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Dental Consult/Cytoprotection Strategies in Management of Oral Effects of RT for Head and Neck Ca

Dental Consult/Cytoprotection Strategies in Management of Oral Effects of RT for Head and Neck Ca

NEW YORK-Externalbeam radiotherapy (EBRT) causes irreversible salivary dysfunction in many patients treated for head and neck cancer. One strategy for reducing treatment-associated morbidity is to get a dental consult to prepare the patient before beginning chemoradiotherapy. Another strategy, now in clinical trials, is to add cytoprotection with amifostine (Ethyol) to the treatment regimen. Both approaches were discussed by Jonathan A. Ship, DMD, professor, Department of Oral Medicine, and director, Bluestone Center for Clinical Research, NYU College of Dentistry. Oral Effects of Tx Significant
"Head and neck cancers cause more deaths annually than malignant melanoma, Hodgkin's disease, and cervical cancer," Dr. Ship said. "Survival rates are poor, with only 50% of patients living 5 years after diagnosis, and all treatments have adverse sequelae. The severe dental and oral effects are often neglected in the rush to multimodality therapy" (see Table 1). Mucositis can be dose-limiting and volume-limiting in combined chemoradiotherapy programs, Dr. Ship said. He also noted that mucositis is a portal of entry for oral microorganisms, leading to potentially life-threatening secondary local and systemic infections. Dental Consult Recommended
"Patients need to see a dentist prior to head-neck radiotherapy. Radiotherapy-induced mucositis develops 7 to 10 days after treatment initiation," he said. He added that there is an incorrect but widespread assumption that dental care would not be reimbursed by Medicare. "Certain procedures in preparing the mouth prior to head-neck radiotherapy are covered by Medicare. This can decrease pain and improve quality of life." Serous salivary glands such as the parotid, he explained, are highly radiosensitive, and serous cells are destroyed within 1 to 6 hours after irradiation with single doses as low as 200 cGy. Noting that cancer treatment doses are being pushed to 65 to 70 Gy, he said a dose of only 25 to 30 Gy can permanently destroy major salivary glands. "The radiation sequela of salivary dysfunction remains a bothersome problem for patients who have received EBRT," Dr. Ship said. "Long-term salivary hypofunction causes new and recurring dental caries; fungal infections; difficulties in chewing, tasting, and swallowing; and impaired retention of dentures, and further, oral-facial pain, nutritional compromise, and impaired communication impair quality of life for many years." High-Density Radiotherapy Plus Amifostine
Dr. Ship described a clinical investigation of combined high- dose rate intraoperative radiotherapy (HD-IORT), EBRT, and amifostine. He has partnered with Dr. Kenneth Hu at Beth Israel Medical Center, New York, for this innovative approach. The protocol included surgery to the primary site and the neck, with intraoperative delivery of 12 to 15 Gy to the site of tumor (brachytherapy), postoperative EBRT (50 to 60 Gy), and concomitant use of amifostine (SC 1 hour prior to RT). He said that HD-IORT dose escalation provides improved locoregional control, shortens total treatment duration, and decreases toxicity by reducing the EBRT dose. Applicators are made of flexible silicon that can be tailored to fit easily into the tumor bed. The study hypothesis is that the combination of HD-IORT and EBRT with a cytoprotectant (amifostine) will reduce radiationinduced mucositis and xerostomia in head and neck cancer patients. Inclusion criteria include oral cavity oropharynx, larynx, and hypopharynx squamous cell carcinoma with spread to regional lymphatics, with surgery of both the primary site and neck, no evidence of distant metastases, and no previous radiotherapy or chemotherapy. Multiple Assessments
Quality of life and performance assessments include ECOG (Eastern Cooperative Oncology Group) Performance Status, RTOG (Radiation Therapy Oncology Group) Late Radiation Morbidity Scoring Scheme, RTOG Pharynx and Esophagus Toxicity Grading, FACT (Functional Assessment of Cancer Therapy) Head and Neck, the Terrell Head and Neck Quality of Life Instrument, and the List Performance Status Survey. Salivary function and xerostomia are assessed using the Xerostomia Score, Xerostomia Questionnaire, Xerostomia Quality of Life Questionnaire, and salivary collection (both unstimulated and stimulated whole saliva). Mucositis and pharyngitis assessment include the WHO (World Health Organization) Mucositis Grade, CTC (Common Toxicology Criteria) v. 2 Mucositis Grade, CTC v. 2 Pharyngitis Grade, CTC v. 2 Dermatitis Grade, and CTC v. 2 Dysphagia Grade. Two Patients Enrolled
Dr. Ship said that so far, the study includes one 50-year-old male enrolled with 9-month post- RT data and one 61-year-old male who just completed RT. The 50- year-old patient who has completed RT had a moderately differentiated squamous cell carcinoma of the right neck (stage IV, N2b M0). He underwent surgical removal of the tumor with unilateral neck dissection and was then treated with 12 Gy of HD-IORT, 50 Gy of EBRT, and 500 mg SC amifostine daily. "There were no significant adverse events and no treatment interruptions," Dr. Ship said. The 50-year-old patient who has completed treatment had mild mucositis with erythema of the mucosa during the second to sixth week of EBRT. "The score returned to baseline (grade 0) at all post-EBRT visits," Dr. Ship reported. Similarly, mucositis, pharyngitis, and dysphagia were grade 0 or 1 during EBRT and all returned to grade 0 at 1 month post-EBRT. Fatigue and radiation dermatitis were grade 0 or 1 during RT and returned to grade 0 at 1 month post-EBRT. Better Salivary Function, QOL
"At the completion of EBRT there was an approximately 80% decrease in both unstimulated and stimulated whole salivary flow rates. There was persistent salivary hypofunction at 9 months post- EBRT, with slight recovery of stimulated flow rates to 65% of pretreatment function. The patient had persistent xerstomia (RTOG Late Radiation Morbidity, grade 2), from treatment until 6 months post-EBRT; it improved to grade 1 at 9 months post-EBRT. The Xerostomia Score decreased to 1 at 9 months post-EBRT," Dr. Ship said. Quality of life scores were striking. The patient had "nearly perfect" scores at 1, 3, 6, and 9 months post-EBRT for Head and Neck QOL Scale, FACT Head and Neck Scale, List Performance Status Survey, and Xerostomia Quality of Life Scale. "HD-IORT and amifostine were well tolerated and may reduce treatment-induced oral mucositis. This combination therapeutic approach did not produce short-term salivary preservation, but there were few xerostomia-related quality- of-life problems," Dr. Ship said. "Despite the dramatic losses in whole unstimulated and stimulated saliva up to 9 months post-RT, complaints of xerostomia were few, and xerostomia-related quality-oflife problems were minimal. This may be due to preservation of mucosal tissues during treatment," he concluded. Dr. Ship cautioned that these results are very preliminary and based on a very small sample size but are worthy of further research.

 
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