BACKGROUND: Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). OBJECTIVES: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. SEARCH STRATEGY: Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 16 February 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 16 February 2011), EMBASE via OVID (1980 to 16 February 2011), CINAHL via EBSCO (1980 to 16 February 2011), CANCERLIT via PubMed (1950 to 16 February 2011), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 16 February 2011) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models. MAIN RESULTS: A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate. AUTHORS' CONCLUSIONS: Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.

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Interventions for treating oral mucositis for patients with cancer receiving treatment.

Purpose
Radiation-induced fibrosis (RIF) is a long-term side effect of external beam radiation therapy for the treatment of cancer. It results in a multitude of symptoms that significantly impact quality of life. Understanding the mechanisms of RIF-induced changes is essential to developing effective strategies to prevent long-term disability and discomfort following radiation therapy. In this review, we describe the current understanding of the etiology, clinical presentation, pathogenesis, treatment, and directions of future therapy for this condition.

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Radiation-induced fibrosis: mechanisms and implications for therapy.

The introduction of stem cell transplantation and the novel anti-myeloma agents, bortezomib, thalidomide, and lenalidomide, have improved the outcome of patients with multiple myeloma. These advances have transformed myeloma into a chronic condition, with multiple relapses and salvage therapies, all of which result in cumulative immunosuppression and higher risk of infection. In addition to the immunodeficiency related to myeloma and its complications, the type of anti-myeloma therapy used also plays a role in the development of infection. Therapy with bortezomib increases the risk for reactivation of herpes simplex and herpes zoster viruses, whereas the application of stem cell transplantation has broadened the spectrum of infection to include those caused by Clostridium difficile, cytomegalovirus, and opportunistic moulds. Key to the management of infection is the understanding of the specific risk factors and periods during which patients are at risk; this allows the anticipation of the likely pathogen(s) and the application of risk-adjusted prophylactic and treatment strategies.

Infections in Patients with Multiple Myeloma in the Era of High-Dose Therapy and Novel Agents

This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact

The aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections. Thirty-nine articles that met the inclusion/exclusion criteria were independently reviewed by two calibrated reviewers, each using a standard form. Information was extracted on a number of variables, including study design, study population, sample size, interventions, blinding, outcome measures, methods, results, and conclusions for each article. Areas of discrepancy between the two reviews were resolved by consensus. Studies were weighted as to the quality of the study design, and recommendations were based on the relative strength of each paper. Statistical analyses were performed to determine the weighted prevalence of clinical oral fungal infection and fungal colonization. For all cancer treatments, the weighted prevalence of clinical oral fungal infection was found to be 7.5% pre-treatment, 39.1% during treatment, and 32.6% after the end of cancer therapy. Head and neck radiotherapy and chemotherapy were each independently associated with a significantly increased risk for oral fungal infection. For all cancer treatments, the prevalence of oral colonization with fungal organisms was 48.2% before treatment, 72.2% during treatment, and 70.1% after treatment. The prophylactic use of fluconazole during cancer therapy resulted in a prevalence of clinical fungal infection of 1.9%. No information specific to oral fungal infections was found on quality of life or cost of care. There is an increased risk of clinically significant oral fungal infection during cancer therapy. Systemic antifungals are effective in the prevention of clinical oral fungal infection in patients receiving cancer therapy. Currently available topical antifungal agents are less efficacious, suggesting a need for better topical agents.

A systematic review of oral fungal infections in patients receiving cancer therapy

Summary Radiotherapy is a treatment modality largely used for head and neck malignancies. However, high doses of radiation in large areas, including the oral cavity, maxilla, mandible and salivary glands may result in several undesired reactions. Mucositis, candidosis, disgeusia, radiation caries, osteoradionecrosis, soft tissue necrosis and xerostomia are some of radiotherapy's complications. Aim The aim of this study is to briefly review the side effects that may be seen in the oral cavity during or after radiotherapy treatment in the head and neck region. Basic method used Review of relevant literature. Study design Literature review. Results Radiotherapy is still associated with several side effects, significantly affecting patients’ quality of life. Conclusions A multidisciplinary treatment, including physicians, dentists, speech therapits, nutritionists, and psychologists, is the best alternative to minimize, or even prevent such reactions.

Oral complications of radiotherapy in the head and neck

Objective The aim of this study was to verify the profile of Candida species responsible for colonizing and infecting the oral cavity of Brazilian patients undergoing radiotherapy (RT). Study design Saliva samples were collected from 21 patients before, during, and immediately after RT. Each sample was distributed in agar Sabouraud dextrose/chlorophenicol and incubated at 37°C for 18 hours. Emerging colonies were identified biochemically and through the germinative tube test. Patients were examined weekly to identify clinical candidiasis. Results Candida colonization continuously increased during RT. Infection occurred in 52% of the patients, and baseline colonization was higher in infected patients. A shift toward non-albicans species was observed in both infected and noninfected patients. Conclusions RT leads to increased colonization and infection by Candida. The shift toward non-albicans species was unrelated to antifungal therapy. There may be epidemiological differences between infected and noninfected patients.

Candida oral colonization and infection in Brazilian patients undergoing head and neck radiotherapy: a pilot study.

A radioterapia e uma forma terapeutica amplamente utilizada para o tratamento das neoplasias malignas da cabeca e pescoco. Porem, altas doses de radiacao em extensos campos que irao incluir a cavidade bucal, maxila, mandibula e glândulas salivares frequentemente resultam em diversas reacoes indesejadas. Dentre as complicacoes da radioterapia estao a mucosite, candidose, disgeusia, carie por radiacao, osteorradionecrose, necrose do tecido mole e xerostomia. OBJETIVO: O objetivo deste artigo e fazer uma breve revisao das reacoes adversas que podem ser detectadas durante o tratamento radioterapico em regiao de cabeca e pescoco. METODO: A literatura pertinente que trata do assunto foi revisada. FORMA DE ESTUDO: Revisao de literatura. RESULTADOS: A radioterapia ainda esta associada a diversas reacoes adversas, que afetam de forma significativa a qualidade de vida dos pacientes. CONCLUSOES: O tratamento multidisciplinar, incluindo a equipe medica, o cirurgiao-dentista, o fonoaudiologo, o nutricionista e o psicologo e a melhor alternativa para minimizar ou mesmo prevenir tais complicacoes.

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Bruno Correia Jham

Papers

Oral complications of radiotherapy in the head and neck

Candida oral colonization and infection in Brazilian patients undergoing head and neck radiotherapy: a pilot study.

Complicações bucais da radioterapia em cabeça e pescoço

A randomized phase III prospective trial of bethanechol to prevent radiotherapy-induced salivary gland damage in patients with head and neck cancer

Ameloblastic fibro-odontoma