Aggressive treatment of malignant disease may produce unavoidable toxicities to normal cells. The mucosal lining of the gastrointestinal tract, including the oral mucosa, is a prime target for treatment-related toxicity by virtue of its rapid rate of cell turnover. The oral cavity is highly susceptible to direct and indirect toxic effects of cancer chemotherapy and ionizing radiation. This risk results from multiple factors, including high rates of cellular turnover for the lining mucosa, a diverse and complex microflora, and trauma to oral tissues during normal oral function. Although changes in soft tissue structures within the oral cavity presumably reflect the changes that occur throughout the gastrointestinal tract, this summary focuses on oral complications of antineoplastic drugs and radiation therapies.
It is essential that a multidisciplinary approach be used for oral management of the cancer patient before, during, and after cancer treatment. A multidisciplinary approach is warranted because the medical complexity of these patients affects dental treatment planning, prioritization, and timing of dental care. In addition, selected cancer patients (e.g., status posttreatment with high-dose head-and-neck radiation) are often at lifelong risk for serious complications such as osteoradionecrosis of the mandible. Thus, a multidisciplinary oncology team that includes oncologists, oncology nurses, and dental generalists and specialists as well as dental hygienists, social workers, dieticians, and related health professionals can often achieve highly effective preventive and therapeutic outcomes relative to oral complications in these patients.
While oral complications may mimic selected systemic disorders, unique oral toxicities emerge in the context of specific oral anatomic structures and their functions.
Frequencies of oral complications vary by cancer therapy; estimates are included in Table 1.
|Complication||Reference Citation||Weighted Prevalence|
|CT = chemotherapy; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; HNC = head and neck cancer; IMRT = intensity-modulated radiation therapy; MASCC/ISOO = Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology; RT = radiation therapy; VAS = visual analog scale.|
|aPain is common in patients with HNCs and is reported by approximately half of patients before cancer therapy, by 81% during therapy, by 70% at the end of therapy, and by 36% at 6 months posttreatment.|
|Bisphosphonate osteonecrosis||||6.1% for all studies (mean)|
|Studies with documented follow-up = 13.3%|
|Studies with undocumented follow-up = 0.7%|
|Epidemiological studies = 1.2%|
|Dysgeusia||||CT only = 56.3% (mean)|
|RT only = 66.5% (mean)|
|Combined CT and RT = 76% (mean)|
|Oral fungal infection||||Of clinical oral fungal infection (all oral candidiasis):|
|Pretreatment = 7.5%|
|During treatment = 39.1%|
|Posttreatment = 32.6%|
|Of oral candidiasis clinical infection by cancer treatment:|
|During HNC RT = 37.4%|
|During CT = 38%|
|Oral viral infection||||In patients treated with CT for hematologic malignancies:|
|Patients with oral ulcerations/sampling oral ulcerations = 49.8%|
|Patients sampling oral ulcerations = 33.8%|
|Patients sampling independently of the presence of oral ulcerations = 0%|
|In patients treated with RT:|
|Patients with RT only/sampling oral ulcerations = 0%|
|Patients with RT and adjunctive CT/sampling oral ulcerations = 43.2%|
|Dental disease||||For dental caries in patients treated with cancer therapy:|
|All studies = 28.1%|
|CT only = 37.3%|
|Post-RT = 24%|
|Post-CT and -RT = 21.4%|
|Of severe gingivitis in patients undergoing CT = 20.3%|
|Of dental infection/abscess in patients undergoing CT = 5.8%|
|Osteoradionecrosis||||In conventional RT = 7.4%|
|In IMRT = 5.2%|
|In RT and CT = 6.8%|
|In brachytherapy = 5.3%|
|Trismus||||For conventional RT = 25.4%|
|For IMRT = 5%|
|For combined RT and CT = 30.7%|
|Oral paina||||VAS pain level (0–100) in HNC patients:|
|Pretreatment = 12/100|
|Immediately posttreatment = 33/100|
|1 mo posttreatment = 20/100|
|EORTC QLQ-C30 pain level (0–100) in HNC patients:|
|Pretreatment = 27/100|
|3 mo posttreatment = 30/100|
|6 mo posttreatment = 23/100|
|12 mo posttreatment = 24/100|
|Salivary gland hypofunction and xerostomia||||Of xerostomia in HNC patients by type of RT:|
|Pre-RT = 6%|
|During RT = 93%|
|1–3 mo post-RT = 74%|
|3–6 mo post-RT = 79%|
|6–12 mo post-RT = 83%|
|1–2 y post-RT = 78%|
|>2 y post-RT = 85%|
|Pre-RT = 10%|
|During RT = 81%|
|1–3 mo post-RT = 71%|
|3–6 mo post-RT = 83%|
|6–12 mo post-RT = 72%|
|1–2 y post-RT = 84%|
|>2 y post-RT = 91%|
|Pre-RT = 12%|
|During RT = 100%|
|1–3 mo post-RT = 89%|
|3–6 mo post-RT = 73%|
|6–12 mo post-RT = 90%|
|1–2 y post-RT = 66%|
|>2 y post-RT = 68%|
The most common oral complications related to cancer therapies are mucositis, infection, salivary gland dysfunction, taste dysfunction, and pain. These complications can lead to secondary complications such as dehydration, dysgeusia, and malnutrition. In myelosuppressed cancer patients, the oral cavity can also be a source of systemic infection. Radiation of the head and neck can irreversibly injure oral mucosa, vasculature, muscle, and bone, resulting in xerostomia, rampant dental caries, trismus, soft tissue necrosis, and osteonecrosis.
