This course was published in the January 2019 issue and expires January 2022. The authors have no commercial conflicts of interest to disclose. This 2 credit hour self-study activity is electronically mediated.
After reading this course, the participant should be able to:
- Describe the incidence of cancer and some of the common oral sequelae associated with the disease and related care.
- Explain the adverse effects of cancer treatment on oral health, and clinical strategies for managing this patient population.
- Discuss the importance of interprofessional communication and regular recall visits when treating these patients.
The number of patients presenting with cancer has been increasing in recent years,1 and these individuals form a unique subpopulation encountered in dental practice. This has particular significance for dental teams, who must treat a variety of oral conditions resulting from the disease and subsequent cancer care. Management of these patients should be based on broad knowledge of these complications. With the goal of optimized care, a special emphasis on prevention and pretreatment screening is warranted, as is close communication with the treating physician and surgeon. If followed diligently, this approach will help minimize and even prevent oral sequelae in cancer patients.
The initial installment of this two-part series discussed managing cancer-related morbidities, including hyposalivation, xerostomia, taste alteration, dental caries and periodontitis. This concluding installment will explore care strategies for patients with oral mucositis, osteoradionecrosis, candidiasis, viral infections and trismus.
The recurrent theme in guidelines in the medical and dental literature for managing patients undergoing cancer treatment emphasizes seeing these individuals before the start of therapy, and at regular recall visits (recommended at three months or less) during the course of cancer care. Although some forms of dental therapy — such as elective surgery — should be postponed until after completion of cancer treatment, other procedures should continue during cancer care. These include oral hygiene maintenance, caries control, and managing incipient problems and oral complications arising from treatment.
Managing these patients is not a static process; rather, it is dynamic and should be modified to suit the patient during and after his or her cancer treatment. As noted, effective communication between the treating physician, surgeon and oral health care team is key to establishing personalized care strategies for patients with cancer.
Oral mucositis is a common adverse effect that is considered among the most morbid and distressing complications in patients treated for cancer. It is characterized by local erythema and pain, and can be associated with ulcer formation. This sequela can lead to poor nutritional intake, as is also associated with dysphagia and dysgeusia.2 The prevalence of oral mucositis has been reported in up to 40% of patients receiving chemotherapy, and approximately 90% of individuals receiving radiotherapy.3–8 In addition to those with leukemia or hematologic malignancy, high-risk individuals include patients receiving localized radiotherapy or 5-fluorouracil infusion. Additional risk factors for oral mucositis include poor oral hygiene, xerostomia, smoking, alcohol consumption and immunosuppression.2 Patients receiving chemotherapy typically develop this condition seven days after treatment has commenced.
Practice guidelines suggest pretreatment screening and maintaining optimal oral hygiene as important tools in managing oral mucositis.9 It is recommended that patients supplement their oral hygiene regimens by rinsing with sterile water or saline, but avoid alcohol-based mouthrinses.10 Management can include pharmacologic and nonpharmacologic methods. Nonpharmacological approaches include cryotherapy and low-level laser therapy. In cryotherapy, ice chips are placed in the mouth five minutes prior to start of the chemotherapy and this practice is continued for 30 minutes. This technique is particularly useful in patients receiving methotrexate analogues and 5-fluorouracil. Low-level laser therapy with a helium-neon laser reportedly holds promise for patients prior to the start of cancer treatment. One guideline does not recommend the routine prescription of chlorhexidine mouthrinse for cancer patients.9 Another pharmacologic agent that shows benefit is amifostine (a thiol compound), which is an antioxidant. It is administered intravenously or subcutaneously, and its potential side effects include nausea, vomiting, hypotension, flushing and allergy.11 An interventional review determined that sufficient evidence exists to support the use of cryotherapy and keratinocyte growth factor (palifermin) for preventing oral mucositis in cancer patients.12
Palliative care of patients who have already developed mucositis is important, because despite the best efforts at preventive therapy, a subset of patients will still experience mucositis. While topical anesthetics, such as lidocaine, have been used to alleviate symptoms, more severe cases must be managed with systemic analgesics — the choice of which is decided by the severity and duration of pain. A medication that contains polyvinylpyrrolidone, glycyrrhetinic acid and sodium hyaluronate has shown promise in clinical studies. Other agents that have been investigated include Aesgen-14 (a mouthrinse containing L-glutamine), iseganan (an analog of protegrin-1), benzydamine (a topical analgesic), triclosan (0.1%) and fibroblast growth factor. More research is needed, however, before these newer agents can be recommended for clinical use.
