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1.
Zinc deficits, mucositis, and mucosal macrophage perturbation: is there a relationship?
Thomsen, M, Vitetta, L
Current opinion in clinical nutrition and metabolic care. 2019;(5):365-370
Abstract
PURPOSE OF REVIEW Mucositis is a common and therapy-limiting adverse effect of cancer treatments including radiotherapy, chemotherapy, and immunotherapy. The optimal zinc formulation, dosage, and timing of administration warrant further research as does the efficacious prevention of febrile mucositis that predisposes to febrile neutropenia. RECENT FINDINGS Metaanalyses concluded that zinc sulfate failed to significantly reduce the incidence or severity of chemotherapy-induced oral mucositis, whereas polaprezinc was associated with a significant reduction. Three new trials were published in 2018. The first trial found that zinc sulfate reduced the incidence and severity of chemotherapy-induced oral mucositis. The second reported that polaprezinc reduced oral mucositis in pediatric patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The third trial demonstrated efficacy for a zinc lozenge for postoperative sore throat induced by an endotracheal intubation. SUMMARY Zinc deficits, dietary or induced by cancer, are common in patients with cancer. Febrile mucositis may better describe the condition linking mucositis with febrile neutropenia. Febrile mucositis disrupts treatment and may be life-threatening. A paradigm shift is needed for a more comprehensive understanding of febrile mucositis. Zinc effects on the thymic immunological network and T lymphocytes during chemoradiotherapy regimens also warrant further investigation.
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2.
Prevention from radiation damage by natural products.
Fischer, N, Seo, EJ, Efferth, T
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018;:192-200
Abstract
BACKGROUND Radiotherapy is a mainstay of cancer treatment since decades. Ionizing radiation (IR) is used for destruction of cancer cells and shrinkage of tumors. However, the increase of radioresistance in cancer cells and radiation toxicity to normal tissues are severe concerns. The exposure to radiation generates intracellular reactive oxygen species (ROS), which leads to DNA damage by lipid peroxidation, removal of thiol groups from cellular and membrane proteins, strand breaks and base alterations. HYPOTHESIS Plants have to deal with radiation-induced damage (UV-light of sun, other natural radiation sources). Therefore, it is worth speculating that radioprotective mechanisms have evolved during evolution of life. We hypothesize that natural products from plants may also protect from radiation damage caused as adverse side effects of cancer radiotherapy. METHODS The basis of this systematic review, we searched the relevant literature in the PubMed database. RESULTS Flavonoids, such as genistein, epigallocatechin-3-gallate, epicatechin, apigenin and silibinin mainly act as antioxidant, free radical scavenging and anti-inflammatory compounds, thus, providing cytoprotection in addition to downregulation of several pro-inflammatory cytokines. Comparable effects have been found in phenylpropanoids, especially caffeic acid phenylethylester, curcumin, thymol and zingerone. Besides, resveratrol and quercetin are the most important cytoprotective polyphenols. Their radioprotective effects are mediated by a wide range of mechanisms mainly leading to direct or indirect reduction of cellular stress. Ascorbic acid is broadly used as antioxidant, but it has also shown activity in reducing cellular damage after irradiation mainly due to its antioxidant capabilities. The metal ion chelator, gallic acid, represents another natural product attenuating cellular damage caused by radiation. CONCLUSIONS Some secondary metabolites from plants reveal radioprotective features against cellular damage caused by irradiation. These results warrant further analysis to develop phytochemicals as radioprotectors for clinical use.
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3.
Pharmacological modulation of radiation-induced oral mucosal complications.