Severe oral toxicities can compromise delivery of optimal cancer therapy protocols. For example, dose reduction or treatment schedule modifications may be necessary to allow for resolution of oral lesions. In cases of severe oral morbidity, the patient may no longer be able to continue cancer therapy; treatment is then usually discontinued. These disruptions in dosing caused by oral complications can directly affect patient survivorship.
Management of oral complications of cancer therapy includes identification of high-risk populations, patient education, initiation of pretreatment interventions, and timely management of lesions. Assessment of oral status and stabilization of oral disease before cancer therapy are critical to overall patient care. Care should be both preventive and therapeutic to minimize risk for oral and associated systemic complications.
Future research targeted at developing technologies is needed to:
- Reduce incidence and severity of oral mucositis.
- Improve infection management.
- Protect salivary gland function.
- Minimize risk of chronic sequelae.
Development of new technologies to prevent cancer therapy–induced complications, especially oral mucositis, could substantially reduce the risk of oral pain, oral and systemic infections, and number of days in the hospital; and could improve quality of life and reduce health care costs. New technologies could also provide a setting in which novel classes of chemotherapeutic drugs, used at increased doses, could lead to enhanced cancer cure rates and durability of disease remission.
As has been noted, it is essential that a multidisciplinary approach be used for oral management of the cancer patient before, during, and after cancer treatment. This collaboration is pivotally important for the advancement of basic, clinical, and translational research associated with oral complications of current and emerging cancer therapies. The pathobiologic complexity of oral complications and the ever-expanding science base of clinical management require this comprehensive interdisciplinary approach.
In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.
- Lalla RV, Brennan MT, Schubert MM: Oral complications of cancer therapy. In: Yagiela JA, Dowd FJ, Johnson BS, et al., eds.: Pharmacology and Therapeutics for Dentistry. 6th ed. St. Louis, Mo: Mosby Elsevier, 2011, pp 782-98.
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- Migliorati CA, Woo SB, Hewson I, et al.: A systematic review of bisphosphonate osteonecrosis (BON) in cancer. Support Care Cancer 18 (8): 1099-106, 2010. [PUBMED Abstract]
- Hovan AJ, Williams PM, Stevenson-Moore P, et al.: A systematic review of dysgeusia induced by cancer therapies. Support Care Cancer 18 (8): 1081-7, 2010. [PUBMED Abstract]
- Lalla RV, Latortue MC, Hong CH, et al.: A systematic review of oral fungal infections in patients receiving cancer therapy. Support Care Cancer 18 (8): 985-92, 2010. [PUBMED Abstract]
- Elad S, Zadik Y, Hewson I, et al.: A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea. Support Care Cancer 18 (8): 993-1006, 2010. [PUBMED Abstract]
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- Peterson DE, Doerr W, Hovan A, et al.: Osteoradionecrosis in cancer patients: the evidence base for treatment-dependent frequency, current management strategies, and future studies. Support Care Cancer 18 (8): 1089-98, 2010. [PUBMED Abstract]
- Bensadoun RJ, Riesenbeck D, Lockhart PB, et al.: A systematic review of trismus induced by cancer therapies in head and neck cancer patients. Support Care Cancer 18 (8): 1033-8, 2010. [PUBMED Abstract]
- Epstein JB, Hong C, Logan RM, et al.: A systematic review of orofacial pain in patients receiving cancer therapy. Support Care Cancer 18 (8): 1023-31, 2010. [PUBMED Abstract]
- Jensen SB, Pedersen AM, Vissink A, et al.: A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer 18 (8): 1039-60, 2010. [PUBMED Abstract]