Department of Veterans Affairs Consensus: Preradiation dental treatment guidelines for patients with head and neck cancer.

Few protocols have been published for the dental management of patients with head and neck cancer to prevent complications from head and neck radiation therapy. Radiation therapy not only affects the tumor cells targeted, but also the dentition, bone, salivary gland, and oral soft tissue structures. A comprehensive dental evaluation prior to head and neck radiation therapy can help prevent many complications. The following clinical guidelines were established by a workgroup of oral health providers within the Department of Veterans Affairs. This workgroup focused on developing a set of recommendations regarding dental care prior to the initiation of head and neck radiation therapy based on the best clinical evidence and expert consensus. A systematic algorithm was developed for the evaluation including pre-exam data gathering, examination, education, and treatment, followed by maintenance and postradiation dental follow-up. This document is evidence-based, patient-centered, consistent with accepted practices of care and safety, and in accordance with applicable statutes and regulations.

Dosimetric distribution to the tooth-bearing regions of the mandible following intensity-modulated radiation therapy for base of tongue cancer.

OBJECTIVES: Osteoradionecrosis is a significant complication following head and neck radiotherapy. The purpose of this study was to determine the intensity-modulated radiation therapy (IMRT) dosages delivered to the tooth-bearing regions of the mandible. STUDY DESIGN: A total of 28 patients with base of tongue cancer with the following stages: T1-2/N2-3 (n = 10), T3-4/N2-3 (n = 10), and T1-4/N0 (n = 8), treated with IMRT, were included. Average mean and maximum doses were calculated for the anterior, premolar, and molar regions. RESULTS: Lower doses were seen in anterior bone with smaller tumors. Large tumors, regardless of laterality, resulted in high doses to the entire mandible, with anterior bone receiving more than 6000 cGy. CONCLUSIONS: Tumor size is important in preradiation dental treatment planning. This information is important in planning pre- and postradiation dental extractions. Dosimetric analyses correlating mean and maximum point dose with clinical presentation and outcomes are needed to determine the best predictor of osteoradionecrosis risk.

Geldanamycin inhibits the production of inflammatory cytokines in activated macrophages by reducing the stability and translation of cytokine transcripts.

OBJECTIVE: Heat-shock protein 90 (Hsp90) is critical in the intracellular signaling pathways that promote inflammatory cytokine production. Geldanamycin (GD) is a benzoquinone ansamycin that inhibits the function of Hsp90. GD inhibits the production of tumor necrosis factor alpha (TNFalpha) in activated macrophages and suppresses the progression of adjuvant-induced arthritis and experimental allergic encephalomyelitis in rodents. GD has been used to investigate the mechanisms by which Hsp90 regulates inflammatory cytokine production. METHODS: The macrophage cell line RAW264.7 (or primary peritoneal macrophages) was activated with lipopolysaccharide in the absence or presence of GD. The effect of GD on the transcription, stability, and translation of inflammatory cytokine messenger RNA (mRNA) was determined using nuclear run-on assays, mRNA decay assays, and sucrose gradient polysome profiles, respectively. RESULTS: Our data revealed that GD potently inhibits the production of TNFalpha, interleukin-6 (IL-6), and IL-1beta in activated macrophages. Although GD did not significantly reduce the transcription of inflammatory cytokine mRNA, it significantly decreased the stability of these transcripts. Polysome profiles indicated that GD also inhibited the translation of TNFalpha and IL-6 transcripts. These effects may be due, in part, to inhibition of p38 mitogen-activated protein kinase, a kinase known to regulate the stability and translation of inflammatory cytokine transcripts. CONCLUSION: These results indicate that the function of Hsp90 is important in the posttranscriptional control of inflammatory cytokine production.