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Dental Management of Patients Who Have Undergone Oral Cancer Therapy

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Dental Management of Patients Who Have Undergone Oral Cancer Therapy Dental Management of Patients Who Have Undergone Oral Cancer Therapy a,b Alessandro Villa, DDS, PhD, MPH , c, Sunday O. Akintoye, BDS, DDS, MS * KEYWORDS Oral mucositis Xerostomia Infections Tissue fibrosis Trismus Osteoradionecrosis KEY POINTS Patients undergoing treatment of oral cancer may experience short-term and long-term oral cavity complications. The most common side effects from oral cancer therapy include mucositis, infections, and osteoradionecrosis of the jaws. Effective dental management of patients with oral cancer involves the coordination of care among several health care professionals. INTRODUCTION Oral cancers remain a major health concern worldwide. The tumor-related and patient- related factors, as well as treatment complications, negatively affect the 5-year survival rate and quality of life of survivors.1 The common treatment modalities for oral cancer include surgery, radiotherapy, chemotherapy, or a combination of these depending on the tumor type, anatomic site, and stage of the cancer. Chemotherapeutic drugs are associated with a wide spectrum of hematologic toxicities that include anemia, leukopenia, neutropenia, and thrombocytopenia.2 Although immunosuppression in pa- tients with oral cancer is usually transient, these patients are still susceptible to a high risk of bacterial, viral, and fungal infections. The major objectives of oral cancer thera- pies are complete tumor control, with minimal treatment complications and improved Disclosures: None. a Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA; b Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital, 1620 Tremont Street, Suite BC3-028, Boston, MA 02118, USA; c Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Robert Schattner Room 211, 240 South 40th Street, Philadelphia, PA 19104, USA * Corresponding author. E-mail address: [email protected] Dent Clin N Am 62 (2018) 131–142 http://dx.doi.org/10.1016/j.cden.2017.08.010 dental.theclinics.com 0011-8532/18/ª 2017 Elsevier Inc. All rights reserved. 132 Villa & Akintoye quality of life. However, acute and long-term toxicities associated with treatment may decrease patients’ tolerance to therapy, leading to a change in treatment schedules. Ultimately, suboptimal treatment schedules translate into poor patient outcomes, increased days of hospitalization, and increased health care costs.3–5 Early complica- tions of oral cancer therapies can result from acute toxic effects of radiotherapy and chemotherapy affecting several orofacial structures. These complications may present as oropharyngeal and gastrointestinal mucositis, salivary gland hypofunction, odonto- genic infections, pain, and neurotoxicity. Late complications often take months or years to develop, and include orofacial soft tissue fibrosis, trismus, osteoradionecrosis (ORN), and cancer recurrence.6 These complications are also associated with significant loss of function and facial disfigurement that lead to diminished quality of life and unwanted psychosocial outcomes.7 Considering the dose-limiting effects and patient outcomes that result from treatment toxicities, it is essential that management of patients with oral cancer involves a multidisciplinary team of health care professionals that includes medical and dental health care providers as well as social workers and nutrition special- ists.5 Prompt diagnosis, treatment planning, and judicious provision of dental care before, during, and after oral cancer therapy are essential aspects of management that may enhance oral cancer survivorship and lead to improved quality of life.8 DENTAL MANAGEMENT CONSIDERATIONS IN ORAL CANCER MANAGEMENT Although oral complications of chemotherapy are limited to a few weeks, the effects of radiotherapy tend to persist for months to years. The combination of surgery with chemoradiotherapy can further exacerbate these complications. It is prudent to consider the impact of treatment complications on all orofacial structures so that dental treatment can be provided effectively (Table 1). Skin The incidence of acute dermatitis in patients with oral cancer receiving radiotherapy can be as high as 95% because of high radiation doses to the skin and the combined effects of chemoradiotherapy.9 Oral cancer therapies promote an imbalance in the activities of proinflammatory and profibrotic cytokines in the skin causing vascular damage and decreased blood perfusion. These effects may result in orofacial skin ulceration and necrosis.10 The patient’s medical history combined with clinical appearance