Maria P; Alves, Marta; Papoila, Ana L; António, Barbosa; Lawlor, Peter G

    2016-10-01

    This study aimed to identify clusters of symptoms, to determine the patient characteristics associated with identified, and determine their strength of association with survival in patients with advanced cancer (ACPs). Consecutively eligible ACPs not receiving cancer-specific treatment, and referred to a Tertiary Palliative Care Clinic, were enrolled in a prospective cohort study. At first consultation, patients rated 9 symptoms through the Edmonton Symptom Assessment System (0-10 scale) and 10 others using a Likert scale (1-5). Principal component analysis was used in an exploratory factor analysis to identify. Of 318 ACPs, 301 met eligibility criteria with a median (range) age of 69 (37-94) years. Three SCs were identified: neuro-psycho-metabolic (NPM) (tiredness, lack of appetite, lack of well-being, dyspnea, depression, and anxiety); gastrointestinal (nausea, vomiting, constipation, hiccups, and dry mouth) and sleep impairment (insomnia and sleep disturbance). Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter survival was observed for patients with the NPM cluster (58 vs. 23, P < 0.001), as well as for patients with two or more SCs (45 vs. 21, P = 0.005). In a multivariable model for survival at 30-days, age (HR: 0.98; 95% CI: 0.97-0.99; P = 0.008), hospitalization at inclusion (HR: 2.27; 95% CI: 1.47-3.51; P < 0.001), poorer performance status (HR: 1.90, 95% CI: 1.24-2.89; P = 0.003), and NPM (HR: 1.64; 95% CI: 1.17-2.31; P = 0.005), were associated with worse survival. Three clinically meaningful SC in patients with advanced cancer were identifiable. The NPM cluster and the presence of two or more SCs, had prognostic value in relation to survival. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. An integrated psychological strategy for advanced colorectal cancer patients

    PubMed Central

    Pugliese, Patrizia; Perrone, Maria; Nisi, Enrica; Garufi, Carlo; Giannarelli, Diana; Bottomley, Andrew; Terzoli, Edmondo

    2006-01-01

    Background There is evidence regarding the usefulness of psychosocial intervention to improve health related quality of life (HRQOL) in adult cancer patients. The aim of this report is to describe an integrated approach and to evaluate its feasibility in routine clinical practice in 98 advanced colorectal cancer (ACC) patients during chronomodulated chemotherapy. Methods A prospective non-randomised design was developed and applied in a cancer out-patient setting. The intervention consisted of an integrated approach, whereby the psycho-oncologist had an active role in the health care team with the physician and routinely included psychological understanding in the medical treatment program. The psychological evaluation assessed: a) adaptation, awareness, psychopathological disorders through a psychodynamic interview; b) anxiety and depression using the HAD scale; c) subjective perception of care quality through a structured interview and d) HRQOL evaluation assessment with the EORTC QLQ C30. Outcomes data were collected before and after 18 weeks of chemotherapy. Results After 18 weeks of chemotherapy a significant improvement of adaptation and awareness was observed. The HADs results showed a significant decrease in anxiety when compared to pre-treatment. The structured interview showed a significant increase of patients who positively experienced the impact of medical treatment on HRQOL, anxiety, depression, interpersonal relationships, free-time and who positively experienced the care quality. Indeed, a majority of patients positively experienced the team relationship modality during the whole treatment. All scales on the EORTC questionnaire remained unchanged during the entire treatment. Conclusion Our results suggest that it is feasible to carry out an integrated approach during chemotherapy. These results seem to support the integrated approach as a tool in aiding advanced colorectal cancer patients' ability to cope with their diagnosis and treatment although

  1. A Phase I Study of the First-in-Class Anti-Mitochondrial Metabolism Agent, CPI-613, in Patients with Advanced Hematologic Malignancies

    PubMed Central

    Pardee, Timothy S.; Lee, King; Luddy, John; Maturo, Claudia; Rodriguez, Robert; Isom, Scott; Miller, Lance D.; Stadelman, Kristin M.; Levitan, Denise; Hurd, David; Ellis, Leslie R.; Harrelson, Robin; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2014-01-01

    Purpose The lipoate derivative CPI-613 is a first-in-class agent that targets mitochondrial metabolism. This study determined the effects of CPI-613 on mitochondrial function and defined the maximally tolerated dose (MTD), pharmacokinetics (PKs), and safety in patients with relapsed or refractory hematologic malignancies. Experimental Design Human leukemia cell lines were exposed to CPI-613 and mitochondrial function was assayed. A phase I trial was conducted in which CPI-613 was given as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days. Results CPI-613 inhibited mitochondrial respiration of human leukemia cells consistent with the proposed mechanism of action. In the phase I trial, 26 patients were enrolled. CPI-613 was well tolerated with no marrow suppression observed. When the infusion time was shortened to 1 hour renal failure occurred in 2 patients. At 3780 mg/m2, there were 2 dose-limiting toxicities (DLTs). At a dose of 2940 mg/m2 over 2 hours, no DLTs were observed, establishing this as the MTD. Renal failure occurred in a total of 4 patients and resolved in all but 1, who chose hospice care. CPI-613 has a triphasic elimination with an alpha half-life of ~1.34 hours. Of 21 evaluable, heavily pretreated, patients, 4 achieved an objective response and 2 achieved prolonged stabilization of disease for a clinical benefit rate of 29%. Following drug exposure, gene expression profiles of peripheral blood mononuclear cells from responders demonstrated immune activation. Conclusion CPI-613 inhibits mitochondrial function and demonstrates activity in a heavily pretreated cohort of patients. PMID:25165100

  2. Breast feeding and childhood hematological malignancy.

    PubMed

    Tripathy, A K; Mishra, L; Bakhshi, Sameer; Arya, L S

    2004-05-01

    Breast milk is known to have anti-infective and immunomodulating effects on infants, but its association with childhood cancer has not been well studied. Artificial feeding may affect the immune response in carcinogenesis. In this communication the authors have reviewed different articles describing the association between breast feeding (BF) and subsequent development of childhood hematological malignancy. It appears that BF may have a protective effect on childhood cancer, both the duration of BF as well as the quantity of milk ingested is probably critical to the beneficial immunological effects of BF against childhood cancer if any.

  3. Combined radiotherapy, 5-fluorouracil continuous infusion and weekly oxaliplatin in advanced rectal cancer: a phase I study.

    PubMed

    François, Eric; Ychou, Marc; Ducreux, Michel; Bertheault-Cvitkovic, Frédérique; Giovannini, Marc; Conroy, Thierry; Lemanski, Claire; Thomas, Olivier; Magnin, Valérie

    2005-12-01

    The aim of this study was to determine the maximum-tolerated dose (MTD) of weekly oxaliplatin combined with 5-fluorouracil (5FU) continuous infusion administered concomitantly with fractionated radiotherapy in patients presenting advanced rectal cancer. Forty-three patients with rectal cancer (stage T3/T4 (n = 24), metastatic (n = 17) and 2 with local recurrence), were included. The radiotherapy dose delivered was 45 Gy over 5 weeks (1.8 Gy/fraction/day, 5 days per week). The initial weekly oxaliplatin dosage was 30 mg/m2 and the 5FU dosage 150 mg/m2/d. The oxaliplatin and 5FU doses were escalated. Eight dose levels were tested. At dose level 8 (oxaliplatin 80 mg/m2, 5FU 225 mg/m2/d), 2 patients out of 4 presented dose-limiting toxicity (severe diarrhoea with dehydration and fatal shock, rectovesical fistula). At dose level 7, 2 further patients presented with grade 3 diarrhoea. The main toxicity of the combination was diarrhoea. The hematological and neurological toxicities were not severe and were not dose-limiting. Out of the 30 patients undergoing surgery, 4 (13.3%) presented with pathological complete response and 4 (13.3%) only presented with microscopic residual disease. The results from this study enabled determination of the recommended weekly oxaliplatin dose (60 mg/m2) combined with 5FU continuous infusion (225 mg/m2) and fractionated radiotherapy (45 Gy) in the pre-operative treatment of advanced rectal cancer. The good safety profile of the regimen, associated with promising results in terms of histological response, suggest that the regimen could be developed in future phase II/III studies.

  4. Matrine promotes the efficacy and safety of platinum-based doublet chemotherapy for advanced non-small cell lung cancer

    PubMed Central

    Rong, Biaoxue; Zhao, Chongchong; Gao, Wenlong; Yang, Shuanying

    2015-01-01

    Purpose: Many studies have investigated the efficacy of matrine combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC). This study is an analytic value of available evidence. Methods: twenty-two studies reporting matrine combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using either the fixed effects model or random effects model. Results: The overall response rate (ORR) and disease control rate (DCR) of matrine combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 15.1% and 19.7% improvement, respectively (P < 0.00001). In addition, the mean survival time (MST) and quality of life (QOL) were improved after the treatment of matrine combined with PBDC (P < 0.00001). The main adverse effects found in this review were hematological reactions, nausea and vomiting. Matrine combined with PBDC had a lower incidence of adverse reactions compared with PBDC alone (P < 0.05). Conclusions: Matrine combined with PBDC was associated with higher RR, DCR, and MST as well as superior QOL profiles compared with PBDC alone. Matrine combined with PBDC decrease the incidence of adverse reactions compared with PBDC alone. PMID:26628952

  5. Comparison of the Efficacy between Gemcitabine-Cisplatin and Capecitabine-Cisplatin Combination Chemotherapy for Advanced Biliary Tract Cancer

    PubMed Central

    Lee, Jieun; Hong, Tae Ho; Lee, In Seok; You, Young Kyoung; Lee, Myung Ah

    2015-01-01

    Purpose Gemcitabine-cisplatin combination chemotherapy has been regarded as standard regimen for advanced or metastatic biliary tract cancer (BTC), based on the ABC-02 trial. To date, however, no studies have compared the efficacies of gemcitabine-platinum and fluoropyrimidine- platinum combination chemotherapy, even though fluoropyrimidine has been widely used as a backbone agent for gastrointestinal cancer. This study compared the efficacy and toxicities of gemcitabine-cisplatin (GP) and capecitabine-cisplatin (XP) combination chemotherapy for treatment of advanced BTC. Materials and Methods We examined 49 patients treated with GP and 44 patients treated with XP from October 2009 to July 2012. All patients had unresectable BTC. The GP regimen comprised gemcitabine (1,000 mg/m2, intravenously [IV], days 1 and 8) and cisplatin (75 mg/m2, IV, day 1). The XP regimen comprised capecitabine (1,250 mg/m2 twice a day, peroral, days 1-14) and cisplatin (60 mg/m2, IV, day 1, every three weeks). We analyzed the response rate (RR), time to progression (TTP), overall survival (OS), and toxicity. Results The RRs were 27.3% and 6.1% in the XP and GP arms, respectively. XP resulted in longer TTP (5.2 months vs. 3.6 months, p=0.016), but OS was not statistically different (10.7 months vs. 8.6 months, p=0.365). Both regimens resulted in grade 3-4 hematologic toxicities, but febrile neutropenia was not noted. Grade 3-4 asthenia, stomatitis, and hand-foot syndrome occurred more frequently in the XP arm. Conclusion XP resulted in a superior TTP and RR compared to GP for treatment of advanced BTC, with comparable toxicity. Conduct of prospective large, randomized trials to evaluate the possibility of XP as another standard therapy is warranted. PMID:25648099

  6. Comparison of the Efficacy between Gemcitabine-Cisplatin and Capecitabine-Cisplatin Combination Chemotherapy for Advanced Biliary Tract Cancer.

