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Targeted therapies oncology

Robert H Press, Jim Zhong, Saumya S Gurbani, Brent D Weinberg, Bree R Eaton, Hyunsuk Shim, Hui-Kuo G Shu
Radiation therapy (RT) plays a critical role in the overall management of many central nervous system (CNS) tumors. Advances in RT treatment planning, with techniques such as intensity modulated radiation therapy, volumetric modulated arc therapy, and stereotactic radiosurgery, now allow the delivery of highly conformal dose with great precision. These techniques rely on high-resolution 3-dimensional anatomical imaging modalities such as computed tomography or magnetic resonance imaging (MRI) scans to accurately and reliably define CNS targets and normal tissue avoidance structures...
December 11, 2018: Neurosurgery
Amber Tahir
Clinical trials with chimeric antigen receptor (CAR) T-cell therapy in oncology have been promising. The spectrum of this novel therapy is being expanded to include autoimmunity. It ensures "targeted treatment," resulting in more selective outcomes, fewer toxic effects, and a permanent restoration of immune system imbalance. The preliminary results of preclinical and clinical studies support the application of CAR therapy in autoimmunity, especially in regulating adverse autoimmune responses. This novel therapy should be considered for the treatment of autoimmune diseases and further clinical studies should be conducted to study all aspects of this treatment modality...
October 3, 2018: Curēus
Afreen Idris Shariff, Sohail Syed, Rebecca A Shelby, Jeremy Force, Jeffrey Melson Clarke, David D'Alessio, Leonor Corsino
Over the last decade, there has been a shift in the focus of cancer therapy from conventional cytotoxic drugs to therapies more specifically directed to cancer cells. These novel therapies include immunotherapy, targeted therapy and precision medicine, each developed in great part with a goal of limiting collateral destruction of normal tissues, while enhancing tumor destruction. Although this approach is sound in theory, even new, specific therapies have some undesirable, 'off target effects', in great part due to molecular pathways shared by neoplastic and normal cells...
February 1, 2019: Journal of Molecular Endocrinology
Puja S Venkat, Neil Parikh, Phillip Beron
PURPOSE OF REVIEW: Radiation has long been a primary treatment modality in locally advanced gynecologic carcinomas and a tool for palliation of metastatic disease. Here we review advances in imaging and radiation technologies and the corresponding clinical evolution of the role for radiation oncology in the treatment of gynecologic malignancies. RECENT FINDINGS: Advances in MRI are impacting diagnosis, radiation target delineation, planning, treatment delivery, and response assessment...
December 10, 2018: Current Opinion in Obstetrics & Gynecology
Jose Batista da Costa, Ewan A Gibb, Timo K Nykopp, Miles Mannas, Alexander W Wyatt, Peter C Black
BACKGROUND: Despite years of slow progress, muscle invasive bladder cancer (MIBC) is finally entering the era of molecularly guided targeted therapy. However, tumor heterogeneity is high in MIBC and may impact treatment response and resistance. The objective of this review is to dissect recent insights into inter- and intratumor heterogeneity (ITH) in MIBC, with emphasis on the clinical implications of this heterogeneity for biomarker-driven strategies and the development of new therapies...
December 8, 2018: Urologic Oncology
Vincent Grégoire, Cai Grau, Michel Lapeyre, Philippe Maingon
Target volume selection and delineation for both the primary tumor and the lymph nodes are critical steps in the treatment of head and neck tumors with Intensity Modulated Radiation therapy (IMRT). These steps should be based on a probabilistic approach, which is that selection and delineation will be considered as optimal when reaching the best compromise between a too tight volume that could be associated to an unacceptable rate of local recurrence, and a too large volume, which could be associated to an unacceptable rate of treatment morbidity...
December 2018: Oral Oncology
Thierry Berghmans, Valérie Durieux, Stéphane Holbrechts, Christiane Jungels, Jean-Jacques Lafitte, Anne-Pascale Meert, Luigi Moretti, Sebahat Ocak, Martine Roelandts, Nicolas Girard
Thymic tumours are rare diseases that for most of the cases are cured with surgery and eventually adjuvant radiotherapy. However, about 30% of patients present with advanced stage or relapsing tumours, which require administration of chemotherapy. While cisplatin-adriamycin-cyclophosphamide combination is regularly prescribed, other drugs have been assessed in the literature. Our aim is to evaluate the effectiveness (response rate) of systemic treatments, whatever the therapeutic line, including chemotherapy, targeted therapies and immunotherapies, in thymoma and thymic carcinoma, using the principles of evidence-based medicine...
