Lisa A. Bellm

Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review

BACKGROUND AND PURPOSE To determine the frequency of mucositis and associated outcomes in patients receiving radiotherapy (RT) for head and neck cancer through a systematic review of recently published literature. MATERIALS AND METHODS According to the study protocol, databases were searched for randomized clinical trials (English only, 1996-1999) of patients with head and neck cancer receiving RT with or without chemotherapy that reported one or more outcomes of interest. RESULTS Thirty-three studies (n=6181 patients) met inclusion criteria. Mucositis was defined using a variety of scoring systems. The mean incidence was 80%. Over one-half of patients (56%) who received altered fractionation RT (RT-AF) experienced severe mucositis (grades 3-4) compared to 34% of patients who received conventional RT. Rates of hospitalization due to mucositis, reported in three studies (n=700), were 16% overall and 32% for RT-AF patients. Eleven percent of patients had RT regimens interrupted or modified because of mucositis in five studies (n=1267) reporting this outcome. Data insufficiency or heterogeneity prohibited analysis of mucositis severity and other associated outcomes, such as oral pain, dysphagia and opioid use. CONCLUSIONS Mucositis is a frequent, severe toxicity in patients treated with RT for head and neck cancer. While it appears that mucositis may lead to hospitalization and treatment interruptions, its overall impact on outcomes has not been adequately investigated.

Complications of radiation therapy for head and neck cancers. The patient's perspective.

Newer treatments for head and neck cancers, including altered fractionation and the use of concomitant radiotherapy and chemotherapy, may provide better local–regional tumor control rates; however, patients may experience more frequent and more severe acute toxicities that result in considerable suffering. Through this study, we sought a better understanding of patients’ experiences when undergoing radiotherapy. Personal interviews were conducted with 33 individuals who had received radiotherapy for head and neck cancers. These individuals described their treatment experiences and identified the most troublesome and debilitating side effects of radiotherapy. Overall, lethargy and weakness, dry mouth, mouth sores and pain, taste changes, and sore throat were the most frequently reported troublesome or debilitating side effects. The single most debilitating side effect was oropharyngeal mucositis that was characterized by patients as sore throat, and mouth sores and pain; both negatively affected the patient’s ability to eat and drink, causing many patients to experience significant weight loss. Trends toward more aggressive management of head and neck cancers underscore the need for new and effective therapies for oropharyngeal mucositis occurring in patients receiving radiotherapy.

Antimicrobial therapy to prevent or treat oral mucositis

Oral mucositis represents a significant source of morbidity after chemotherapy and radiation therapy. Since infection may have an important role in the pathophysiology of oral mucositis, several antimicrobial agents have been investigated for their efficacy in preventing and treating this disease. We sought to establish the weight of evidence for antimicrobial treatment and identified 31 prospectively designed clinical trials of which 13 reported some benefit and 15 did not. No clear pattern was identified regarding patient type, cancer treatment, or type of antimicrobial agent used, and inconsistent assessment of oral mucositis made comparison of outcomes difficult. Newer drugs, such as the topical antimicrobial peptide iseganan HCl initially showed promise in reducing mucositis and the related oral pain but the results of a phase 3 trial were disappointing and the line of enquiry was abandoned altogether. Hence, there is a need to better understand the role of the microflora in the cause of oral mucositis if an antimicrobial agent for prevention and treatment of this disease is to be developed.

Mucositis-Related Morbidity and Resource Utilization in Head and Neck Cancer Patients Receiving Radiation Therapy With or Without Chemotherapy