Bockel, S, Vallard, A, Lévy, A, François, S, Bourdis, M, Le Gallic, C, Riccobono, D, Annede, P, Drouet, M, Tao, Y, et al
Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique. 2018;(5):429-437
Abstract
Radiation-induced mucositis is a common toxicity, especially in patients with head and neck cancers. Despite recent technological advances in radiation therapy, such as intensity-modulated radiotherapy, radiation-induced mucositis is still causing treatment disruptions, negatively affecting patients' long and short term quality of life, and impacting medical resources use with economic consequences. The objective of this article was to review the latest updates in the management of radiation-induced mucositis, with a focus on pharmaceutical strategies for the prevention or treatment of mucositis. Although numerous studies analysing the prevention and management of oral radiation-induced mucositis have been conducted, there are still few reliable data to guide daily clinical practice. Furthermore, most of the tested drugs have shown no (anti-inflammatory cytokine, growth factors) or limited (palifermin) effect. Therapies for acute oral mucositis are predominantly focused on improving oral hygiene and providing symptoms control. Although low-level laser therapy proved efficient in preventing radiation-induced oral mucositis in patients with head and neck cancer, this intervention requires equipment and trained medical staff, and is therefore insufficiently developed in clinical routine. New effective pharmacological agents able to prevent or reverse radio-induced mucositis are required.
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4.
Efficacy of the combination neurokinin-1 receptor antagonist, palonosetron, and dexamethasone compared to others for the prophylaxis of chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.
Chow, R, Tsao, M, Chiu, L, Popovic, M, Milakovic, M, Lam, H, DeAngelis, C
Annals of palliative medicine. 2018;(2):221-233
Abstract
BACKGROUND Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's compliance with anticancer therapy, and result in the manifestation of adverse events such as electrolyte imbalance, dehydration and malnutrition. The most recent guidelines published by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) recommend the combination of dexamethasone (DEX), a 5-hydroxytrypatmine-3 receptor antagonist (5-HT3RA), preferably palonosetron (PALO), and a neurokinin-1 receptor antagonist (NK1RA) for prophylactic treatment of CINV in patients receiving highly emetogenic chemotherapy (HEC). The aim of this review was to examine the efficacy of triple agent, as reported in randomized controlled trials (RCTs), compared to any other prophylactic treatments. METHODS A literature search was conducted in Ovid MEDLINE(R), Embase Classic & Embase, and the Cochrane Central Register of Controlled Trials. The primary endpoint was the proportion of patients achieving complete response (CR) in the acute, delayed and overall phase. Secondary endpoints included the percentage of patients who achieved complete control (CC), no nausea and no vomiting in the acute, delayed and overall phases. RESULTS A total of 17 RCTs were included in this review, of which 3,146 patients were randomized to receive NK1RA, PALO and DEX, and 2,987 patients to receive other antiemetic treatments. The combination was not superior to other treatments in five endpoints-CC and CR in the acute phase, nausea and emesis control in the delayed phase, and nausea in the overall phase-but was superior in the other 11 endpoints. When looking only at HEC and moderately emetogenic chemotherapy (MEC) studies, the combination was only superior to others in three endpoints (delayed and overall CC, and overall emesis control) in HEC setting, which is less than the nine identified endpoints (delayed and overall CR, delayed and overall CC, acute and overall nausea control, and acute, delayed and overall phases for emesis control) in the MEC setting. CONCLUSIONS The combination of NK1RA, PALO and DEX is superior in the majority of assessed endpoints of this meta-analysis. Further studies should investigate the efficacy and safety of the triple regimen compared to regimens lacking NK1RA, to add to the discussions about whether future CINV prophylaxis guidelines should include NK1RA as a first-line treatment in the MEC setting.
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5.
Nutritional strategies to prevent gastrointestinal toxicity during pelvic radiotherapy.
Wedlake, LJ
The Proceedings of the Nutrition Society. 2018;(4):357-368
Abstract
Radiotherapy-induced damage to non-cancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option with sound rationale for intervention. The aim of this review was to synthesise published evidence for the use of elemental formulae, low or modified fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the bowel from gastrointestinal side effects during long-course, radical pelvic radiotherapy. Thirty original studies (recruiting n 3197 patients) were identified comprising twenty-four randomised controlled trials, four cohort studies and two comparator trials. Endpoints varied and included symptom scales (Inflammatory Bowel Disease Questionnaire, Common Technology Criteria for Adverse Events, Radiation Therapy Oncology Group) and Bristol Stool Scale. Dietary and supplement interventions were employed with many studies using a combination of interventions. Evidence from RCT was weak for elemental, low or modified fat and low-lactose interventions and modestly positive for the manipulation of fibre during radiotherapy. Evidence for probiotics as prophylactic interventional agents was more promising with a number of trials reporting positive results but strength and strains of interventions vary, as do methodologies and endpoints making it difficult to arrive at firm conclusions with several studies lacking statistical power. This consolidated review concludes that there is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula could be effective in severe toxicity but this is unproven. Probiotics offer promise but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients.
