Bela B. Toth

Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates.

Introduction: Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates. The incidence and risk factors associated with this disorder have not been clearly defined.

Comparison of low-dose isotretinoin with beta carotene to prevent oral carcinogenesis.

BACKGROUND High-dose isotretinoin therapy has been determined to be an effective treatment for leukoplakia. However, a high rate of relapses and toxic reactions led us to conduct a trial of a much lower dose of isotretinoin in the hope of maintaining a response and limiting toxicity. METHODS In the first phase of the study, 70 patients with leukoplakia underwent induction therapy with a high dose of isotretinoin (1.5 mg per kilogram of body weight per day) for three months; in the second phase, patients with responses or stable lesions were randomly assigned to maintenance therapy with either beta carotene (30 mg per day) or a low dose of isotretinoin (0.5 mg per kilogram per day) for nine months. RESULTS In the first phase, the rate of response to high-dose induction therapy in the 66 patients who could be evaluated was 55 percent (36 patients). The lesions of seven patients progressed, and therefore they did not participate in the second phase of the trial. Of the 59 patients included in the second phase, 33 were assigned to beta carotene therapy and 26 to low-dose isotretinoin therapy; these two groups did not differ significantly in prognostic factors. Of the 53 patients who could be evaluated, 22 in the low-dose isotretinoin group and 13 in the beta carotene group responded to maintenance therapy or continued to have stable lesions (92 percent vs. 45 percent, P < 0.001). In situ carcinoma developed in one patient in each group, and invasive squamous-cell carcinoma in five patients in the beta carotene group. Toxicity was generally mild, though greater in the group given low-dose isotretinoin therapy. CONCLUSIONS When preceded by high-dose induction therapy, low-dose isotretinoin therapy was significantly more active against leukoplakia than beta carotene and was easily tolerated.

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.

Salivary flow rates in patients with head and neck cancer 0. 5 to 25 years after radiotherapy

In this clinical study at the University of Texas M. D. Anderson Cancer Center, unstimulated and stimulated salivary flow rates were obtained from 47 patients with head and neck cancer who had received mantle, unilateral facial, or bilateral facial field radiotherapy from 0.5 to 25 years earlier. The magnitude of salivary flow rate reduction compared with a healthy control group was primarily related to the radiation dosage and the amount of salivary gland tissue included in the irradiated fields. Flow rates were lower for women in all groups, but these differences were not statistically significant.

Epidemiology and risk factors for osteonecrosis of the jaw in cancer patients

Osteonecrosis of the jaw (ONJ), previously an entity associated with radiation therapy to the head and neck, has been observed in patients treated with bisphosphonates. Patients with metastatic breast cancer and myelomatous bone disease, commonly treated with high‐potency nitrogen‐containing bisphosphonates for a prolonged period of time, have the greatest risk of ONJ development. The reported frequency of ONJ ranges from 0.6% to 6.2% in breast cancer and from 1.7% to 15% in patients with multiple myeloma. Osteonecrosis of the jaw has also been observed in patients with other cancers such as prostate cancer and in benign bone disorders such as osteoporosis and Pagets disease in which the incidence is low. Risk factors associated with the development of ONJ include dental extractions, length of bisphosphonate treatment, and the type of bisphosphonate used. In this review, we summarize the reported incidence and risk factors associated with ONJ.

Effects of total body irradiation on salivary gland function and caries-associated oral microflora in bone marrow transplant patients

Forty-one cancer patients who received chemoradiotherapy conditioning with bone marrow transplantation were examined for changes in salivary gland function and caries-associated oral microflora. Salivary flow rates (stimulated and unstimulated) and Streptococcus mutans levels decreased after pretransplant cytoreductive therapy and posttransplant prophylactic antibiotic therapy. Normal levels returned with time after the patients left the protected environment. Lactobacillus counts were not affected. Chronic graft-versus-host disease did not significantly influence saliva production. Results indicate that irradiation is probably the major factor responsible for the transient xerostomia.

Oral and dental management of the cancer patient: prevention and treatment of complications

Aggressive cancer therapy places patients at greater risk for oral complications and treatment-related consequences. Unfortunately, prevention and/or treatment of such oral sequelae has become an often overlooked priority of the treatment team. We describe a philosophy of management of the cancer patient that specifically emphasizes the prevention and treatment of oral complications associated with cancer therapy. These concepts and principles are based on treatment protocols and ongoing clinical research at The University of Texas M. D. Anderson Cancer Center in Houston, Texas.

Effect of radioactive iodine therapy on salivary flow rates and oral Streptococcus mutans prevalence in patients with thyroid cancer

Unstimulated and stimulated salivary flow rates, Streptococcus mutans samples, and dental caries data were obtained from 50 patients with thyroid cancer who had received radioactive iodine, I131, from 0.3 to 20 years earlier. The salivary flow rates were compared with a healthy control group, and the S. mutans counts were compared to a group of patients with head and neck cancer who were sampled before radiotherapy. Flow rates were found to be significantly lower in the patients with thyroid cancer, and S. mutans levels were slightly but not significantly higher than the controls. Longitudinal flow rate data taken on four patients, who served as their own controls before and after I131 therapy, indicated a trend in saliva reduction.

Dental implants and chemotherapy complications

The cancer patient receiving chemotherapy often suffers severe oral complications related to the administration of antineoplastic drugs. Cancer patients who also have transmucosal or endosseous dental implants pose special problems for medical oncologists and dentists, both when planning for chemotherapy and when providing supportive care during the course of treatment. The relationship between dental implants and cancer chemotherapy is described and complications experienced by implant patients treated with chemotherapy at The University of Texas M.D. Anderson Cancer Center are reviewed. Recommendations on various aspects of management involving implant evaluation and the removal or retention of dental implants are discussed.

Oral complications associated with aspergillosis in patients with a hematologic malignancy. Presentation and treatment.

Opportunistic mycotic infections, such as aspergillosis, can produce morbid consequences with or without aggressive therapy in an immunocompromised patient. Treatment including amphotericin B and resection of the infected tissue must be considered early in the overall management of the patient. We describe two patients with acute myelogenous leukemia who underwent intense cytoreductive therapy with bone marrow transplantation and an associated fungal infection treated with an investigational form of amphotericin B.