    PubMed

    Lee, Jieun; Hong, Tae Ho; Lee, In Seok; You, Young Kyoung; Lee, Myung Ah

    2015-04-01

    Gemcitabine-cisplatin combination chemotherapy has been regarded as standard regimen for advanced or metastatic biliary tract cancer (BTC), based on the ABC-02 trial. To date, however, no studies have compared the efficacies of gemcitabine-platinum and fluoropyrimidine- platinum combination chemotherapy, even though fluoropyrimidine has been widely used as a backbone agent for gastrointestinal cancer. This study compared the efficacy and toxicities of gemcitabine-cisplatin (GP) and capecitabine-cisplatin (XP) combination chemotherapy for treatment of advanced BTC. We examined 49 patients treated with GP and 44 patients treated with XP from October 2009 to July 2012. All patients had unresectable BTC. The GP regimen comprised gemcitabine (1,000 mg/m(2), intravenously [IV], days 1 and 8) and cisplatin (75 mg/m(2), IV, day 1). The XP regimen comprised capecitabine (1,250 mg/m(2) twice a day, peroral, days 1-14) and cisplatin (60 mg/m(2), IV, day 1, every three weeks). We analyzed the response rate (RR), time to progression (TTP), overall survival (OS), and toxicity. The RRs were 27.3% and 6.1% in the XP and GP arms, respectively. XP resulted in longer TTP (5.2 months vs. 3.6 months, p=0.016), but OS was not statistically different (10.7 months vs. 8.6 months, p=0.365). Both regimens resulted in grade 3-4 hematologic toxicities, but febrile neutropenia was not noted. Grade 3-4 asthenia, stomatitis, and hand-foot syndrome occurred more frequently in the XP arm. XP resulted in a superior TTP and RR compared to GP for treatment of advanced BTC, with comparable toxicity. Conduct of prospective large, randomized trials to evaluate the possibility of XP as another standard therapy is warranted.

  7. A phase I trial investigating pulsatile erlotinib in combination with gemcitabine and oxaliplatin in advanced biliary tract cancers.

    PubMed

    Goff, Laura W; Cardin, Dana B; Whisenant, Jennifer G; Du, Liping; Koyama, Tatsuki; Dahlman, Kimberly B; Salaria, Safia N; Young, Ruth T; Ciombor, Kristen K; Gilbert, Jill; Smith, Stephen James; Chan, Emily; Berlin, Jordan

    2017-02-01

    Advanced biliary tract cancers (ABTC) are among the deadliest malignancies with limited treatment options after progression on standard-of-care chemotherapy, which includes gemcitabine (GEM) and oxaliplatin (OX). The epidermal growth factor receptor inhibitor erlotinib has been explored in ABTC with modest efficacy. Erlotinib given continuously may antagonize the action of chemotherapy against cycling tumor cells, but pulsatile dosing of erlotinib with chemotherapy may improve efficacy. The purpose of this study was to assess the safety of pulsatile erlotinib with GEMOX. This was a single-institution phase Ib study that enrolled adult patients with unresectable or metastatic biliary tract, pancreas, duodenal, or ampullary carcinomas that have not received any prior treatment for their disease. Dose escalation followed a standard 3 + 3 design, and dose-limiting toxicities (DLTs) were any treatment-related, first course non-hematologic grade ≥ 3 toxicity, except nausea/vomiting, or grade 4 hematologic toxicity. A dose expansion cohort in ABTC was treated at the MTD. Twenty-eight patients were enrolled and 4 dose levels were explored. The MTD was erlotinib 150 mg + GEM 800 mg/m(2) + OX 85 mg/m(2). DLTs were diarrhea and anemia. Most frequent toxicities were nausea (78 %), fatigue (71 %), neuropathy (68 %), and diarrhea (61 %), predominantly grade 1-2. In the ABTC patients, the objective response and disease control rates were 29 % and 94 %, respectively, and median overall survival was 18 months. Erlotinib plus GEMOX was well tolerated. Encouraging anti-tumor activity was seen as evidenced by a high disease control rate and longer median OS than standard chemotherapy in the patients with ABTC.

  8. Impact of the pretreatment Glasgow prognostic score on treatment tolerance, toxicities, and survival in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy.

    PubMed

    Chang, Pei-Hung; Yeh, Kun-Yun; Wang, Cheng-Hsu; Chen, Eric Yen-Chao; Yang, Shih-Wei; Huang, Jen-Seng; Chou, Wen-Chi; Hsieh, Jason Chia-Hsun

    2017-10-01

    The purpose of this study was to evaluate the impact of the pretreatment Glasgow prognostic score on treatment-related toxicities, tolerance, and survival in patients with advanced head and neck cancers undergoing concurrent chemoradiotherapy (CRT). We retrospectively analyzed and compared the clinical characteristics, toxicities, and survival of 143 patients with stages III, IVA, and IVB head and neck cancer treated with concurrent CRT according to their Glasgow prognostic score between 2007 and 2010. The Glasgow prognostic score was correlated with advanced tumor stage and T/N classification. Patients with a higher Glasgow prognostic score were less likely to tolerate concurrent CRT, experienced more weight loss, required tube feeding support more frequently, and had higher percentage of grade ≥3 hematological toxicities, sepsis, and toxic death. Patients with a Glasgow prognostic score of 0 had better overall and recurrence-free survival than those with a Glasgow prognostic score of 1 or 2. Pretreatment Glasgow prognostic score predicts treatment tolerance, toxicity, and survival in patients with advanced head and neck cancer undergoing concurrent CRT. © 2017 Wiley Periodicals, Inc.

  9. Advances in small molecule inhibitors of androgen receptor for the treatment of advanced prostate cancer.

    PubMed

    Sadar, Marianne D

    2012-06-01

    Current treatments for localized prostate cancer include brachytherapy, external beam radiation, surgery, and active surveillance. Unfortunately, 20-40% of prostate cancer patients will experience recurrence and require hormonal therapies. These therapies involve androgen ablation by chemical or surgical castration and application of antiandrogens. Hormonal therapy is initially effective, but will inevitably fail and the disease will progress to lethal castration-resistant prostate cancer (CRPC) from which patients succumb within 2 years. CRPC is considered to be dependent on transcriptionally active androgen receptors (AR). This article reviews recent advances in the discovery and development of small molecule inhibitors of AR. A PubMed database search was performed for articles focused on small molecule inhibitors of AR for potential development for the treatment of prostate cancer. Compounds with broad effects on other pathways were not included. Currently, there are several novel antiandrogens being tested in the clinic that have improved affinity for the AR and work by different mechanisms to the current battery of approved antiandrogens that are discussed. Small molecule inhibitors that interact with regions other than the AR ligand-binding pocket have been also been discovered. These small molecules include allosteric inhibitors of the LBD, compounds that alter AR conformation, and antagonists to the AR NTD and are highlighted. CRPC is dependent upon transcriptionally active AR. Survival improvement may be achieved by complete blockade of all AR activity using novel small molecule inhibitors with unique mechanisms of action.

  10. Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis

    PubMed Central

    Wang, Yuan; Hu, Guo-fang; Zhang, Qian-qian; Tang, Ning; Guo, Jun; Liu, Li-yan; Han, Xiao; Wang, Xia; Wang, Zhe-hai

    2016-01-01

    Background Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo) for patients with advanced pancreatic cancer using the currently available evidence. Methods PubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively. Results A total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%–17.7%), disease control rate was 55.0% (95% CI: 51.5%–58.5%), and 1-year survival rate was 28.5% (95% CI: 24.0%–33.4%). Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As for the toxicity profile, the most common adverse events (AEs) were hematologic reactions, skin rash, and gastrointestinal reactions. Other severe AEs, which had low incidence, included treatment-induced death and interstitial lung disease. Conclusion Our study showed that GemErlo is associated with reasonable activity in treating

  11. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  12. A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment

    DTIC Science & Technology

    2015-10-01

    There is an urgent need to develop effective therapies for the treatment of advanced stage prostate cancer (PrCa) due to their limited or no response to...Award Number: W81XWH-141-0154 TITLE: “A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment” PRINCIPAL INVESTIGATOR...Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment” 5a. CONTRACT NUMBER: 5b. GRANT NUMBER: W81XWH-14-1-0154 5c. PROGRAM ELEMENT

  13. A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent Hormonal Therapies

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-1-0275 TITLE: A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent...TYPE Annual 3. DATES COVERED 30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Changing Landscape of Advanced Prostate Cancer...not curative, and all patients ultimately develop resistance. Therefore, the clinical and molecular landscape of advanced prostate cancer is changing

  14. MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-05-16

    Advanced Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma; Recurrent Gallbladder Carcinoma; Stage IV Distal Bile Duct Cancer; Stage IV Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Carcinoma; Unresectable Gallbladder Carcinoma

  15. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer.

    PubMed Central

    Ikeda, Y.; Mori, M.; Kamakura, T.; Haraguchi, Y.; Saku, M.; Sugimachi, K.

