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Background: Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis., Methods: A literature search was conducted to identify eligible published articles, based on predefined inclusion/exclusion criteria. Each article was independently reviewed by 2 reviewers. Studies were rated according to the presence of major and minor flaws as per previously published criteria. The body of evidence for each intervention, in each treatment setting, was assigned a level of evidence, based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible., Results: The literature search identified 8279 papers, 1032 of which were retrieved for detailed evaluation based on titles and abstracts. Of these, 570 qualified for final inclusion in the systematic reviews. Sixteen new guidelines were developed for or against the use of various interventions in specific treatment settings. In total, the MASCC/ISOO Mucositis Guidelines now include 32 guidelines: 22 for oral mucositis and 10 for gastrointestinal mucositis. This article describes these updated guidelines., Conclusions: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis will help clinicians provide evidence-based management of mucositis secondary to cancer therapy., (© 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

Considerable progress in research and clinical application has been made since the original guidelines for managing mucositis in cancer patients were published in 2004, and the first active drug for the prevention and treatment of this condition has been approved by the United States Food and Drug Administration and other regulatory agencies in Europe and Australia. These changes necessitate an updated review of the literature and guidelines. Panel members reviewed the biomedical literature on mucositis published in English between January 2002 and May 2005 and reached a consensus based on the criteria of the American Society of Clinical Oncology. Changes in the guidelines included recommendations for the use of palifermin for oral mucositis associated with stem cell transplantation, amifostine for radiation proctitis, and cryotherapy for mucositis associated with high-dose melphalan. Recommendations against specific practices were introduced: Systemic glutamine was not recommended for the prevention of gastrointestinal mucositis, and sucralfate and antimicrobial lozenges were not recommended for radiation-induced oral mucositis. Furthermore, new guidelines suggested that granulocyte-macrophage-colony stimulating factor mouthwashes not be used for oral mucositis prevention in the transplantation population. Advances in mucositis treatment and research have been complemented by an increased rate of publication on mucosal injury in cancer. However, additional and sustained efforts will be required to gain a fuller understanding of the pathobiology, impact on overall patient status, optimal therapeutic strategies, and improved educational programs for health professionals, patients, and caregivers. These efforts are likely to have significant clinical and economic impact on the treatment of cancer patients. Cancer 2007;109:820-31. (c) 2007 American Cancer Society.

Background: Oral mucositis (OM) is a frequent complication of mucotoxic cancer therapy, causing significant oral pain, increased infection risk, and impaired functioning. The efficacy and safety of Saforis (glutamine) powder in UpTec for oral suspension was evaluated for the prevention and treatment of OM., Methods: Three hundred twenty-six patients developing World Health Organization (WHO) grade >or=2 OM during a chemotherapy screening cycle were randomized to Saforis (n = 163) or placebo (n = 163) 3 times/day during their next chemotherapy cycle (Treatment Cycle 1). Patients were crossed over to the alternate treatment during Treatment Cycle 2. As prespecified in the statistical plan, because of a carryover effect in Treatment Cycle 2 the primary efficacy analysis was based on Treatment Cycle 1 only., Results: Compared with placebo, Saforis significantly reduced the incidence of clinically significant WHO grade >or=2 OM (38.7% vs. 49.7%; P = .026) and severe WHO grade >or=3 OM (1.2% vs. 6.7%; P = .005) in Treatment Cycle 1. Saforis also significantly reduced the worst Oral Mucositis Assessment Scale ulceration score in Treatment Cycle 1 compared with placebo (mean, 0.23 +/- 0.39 vs. 0.32 +/- 0.45; P = .013). Patients receiving Saforis in Treatment Cycle 1 had a lower-than-expected OM incidence when crossed over to placebo in Treatment Cycle 2, indicating a significant carryover effect (P = .027). The incidence of treatment-emergent adverse events was similar between groups., Conclusions: Saforis is safe and effective for preventing and treating OM in patients receiving mucotoxic cancer chemotherapy.

Background: The current report presented 17 patients with cancer with bone metastases and 1 patient with osteopenia who received treatment with bisphosphonates and who subsequently developed osteonecrosis of the mandible and/or maxilla., Methods: The authors reviewed information on 18 patients who were referred to oral medicine or oral surgery specialists for evaluation and treatment of mandibular and/or maxillary bone necrosis from June 2002 to September 2004. To be included in the current review, patients must have been treated with either pamidronate or zoledronic acid to control or prevent metastatic disease, or with alendronate for osteoporosis. All patients with cancer had received chemotherapy while receiving bisphosphonate management., Results: The 17 patients with cancer were receiving active medical care for a malignancy. Cancer treatment included a variety of chemotherapeutic agents. They presented with metastatic disease to bone and were treated intravenously with the bisphosphonates pamidronate or zoledronic acid for a mean time of 25 months (range, 4-41 mos). There were 14 females and 4 males with a mean age of 62 years (range, 37-74 yrs). Malignancies included breast carcinoma (n = 10), multiple myeloma (n = 3), prostate carcinoma (n = 1), ovarian carcinoma (n = 1), prostate carcinoma/lymphoma (n = 1), and breast/ovarian carcinoma (n = 1). One female patient with osteopenia received alendronate. The most common clinical osteonecrosis presentations included infection and necrotic bone in the mandible. Associated events included dental extractions, infection, and trauma. Two patients appeared to develop disease spontaneously, without any clinical or radiographic evidence of local pathology. Despite surgical intervention, antibiotic therapy, hyperbaric oxygen therapy, and topical use of chemotherapeutic mouth rinses, most of the lesions did not respond well to therapy. Discontinuation of bisphosphonate therapy did not assure healing. However, 1 patient with cancer healed after discontinuation of bisphosphonate therapy for 4 months., Conclusions: The findings in the patient population combined with recent literature reports suggested that bisphosphonates may contribute to the pathogenesis of the oral lesions. The risk factors and precise mechanism involved in the formation of the osteonecrosis are not known. This condition represents a new oral complication in patients with cancer and can be termed bisphosphonate-associated osteonecrosis. Lesions in patients with osteoporosis are worrisome and need to be further evaluated.