The objective of this study was to estimate health care-resource utilization in head and neck cancer (HNC) patients. This was a prospective, longitudinal, multicenter, noninterventional study of mucositis in patients receiving radiation with or without chemotherapy for HNC. Mouth and throat soreness and functional impairment were measured using the Oral Mucositis Weekly Questionnaire-HNC. Resource utilization data were obtained from patient interviews and recorded from the patients medical chart. Seventy-five patients were enrolled from six centers. Fifty (67%) patients received concurrent chemoradiation therapy; 34 (45%) received intensity-modulated radiation therapy. Over the course of treatment, 57 (76%) patients reported severe mouth and throat soreness. Pain and functional impairment because of mouth and throat soreness increased during the course of therapy despite the use of opioid analgesics in 64 (85%) of the patients. Complications of radiation therapy resulted in increased patient visits to physicians, nurses, and nutritionists. Thirty-eight (51%) patients had a feeding tube placed. Twenty-eight patients (37%) were hospitalized, five of whom were hospitalized twice; of the 33 admissions, 10 (30%) were designated as secondary to mucositis by their treating physician. Mean length of hospitalization was 4.9 days (range: 1-16). This study demonstrates that mucositis-related pain and functional impairment is associated with increased use of costly health resources. Effective treatments to reduce the pain and functional impairment of oral mucositis are needed in this patient population.

Defining clinically meaningful outcomes in the evaluation of new treatments for oral mucositis: Oral mucositis patient provider advisory board

Oral mucositis (OM)-related outcomes constituting a meaningful clinical advance in bone marrow transplant patients were considered by an interdisciplinary panel. Meaningful outcomes are essential in product development for OM, a condition without effective prevention or treatment. The most important outcomes to measure, the feasibility of measuring these in a clinical trial, and clinically meaningful differences in these outcomes were determined by the panel. Most important are reduction in oral pain and use of opioid analgesics, improvement in oral intake and quality of life, and reduction of hospitalization duration. Reduction in the severity of OM measured by an objective evaluation of oral mucosa could provide insight regarding the biologic activity of an intervention. Further data are required to define the precise relationship between reduction in visible OM and improvement in outcome. Minimally, clinical trials for OM should assess oral pain, opioid use, oral intake, and include objective assessment of OM.

Iseganan HCl: a novel antimicrobial agent

Iseganan HCl is an antimicrobial peptide under development for the prevention of oral mucositis, a severe consequence of some chemotherapy and radiation therapy regimens. Several attributes of iseganan make it an optimal candidate for study in this clinical situation where both local and systemic host defenses may be impaired. These include broad spectrum and rapid bactericidal activity, a lack of observed resistance and cross-resistance and stability in biological fluids. Clinical trials of patients receiving stomatotoxic chemotherapy followed by a haematopoietic stem cell transplant show iseganan reduces the occurrence of oral mucositis and ameliorates sequelae such as mouth pain, throat pain and difficulty swallowing. Iseganan is well-tolerated, which is partly attributable to a lack of systemic absorption following topical oral administration. Other promising areas of investigation include topical oral application for the prevention of ventilator-associated pneumonia and nebulisation for treatment of chronic lung infection in patients with cystic fibrosis. Future studies will expand on the role of iseganan as a novel antimicrobial.

Head and Neck Carcinoma in the United States First Comprehensive Report of the Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN)

Detailed information about how patients with head and neck carcinoma (HNC) are treated across practice settings does not exist. The authors conducted a prospective, observational study to examine the patterns of care for a series of patients with newly diagnosed HNC in the United States and to test 2 hypotheses: 1) There is no difference in the pattern of care between community and academic settings; and 2) the results of major randomized clinical trials will change the pattern of care in both practice settings within 1 year of publication in peer‐reviewed journals.

Longitudinal oncology registry of head and neck carcinoma (LORHAN)

A study was undertaken to examine the patterns of systemic therapy use in conjunction with radiation therapy for patients with locally advanced head and neck squamous cell cancer.

Oral Mucositis: Time for More Studies

Abstract Oral Mucositis (OM) is a frequent cause of severe morbidity in patients receiving chemotherapy and/or radiotherapy. The pathophysiology of OM involves direct cytotoxic effects, local inflammatory responses, and alterations in oral microflora. There are currently no approved agents for the prevention or treatment of OM. In this review we briefly describe current knowledge of the pathophysiology, clinical presentation, and management of OM. We then discuss investigational agents being studied in OM with a particular focus on local antimicrobial agents, hemopoietic growth factors, and cytokines. Measures to reduce the incidence of OM and/or alleviate its clinical sequelae should be incorporated into all chemotherapy or radiotherapy studies.

A prospective cohort study of patients with peripheral T-cell lymphoma in the United States

Long‐term survival in patients with aggressive peripheral T‐cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States.