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Union of light ion therapy centers in Europe (ULICE EC FP7) - Objectives and achievements of joint research activities.
Pötter, R, Balosso, J, Baumann, M, Bert, C, Davies, J, Enghardt, W, Fossati, P, Harris, S, Jones, B, Krämer, M, et al
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2018;(1):83-100
Abstract
Under the umbrella of the European Network for Light Ion Therapy (ENLIGHT), the project on Union of Light Ion Centers in Europe (ULICE), which was funded by the European Commission (EC/FP7), was carried out from 2009 to 2014. Besides the two pillars on Transnational Access (TNA) and Networking Activities (NA), six work packages formed the pillar on Joint Research Activities (JRA). The current manuscript focuses on the objectives and results achieved within these research work packages: "Clinical Research Infrastructure", "Biologically Based Expert System for Individualized Patient Allocation", "Ion Therapy for Intra-Fractional Moving Targets", "Adaptive Treatment Planning for Ion Radiotherapy", "Carbon Ion Gantry", "Common Database and Grid Infrastructures for Improving Access to Research Infrastructures". The objectives and main achievements are summarized. References to either publications or open access deliverables from the five year project work are given. Overall, carbon ion radiotherapy is still not as mature as photon or proton radiotherapy. Achieved results and open questions are reflected and discussed in the context of the current status of carbon ion therapy and particle and photon beam therapy. Most research topics covered in the ULICE JRA pillar are topical. Future research activities can build upon these ULICE results. Together with the continuous increase in the number of particle therapy centers in the last years ULICE results and proposals may contribute to the further growth of the overall particle therapy field as foreseen with ENLIGHT and new joint initiatives such as the European Particle Therapy Network (EPTN) within the overall radiotherapy community.
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7.
A Perspective on the Evolving Story of PSMA Biology, PSMA-Based Imaging, and Endoradiotherapeutic Strategies.
O'Keefe, DS, Bacich, DJ, Huang, SS, Heston, WDW
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;(7):1007-1013
Abstract
In this review, we cover the evolution of knowledge on the biology of prostate-specific membrane antigen (PSMA) and its translation to therapy. The usual key to discovery is a realistic model for experimentation and for testing a hypothesis. A realistic model is especially needed in the case of the human prostate, which differs significantly from the prostate of species often used as research models. We will emphasize the genetic characterization of PSMA, the nature of the PSMA protein, and its role as a carboxypeptidase, with differing important substrates and products in different tissues. We give special prominence to the importance of PSMA as a target for imaging and therapy in prostate cancer and its underdeveloped role for imaging and targeting the neovasculature of tumors other than prostate cancer. Lastly, we bring attention to its importance in other nonprostatic tissues.
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8.
Role of Platelet-Derived Transforming Growth Factor-β1 and Reactive Oxygen Species in Radiation-Induced Organ Fibrosis.