Background: A frequent complication of anticancer treatment, oral and gastrointestinal (GI) mucositis, threatens the effectiveness of therapy because it leads to dose reductions, increases healthcare costs, and impairs patients' quality of life. The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an international multidisciplinary panel of experts to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis., Methods: The panelists examined medical literature published from January 1966 through May 2002, presented their findings at two separate conferences, and then created a writing committee that produced two articles: the current study and another that codifies the clinical implications of the panel's findings in practice guidelines., Results: New evidence supports the view that oral mucositis is a complex process involving all the tissues and cellular elements of the mucosa. Other findings suggest that some aspects of mucositis risk may be determined genetically. GI proapoptotic and antiapoptotic gene levels change along the GI tract, perhaps explaining differences in the frequency with which mucositis occurs at different sites. Studies of mucositis incidence in clinical trials by quality and using meta-analysis techniques produced estimates of incidence that are presented herein for what to our knowledge may be a broader range of cancers than ever presented before., Conclusions: Understanding the pathobiology of mucositis, its incidence, and scoring are essential for progress in research and care directed at this common side-effect of anticancer therapies., (Copyright 2004 American Cancer Society.)

Background: Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence-based guidelines for preventing, evaluating, and treating mucositis., Methods: Thirty-six panelists reviewed literature published between January 1966 and May 2002. An initial meeting in January 2002 produced a preliminary draft of guidelines that was reviewed at a second meeting the same year. Thereafter, a writing committee produced a report on mucositis pathogenesis, epidemiology, and scoring (also included in this issue), as well as clinical practice guidelines., Results: Panelists created recommendations from higher levels of evidence and suggestions when evidence was of a lower level and there was a consensus regarding the interpretation of the evidence by the panel. Panelists identified gaps in evidence that made it impossible to recommend or not recommend use of specific agents., Conclusions: Oral/GI mucositis is a common side effect of many anticancer therapies. Evidence-based clinical practice guidelines are presented as a benchmark for clinicians to use for routine care of appropriate patients and as a springboard to challenge clinical investigators to conduct high-quality trials geared toward areas in which data are either lacking or conflicting., (Copyright 2004 American Cancer Society.)

Background: Benzydamine was evaluated in patients with head and neck carcinoma for treatment of radiation-induced oral mucositis, a frequent complication of radiation therapy (RT) for which there is no predictable therapy or preventive treatment currently available., Methods: The safety and efficacy of 0.15% benzydamine oral rinse in preventing or decreasing erythema, ulceration, and pain associated with oral mucositis during RT were evaluated in a randomized, placebo-controlled trial conducted in patients with head and neck carcinoma. Subjects were to rinse with 15 mL for 2 minutes, 4-8 times daily before and during RT, and for 2 weeks after completion of RT; study evaluations were conducted before RT and routinely thereafter up to 3 weeks after RT., Results: During conventional RT, regimens up to cumulative doses of 5000 centigrays (cGy) benzydamine (n = 69) significantly (P = 0.006) reduced erythema and ulceration by approximately 30% compared with the placebo (n = 76); greater than 33% of benzydamine subjects remained ulcer free compared with 18% of placebo subjects (P = 0.037), and benzydamine significantly delayed the use of systemic analgesics compared with placebo (P < 0.05). Benzydamine was not effective in subjects (n = 20) receiving accelerated RT doses (> or = 220 cGy/day). The incidence of adverse events between treatment groups was comparable without significant differences. Early discontinuation because of adverse events occurred in 6% of benzydamine subjects and 5% of placebo subjects, and there was 1 death (related to the primary diagnosis) in a placebo subject., Conclusions: Benzydamine oral rinse was effective, safe, and well tolerated for prophylactic treatment of radiation-induced oral mucositis., (Copyright 2001 American Cancer Society.)

