In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed.

PISA quantifies the inflammatory burden posed by periodontitis and can be easily and broadly applied.

Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.

Objective. To investigate the safety and efficacy of B cell depletion treatment of patients with active primary Sjögren's syndrome of short duration (early primary SS) and patients with primary SS and mucosaassociated lymphoid tissue (MALT)-type lymphoma (MALT/primary SS).Methods. Fifteen patients with primary SS were included in this phase II trial. Inclusion criteria for the early primary SS group were B cell hyperactivity (IgG >15 gm/liter), presence of autoantibodies (IgM rheumatoid factor, anti-SSA/SSB), and short disease duration (<4 years). Inclusion criteria for the MALT/ primary SS group were primary SS and an associated MALT-type lymphoma (Ann Arbor stage IE) localized in the parotid gland. Patients were treated with 4 infusions of rituximab (375 mg/m 2 ) given weekly after pretreatment with prednisone (25 mg) and clemastine. Patients were evaluated, using immunologic, salivary/ lacrimal function, and subjective parameters, at baseline and at 5 and 12 weeks after the first infusion.Results. Significant improvement of subjective symptoms and an increase in salivary gland function was observed in patients with residual salivary gland function. Immunologic analysis showed a rapid decrease of peripheral B cells and stable levels of IgG. Human antichimeric antibodies (HACAs) developed in 4 of 15 patients (27%), all with early primary SS. Three of these patients developed a serum sickness-like disorder. Of the 7 patients with MALT/primary SS, complete remission was achieved in 3, and disease was stable in 3 and progressive in 1.Conclusion. Findings of this phase II study suggest that rituximab is effective in the treatment of primary SS. The high incidence of HACAs and associated side effects observed in this study needs further evaluation.

Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

The location of the primary tumor or lymph node metastases dictates the inclusion of the oral cavity, salivary glands, and jaws in the radiation treatment portals for patients who have head and neck cancer. The clinical sequelae of the radiation treatment include mucositis, hyposalivation, loss of taste, osteoradionecrosis, radiation caries, and trismus. These sequelae may be dose-limiting and have a tremendous effect on the patient's quality of life. Most treatment protocols to prevent these sequelae are still based on clinical experience, but alternatives based on fundamental basic and clinical research are becoming more and more available. Many of these alternatives either need further study before they can be incorporated into the protocols commonly used to prevent and treat the radiation-related oral sequelae or await implementation of these protocols. In this review, the various possibilities for prevention and/or treatment of radiation-induced changes in healthy oral tissues and their consequences are discussed.

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BACKGROUND. The risk, severity, and patient‐reported outcomes of radiation‐induced mucositis among head and neck cancer patients were prospectively estimated. METHODS. A validated, patient‐reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales were used to measure mucositis (reported as mouth and throat soreness), daily functioning, and use of analgesics. Patients were studied before radiotherapy (RT), daily during RT, and for 4 weeks after RT. RESULTS. Contrary to previous reports, the risk of mucositis was virtually identical in the 126 patients with oral cavity or oropharynx tumors (99% overall; 85% grade 3‐4) compared with 65 patients with tumors of the larynx or hypopharynx (98% overall; 77% grade 3‐4). The mean QOL score decreased significantly during RT, from 85.1 at baseline to 69.0 at Week 6, corresponding with the peak of mucositis severity. The mean functional status score decreased by 33% from 18.3 at baseline to 12.3 at Week 6. The impact of mucositis on QOL was proportional to its severity, although even a score of 1 or 2 (mild or moderate) was associated with a significant reduction in QOL (from 93.6 at baseline to 74.7 at Week 6). Despite increases in analgesic use from 34% at baseline to 80% at Week 6, mean mucositis scores exceeded 2.5 at Week 6. CONCLUSIONS. Mucositis occurs among virtually all patients who are undergoing radiation treatment of head and neck cancers. The detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief. Preventive rather than symptom palliation measures are needed. Cancer 2008. © 2008 American Cancer Society.