Osteonecrosis is perhaps the most severe oral side effect of cancer care and is defined as an inflammatory condition of bone that has been devitalized due to irradiation or bone-sparing medications, leading to poor healing, even after prolonged periods (three to six months, for example).13–16 Besides radiation-induced osteoradionecrosis, other forms include medication-related osteonecrosis of the jaw and antiresorptive drug-related osteonecrosis of the jaw. Radiotherapy can cause changes in microvascular circulation, as well as the cellular content of the bone, followed by hypoxia that reduces the healing potential and increases risk of osteoradionecrosis, atrophy and pathological fractures.17,18
The reported incidence of osteoradionecrosis ranges from 1% to 37%,19 and it can present as an early (within two years) or late complication. Tooth extraction is the most common triggering factor, with the mandible demonstrating a higher preponderance than the maxilla. Several risk factors exist for osteonecrosis; these include high irradiation dose (> 60 Gy), poor oral hygiene, long-term use of bisphosphonates or other bone-sparing medications (particularly those administered intravenously), immunodeficiency, trauma in the form of tooth extraction or prosthesis, and fractionated radiotherapy regimens.20 Clinical manifestations can include pain, fistula or pathological fractures. The exposure of bone and lack of healing can sometimes be noticed for longer than three months. Radiographic features include ill-defined bone destruction, sometimes accompanied by the formation of a sequestrum.21
Management is dictated by the extent and severity of involvement. It must be emphasized that osteonecrosis can be prevented by performing a thorough examination prior to the start of therapy and offering appropriate treatment. This includes oral hygiene counseling, treatment of periodontal and/or endodontic problems, and extraction of hopeless teeth.22 Once osteonecrosis has been diagnosed, management includes improvement in oral hygiene, use of a chlorhexidine mouthrinse, removal of sequestrum, nutritional counseling and systemic antibiotics. The use of hyperbaric oxygen, especially when combined with surgery, has shown moderate benefit, with improvements reported in 18% to 90% of patients.23–25 Additionally, nutritional supplements in the form of pentoxifylline and vitamin E have shown some benefit, both with and without adjunct clodronate. Other emerging strategies include the use of platelet-rich plasma, osteoblast stimulation, bone morphogenetic protein, and microvascular surgery to transplant bone from other areas of the body to the irradiated site if significant bone necrosis is evident.26,27
Oral fungal infection is common in patients with cancer, and estimates range from 40% during cancer care to 30% following therapy.28 As the most common form of fungal infection, oropharyngeal candidiasis can cause significant morbidity, including mucosal pain, taste alteration and dysphagia (if it extends to the esophagus).29 The presentation can include any one of its forms, such as pseudomembranous, hyperplastic erythematous, angular cheilitis and other invasive forms.29 Depending on the form and severity, symptoms can range from no symptoms to pain, a burning sensation, coating, oral malodor and altered taste (such as a metallic taste). In patients who have immunosuppression and/or myelosuppression, the early detection and treatment of these infections is critical before local or systemic spread. Because oropharyngeal candidiasis can mimic symptoms of other conditions commonly seen in cancer patients, including mucositis,29 diagnosis is made clinically, with appropriate consultation with an oral pathologist and use of cytological techniques in hard-to-distinguish cases.
