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      Clinical Studies of Nonpharmacological Methods to Minimize Salivary Gland Damage after Radioiodine Therapy of Differentiated Thyroid Carcinoma: Systematic Review

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          Abstract

          Purpose. To systematically review clinical studies examining the effectiveness of nonpharmacological methods to prevent/minimize salivary gland damage due to radioiodine treatment of differentiated thyroid carcinoma (DTC). Methods. Reports on relevant trials were identified by searching the PubMed, CINHAL, Cochrane, and Scopus electronic databases covering the period 01/2000–10/2015. Inclusion/exclusion criteria were prespecified. Search yielded eight studies that were reviewed by four of the present authors. Results. Nonpharmacological methods used in trials may reduce salivary gland damage induced by radioiodine. Sialogogues such as lemon candy, vitamin E, lemon juice, and lemon slice reduced such damage significantly ( p < 0.0001, p < 0.05, p < 0.10, and p < 0.05, resp.). Parotid gland massage also reduced the salivary damage significantly ( p < 0.001). Additionally, vitamin C had some limited effect ( p = 0.37), whereas no effect was present in the case of chewing gum ( p = 0.99). Conclusion. The review showed that, among nonpharmacological interventions, sialogogues and parotid gland massage had the greatest impact on reducing salivary damage induced by radioiodine therapy of DTC. However, the studies retrieved were limited in number, sample size, strength of evidence, and generalizability. More randomized controlled trials of these methods with multicenter scope and larger sample sizes will provide more systematic and reliable results allowing more definitive conclusions.

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          Most cited references22

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          Complications of radioactive iodine treatment of thyroid carcinoma.

          Nelson Lee (2010)
          Radioactive iodine (RAI) in the form of (131)I has been used to treat thyroid cancer since 1946. RAI is used after thyroidectomy to ablate the residual normal thyroid remnant, as adjuvant therapy, and to treat thyroid cancer metastases. Although the benefits of using RAI in low-risk patients with thyroid cancer are debated, it is frequently used in most patients with thyroid cancer and is clearly associated with acute and long-term risks and side effects. Acute risks associated with RAI therapy include nausea and vomiting, ageusia (loss of taste), salivary gland swelling, and pain. Longer-term complications include recurrent sialoadenitis associated with xerostomia, mouth pain, dental caries, pulmonary fibrosis, nasolacrimal outflow obstruction, and second primary malignancies. This article summarizes the common complications of RAI and methods to prevent and manage these complications.
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            Neurologic complications of chemotherapy agents.

            To review neurologic complications of common and recently developed chemotherapeutic agents, as well as recent research regarding 'chemobrain'. Bortezomib, a new anticancer agent, has a propensity toward causing a largely sensory and reversible peripheral neuropathy. Infusion of magnesium and calcium pre and post-oxaliplatin infusion reduces neuropathy but may interfere with clinical response to oxaliplatin. No other measures currently reduce the incidence or severity of neuropathy related to platinum compounds, taxanes, or thalidomide. Chemobrain, cognitive decline attributed to chemotherapy, has garnered research interest. Prevalence and epidemiology of chemobrain are poorly understood. Potential underlying mechanisms are under investigation in animal models and include effects on long-term potentiation and cerebral blood flow. Blood-brain barrier permeability, efficiency of cellular efflux pumps, DNA damage, telomere shortening, alteration of cytokine regulation, defects in neural repair, and oxidative stress may play roles in the effects of chemotherapy on central nervous system function. Data on prevention and treatment of chemotherapy-induced peripheral neuropathy are limited. Calcium and magnesium infusions for oxaliplatin administration have the most scientific support and are widely used in practice but may interfere with the clinical efficacy of oxaliplatin. Some novel agents, particularly bortezomib, have significant risk of chemotherapy-induced peripheral neuropathy. Animal models are beginning to reveal the mechanisms underlying the impact of individual chemotherapeutic drugs on cognition.
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              Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer.

              A randomized phase 2 study was performed to investigate the efficacy/toxicity of combining concomitant boost radiation and weekly carboplatin/paclitaxel with or without amifostine in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Patients with newly diagnosed, locally advanced stage III or IV SCCHN received 4 weekly doses of carboplatin (area under the curve, 1.5) and paclitaxel (45 mg/m(2)) concurrently with concomitant boost radiation consisting of 72 grays in 42 fractions over 6 weeks (every day for 18 days, twice a day for 12 days) (grading determined according to the TNM staging system). All patients were randomized to subcutaneous daily amifostine at a dose of 500 mg (Arm A) or no amifostine (Arm B). Toxicity data were collected weekly, and saliva collection was performed with and without citric acid stimulation. To evaluate the correlation between serum cytokine levels and the severity of oral mucositis, we evaluated a subset (13 patients in Arm A and 11 patients in Arm B) of subjects at baseline and then on alternate weeks. Fifty-eight patients were enrolled, 29 in each arm. The majority of patients were men (90%), had stage IV disease (82%), and had the oropharynx as the primary tumor site (60%). Major toxicities encountered were similar in both arms and included grade 3 (as determined by Common Terminology Criteria for Adverse Events, version 3.0) mucositis (75% in Arm A and 70% in Arm B) and grade 2 xerostomia (41% in both arms). The median number of amifostine doses delivered was 28, with skin toxicity (grade 3 in 11 patients) as the limiting factor. Saliva production showed no difference between the arms. The median follow-up was 34 months, and only 5 failures had been encountered (2 local and 3 distant) at the time of last follow-up, with an overall survival rate of 89%. Neck dissection was performed in 25 patients; 5 patients demonstrated persistent disease and 4 patients were alive without disease recurrence at the time of last follow-up. The median time to percutaneous endoscopic gastrostomy removal was 9.6 months in Arm A and 10.4 months in Arm B. Only 1 patient remained percutaneous endoscopic gastrostomy-dependent at the time of last follow-up. A correlation was noted between levels of selected cytokines and mucositis severity, in which higher levels of proinflammatory cytokines (tumor necrosis factor, interleukin [IL]-1, and IL-6) and lower levels of anti-inflammatory cytokines (IL-13) were noted. No changes in C-reactive protein levels were noted. Four weekly doses of carboplatin/paclitaxel with concomitant boost radiation was found to be a highly effective regimen in this patient population with advanced SCCHN. The overall survival rate was 89%. The time to percutaneous endoscopic gastrostomy removal was prolonged. Amifostine given subcutaneously did not improve the rates of xerostomia and mucositis with this fairly intensive chemoradiotherapy regimen. 2009 American Cancer Society.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi Publishing Corporation
                1741-427X
                1741-4288
                2016
                30 June 2016
                30 June 2016
                : 2016
                : 6795076
                Affiliations
                1Department of Nursing, School of Health Sciences, Cyprus University of Technology, 3036 Limassol, Cyprus
                2Thyroid Cancer Unit, Nuclear Medicine Department, Bank of Cyprus Oncology Center, 2006 Nicosia, Cyprus
                3University of Turku, 20014 Turku, Finland
                Author notes

                Academic Editor: Deborah A. Kennedy

                Author information
                http://orcid.org/0000-0001-7303-4955
                http://orcid.org/0000-0002-8515-007X
                http://orcid.org/0000-0003-4050-031X
                Article
                10.1155/2016/6795076
                4944032
                27446226
                ae10ecde-54ca-4bf4-a6fe-b842630d19f8
                Copyright © 2016 Andri Christou et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 March 2016
                : 23 May 2016
                : 5 June 2016
                Categories
                Review Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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