December 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Kristen M Cunanan, Alexia Iasonos, Ronglai Shen, Mithat Gönen
BACKGROUND: In the era of targeted therapies, clinical trials in oncology are rapidly evolving, wherein patients from multiple diseases are now enrolled and treated according to their genomic mutation(s). In such trials, known as basket trials, the different disease cohorts form the different baskets for inference. Several approaches have been proposed in the literature to efficiently use information from all baskets while simultaneously screening to find individual baskets where the drug works...
December 7, 2018: Clinical Trials: Journal of the Society for Clinical Trials
Krzysztof Adamowicz, Zuzanna Baczkowska-Waliszewska
Colorectal cancer (CRC) is the third most common malignancy in the world and the second cause of cancer-related deaths. Despite the search for new therapeutic agents, there are still many doubts concerning the quality of life (QOL) improvement in palliative patients. In this study, we assessed the impact of oncology knowledge on QOL and the relationship between QOL and various environmental factors and unconventional treatment methods in patients with CRC treated with chemotherapy and targeted therapy. The results of first-line palliative chemotherapy in 330 patients with colorectal cancer treated between January 2010 and December 2016 in two centers were analyzed...
December 6, 2018: Journal of Cancer Education: the Official Journal of the American Association for Cancer Education
Jake S O'Donnell, Michele W L Teng, Mark J Smyth
Anticancer immunotherapies involving the use of immune-checkpoint inhibitors or adoptive cellular transfer have emerged as new therapeutic pillars within oncology. These treatments function by overcoming or relieving tumour-induced immunosuppression, thereby enabling immune-mediated tumour clearance. While often more effective and better tolerated than traditional and targeted therapies, many patients have innate or acquired resistance to immunotherapies. Cancer immunoediting is the process whereby the immune system can both constrain and promote tumour development, which proceeds through three phases termed elimination, equilibrium and escape...
December 6, 2018: Nature Reviews. Clinical Oncology
Noémi Kovács, Krisztián Szigeti, Nikolett Hegedűs, Ildikó Horváth, Dániel S Veres, Michael Bachmann, Ralf Bergmann, Domokos Máthé
Radiotherapy is one of the most frequently applied treatments in oncology. Tissue-absorbed ionizing radiation damages not only targeted cells but the surrounding cells too. The consequent long-term induced oxidative stress, irreversible tissue damage, or second malignancies draw attention to the urgent need of a follow-up medical method by which personalized treatment could be attained and the actually dose-limiting organ could be monitored in the clinical practice. We worked out a special hemisphere irradiation technique for mice which mimics the radiation exposure during radiotherapy...
2018: Contrast Media & Molecular Imaging
Junaid Raja, Johannes M Ludwig, Scott N Gettinger, Kurt A Schalper, Hyun S Kim
BACKGROUND: Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques...
December 4, 2018: Journal for Immunotherapy of Cancer
Elisa Caiola, Francesca Falcetta, Silvia Giordano, Mirko Marabese, Marina C Garassino, Massimo Broggini, Roberta Pastorelli, Laura Brunelli
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease, with multiple different oncogenic mutations. Approximately 25-30% of NSCLC patients present KRAS mutations, which confer poor prognosis and high risk of tumor recurrence. About half of NSCLCs with activating KRAS lesions also have deletions or inactivating mutations in the serine/threonine kinase 11 (LKB1) gene. Loss of LKB1 on a KRAS-mutant background may represent a significant source of heterogeneity contributing to poor response to therapy...
December 4, 2018: Journal of Experimental & Clinical Cancer Research: CR
Marieke van Son, Max Peters, Marinus Moerland, Linda Kerkmeijer, Jan Lagendijk, Jochem van der Voort van Zyp
Over the last decades, primary prostate cancer radiotherapy saw improving developments, such as more conformal dose administration and hypofractionated treatment regimens. Still, prostate cancer recurrences after whole-gland radiotherapy remain common, especially in patients with intermediate- to high-risk disease. The vast majority of these patients are treated palliatively with androgen deprivation therapy (ADT), which exposes them to harmful side-effects and is only effective for a limited amount of time...