    1995-01-01

    The data on 912 patients with early cancer and 1245 with advanced cancer who were seen between 1971 and 1990 were compared. The incidence of undifferentiated-type cancer increased significantly in patients with advanced gastric cancer, but not in patients with early gastric cancer. When the histological types were compared with regard to sex, age and location in patients with early gastric cancer the undifferentiated type was found to increase only in males, while in patients with advanced gastric cancer the undifferentiated type increased in both sexes as well as in younger patients and in both the upper and middle third of the stomach. These differences in the trends between early and advanced cancers are probably due to the different degrees of diagnostic accuracy for the early detection of histological types. PMID:7640228

  16. Advancing the evidence base in cancer: psychosocial multicenter trials

    PubMed Central

    2012-01-01

    Background The diagnosis and treatment of cancer is associated with significant distress and psychosocial morbidity. Although psychosocial interventions have been developed in an attempt to improve psychosocial outcomes in cancer patients and survivors, there is continued debate about whether there is adequate high-level evidence to establish the effectiveness of these interventions. The evidence base is limited as a result of numerous challenges faced by those attempting to conduct psychosocial intervention trials within the health system. Barriers include insufficient participant recruitment, difficulty generalizing from single-trial studies, difficulty in building and managing research teams with multidisciplinary expertise, lack of research design expertise and a lack of incentives for researchers conducting intervention research. To strengthen the evidence base, more intervention studies employing methodologically rigorous research designs are necessary. Methods In order to advance the evidence base of interventions designed to improve psychosocial outcomes for cancer patients and survivors, we propose the formation of a collaborative trials group that conducts multicenter trials to test the effectiveness of such interventions. Results Establishment of such a group would improve the quality of the evidence base in psychosocial research in cancer patients, by increasing support for conducting intervention research and providing intervention research training opportunities. A multidisciplinary collaborative group conducting multicenter trials would have the capacity to overcome many of the barriers that currently exist. Conclusions A stronger evidence base is necessary to identify effective psychosocial interventions for cancer patients. The proposed formation of a psycho-oncology collaborative trials group that conducts multicenter trials to test the effectiveness of psychosocial interventions would assist in achieving this outcome. PMID:22992443

  17. Therapeutic implication of HER2 in advanced biliary tract cancer

    PubMed Central

    Cha, Yongjun; Ha, Hyerim; Park, Ji Eun; Bang, Ju-Hee; Jin, Mei Hua; Lee, Kyung-Hun; Kim, Tae-Yong; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Oh, Do-Youn; Bang, Yung-Jue

    2016-01-01

    Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. PMID:27517322

  18. Locally advanced rectal cancer: time for precision therapeutics.

    PubMed

    Weiser, Martin R; Zhang, Zhen; Schrag, Deborah

    2015-01-01

    The year 2015 marks the 30th anniversary of the publication of NSABP-R01, a landmark trial demonstrating the benefit of adding pelvic radiation to the treatment regimen for locally advanced rectal cancer with a resultant decrease in local recurrence from 25% to 16%. These results ushered in the era of multimodal therapy for rectal cancer, heralding modern treatment and changing the standard of care in the United States. We have seen many advances over the past 3 decades, including optimization of the administration and timing of radiation, widespread adoption of total mesorectal excision (TME), and the implementation of more effective systemic chemotherapy. The current standard is neoadjuvant chemoradiation with 5-fluorouracil (5-FU) and a radiosensitizer, TME, and adjuvant chemotherapy including 5-FU and oxaliplatin. The results of this regimen have been impressive, with a reported local recurrence rate of less than 10%. However, the rates of distant relapse remain 30% to 40%, indicating room for improvement. In addition, trimodality therapy is arduous and many patients are unable to complete the full course of treatment. In this article we discuss the current standard of care and alternative strategies that have evolved in an attempt to individualize therapy according to risk of recurrence.

  19. [Vital prognosis in advanced cancer patients: a systematic literature review].

    PubMed

    Tavares, Teresa; Gonçalves, Edna

    2013-01-01

    Prognostication is a critical medical task for the adequacy of treatment and management of priorities and expectations of patients and families. In 2005, the European Association of Palliative Care (EAPC) published recommendations on the formulation of vital prognosis in advanced cancer patients. The aim of this study is to analyze the literature subsequent to this review and to update the presented recommendations. Using the same strategy of the EAPC group, we performed a systematic literature search in the electronic databases PubMed and Scopus, which included original studies in adults with advanced cancer, without tumor-directed treatment, with a median survival of less than 90 days. The articles were analyzed and classified according to the level of evidence by two independent reviewers. The 41 articles analyzed allowed to keep grade A recommendations for clinical estimation of survival and Palliative Prognostic score and now also for Palliative Prognostic Index, performance status, dyspnea, lymphopenia and lactate dehydrogenase. Recommendations regarding the use of C-reactive protein, leukocytosis, azotemia, hypoalbuminemia and male gender as predictors reached grade B. To formulate the vital prognosis and to communicate it properly to the patient and family are core competencies of physicians, particularly of those who deal with end of life patients. The clinical impression combined with scientific evidence allows us to estimate more accurately the survival, allowing prioritizing and managing more appropriately the existing resources.

  20. Advances in silica based nanoparticles for targeted cancer therapy.

    PubMed

    Yang, Yannan; Yu, Chengzhong

    2016-02-01

    Targeted delivery of anticancer drug specifically to tumor site without damaging normal tissues has been the dream of all scientists fighting against cancer for decades. Recent breakthrough on nanotechnology based medicines has provided a possible tool to solve this puzzle. Among diverse nanomaterials that are under development and extensive study, silica based nanoparticles with vast advantages have attracted great attention. In this review, we concentrate on the recent progress using silica based nanoparticles, particularly mesoporous silica nanoparticles (MSNs), for targeted drug delivery applications. First, we discuss the passive targeting capability of silica based nanoparticles in relation to their physiochemical properties. Then, we focus on the recent advances of active targeting strategies involving tumor cell targeting, vascular targeting, nuclear targeting and multistage targeting, followed by an introduction to magnetic field directed targeting approach. We conclude with our personal perspectives on the remaining challenges and the possible future directions. Chemotherapy has been one of the mainstays of cancer treatment. The advances in nanotechnology has allowed the development of novel carrier systems for the delivery of anticancer drugs. Mesoporous silica has shown great promise in this respect. In this review article, the authors provided a comprehensive overview of the use of this nanoparticle in both passive, as well as active targeting in the field of oncology. The advantages of this particle were further discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Biweekly docetaxel as second-line chemotherapy of patients with advanced non-small cell lung cancer: a phase II study of the Galician Lung Cancer Group (GGCP 006-00).

    PubMed

    Vázquez, Sergio; Grande, Carlos; Amenedo, Margarita; Fírvida, José Luis; Lázaro, Martín; Alonso, Guillermo; Curiel, Teresa; Huidobro, Gerardo; Mel, José Ramón; Ramos, Manuel

    2004-06-01

    This phase II trial assessed the antitumoral activity and toxicity of docetaxel 50 mg/m (1-h i.v. infusion) administered every 2 weeks as second-line treatment in 45 patients with advanced non-small cell lung cancer (NSCLC). A total of 251 infusions (median 4 per patient) were administered. The actual and relative median dose intensity values were 24.2 mg/m/week and 0.97, respectively. Thirty-seven patients were evaluable for tumor response. The overall response rate was 20% [95% confidence interval (CI) 8-32%] and included one complete response (2%) and eight partial responses (18%). Stable disease was found in seven patients (16%). With a median follow-up of 4 months, the median time to disease progression was 2.8 months (95% CI 1.9-3.7), the median overall survival was 4.0 months (95% CI 3.4-4.6) and the 1-year survival rate was 23% (95% CI 9-37). The every-2-weeks docetaxel schedule was well tolerated. Grade 3/4 non-hematological toxicities showed rates of 5% or less of patients and 2% or less of cycles. The main grade 3/4 hematological toxicity was neutropenia (16% of patients and 8% of cycles). No febrile neutropenia was found. Nevertheless, one toxic death was reported. We conclude that the biweekly docetaxel schedule showed an antitumoral activity similar to that found with the every-3-weeks or weekly docetaxel schedule in a second-line setting for advanced NSCLC. This antitumoral effect was associated with a marked reduction in hematological toxicity, therefore suggesting that this new docetaxel schedule might be useful in the design of combined second-line schedules for treating NSCLC.

  2. Locally advanced breast cancer in the elderly: curettage mastectomy.

    PubMed

    Solej, Mario; Ferronato, Marco; Nano, Mario

    2005-01-01

    Locally advanced breast tumor represents 5-20% of new cases diagnosed every year. The purpose of this study was to report our experience and to compare it with the literature. From 1998 to 2003 at the Molinette Hospital in the Turin University Third Division of General Surgery, there were 34 cases of breast cancer in older women (between 70 and 94 years of age), 14 of which (41.18%) were locally advanced breast tumor. We evaluated the type of surgical intervention and anesthesia used, muscular invasion, the presence of receptors positive to estrogens and progesterone, the operative mortality, the percentage of local-regional recurrence, and relapses after a period of time. Among the patients with locally advanced breast tumor, 21.43% (3/14) were at stage IIIA and 78.57% (11/14) at stage IIIB. In 14.29% (2/14) of the cases, Patey's radical mastectomy was performed, in 57.14% (8/14) Halsted's radical mastectomy, and in 28.57% (4/14) a simple mastectomy with the removal of the fascia of the major pectoral muscle. Three (21.43%) patients underwent a second intervention for local-regional disease. None of the patients had distant metastasis in the first 2 years after the operation. Mortality after 2 years was 23.1% (3/13). None of the patients who underwent surgery had adjuvant therapy, usually because it was refused by the patients themselves or their families. All the negative and positive hormone receptor patients received tamoxifen. Locally advanced breast tumors are frequent in elderly women. In the past, there has been a tendency to surgical under-treatment. As regards locally advanced breast tumor, curettage operations represent the only possibility to improve the quality of life of the elderly. These should be performed after carefully evaluating a series of variables in the general and local condition of the patient, the aggressiveness of the intervention and the life expectancy.