Background: An impediment to mucositis research has been the lack of an accepted, validated scoring system. The objective of this study was to design, test, and validate a new scoring system for mucositis that can be used easily, is reproducible, and provides an accurate system for research applications., Methods: A panel of experts, convened to design an objective, simple, and reproducible assessment tool to evaluate mucositis with specific application to multicenter clinical trials, developed a scale that measured objective and subjective indicators of mucositis. Nine centers participated in the study's validation. Paired investigators at each center evaluated patients receiving chemotherapy or head and neck radiation. Objective measures of mucositis evaluated ulceration/pseudomembrane formation and erythema. Subjective outcomes of mouth pain, ability to swallow, and function were measured. Analgesia use for mouth sensitivity was recorded., Results: One hundred eight chemotherapy and 56 radiation therapy patients were evaluated. Seventy-eight percent of chemotherapy patients and 64% of radiation therapy patients had clinically significant mucositis. Cumulative daily mucositis scores demonstrated a high correlation among observers. Using area under the curve analysis, it was found that for chemotherapy patients, the highest correlations (correlation coefficient > 0.92) occurred for the scores that selected the three highest daily values over the course of mucositis assessment. High interobserver correlations were noted for patients receiving radiation therapy. Objective mucositis scores demonstrated strong correlation with symptoms., Conclusions: The scoring system evaluated was easily used, showed high interobserver reproducibility, was responsive over time, and measured those elements deemed to be associated with mucositis. The use of concomitant symptomatic measurements appeared to be unnecessary.

Background: Oral mucositis is a common complication of bone marrow transplantation (BMT) conditioning therapy. Sequelae consist of increased risk for infection, moderate to severe pain, compromised oral function, and bleeding. This study investigated helium-neon laser treatment for prevention of conditioning-induced oral mucositis in BMT patients. Patterns and severity of mucositis for specific conditioning drug regimens also were analyzed., Methods: Twenty patients received laser radiation to their oral mucosa, either left or right of midline. The contralateral side was sham-treated and served as a control. Mucositis severity was scored independently by two modified versions of the Oral Mucositis Index Scale (OMI-A and OMI-B) and the Eastern Cooperative Oncology Group (ECOG) Oral Toxicity Scale; pain severity was scored by subjects on a visual analogue scale (VAS). Cumulative scores were analyzed for differences between the laser-treated and sham-treated sides., Results: Oral mucositis and pain scores were significantly lower for the treated versus the untreated side by OMI-A and B (P < 0.005) and VAS (P = 0.027) criteria, respectively. Ulcerative lesions occurred in all patients bilaterally; severity increased until Day +6, and lesions resolved by Day +21. Mucositis was more severe for patients conditioned with busulfan/carboplatin/thiotepa than for patients conditioned with busulfan/cyclophosphamide/etoposide., Conclusions: Helium-neon laser treatment was well-tolerated and reduced the severity of conditioning-induced oral mucositis in BMT patients.

Aspergillus infection can be a major cause of morbidity in immunocompromised patients, especially when there is pulmonary involvement. Diagnosis of aspergillosis is often complicated by the varied clinical presentation and compromised medical status of such patients. Four cases of head and neck Aspergillus infections in bone marrow transplant patients are presented. Involvement predominantly was limited to the oral cavity and/or sinuses, and in one case, the ear. Two cases were successfully managed with a combined antibiotic and surgical approach, and one case with antibiotics only. The fourth case was managed with antibiotics and surgery, but fatal hemorrhage secondary to sinus involvement developed.

The clinical course of an adult patient with relapsed acute myelogenous leukemia and leukemic infiltrate periapical to the dentition is described. While the oral symptoms were indicative of pulpal disease requiring dental therapy to resolve the patient's complaint, roentgenographic, dental pulp testing, and histologic analysis revealed extramedullary infiltrate apical to a mandibular molar. The findings developed coincident with relapse of leukemia; the medical and dental testing described above were essential in establishing an accurate diagnosis. While most oral leukemic infiltrates affect the gingiva, in this patient the infiltrate involved periapical tissue which was not clinically observable.

Paranasal sinusitis occurred in 52 immunosuppressed cancer patients treated over 5 years at the University of Maryland Cancer Center. Twenty-one patients had aspergillus sinusitis; Aspergillus sp, including flavus and niger were directly recovered from sinus in 19 of the 21 infections. Two other patients with sinus involvement and positive nose cultures for Aspergillus flavus or fumigatus and microbiologically documented pulmonary aspergillosis were considered clinically, although not microbiologically, documented. Predisposing factors for aspergillus sinusitis during the 60 days prior to infection diagnosis were granulocyte count less than 500 microliter (mean duration, 42 days versus 14 days for sinusitis of other etiology; P less than 0.001), prolonged hospitalization (mean duration, 22 days versus 14 days for patients with nonfungal sinusitis; P less than 0.001), and prolonged antibiotic therapy (mean duration, 22 days versus 9 days; P less than 0.001). Treatment with amphotericin B was initially successful for 18 of 21 patients; however, 11 of 18 patients had infection recurrence that always developed at time of tumor exacerbation and reinstitution or intensification of chemotherapy. These findings suggest that aspergillus sinusitis in cancer patients is seen in association with prolonged neutropenia and antibiotic therapy, is amenable to therapy, but tends to recur with relapse of malignancy.