Ahamed, J, Laurence, J
Antioxidants & redox signaling. 2017;(13):977-988
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Abstract
SIGNIFICANCE This review evaluates the role of platelet-derived transforming growth factor (TGF)-β1 in oxidative stress-linked pathologic fibrosis, with an emphasis on the heart and kidney, by using ionizing radiation as a clinically relevant stimulus. Current radiation-induced organ fibrosis interventions focus on pan-neutralization of TGF-β or the use of anti-oxidants and anti-proliferative agents, with limited clinical efficacy. Recent Advances: Pathologic fibrosis represents excessive accumulation of collagen and other extracellular matrix (ECM) components after dysregulation of a balance between ECM synthesis and degradation. Targets based on endogenous carbon monoxide (CO) pathways and the use of redox modulators such as N-acetylcysteine present promising alternatives to current therapeutic regimens. CRITICAL ISSUES Ionizing radiation leads to direct DNA damage and generation of reactive oxygen species (ROS), with TGF-β1 activation via ROS, thrombin generation, platelet activation, and pro-inflammatory signaling promoting myofibroblast accumulation and ECM production. Feed-forward loops, as TGF-β1 promotes ROS, amplify these profibrotic signals, and persistent low-grade inflammation insures their perpetuation. We highlight differential roles for platelet- versus monocyte-derived TGF-β1, establishing links between canonical and noncanonical TGF-β1 signaling pathways in relationship to macrophage polarization and autophagy, and define points where pharmacologic agents can intervene. FUTURE DIRECTIONS Additional studies are needed to understand mechanisms underlying the anti-fibrotic effects of current and proposed therapeutics, based on limiting platelet TGF-β1 activity, promotion of macrophage polarization, and facilitation of collagen autophagy. Models incorporating endogenous CO and selective TGF-β1 pathways that impact the initiation and progression of pathologic fibrosis, including nuclear factor erythroid 2-related factor (Nrf2) and redox, are of particular interest. Antioxid. Redox Signal. 27, 977-988.
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9.
Cardiovascular disease in cancer survivors.
Okwuosa, TM, Anzevino, S, Rao, R
Postgraduate medical journal. 2017;(1096):82-90
Abstract
Certain cancer therapies, including radiation therapy and some types of chemotherapies, are associated with increased risk of cardiovascular disease (CVD) and events. Some of these effects such as those presented by anthracyclines, radiation therapy, cisplatin, as well as those presented by hormone therapy for breast cancer-usually taken for many years for some breast and prostate cancers-are long-lasting and associated with cardiovascular events risk more than 20 years after cancer treatment. Cardiovascular testing, diagnostic assessment of suspected cardiovascular symptomatology, as well as laboratory tests for CVD risk factors are imperative. The early recognition and treatment of CVD processes that arise in survivorship years is pivotal, with specific attention to some CVD processes with specific suggested treatment modalities. Preventive measures include adequate screening, the use of medications such as ACE inhibitors/angiotensin receptor blockers and/or beta blockers, statin therapy and aspirin in persons who warrant these medications, as well as therapeutic lifestyle modifications such as exercise/physical activity, weight loss and appropriate diet for a healthy lifestyle. Periodic follow-up with a good primary care physician who understands the risks associated with cancer therapy is important, and referral to onco-cardiology for further management of cardiovascular risk in these survivors is based on a patient's cardiovascular risk level and the type, amount and duration of cancer therapies received during the patient's lifetime.
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A systematic review of smell alterations after radiotherapy for head and neck cancer.
Álvarez-Camacho, M, Gonella, S, Campbell, S, Scrimger, RA, Wismer, WV
Cancer treatment reviews. 2017;:110-121
Abstract
PURPOSE To review the current knowledge on radiotherapy associated olfactory dysfunction among head and neck cancer (HNC) patients. METHODS A systematic review of RT-related olfactory dysfunction in HNC was performed. Searches were conducted in several databases (Medline, EMBASE, CINAHL, CAB Abstracts, SCOPUS, Proquest Dissertations and Theses, PROSPERO, ALLEBM Reviews - Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED). Publications investigating olfactory dysfunction as an explicit side effect of Radiotherapy (RT, or RT-chemo or RT-monoclonal antibodies) were eligible, no limits were applied. RESULTS Two hundred and twenty-nine papers were screened and 23 met inclusion criteria. CONCLUSIONS Odor detection, identification and discrimination are olfactory functions impaired after RT for HNC. An RT dose-effect has been calculated for odor identification and odor discrimination. There were no studies of the effect of olfactory dysfunction on weight loss or energy intake among RT-treated HNC patients. To improve our understanding of RT associated olfactory dysfunction among HNC patients, future studies should include a multi-dimensional assessment of olfactory function in a longitudinal design, track other conditions affecting olfaction, assess retronasal olfactory perception, adopt validated self-report tools and explore the impact of olfactory dysfunction on the eating experience of HNC patients.