  3. Effect of Obesity and Chronic Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer

    DTIC Science & Technology

    2014-04-01

    Inflammation on TRAIL-Based Immunotherapy for Advanced Breast Cancer PRINCIPAL INVESTIGATOR: Thomas S. Griffith, Ph.D. CONTRACTING ORGANIZATION...CONTRACT NUMBER Immunotherapy for Advanced Breast Cancer 5b. GRANT NUMBER W81XWH-11-1-0271 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Thomas...increased risk of developing cancers , including breast cancer . The reasons for this are likely complex and multi- factorial, but a state of generalized

  4. Operative management of locally advanced, differentiated thyroid cancer

    PubMed Central

    Wang, Laura Y.; Nixon, Iain J.; Patel, Snehal G.; Palmer, Frank L.; Tuttle, R. Michael; Shaha, Ashok; Shah, Jatin P.; Ganly, Ian

    2016-01-01

    Background The majority of differentiated thyroid cancer tends to present with limited locoregional disease, leading to excellent long-term survival after operative treatment. Even patients with advanced local disease may survive for long periods with appropriate treatment. The aim of this study is to present our institutional experience of the management of locally advanced differentiated thyroid cancer and to analyze factors predictive of outcome. Methods We reviewed our institutional database of 3,664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010. A total of 153 patients had tumor extension beyond the thyroid capsule that invaded the subcutaneous soft tissues, recurrent laryngeal nerve, larynx, trachea, or esophagus. Details on extent of operation and adjuvant therapy were recorded. Disease-specific survival and locoregional recurrence-free probability were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by multivariate analysis. Results The median age of the 153 patients with tumor extension beyond the thyroid capsule was 55 years (range 11–91 years). Eighty-nine patients (58.2%) were female. Twenty-three patients (15.0%) were staged as M1 at presentation, and 122 (79.7%) had pathologically involved lymph nodes. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (51.0%) followed by the trachea (46.4%) and esophagus (39.2%). Sixty-three patients (41%) required resection of the recurrent laryngeal nerve due to tumor involvement. After surgery, 20 patients (13.0%) had gross residual disease (R2), 63 (41.2%) had a positive margin of resection (R1), and 70 (45.8%) had complete resection with negative margins (R0). With a median follow-up of 63.9 months, 5-year, disease-specific survival, when stratified by R0/R1/R2 resection, was 94.4%, 87.6%, and 67.9%, respectively (P = .030). The data do not demonstrate a statistical difference in survival

  5. Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

    PubMed

    Ozols, Robert F; Herbst, Roy S; Colson, Yolonda L; Gralow, Julie; Bonner, James; Curran, Walter J; Eisenberg, Burton L; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Reaman, Gregory H; Sawaya, Raymond; Schilsky, Richard L; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Winn, Rodger J

    2007-01-01

    A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries

  6. Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2017-07-05

    Adenocarcinoma of the Gastroesophageal Junction; Colorectal Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Non-Resectable Cholangiocarcinoma; Non-Resectable Hepatocellular Carcinoma; Recurrent Cholangiocarcinoma; Recurrent Colorectal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Small Intestinal Carcinoma; Small Intestinal Adenocarcinoma; Stage III Colorectal Cancer; Stage III Gastric Cancer; Stage III Hepatocellular Carcinoma; Stage III Pancreatic Cancer; Stage III Small Intestinal Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Hepatocellular Carcinoma; Stage IIIA Small Intestinal Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Hepatocellular Carcinoma; Stage IIIB Small Intestinal Cancer; Stage IIIC Gastric Cancer; Stage IV Colorectal Cancer; Stage IV Gastric Cancer; Stage IV Hepatocellular Carcinoma; Stage IV Pancreatic Cancer; Stage IV Small Intestinal Cancer; Stage IVA Colorectal Cancer; Stage IVA Hepatocellular Carcinoma; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Hepatocellular Carcinoma; Stage IVB Pancreatic Cancer; Unresectable Pancreatic Carcinoma; Unresectable Small Intestinal Carcinoma

  7. Pulmonary Rehabilitation in Advanced Lung Cancer Patients During Chemotherapy.

    PubMed

    Jastrzębski, D; Maksymiak, M; Kostorz, S; Bezubka, B; Osmanska, I; Młynczak, T; Rutkowska, A; Baczek, Z; Ziora, D; Kozielski, J

    2015-01-01

    The aim of this study was to investigate the utility of pulmonary rehabilitation for improving of exercises efficiency, dyspnea, and quality of life of patients with lung cancer during chemotherapy. After the enrollment selection, the study included 20 patients with newly diagnosed advanced lung cancer and performance status 0-2. There were 12 patients randomly allocated to the pulmonary rehabilitation group and another 8 constituted the control group that did not undergo physical rehabilitation. Both groups of patients had continual cycles of chemotherapy. Data were analyzed before and after 8 weeks of physical rehabilitation, and before and after 8 weeks of observation without rehabilitation in controls. The inpatient rehabilitation program was based on exercise training with ski poles and respiratory muscle training. We found a tendency for enhanced mobility (6 Minute Walk Test: 527.3 ± 107.4 vs. 563.9 ±64.6 m; p > 0.05) and a significant increase in forced expired volume in 1 s (66.9 ± 13.2 vs. 78.4 ± 17.7 %predicted; p = 0.016), less dyspnea (p = 0.05), and a tendency for improvement in the general quality of life questionnaire after completion of pulmonary rehabilitation as compared with the control group. This report suggests that pulmonary rehabilitation in advanced lung cancer patients during chemotherapy is a beneficial intervention to reduce dyspnea and enhance the quality of life and mobility.

  8. Race and competing mortality in advanced head and neck cancer.

    PubMed

    Zakeri, Kaveh; MacEwan, Iain; Vazirnia, Aria; Cohen, Ezra E W; Spiotto, Michael T; Haraf, Daniel J; Vokes, Everett E; Weichselbaum, Ralph R; Mell, Loren K

    2014-01-01

    Black patients with head and neck cancer (HNC) have poorer survival and disease control compared to non-black patients, but disparities in death from non-cancer causes (i.e., competing mortality) are less well-studied. We conducted an analysis of 538 patients (169 black, 369 non-black) with stage III-IV HNC treated on one of six multi-institutional protocols between 1993 and 2004 involving multi-agent chemoradiotherapy with or without surgery. Competing mortality was defined as death due to intercurrent comorbid disease, treatment-related morbidity, or unknown cause in the absence of disease recurrence, progression, or second malignancy. Cox proportional hazards and competing risks regression were used to estimate the effect of black race on competing mortality. Black race was associated with increased rates of comorbidity, smoking, heavy alcohol use, advanced tumor stage, and poorer performance status (p<.001 for all). Compared to non-black patients, black HNC patients had a higher 5 year cumulative incidence of disease progression (31.4%; 95% CI, 24.4-38.5% vs 23.4%; 95% CI, 19.1-28.1%) and competing mortality (28.1%; 95% CI, 21.2-35.3% vs 14.5%; 95% CI, 11.0-18.5%). When adjusting for age, male sex, body mass index, distance traveled, smoking and alcohol use, performance status, comorbidity, and tumor stage, the black race was associated with death from comorbid disease (Cox hazard ratio 2.13; 95% CI, 1.06-4.28, p=0.033). Black patients with advanced HNC are at increased risk of both disease progression and death from competing non-cancer mortality, particularly death from comorbid disease. Improved strategies to manage comorbid disease may increase the benefit of treatment intensification in black patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Guarana (Paullinia cupana) Improves Anorexia in Patients with Advanced Cancer.

    PubMed

    Palma, Cláudia G Latorre; Lera, Andrea Thaumaturgo; Lerner, Tatiana; de Oliveira, Manuella Missawa; de Borta, Thaís Mazará; Barbosa, Renata Possebon; Brito, Gisele Mendes; Guazzelli, Camila Ada; Cruz, Felipe José Melo; del Giglio, Auro

    2016-01-01

    Anorexia is prevalent in cancer patients with advanced disease. In this pilot phase II, open label, nonrandomized trial, we evaluated the efficacy and safety of guarana (Paullinia cupana) in patients with cancer and weight loss. We included advanced cancer patients with decreased appetite and weight loss of more than 5% from their baseline. All of the patients received 50 mg of the crude dry extract of guarana twice a day for 4 weeks. The trial was designed in two phases (Simon model). We considered a positive response in the first phase to be at least 5% weight gain or a three-point improvement in the appetite scale in at least three of the first 18 evaluable patients. Of the 34 eligible patients, 30 were included and 18 completed the protocol. Only one patient abandoned the protocol due to toxicity (grade II arthralgia). No grade 3 or 4 toxicities and no significant differences in nausea, weight loss, or quality of life (FACT-G) occurred. Only two of the 18 patients who completed the study had weight gain above 5% from their baseline, whereas six patients had at least a 3-point improvement in the visual appetite scale. The M.D. Anderson Symptom Inventory (MDASI) was used to evaluate several symptoms, and we observed a significant decrease in the lack of appetite (p = 0.02) and in somnolence (p = 0.0142). We concluded that the weight stabilization and increased appetite that we observed in this study justify further studies of guarana in this patient population.

  10. Emerging Nanotechnology and Advanced Materials for Cancer Radiation Therapy.

    PubMed

    Song, Guosheng; Cheng, Liang; Chao, Yu; Yang, Kai; Liu, Zhuang

    2017-08-01

    Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia-associated radiation resistance is a well-known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation-induced DNA damages. With the development in nanotechnology, there have been great interests in using nanomedicine strategies to enhance radiation responses of tumors. Nanomaterials containing high-Z elements to absorb radiation rays (e.g. X-ray) can act as radio-sensitizers to deposit radiation energy within tumors and promote treatment efficacy. Nanoscale carriers are able to deliver therapeutic radioisotopes into tumors for internal RIT, or chemotherapeutic drugs for synergistically combined chemo-radiotherapy. As uncovered in recent studies, the tumor microenvironment could be modulated by various nanomedicine approaches to overcome hypoxia-associated radiation resistance. Herein, the authors will summarize the applications of nanomedicine for RT cancer treatment, and pay particular attention to the latest development of 'advanced materials' for enhanced cancer RT. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Assessing needs of family members of inpatients with advanced cancer.