In patients undergoing cancer therapy, the first-line treatment of candidiasis localized to the oral cavity is the use of topical antifungal agents in the form of mouthrinses, creams, lozenges, gels or patches. Azole (such as fluconazole) and polyene (such as nystatin) antifungal agents are topical drugs for treating oral candidiasis. For cancer patients, it is important to use formulations that don’t contain sugar (like some mouthrinses, for example), as it can trigger progression of rampant caries. In myelosuppressed patients and individuals who don’t respond to topical agents, systemic antifungal agents are indicated. The first-line systemic drug is usually fluconazole, which is given as a 200-mg loading dose, followed by 100 mg/day.30 Resistance to flucanazole has been observed in Candida species. In such cases, clinicians should consider the use of amphotericin B or echinocandins, in addition to topical agents, as long as the daily dosage is within recommended limits.22
Viral infections can occur secondary to immune suppression in patients who are receiving cancer care. The most common viral infection in these patients is herpes simplex, which can be treated with acyclovir.31 This virus demonstrates a high propensity for reactivation after chemotherapy for leukemia and lymphoma patients, with an aggressive presentation and atypical clinical manifestation. Herpes zoster can also be reactivated in patients with cancer, especially those with lymphoma. Cytomegalovirus reactivation can occur in the oral cavity because it tends to remain latent in the salivary glands.32 Epstein-Barr virus-induced infections can be seen in severely immunocompromised patients, and can manifest as ulcers or oral hairy leukoplakia, as well as other malignancies. Diagnosis is usually based on clinical findings, and biopsy may be indicated to confirm the type of infection. First-line drugs commonly include acyclovir and valacyclovir, but in cases of resistant infections, ganciclovir or foscarnet can be prescribed.22
Trismus is a complication arising from radiotherapy or surgery to the head and neck area due to their effects on the muscles involved in mastication. Active motion devices can be considered as part of a preventive protocol before trismus becomes established. Additionally, the use of resistance devices during jaw exercises can improve jaw motion. Other management therapies under investigation include botulinum toxin and pentoxifylline.22
All patients undergoing cancer therapy will benefit from an effective recall program, as well as treatment of oral issues in their earliest stages. A thorough examination of the oral cavity should be performed at routine intervals to detect possible recurrence or posttreatment metastasis in this patient population.33,34 Any oral health conditions that could not be addressed prior to or during cancer care can be initiated once therapy is complete.34
Additionally, some adverse effects of cancer treatment can be long-standing and often lifelong, which further underscores the importance of an effective recall program. The duration of the recall should be individualized for each patient, based on the nature of his or her cancer care, time in remission, oral hygiene and home care, as well as the prevalence of other oral conditions. A continued emphasis on oral hygiene and caries prevention is warranted until the patient’s salivary function and immunity are fully restored. Clinicians should also consider referral to a diet counselor if there is a compromise in the patient’s nutritional status due to cancer treatment. In addition, posttreatment reconstruction of lost teeth and oral tissues can be considered at this stage (after appropriate assessment of the risk of posttreatment osteoradionecrosis).
In light of the growing number of patients presenting with cancer,1 and increasing survival rates due to advances in therapy, dental professionals would be well served by developing a keen understanding of the oral complications that can result from cancer and its treatment. Close communication with the patient’s medical team will help practitioners develop highly individualized treatment plans designed to support oral health. While some types of treatment should be postponed during cancer care, dental teams should continue to help patients maintain oral hygiene, control caries, and manage complications resulting from cancer treatment. When managing this population, pretreatment screening and preventive efforts, as well as a regular recall program, are the cornerstones of effective care.
- Cancer Research UK. Worldwide Cancer Statistics 2015. Available at: cancerresearchuk.org/health-professional/cancer-statistics/worldwide-cancer. Accessed November 27, 2018.
- Saadeh CE. Chemotherapy- and radiotherapy-induced oral mucositis: review of preventive strategies and treatment. Pharmacotherapy. 2005;25:540–554.
- Epstein JB, Schubert MM. Oropharyngeal mucositis in cancer therapy. Review of pathogenesis, diagnosis, and management. Oncology (Williston Park). 2003;17:1767–1782,1791,1792.
- Wilkes JD. Prevention and treatment of oral mucositis following cancer chemotherapy. Semin Oncol. 1998;25:538–551.
- Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003;98:1531–1539.
- Sonis ST, Fey EG. Oral complications of cancer therapy. Oncology (Williston Park). 2002;16:680–686,691,692,695.
- Alvarado Y, Bellm LA, Giles FJ. Oral mucositis: time for more studies. Hematol. 2002;7:281–289.
- Meta-Analysis Group In Cancer, Lévy E, Piedbois P, et al. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol. 1998;16:3537–3541.
