Mark M. Schubert

Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis.

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.

Updated clinical practice guidelines for the prevention and treatment of mucositis

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.

Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy

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.

Practical Guidelines for the Prevention, Diagnosis, and Treatment of Osteonecrosis of the Jaw in Patients With Cancer

PURPOSE This article discusses osteonecrosis of the jaw (ONJ) and offers health care professionals practical guidelines and recommendations for the prevention, diagnosis, and management of ONJ in cancer patients receiving bisphosphonate treatment. METHODS A panel of experts representing oral and maxillofacial surgery, oral medicine, endocrinology, and medical oncology was convened to review the literature and clinical evidence, identify risk factors for ONJ, and develop clinical guidelines for the prevention, early diagnosis, and multidisciplinary treatment of ONJ in patients with cancer. The guidelines are based on experience and have not been evaluated within the context of controlled clinical trials. RESULTS ONJ is a clinical entity with many possible etiologies; historically identified risk factors include corticosteroids, chemotherapy, radiotherapy, trauma, infection, and cancer. With emerging concern for potential development of ONJ in patients receiving bisphosphonates, the panel recommends a dental examination before patients begin therapy with intravenous bisphosphonates. Dental treatments and procedures that require bone healing should be completed before initiating intravenous bisphosphonate therapy. Patients should be instructed on the importance of maintaining good oral hygiene and having regular dental assessments. For patients currently receiving bisphosphonates who require dental procedures, there is no evidence to suggest that interrupting bisphosphonate therapy will prevent or lower the risk of ONJ. Frequent clinical assessments and conservative dental management are suggested for these patients. For treatment of patients who develop ONJ, a conservative, nonsurgical approach is strongly recommended. CONCLUSION An increased awareness of the potential risk of ONJ in patients receiving bisphosphonate therapy is needed. Close coordination between the treating physician and oral surgeon and/or a dental specialist is strongly recommended in making treatment decisions.

Graft-vs.-Host Disease

Bone marrow transplantation (BMT) is the treatment of choice for many leukemias, lymphomas, bone marrow failure syndromes, and immunodeficiency disorders, and is the primary and salvage therapy for many solid malignancies. With the establishment of national and international marrow banks, unrelated allogeneic BMT is being performed with increasing frequency. Graft-vs.-host disease (GVHD) remains a major complication of allogeneic BMT, occurring in 25% to 70% of patients despite GVHD prophylaxis, with the skin, gastro-intestinal tract, and liver as primary target organs. Oral findings are seen in both acute and chronic GVHD. In acute GVHD, the oral lesions are often painful, erythematous, ulcerative, and desquamative. In chronic GVHD, they are lichenoid with associated erythema and ulcerations; additionally, they may be associated with a sicca syndrome characterized by xerostomia and progressive salivary gland atrophy. General principles of BMT are discussed, as are systemic and local therapeutic options for oral GVHD.

Low energy Helium-Neon laser in the prevention of oral mucositis in patients undergoing bone marrow transplant: Results of a double blind randomized trial

PURPOSE To evaluate the efficiency of Helium-Neon (He-Ne) laser in the prevention of oral mucositis induced by high dose chemoradiotherapy before autologous bone marrow transplantation (BMT). METHODS AND MATERIALS Between 1993 and 1995, 30 consecutive patients receiving an autologous peripheral stem-cell or bone marrow transplant (BMT) after high dose chemoradiotherapy were randomized to possibly receive prophylactic laser to the oral mucosa after giving informed consent. Chemotherapy consisted of cyclophosphamide, 60 mg/kg intravenously (I.V.) on day (d)-5 and d-4 in 27 cases, or melphalan 140 mg/kg I.V. on d-4 in three cases. Total body irradiation (TBI) consisted of 12 Gy midplane dose in six fractions (4 Gy/day for three days). He-Ne laser (632.8 nm wavelength, power 60 mW) applications were performed daily from d-5 to d-1 on five anatomic sites of the oral mucosa. Oral examination was performed daily from d0 to d + 20. Mucositis was scored according to an oral exam guide with a 16 item scale of which four were assessed by the patients themselves. Mean daily self assessment scores for oral pain, ability to swallow and oral dryness were measured. A daily mucositis index (DMI) and a cumulative oral mucositis score (COMS) were established. Requirement for narcotics and parenteral nutrition was recorded. RESULTS The COMS was significantly reduced among laser treated (L+) patients (p = 0.04). The improvement of DMI in L+ patients was also statistically significant (p < 0.05) from d + 2 to d + 7. Occurrence and duration of grade III oral mucositis were reduced in L+ patients (p = 0.01). Laser applications reduced oral pain as assessed by patients (p = 0.05) and L+ patients required less morphine (p = 0.05). Xerostomia and ability to swallow were improved among the L+ patients (p = 0.005 and p = 0.01, respectively). Requirement for parenteral nutrition was not reduced (p = NS). CONCLUSION Helium-Neon laser treatment was well tolerated, feasible in all cases, and reduced high dose chemoradiotherapy-induced oral mucositis. Optimal laser treatment schedules still needs to be defined.

Benzydamine HCl for prophylaxis of radiation-induced oral mucositis

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.

Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation. Development of an oral mucositis index.

Oral complications can be serious and disabling problems for patients undergoing cancer therapy. Therefore, the authors wanted to develop a sensitive and specific instrument to measure oral mucosal changes during therapy. The Oral Mucosa Rating Scale (OMRS) has an examination rating scale to quantify the type and severity of clinically evident oral mucosal changes (atrophy, erythema, ulceration, and pseudomembranous, hyperkeratotic, lichenoid, and edematous changes), with a scale ranging from 0 to 3 (normal to severe). Separate visual analogue scales are obtained for oral pain and dryness. One hundred eighty‐eight bone marrow transplant recipients were studied from before transplant through day 42 after transplant. The OMRS then was used to develop a specific index for assessing acute oral mucositis after bone marrow transplant the Oral Mucositis Index (OMI). The OMI internal consistency measures (Chronbach alpha and Guttman split‐half coefficients) were strong (range, 0.84 to 0.93). Support for the validity of the OM1 is presented. These scales should help improve the study of oral complications of cancer therapy. Cancer 1992; 69:2469‐2477.

Clinical Science Age-dependent Decreases in Human Submandibular Gland Flow Rates as Measured Under Resting and Post-stimulation Conditions

Submandibular saliva samples were obtained with a new collection device, under resting and post-stimulation conditions, from 28 healthy individuals between 70 and 91 years of age, and from 30 healthy individuals between 18 and 39 years of age. The salivary flow rates were significantly decreased in the aged group compared with the control group. The mean resting and post-stimulation flow rates for the aged group averaged 22% and 39%, respectively, of control values.

Helium-neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients

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.