    PubMed

    Bužgová, R; Špatenková, N; Fukasová-Hajnová, E; Feltl, D

    2016-07-01

    To provide high-quality and effective cancer care, problems and unmet needs of family members during their relatives' hospitalisation have to be identified as well. The aims were to determine how needs of family members of patients with terminal cancer are met and to analyse factors that influence them. The needs were assessed with the Family Inventory of Needs. Each item (n = 20) represents one need of family members, for which the importance and satisfaction are rated. The study comprised 270 family members of hospitalised advanced cancer patients staying in the University Hospital Ostrava who were receiving palliative care. The family members preferred sufficient basic information and patient comfort. The unmet needs were support of hope (73%) and provision of information (65%). The unmet needs were more frequently identified by women, individuals with lower education, younger persons, unemployed, patients' children and family members of patients with generally unfavourable health status (P < 0.05). There was a correlation between lower quality of life and higher numbers of unmet needs. Targeted interventions aimed at meeting important needs of the family members may improve their quality of life.

  12. [Contemporary methods of treatment in local advanced prostate cancer].

    PubMed

    Brzozowska, Anna; Mazurkiewicz, Maria; Starosławska, Elzbieta; Stasiewicz, Dominika; Mocarska, Agnieszka; Burdan, Franciszek

    2012-10-01

    The prostate cancer is one of the most often cancers amongst males. Its frequency is increasing with age. Thanks to widespread of screening denomination of specific prostate specific antigen (PSA), ultrasonography including the one in transrectal (TRUS), computed tomography, magnetic resonance and especially the awareness of society, the number of patients with low local advance of illness is increasing. The basic method of treatment in such cases is still the surgical removal of prostate with seminal bladder or radiotherapy. To this purpose tele-(IMRT, VMAT) or brachytherapy (J125, Ir192, Pa103) is used. In patients with higher risk of progression the radiotherapy may be associated with hormonotherapy (total androgen blockage-LH-RH analog and androgen). Despite numerous clinical researches conducted there is still no selection of optimal sequence of particular methods. Moreover, no explicit effectiveness was determined. The general rule of treatment in patients suffering from prostate cancer still remains individual selection of therapeutic treatment depending on the age of a patient, general condition and especially patient's general preferences. In case of elderly patients and patients with low risk of progression, recommendation of direct observation including systematical PSA denomination, clinical transrectal examination, TRUS, MR of smaller pelvis or scintigraphy of the whole skeleton may be considered.

  13. The role of surgery in advanced epithelial ovarian cancer

    PubMed Central

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  14. Modeling Signaling Networks to Advance New Cancer Therapies.

    PubMed

    Saez-Rodriguez, Julio; MacNamara, Aidan; Cook, Simon

    2015-01-01

    Cell signaling pathways control cells' responses to their environment through an intricate network of proteins and small molecules partitioned by intracellular structures, such as the cytoskeleton and nucleus. Our understanding of these pathways has been revised recently with the advent of more advanced experimental techniques; no longer are signaling pathways viewed as linear cascades of information flowing from membrane-bound receptors to the nucleus. Instead, such pathways must be understood in the context of networks, and studying such networks requires an integration of computational and experimental approaches. This understanding is becoming more important in designing novel therapies for diseases such as cancer. Using the MAPK (mitogen-activated protein kinase) and PI3K (class I phosphoinositide-3' kinase) pathways as case studies of cellular signaling, we give an overview of these pathways and their functions. We then describe, using a number of case studies, how computational modeling has aided in understanding these pathways' deregulation in cancer, and how such understanding can be used to optimally tailor current therapies or help design new therapies against cancer.

  15. Management of locally advanced and disseminated breast cancer--chemotherapy.

    PubMed

    Bisel, H F

    1980-08-15

    Breast cancer is one of the most responsive of the common solid tumors when systemic therapy is indicated in the treatment of locally advanced or disseminated cancer. Many single agents have been useful in inducing remission in mammary carcinoma, but in recent years various drug combinations have been developed that appear more effective than individual drugs and in some instances with reduced toxicity levels. Adriamycin is the most interesting of the newer drugs and is the most effective single agent. Polychemotherapy of breast cancer was tried years ago, but remained for Cooper to arouse professional interest in multiple-drug therapy. Many modifications of this original five-drug regimens have been tried. One of the most widely used combinations is the CMF program, which includes cyclophosphamide, methotrexate, and 5-fluorouracil. The program that we have come to regard as our standard program in controlled clinical trials (CFP) employs cyclophosphamide, 5-fluorouracil, and prednisone. Toxicity with this program has been clinically acceptable, and in multiple comparative trials we have found no combination with greater therapeutic efficacy.

  16. Outcomes of temporal bone resection for locally advanced parotid cancer.

    PubMed

    Mehra, Saral; Morris, Luc G; Shah, Jatin; Bilsky, Mark; Selesnick, Samuel; Kraus, Dennis H

    2011-11-01

    This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death.

  17. Outcomes of Temporal Bone Resection for Locally Advanced Parotid Cancer

    PubMed Central

    Mehra, Saral; Morris, Luc G.; Shah, Jatin; Bilsky, Mark; Selesnick, Samuel; Kraus, Dennis H.

    2011-01-01

    This study was conducted to report outcomes and identify factors predictive of survival and recurrence in patients undergoing lateral temporal bone resection (LTBR) as part of an extended radical parotidectomy for parotid cancer. This is a retrospective cohort study which includes all patients undergoing LTBR for parotid cancer between 1994 and 2010 at two affiliated academic centers. Survival and recurrence rates were analyzed using the Kaplan-Meier method and Cox multivariate regression. A total of 12 patients with median follow-up duration of 30.6 months were included: 6 de novo cases and 6 patients referred after local recurrence. Actuarial locoregional control at 2 years was 73%. Most patients (11; 92%) developed disease recurrence with distant metastases the most common site of first failure (83%). Overall and disease-specific survival rates were 80% at 2 years and 22.5% at 5 years. Recurrence-free survival (RFS) was 67% at 2 years and 8.3% at 5 years. On multivariate analysis, surgical margin status was an independent predictor of RFS (hazard ratio = 3.85, p = 0.045). In advanced parotid cancer, LTBR with a goal of gross total resection offers good locoregional control with an acceptable complication rate. The benefits of this surgery must be balanced with the morbidity and low likelihood of long-term survival, with most patients ultimately experiencing disease recurrence and death. PMID:22547966

  18. Oncolytic Virotherapy for Hematological Malignancies

    PubMed Central

    Bais, Swarna; Bartee, Eric; Rahman, Masmudur M.; McFadden, Grant; Cogle, Christopher R.

    2012-01-01

    Hematological malignancies such as leukemias, lymphomas, multiple myeloma (MM), and the myelodysplastic syndromes (MDSs) primarily affect adults and are difficult to treat. For high-risk disease, hematopoietic stem cell transplant (HCT) can be used. However, in the setting of autologous HCT, relapse due to contamination of the autograft with cancer cells remains a major challenge. Ex vivo manipulations of the autograft to purge cancer cells using chemotherapies and toxins have been attempted. Because these past strategies lack specificity for malignant cells and often impair the normal hematopoietic stem and progenitor cells, prior efforts to ex vivo purge autografts have resulted in prolonged cytopenias and graft failure. The ideal ex vivo purging agent would selectively target the contaminating cancer cells while spare normal stem and progenitor cells and would be applied quickly without toxicities to the recipient. One agent which meets these criteria is oncolytic viruses. This paper details experimental progress with reovirus, myxoma virus, measles virus, vesicular stomatitis virus, coxsackievirus, and vaccinia virus as well as requirements for translation of these results to the clinic. PMID:22312362

  19. Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer

    ClinicalTrials.gov

    2017-09-28

    Recurrent Colorectal Carcinoma; Solid Neoplasm; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  20. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer

    PubMed Central

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  1. [A case of early gastric cancer completely responding to adjuvant chemotherapy for advanced colon cancer].

    PubMed

    Tanaka, Ryo; Kameyama, Hitoshi; Nakano, Mae; Ichikawa, Hiroshi; Hanyu, Takaaki; Nakano, Masato; Ishikawa, Takashi; Shimada, Yoshifumi; Sakata, Jun; Kobayashi, Takashi; Kosugi, Shinichi; Minagawa, Masahiro; Koyama, Yu; Wakai, Toshifumi

    2014-11-01

    A 70-year-old man was referred to our hospital with ascending colon cancer (cT3N1M0, Stage IIIa), which was found during examinations following a positive fecal occult blood test. The patient was also diagnosed with early gastric cancer (cT1a, N0, M0, Stage IA)during a preoperative gastroscopy examination. A laparoscopically assisted right colectomy and D3 lymphadenectomy was performed for the ascending colon cancer. The postoperative pathological diagnosis was Stage IIIb (pT3N2), he was administered in combination with capecitabine plus oxaliplatin (CapeOX) as adjuvant chemotherapy before the treatment for the colon cancer. After 6 months of adjuvant chemotherapy, we were unable to detect any gastric lesions at the same location using gastroscopy, and so diagnosed a clinical complete response. A follow-up gastroscopy 6 months later showed the same findings. The patient has had no recurrence of gastric cancer for 18 months after the initial operation. He will continue to be followed up closely using gastroscopy. In this case, CapeOX as adjuvant chemotherapy for advanced colon cancer was also effective for early gastric cancer.

  2. FOREWORD: Conference on Advanced Metrology for Cancer Therapy 2011 Conference on Advanced Metrology for Cancer Therapy 2011

    NASA Astrophysics Data System (ADS)

    Ankerhold, Ulrike

    2012-10-01

    Although physical treatments play a central role in cancer therapy, SI-traceable metrology has only been established for some of them. Several forms of treatment currently used (particularly intensity-modulated radiation therapy (IMRT), hadron therapy, high-intensity therapeutic ultrasound (HITU) and brachytherapy) suffer from the limited metrological support, which restricts the success of these techniques. Recognizing this deficit, the European Union identified metrology for health as one of the first four Targeted Programmes in the framework of the European Metrology Research Programme (EMRP) running from 2008 to 2011. This programme included two EMRP projects addressing metrology for cancer therapy: project T2.J06 dealing with brachytherapy project T2.J07 dealing with external beam cancer therapy using ionizing radiation and high-intensity therapeutic ultrasound. Primary measurement standards applicable to modern treatment conditions were developed under both projects, together with measurement techniques which are meant as a basis for future protocols for dosimetry, treatment planning and monitoring. In order to provide a platform for the presentation of current developments in clinical measurement techniques for cancer therapy, together with the achievements of both projects, an international Conference on Advanced Metrology for Cancer Therapy (CAMCT) was held from 29 November to 1 December 2011 at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The main sessions of the conference: Primary and secondary standards of absorbed dose to water for IMRT and brachytherapy, 3D dose distributions and treatment planning for IMRT and brachytherapy, Hadron therapy (protons and carbon ions), High-intensity therapeutic ultrasound (HITU), were geared to the main foci of the projects. Metrologists and medical physicists from countries all over the world attended the conference and made it into a forum for the exchange of information and expertise

  3. Hematology and immunology studies

    NASA Technical Reports Server (NTRS)

    Kimzey, S. L.; Fischer, C. L.; Johnson, P. C.; Ritzmann, S. E.; Mengel, C. E.