December 3, 2018: Cancers
Stefano Palma, Mohammad Keilani, Timothy Hasenoehrl, Richard Crevenna
PURPOSE: To systematically review literature for interventional studies and their impact on autonomic dysfunction assessed by heart rate variability in cancer patients. METHODS: Research was conducted using the databases Medline/Pubmed, Scopus, and Web of science from their inception to October 2017. Original articles with an interventional design that reported changes in at least one heart rate variability parameter as outcome parameter were included and described...
December 4, 2018: Disability and Rehabilitation
B Malicherova, T Burjanivova, E Minarikova, I Kasubova, T Pecova, M Bobrovska, I Homola, Z Lasabova, L Plank
Malignant melanoma is an oncological disease characterized by etiologic heterogeneity and it has increasing incidence and mortality in the Slovak Republic. While it is treated surgically in combination with chemotherapy, targeted therapy, and immunotherapy, malignant melanomas can ulcerate and are susceptible to infections. These are highly aggressive cancers with metastasis, and recent studies have shown the presence of mutations in RAC1, PPP6C and STK19 genes in melanoma patients. Mutations in these genes are driver mutations; important in oncogenesis and providing selective advantage to tumor cells...
August 9, 2018: Neoplasma
Maria Stenman, Michael Staehler, Bernadett Szabados, Per Sandström, Anna Laurell, Magnus Lindskog, Ulrika Harmenberg
BACKGROUND: Metastatic papillary renal cell carcinoma (mPRCC) is understudied. The disease is often aggressive and specific treatment options are lacking. PATIENTS AND METHODS: mPRCC patients (n = 86) referred to three academic centres in Sweden and Germany in the years 2005-2015 were retrospectively identified from medical records. Statistical analyses included Kaplan-Meier curves and calculation of Cox proportional hazards, generating hazard ratios with 95% confidence intervals...
December 3, 2018: Acta Oncologica
Jacqueline Veera, Karen Lim, Jason A Dowling, Chelsie O'Connor, Lois C Holloway, Shalini K Vinod
INTRODUCTION: Magnetic Resonance Imaging (MRI) provides excellent soft tissue definition of pelvic tumours and organs. The aim of this study was to quantify differences in delineated clinical target volumes (CTVs) between computed tomography (CT) and MRI. METHODS: Twenty patients with locally advanced gynaecological malignancies were recruited. Patients underwent dedicated MRI simulation following CT simulation. Four clinicians independently contoured each CT and MRI...
December 3, 2018: Journal of Medical Imaging and Radiation Oncology
Niki Karachaliou, Manuel Fernandez-Bruno, Jillian Wilhelmina Paulina Bracht, Rafael Rosell
Over the last 20 years there have been great advances in the treatment of lung cancer. Immune checkpoint blockade together with targeted therapies have provided oncologists with the means to improve survival of non-small cell lung cancer (NSCLC) and patients with a better quality of life and therapies with manageable toxicity. Maybe in a short period of time the possibility of a cure in metastatic NSCLC will be raised. Therefore, continued research into new drugs, biomarkers and especially combination therapies is necessary in order to expand the clinical benefit of the current treatments to a broader population of NSCLC patients...
December 2018: Translational Lung Cancer Research
Bárbara Meléndez, Claude Van Campenhout, Sandrine Rorive, Myriam Remmelink, Isabelle Salmon, Nicky D'Haene
Immunotherapies based on immune checkpoint inhibitors are emerging as an innovative treatment for different types of advanced cancers. While the utility of immune checkpoint inhibitors has been clearly demonstrated, the response rate is highly variable across individuals. Due to the cost and toxicity of these immunotherapies, a critical challenge in this field is the identification of predictive biomarkers to discriminate which patients may respond to immunotherapy. Recently, a high tumor mutational burden (TMB) has been identified as a genetic signature that is associated with a favorable outcome for immune checkpoint inhibitor therapy...
December 2018: Translational Lung Cancer Research
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