- Rubenstein EB, Peterson DE, Schubert M, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer. 2004;100(Suppl 9):2026–2046.
- Larson PJ, Miaskowski C, MacPhail L, et al. The PRO-SELF Mouth Aware program: an effective approach for reducing chemotherapy-induced mucositis. Cancer Nurs. 1998;21:263–268.
- Schuchter LM, Hensley ML, Meropol NJ, Winer EP, American Society of Clinical Oncology Chemotherapy and Radiotherapy Expert Panel. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2002;15:20:2895–2903.
- Lang DS. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Clin J Oncol Nurs. 2013;17:340.
- Beumer J, Harrison R, Sanders B, Kurrasch M. Osteoradionecrosis: predisposing factors and outcomes of therapy. Head Neck Surg. 1984;6:819–827.
- Harris M. The conservative management of osteoradionecrosis of the mandible with ultrasound therapy. Br J Oral Maxillofac Surg. 1992;30:313–318.
- Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983;41:283–288.
- Støre G, Boysen M. Mandibular osteoradionecrosis: clinical behaviour and diagnostic aspects. Clin Otolaryngol Allied Sci. 2000;25:378–384.
- Johnson JT, Ferretti GA, Nethery WJ, et al. Oral pilocarpine for post-irradiation xerostomia in patients with head and neck cancer. N Engl J Med. 1993;329:390–395.
- Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP. Oral sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med. 2003;14:199–212.
- Sciubba JJ, Goldenberg D. Oral complications of radiotherapy. Lancet Oncol. 2006;7:175–183.
- Jawad H, Hodson NA, Nixon PJ. A review of dental treatment of head and neck cancer patients, before, during and after radiotherapy: part 1. Br Dent J. 2015;218:65–68.
- Mitchell MJ, Logan PM. Radiation-induced changes in bone. Radiographics. 1998;18:1125–1136.
- Epstein JB, Thariat J, Bensadoun R-J, et al. Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA Cancer J Clin. 2012;62:400–422.
- Delanian S, Chatel C, Porcher R, Depondt J, Lefaix JL. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys. 2011;80:832–839.
- Fritz GW, Gunsolley JC, Abubaker O, Laskin DM. Efficacy of pre- and postirradiation hyperbaric oxygen therapy in the prevention of postextraction osteoradionecrosis: a systematic review. J Oral Maxillofac Surg. 2010;68:2653–2660.
- Epstein J, van der MeiJ E, McKenzie M, Wong F, Stevenson-Moore P. Hyperbaric oxygen therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996;81:265–256.
- Epstein MS, Ephros HD, Epstein JB. Review of current literature and implications of RANKL inhibitors for oral health care providers. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116:e437–e442.
- Migliorati CA, Epstein JB, Abt E, Berenson JR. Osteonecrosis of the jaw and bisphosphonates in cancer: a narrative review. Nat Rev Endocrinol. 2011;7:34–42.
- Lalla RV, Latortue MC, Hong CH, et al. A systematic review of oral fungal infections in patients receiving cancer therapy. Support Care Cancer. 2010;18:985–992.
- Sroussi HY, Epstein JB, Bensadoun RJ, et al. Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med. 2017;6:2918–2931.
- Finlay PM, Richardson MD, Robertson AG. A comparative study of the efficacy of fluconazole and amphotericin B in the treatment of oropharyngeal candidosis in patients undergoing radiotherapy for head and neck tumours. Br J Oral Maxillofac Surg. 1996;34:23–25.
- Andrews N, Griffiths C. Dental complications of head and neck radiotherapy: part 2. Aust Dent J. 2001;46:174–182.
- Samonis G, Mantadakis E, Maraki S. Orofacial viral infections in the immunocompromised host. Oncol Rep. 2000;7:1389–1394.
- Brennan MT, Woo SB, Lockhart PB. Dental treatment planning and management in the patient who has cancer. Dent Clin North Am. 2008;52:19–37,vii.
- Hancock PJ, Epstein JB, Sadler GR. Oral and dental management related to radiation therapy for head and neck cancer. J Can Dent Assoc. 2003;69:585–590.
Featured image by JCPJR/ISTOCK/GETTY IMAGES PLUS
From Decisions in Dentistry. January 2019;5(1):42–45.