    1975-01-01

    The hematology and immunology program conducted in support of the Apollo missions was designed to acquire specific laboratory data relative to the assessment of the health status of the astronauts prior to their commitment to space flight. A second objective was to detect and identify any alterations in the normal functions of the immunohematologic systems which could be attributed to space flight exposure, and to evaluate the significance of these changes relative to man's continuing participation in space flight missions. Specific changes observed during the Gemini Program formed the basis for the major portion of the hematology-immunology test schedule. Additional measurements were included when their contribution to the overall interpretation of the flight data base became apparent.

  4. Early palliative care for adults with advanced cancer.

    PubMed

    Haun, Markus W; Estel, Stephanie; Rücker, Gerta; Friederich, Hans-Christoph; Villalobos, Matthias; Thomas, Michael; Hartmann, Mechthild

    2017-06-12

    Incurable cancer, which often constitutes an enormous challenge for patients, their families, and medical professionals, profoundly affects the patient's physical and psychosocial well-being. In standard cancer care, palliative measures generally are initiated when it is evident that disease-modifying treatments have been unsuccessful, no treatments can be offered, or death is anticipated. In contrast, early palliative care is initiated much earlier in the disease trajectory and closer to the diagnosis of incurable cancer. To compare effects of early palliative care interventions versus treatment as usual/standard cancer care on health-related quality of life, depression, symptom intensity, and survival among adults with a diagnosis of advanced cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, OpenGrey (a database for grey literature), and three clinical trial registers to October 2016. We checked reference lists, searched citations, and contacted study authors to identify additional studies. Randomised controlled trials (RCTs) and cluster-randomised controlled trials (cRCTs) on professional palliative care services that provided or co-ordinated comprehensive care for adults at early advanced stages of cancer. We used standard methodological procedures as expected by Cochrane. We assessed risk of bias, extracted data, and collected information on adverse events. For quantitative synthesis, we combined respective results on our primary outcomes of health-related quality of life, survival (death hazard ratio), depression, and symptom intensity across studies in meta-analyses using an inverse variance random-effects model. We expressed pooled effects as standardised mean differences (SMDs, or Hedges' adjusted g). We assessed certainty of evidence at the outcome level using GRADE (Grading of Recommendations Assessment, Development, and

  5. [Centralization versus decentralization. Hematology].

    PubMed

    Borregaard, Niels

    2006-04-10

    Clinical haematology is the result of teamwork among dedicated specialists in pathology, molecular diagnostics, imaging, radiotherapy and the haematologist, who in turn can focus on only a limited fraction of the various and highly complex diseases that together constitute clinical haematology. The treatment of patients should be centralized in departments large enough to permit internal subspecialization and to provide expert service focused on haematology. No more than three such hematology centers are needed in Denmark.

  6. Hematology of camelids.

    PubMed

    Vap, Linda; Bohn, Andrea A

    2015-01-01

    Interpretation of camelid hematology results is similar to that of other mammals. Obtaining accurate results and using appropriate reference intervals can be a bit problematic, particularly when evaluating the erythron. Camelid erythrocytes vary from other mammals in that they are small, flat, and elliptical. This variation makes data obtained from samples collected from these species prone to error when using some automated instruments. Normal and abnormal findings in camelid blood are reviewed as well as how to ensure accurate results.

  7. Advances in cancer therapy with plant based natural products.

    PubMed

    Mukherjee, A K; Basu, S; Sarkar, N; Ghosh, A C

    2001-10-01

    Natural Products have long been a fertile source of cure for cancer, which is projected to become the major causes of death in this century. However, there is a continuing need for development of new anticancer drugs, drug combinations and chemotherapy strategies, by methodical and scientific exploration of enormous pool of synthetic, biological and natural products. There are at least 250,000 species of plants out of which more than one thousand plants have been found to possess significant anticancer properties. While many molecules obtained from nature have shown wonders, there are a huge number of molecules that still either remains to be trapped or studied in details by the medicinal chemists. The article reviews many such structures and their related chemistry along with the recent advances in understanding mechanism of action and structure-function relationships of nature derived anti-cancer agents at the molecular, cellular and physiological levels. Taxol, one of the most outstanding agents, has been found beneficial in treatment of refractory ovarian, breast and other cancers. Another prominent molecule includes Podophyllotoxin. Synthetic modification of this molecule led to the development of Etoposide, known to be effective for small cell cancers of the lungs and testes. Camptothecin isolated from Camptotheca acuminata also have been extensively studied. Other important molecules discussed include Vincristine, Vinblastine, Colchicine, Ellipticine and Lepachol along with Flavopiridol, a semi-synthetic analogue of the chromone alkaloid Rohitukine from India, a pyridoindole alkaloid from leaves of Ochrosia species and many more. The review also deals with the lesser-known plants of sub-Himalayan region.

  8. Critical values in hematology.

    PubMed

    McFarlane, A; Aslan, B; Raby, A; Bourner, G; Padmore, R

    2015-02-01

    Critical values are life-threatening results that require immediate notification to the patient's healthcare provider. Accreditation bodies require laboratories to establish critical values. A survey of Ontario laboratories was conducted to determine current practice for critical values in hematology. The survey was sent to 182 participants questioning sources for establishing critical values, levels, review frequency, delta checks, and reporting. The survey was completed by laboratory managers, supervisors, technical specialists, senior technologists, and bench technologists working in hematology. The majority of participating laboratories have established critical values limits for hemoglobin, leukocyte counts, and platelet counts. Most laboratories also include the presence of malaria parasites and blast cells. Some laboratories reported the presence of plasma cells, sickle cells, schistocytes, and spherocytes as critical values. Multiple sources are used for establishing a critical value policy. There was variability for the frequency of critical values review. Rules may differ for a first-time patient sample vs. a repeat patient sample. Delta checks are seldom used to determine whether a result should be called a critical value. Most participants require the individual taking the critical result(s) to read back and confirm that they are directly involved with the patient's care. There is a lack of consensus for critical values reporting in hematology. As critical value reporting is crucial for patient safety, standardization of this practice would be beneficial. © 2014 John Wiley & Sons Ltd.

  9. A phase II study tests a new drug for patients with advanced thyroid cancer | Center for Cancer Research

    Cancer.gov

    A phase II trial of CUDC-907, a new drug that may be able to shrink thyroid tumors that have spread or gotten worse, is being tested in metastatic or advanced thyroid cancer.  Currently, there is no standard or effective treatment for the most aggressive types of thyroid cancer such as anaplastic and poorly differentiated thyroid cancer.  Learn more...

  10. Megestrol acetate for the palliation of anorexia in advanced, incurable cancer patients.

    PubMed

    Mateen, Farrah; Jatoi, Aminah

    2006-10-01

    Anorexia, or loss of appetite, is a troubling symptom for many patients with advanced cancer. The early observation that breast cancer patients, who were prescribed megestrol acetate as a cancer treatment, went on to increase their appetite and gain weight has given rise to a large number of clinical trials that have tested this progestational drug as a palliative agent for the cancer anorexia/weight loss syndrome. This review focuses on these trials, summarizing their findings and providing a practical approach for prescribing megestrol acetate to advanced cancer patients who suffer from the cancer anorexia/weight loss syndrome.

  11. Determinants of death anxiety in patients with advanced cancer.

    PubMed

    Neel, Caroline; Lo, Chris; Rydall, Anne; Hales, Sarah; Rodin, Gary

    2015-12-01

    To examine the presence of death anxiety in patients with advanced cancer and to identify the psychosocial and disease-related factors associated with it. Cross-sectional analysis of baseline data from a phase 2 pilot intervention trial. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. 60 adult outpatients with metastatic breast, endocrine, gastrointestinal, gynaecological, genitourinary and lung cancer. Death anxiety, as measured by the Death and Dying Distress Scale (DADDS). Thirty-two per cent of the sample reported death anxiety of at least moderate severity. The most distressing concern involved fears about the impact of one's death on others, and the least distressing concerns were related to dying alone or suddenly. According to regression analyses, death anxiety was negatively associated with self-esteem, b=-1.73, CI0.95 (-2.57 to -0.90) and positively associated with physical symptom burden, b=1.38, CI0.95 (0.44 to 2.31), having children under 18 years of age in the family, b=13.3, CI0.95 (2.15 to 24.5), and age, b=0.40, CI0.95 (0.0023 to 0.79). The physical symptoms most strongly associated with death anxiety were changes in physical appearance, b=18.8, CI0.95 (8.21 to29.5), and pain, b=10.1, CI0.95 (0.73 to 19.5). The findings suggest that death anxiety in patients with advanced cancer is common and determined by the interaction of individual factors, family circumstances and physical suffering. Multidimensional interventions that take into account these and other factors may be most likely to be effective to alleviate this death-related distress. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. Survival impact of integrative cancer care in advanced metastatic breast cancer.

    PubMed

    Block, Keith I; Gyllenhaal, Charlotte; Tripathy, Debu; Freels, Sally; Mead, Mark N; Block, Penny B; Steinmann, William C; Newman, Robert A; Shoham, Jacob

    2009-01-01

    Integrative cancer treatment is of substantial interest to many cancer patients. Research is needed to evaluate the effects of integrative treatment on patient outcomes. We report survival data for a consecutive case series of advanced metastatic breast cancer patients who received a comprehensive clinical program combining conventional treatments with nutrition and supplementation, fitness and mind-spirit instruction at the Block Center for Integrative Cancer Treatment. Treatment outcomes using integrative care for this disease have not previously been documented; survival data will thus contribute to decisions concerning future research directions and design. Ninety consecutive patients with metastatic breast cancer diagnosed during 1984-1997 who received chemotherapy at the integrative cancer center were included. Prognostic factors, treatments and survival from onset of metastases were determined from analysis of scans, labs, pathology and medical records. The log-rank test and Cox proportional hazards analyses were used, and a Kaplan-Meier curve was calculated. All patients had metastatic disease at baseline, 96% were relapsed and 52% had received prior chemotherapy for metastatic disease. Median age at onset of metastasis was 46 years. Median survival was 38 months (95% CI 27,48). Published literature on populations with somewhat more favorable prognostic factors treated in conventional clinics showed median survivals of 20 to 23 months. Through the 1990s, median survival reported in metastatic breast cancer trials or observations generally ranged from 12 to 24 months. Five-year survival was 27% for Center versus 17% for comparison patients. Despite a higher proportion of younger and relapsed patients, survival of metastatic breast cancer patients at the Center was approximately double that of comparison populations and possibly even higher compared to trials published during this period. Explanations for the advantage relative to conventional treatment alone

  13. Differences in end-of-life communication for children with advanced cancer who were referred to a palliative care team.

    PubMed

    Kassam, Alisha; Skiadaresis, Julia; Alexander, Sarah; Wolfe, Joanne

    2015-08-01

    There is a general consensus that involving a specialized palliative care team in the care of children with advanced cancer can help optimize end-of-life communication; however, how this compares to standard oncology care is still unknown. We aimed to determine whether there was an association between specialist palliative care involvement and improved end-of-life communication for children with advanced cancer and their families. We administered questionnaires to 75 bereaved parents (response rate 54%). Outcome measures were presence or absence of 11 elements related to end-of-life communication. Parents were significantly more likely to receive five communication elements if their child was referred to a palliative care team. These elements are: discussion of death and dying with parents by the healthcare team (P<0.01); discussion of death and dying with child by the healthcare team when appropriate (P < 0.01); providing parents with guidance on how to talk to their child about death and dying when appropriate (P < 0.01); preparing parents for medical aspects surrounding death (P = 0.02) and sibling support (P = 0.02). Children were less likely to be referred to a palliative care team if they had a hematologic malignancy. Children who receive standard oncology care are at higher risk of not receiving critical communication elements at end of life. Strategies to optimize end-of-life communication for children who are not referred to a palliative care team are needed. © 2015 Wiley Periodicals, Inc.

  14. FOLFOX-4 as second-line therapy after failure of gemcitabine and platinum combination in advanced gall bladder cancer patients.

    PubMed

    Dodagoudar, Chandragouda; Doval, Dinesh Chandra; Mahanta, Anupam; Goel, Varun; Upadhyay, Amitabh; Goyal, Pankaj; Talwar, Vineet; Singh, Sajjan; John, Mithun Chacko; Tiwari, Srikant; Patnaik, Nivedita

    2016-01-01

    There is no standard second-line chemotherapy after progression on first-line therapy including gemcitabine and platinum combination in advanced gall bladder cancer patients. So this study was undertaken to assess the efficacy and safety of FOLFOX-4 regimen in this setting. In this observational study, patients with performance status ≤2, who progressed on first-line therapy, were enrolled from May 2010 to June 2014. FOLFOX-4 based treatment was administered until progression, unacceptable toxicity or up to 12 cycles. A total of 66 patients were enrolled in this study. The median age of patients was 52.5 years (32-66 years),of which 24 (36.36%) were males and 42 (63.63%) were females. The median number of cycles could be given were 9.5 (2-12). Only 43.93% patients in this study completed full 12 cycles of chemotherapy. Sixteen patients (24.24%) in this study required the dose reduction at least in one cycle of chemotherapy due to toxicities. Disease control rate was seen in 39 (59.09%) patients, with complete response in none, partial response in 16 (24.24%), stable disease in 23 (34.84%) and progressive disease in 27 (40.90%) patients. The median progression free survival was 3.9 months; median overall survival was 7.6 months. The main Grade 3/4 side effects seen were hematological in 31.81% (n = 21) and gastrointestinal in 25.75% (n = 17) patients. Majority of patients (46%) had Grade 1/2 peripheral neuropathy. FOLFOX-4 is an effective and well-tolerated regimen as a second-line treatment in advanced gall bladder cancer patients. Further studies are required, especially in the Indian subcontinent. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Mental health, treatment preferences, advance care planning, location, and quality of death in advanced cancer patients with dependent children.

    PubMed

    Nilsson, Matthew E; Maciejewski, Paul K; Zhang, Baohui; Wright, Alexi A; Trice, Elizabeth D; Muriel, Anna C; Friedlander, Robert J; Fasciano, Karen M; Block, Susan D; Prigerson, Holly G

    2009-01-15

    Clinicians observe that advanced cancer patients with dependent children agonize over the impact their death will have on their children. The objective of this study was to determine empirically whether advanced cancer patients with and without dependent children differ in treatment preferences, mental health, and end-of-life (EOL) outcomes. Coping with Cancer is a National Cancer Institute/National Institute of Mental Health-funded, multi-institutional, prospective cohort study of 668 patients with advanced cancer. Patients with and without dependent children were compared on rates of psychiatric disorders, advance care planning (ACP), EOL care, quality of their last week of life, and location of death. In adjusted analyses, patients with advanced cancer who had dependent children were more likely to meet panic disorder criteria (adjusted odds ratio [AOR], 5.41; 95% confidence interval [95% CI], 2.13-13.69), more likely to be worried (mean difference in standard deviations [delta], 0.09; P=.006), and more likely to prefer aggressive treatment over palliative care (AOR, 1.77; 95% CI, 1.07-2.93). Patients with dependent children were less likely to engage in ACP (eg, do not resuscitate orders: AOR, 0.44; 95% CI, 0.26-0.75) and had a worse quality of life in the last week of life (delta, 0.15; P=.007). Among spousal caregivers, those with dependent children were more likely to meet criteria for major depressive disorder (AOR, 4.53; 95% CI, 1.47-14) and generalized anxiety disorder (AOR, 3.95; 95% CI, 1.29-12.16). Patients with dependent children were more anxious, were less likely to engage in ACP, and were more likely to have a worse quality of life in their last week of life. Advanced cancer patients and spousal caregivers with dependent children represent a particularly distressed group that warrants further clinical attention, research, and support. Copyright (c) 2009 American Cancer Society.

  16. Palliative Care Improves Survival, Quality of Life in Advanced Lung Cancer | Division of Cancer Prevention

    Cancer.gov

    Results from the first randomized clinical trial of its kind have revealed a surprising and welcome benefit of early palliative care for patients with advanced lung cancer—longer median survival. Although several researchers said that the finding needs to be confirmed in other trials of patients with other cancer types, they were cautiously optimistic that the trial results could influence oncologists’ perceptions and use of palliative care. |

  17. Advances in Breast Cancer – Looking Back over the Year

    PubMed Central

    Lüftner, D.; Lux, M. P.; Maass, N.; Schütz, F.; Schwidde, I.; Fasching, P. A.; Fehm, T.; Janni, W.; Kümmel, S.; Kolberg, H.-C.

    2012-01-01

    Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, yet not every new, promising combination achieves a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also the genetic disposition of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Health-economic concerns are also being taken into consideration more frequently, meaning political decisions may also become a factor. This review presents the trends over the past year. PMID:26640285

  18. Recent advances in oral anticancer agents for colon cancer.

    PubMed

    Shukla, Raj Kumar

    2013-12-01

    To provide therapeutic alternatives to intravenous colon chemotherapy major recent research is focusing on the development of oral chemotherapeutic agents with the intention to improve the quality of life of patients. Initially 5-fluorouracil was most commonly used for the treatment of colorectal cancer but currently oxaliplatin and irinotecan are also available. The majority of these new drugs are pyrimidines and their analogs. The rationale for using oral anticancer agents is discussed and new drugs, such as farnesyl protein transferase inhibitor S-1, rubitecan, ZD9331, MMI-166, eflornithine, sulindac, and oral camptothecin analogs, among others, are presented with the results of their preclinical and clinical developments. This article focuses on the advancement of clinical development and also discusses the relative merits and demerits of these agents. The accelerated approval of these agents by regulatory authorities is supported by survival benefit, response rate and time to progression.

  19. [Intraperitoneal chemotherapy in the treatment of advanced ovarian cancer].

    PubMed

    Classe, J-M; Muller, M; Frenel, J-S; Berton Rigaud, D; Ferron, G; Jaffré, I; Gladieff, L

    2010-05-01

    The standard treatment for advanced ovarian cancer consist in complete surgical debulking and intravenous platin and taxane based chemotherapy. Despite research efforts, a lot of patients still die from peritoneal carcinomatosis. The aim of our work was to present the state of art about intraperitoneal chemotherapy. Intraperitoneal chemotherapy (IPC): three multi-institutional randomised trials showed that platin based IPC gave better results in term of overall and disease free survival when compared to standard intravenous treatment. Even so, IPC is not yet becoming a new international standard of treatment because a high rate of morbidity. Hyperthermic Intraperitoneal chemotherapy (HIPEC) represents an innovative alternative to IPC. HIPEC is based on a complete surgical debulking without any visible mass and an intraperitoneal chemotherapy with synergy of hyperthermia. Phase II trails have shown its feasibility. Randomised trials are needed to assess its efficiency in improving survival. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  20. Cancer Related Fatigue and Quality of Life in Patients with Advanced Prostate Cancer Undergoing Chemotherapy

    PubMed Central

    Charalambous, Andreas; Kouta, Christiana

    2016-01-01

    Cancer related fatigue (CRF) is a common and debilitating symptom that can influence quality of life (QoL) in cancer patients. The increase in survival times stresses for a better understanding of how CRF affects patients' QoL. This was a cross-sectional descriptive study with 148 randomly recruited prostate cancer patients aiming to explore CRF and its impact on QoL. Assessments included the Cancer Fatigue Scale, EORTC QLQ-C30, and EORTC QLQ-PR25. Additionally, 15 in-depth structured interviews were performed. Quantitative data were analyzed with simple and multiple regression analysis and independent samples t-test. Qualitative data were analyzed with the use of thematic content analysis. The 66.9% of the patients experienced CRF with higher levels being recorded for the affective subscale. Statistically significant differences were found between the patients reporting CRF and lower levels of QoL (mean = 49.1) and those that did not report fatigue and had higher levels of QoL (mean = 72.1). The interviews emphasized CRF's profound impact on the patients' lives that was reflected on the following themes: “dependency on others,” “loss of power over decision making,” and “daily living disruption.” Cancer related fatigue is a significant problem for patients with advanced prostate cancer and one that affects their QoL in various ways. PMID:26981530

  1. TAS-102 in Treating Advanced Biliary Tract Cancers

    ClinicalTrials.gov

    2017-09-07

    Cholangiocarcinoma; Stage III Gallbladder Cancer AJCC v7; Stage IIIA Gallbladder Cancer AJCC v7; Stage IIIB Gallbladder Cancer AJCC v7; Stage IV Gallbladder Cancer AJCC v7; Stage IVA Gallbladder Cancer AJCC v7; Stage IVB Gallbladder Cancer AJCC v7

  2. Determinants of Patient-Oncologist Prognostic Discordance in Advanced Cancer.

    PubMed

    Gramling, Robert; Fiscella, Kevin; Xing, Guibo; Hoerger, Michael; Duberstein, Paul; Plumb, Sandy; Mohile, Supriya; Fenton, Joshua J; Tancredi, Daniel J; Kravitz, Richard L; Epstein, Ronald M

    2016-11-01

    Patients with advanced cancer often report expectations for survival that differ from their oncologists' expectations. Whether patients know that their survival expectations differ from those of their oncologists remains unknown. This distinction is important because knowingly expressing differences of opinion is important for shared decision making, whereas patients not knowing that their understanding differs from that of their treating physician is a potential marker of inadequate communication. To describe the prevalence, distribution, and proportion of prognostic discordance that is due to patients' knowingly vs unknowingly expressing an opinion that differs from that of their oncologist. Cross-sectional study conducted at academic and community oncology practices in Rochester, New York, and Sacramento, California. The sample comprises 236 patients with advanced cancer and their 38 oncologists who participated in a randomized trial of an intervention to improve clinical communication. Participants were enrolled from August 2012 to June 2014 and followed up until October 2015. We ascertained discordance by comparing patient and oncologist ratings of 2-year survival probability. For discordant pairs, we determined whether patients knew that their opinions differed from those of their oncologists by asking the patients to report how they believed their oncologists rated their 2-year survival. Among the 236 patients (mean [SD] age, 64.5 [11.4] years; 54% female), 161 patient-oncologist survival prognosis ratings (68%; 95% CI, 62%-75%) were discordant. Discordance was substantially more common among nonwhite patients compared with white patients (95% [95% CI, 86%-100%] vs 65% [95% CI, 58%-73%], respectively; P = .03). Among 161 discordant patients, 144 (89%) did not know that their opinions differed from that of their oncologists and nearly all of them (155 of 161 [96%]) were more optimistic than their oncologists. In this study, patient-oncologist discordance

  3. Letrozole in advanced breast cancer: the PO25 trial

    PubMed Central

    2007-01-01

    Tamoxifen has been a standard first-line endocrine therapy for post-menopausal women with hormone-responsive advanced breast cancer, but more than half of patients fail to respond and time to progression is less than 12 months in responders. The third-generation aromatase inhibitors were developed to provide more effective alternatives to tamoxifen. In the Femara Study PO25, post-menopausal women with advanced breast cancer were randomized to receive letrozole 2.5 mg (n = 453) or tamoxifen 20 mg (n = 454) given orally daily until progressive disease occurred. Patients were permitted to cross over to the other treatment at progression. In the primary efficacy analysis, median time to progression (TTP) was significantly longer with letrozole than with tamoxifen (9.4 months vs. 6.0 months, respectively; P < 0.0001). The objective response rate (ORR) was significantly higher for letrozole than for tamoxifen (32% vs. 21%; P = 0.0002). Prospectively planned analyses of the intent-to-treat population showed that letrozole significantly improved overall survival (OS) compared with tamoxifen over the first 24 months of the trial. An exploratory analysis of patients, who did not cross over, indicated a median OS benefit of 14 months for letrozole compared with tamoxifen. Letrozole is the only third-generation aromatase inhibitor that has demonstrated significant improvements in ORR, TTP, and early OS. PMID:17333340

  4. Effects of sequential paclitaxel–carboplatin followed by gemcitabine-based chemotherapy compared with paclitaxel-carboplatin therapy administered to patients with advanced epithelial ovarian cancer

    PubMed Central

    Wang, Fei; Du, Xuelian; Li, Xiaoxia; Liu, Naifu; Yu, Hao; Sheng, Xiugui

    2016-01-01

    Abstract We aimed to compare the efficacy of paclitaxel and carboplatin followed by gemcitabine-based combination chemotherapy with paclitaxel–carboplatin for treating advanced epithelial ovarian cancer in this retrospective, STROBE-compliant study. Patients’ tolerance to treatment was also assessed. We retrospectively analyzed the records of 178 women who underwent initial optimal debulking surgery between January 2003 and December 2011 to treat FIGO stage IIIc epithelial ovarian cancer. Patients in arm 1 (n = 88) received 4 cycles of paclitaxel and carboplatin followed by 2 to 4 cycles of gemcitabine-based combination chemotherapy. Patients in arm 2 (n = 90) received 6 to 8 cycles of paclitaxel and carboplatin. The granulocyte-colony stimulating factor was administered prophylactically to all patients. The median follow-up for both arms was 62 months. Medianprogression-free survival (PFS) between arms 1 and 2 (28 and 19 months [P = 0.003]) as well as 5-year OS (34.1% and 18.9% [P = 0.021]) differed significantly. The neurotoxicity rate was significantly higher in arm 2 than in arm 1 (45.2% vs 27.1%, P = 0.026). There was no significant difference between study arms in hematological toxicity. The sequential regimen significantly improved PFS and 5-year OS with tolerable toxicity compared with the single regimen, and offers an alternative for treating patients with advanced epithelial ovarian cancer. PMID:28002342

  5. Evaluation of Instrumental Activities of Daily Living in Greek Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Mystakidou, Kyriaki; Parpa, Efi; Tsilika, Eleni; Panagiotoua, Irene; Roumeliotou, Anna; Symeonidi, Matina; Galanos, Antonis; Kouvaris, Ioannis

    2013-01-01

    Translation of the instrumental activities of daily living (IADL) was carried out and its psychometric properties were assessed in a Greek sample of patients with advanced cancer. The scale was translated with the forward-backward procedure into the Greek language. It was initially administered to 136 advanced cancer patients. To assess…

  6. Evaluation of Instrumental Activities of Daily Living in Greek Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Mystakidou, Kyriaki; Parpa, Efi; Tsilika, Eleni; Panagiotoua, Irene; Roumeliotou, Anna; Symeonidi, Matina; Galanos, Antonis; Kouvaris, Ioannis

    2013-01-01

    Translation of the instrumental activities of daily living (IADL) was carried out and its psychometric properties were assessed in a Greek sample of patients with advanced cancer. The scale was translated with the forward-backward procedure into the Greek language. It was initially administered to 136 advanced cancer patients. To assess…

  7. Tolerability and toxicity of prophylactic cranial irradiation in patients with non-small cell lung cancer – Results of a phase II study (with estimation of hematological toxicity, pituitary function and magnetic resonance spectra changes)

    PubMed Central

    Marzena, Gawkowska-Suwińska; Sławomir, Blamek; Alicja, Heyda; Łukasz, Boguszewicz; Anna, Cichoń; Łukasz, Zarudzki; Elżbieta, Nowicka; Katarzyna, Behrendt; Beata, Smolska-Ciszewska; Grzegorz, Plewicki; Aleksander, Zajusz; Rafał, Tarnawski

    2014-01-01

    Aim To evaluate the tolerability and toxicity of PCI in patients with NSCLC. Background Prophylactic cranial irradiation (PCI) is a standard treatment for patients with small cell lung cancer. There are data showing a decreasing ratio of brain metastases after PCI for non-small cell lung cancer (NSCLC-non small cell lung cancer) patients but, so far, there is no evidence for increasing overall survival. The main concern in this setting is the tolerance and toxicity of the treatment. Materials and methods From 1999 to 2007, 50 patients with NSCLC treated with radical intent underwent PCI (30 Gy in 15 fractions). Mean follow-up was 2.8 years. The tolerability and hematological toxicity were evaluated in all patients, a part of participants had done neuropsychological tests, magnetic resonance imaging with 1H nuclear magnetic resonance spectra, and estimation of pituitary function. Results During follow-up, 20 patients developed distant metastases, 4-brain metastases. Fourteen (30%) patients had acute side effects: (headache, nausea, erythema of the skin). The symptoms did not require treatment breaks. Six patients complained of late side effects (vertigo, nausea, anxiety, lower extremity weakness, deterioration of hearing and olfactory hyperesthesia). Hematological complications were not observed. Testosterone levels tended to decrease (p = 0.062). Visual-motor function deteriorated after treatment (p < 0.059). Performance IQ decreased (p < 0.025) and the difference between performance IQ and verbal IQ increased (p < 0.011). Degenerative periventricular vascular changes were observed in two patients. Analysis of the spectroscopic data showed metabolic but reversible alterations after PCI. Conclusion PCI in the current series was well tolerated and associated with a relatively low toxicity. PMID:25337408

  8. Drug-Induced Hematologic Syndromes

    PubMed Central

    Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

    2009-01-01

    Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

  9. New treatments for advanced cancer: an approach to prioritization

    PubMed Central

    Ferguson, J S J; Summerhayes, M; Masters, S; Schey, S; Smith, I E

    2000-01-01

    The allocation of funding for new anticancer treatments within the UK has not kept pace with demand. Clinicians find themselves restricted in the use of licensed drugs which they feel are in the best interests of individual patients. Against this, health authorities have a duty to ensure that scarce resources are used equitably to meet the needs of the local population as a whole. Differential levels of funding for new treatments across the country have led to concerns about rationing by postcode. This paper outlines an approach to the prioritization of new treatment for advanced cancer developed jointly by clinicians and health authorities in South London. The approach involves evidence reviews and consensus meetings. Existing and new treatments are rated on a four-point ‘relative effectiveness scale’, which takes account of the impact of the treatment on quality of life and on survival. The strength of evidence supporting each effectiveness rating is also classified. Health Authorities have used these ratings to determine overall fundin