make the diagnosis of radiation dermatitis straightforward. It is vital to prevent and control acute dermatitis as much as possible so that the radiochemother- apeutic regimen is uninterrupted. Avoiding unnecessary skin irradiation is the best preventive approach to minimizing the occurrence of radiation dermatitis. Chronic skin ulceration and infected wounds require special dressings that promote healing. Surgical care combined with skin grafting may be necessary when extensive necrosis has already set in. The use of low-intensity laser therapy may be beneficial to improve vascularization and promote healing in the damaged skin.11 More recently, the admin- istration of glutamine to promote protein synthesis and cell proliferation has been found to be an effective therapy for radiation dermatitis.12 Oral Mucosa Oral cancer therapies can cause oral mucositis, an acute reaction characterized by erythema, mucosal ulceration, oropharyngeal pain, and speech difficulties (Fig. 1). Radiation-induced oral mucositis develops when radiation doses exceed 30 Gy. The frequency of oral mucositis secondary to chemotherapy ranges from 20% to 40%, and the incidence is 50% for those patients who receive induction Dental Management After Oral Cancer Therapy 133 Table 1 Complications associated with oral cancer therapies Potential Outcomes of Chemotherapy, Affected Structures Radiotherapy, and Surgery Skin Radiation dermatitis Oral mucosa Mucositis Infections: fungal, viral, bacterial Teeth Caries caused by hyposalivation Jaws/bone Chemotoxicity Osteoradionecrosis Secondary infections Mastication difficulties Salivary glands Hyposalivation/xerostomia Muscles and soft tissues Fibrosis Mastication Dysphagia Speech difficulties Temporomandibular joint Fibrosis and trismus Tongue and taste buds Taste dysfunction Others Pain Dentofacial abnormalities Altered quality of life Modified from Turner L, Mupparapu M, Akintoye SO. Review of the complications associated with treatment of oropharyngeal cancer: a guide for the dental practitioner. Quintessence Int 2013;44(3):267–79. chemotherapy.13,14 Methotrexate, cyclophosphamide, cisplatin, and 5-fluorouracil are associated with the highest risk for mucositis. The first signs of mucositis typically begin 3 to 4 days following the administration of the chemotherapeutic drug and last for about 15 days. Patients complain of oral sensitivity and burning, which are followed by the formation of painful ulcers.8,15 The risks of developing mucositis depend on the chemotherapy cycle, whereas the severity of mucositis increases with the intensity of therapy.8,15 Fig. 1. Mucositis after radiation therapy. Oral mucositis in a young male patient with nasopharyngeal rhabdomyosarcoma after radiotherapy. 134 Villa & Akintoye Preventive strategies used to attenuate the severity of oral mucositis secondary to oral cancer therapy include maintenance of optimal oral hygiene and the implementa- tion of oral care protocols. Rinsing the mouth frequently with 0.9% saline or sodium bicarbonate and meticulous daily tooth brushing and flossing decrease bacterial colo- nization of the oral ulcers and therefore shorten the ulcer healing time.5,16,17 Ill-fitting dentures and orthodontic appliances that have the potential to cause local trauma to the mouth should be adjusted or removed.5 Oral cryotherapy for 30 minutes is a recommended preventive measure in patients receiving boluses of 5-fluorouracil chemotherapy.16 Also, benzydamine hydrochloride oral rinse effectively reduces the severity of oral mucositis based on its antiinflamma- tory properties in patients with oral cancer treated with less than 50-Gy doses of radio- therapy.16 More recent evidence indicates that patients treated with doses greater than 50 Gy still benefit from the antiinflammatory properties of benzydamine hydro- chloride.18 The only medication approved for mucositis by the US Food and Drug Administration (FDA) is palifermin (keratinocyte growth factor). Palifermin is not used in oral cancer settings. It is used more appropriately to treat mucositis secondary to conditioning regimens in bone marrow transplant patients.19 Similarly, low-level laser therapy (LLLT) or photobiomodulation has been used with promising results in hematopoietic stem cell transplants patients receiving high-dose chemotherapy, but it is not recommended for the treatment of chemoradiation-induced mucositis.20,21 Laser light promotes angiogenesis; stimulates the production of serotonin, collagen, and cortisol; and increases DNA and RNA synthesis and cellular metabolism.22 As such, LLLT may negatively affect tumor behaviors or increase resistance to oral can- cer therapy. Several agents are recommended for pain management in patients with mucositis, although their efficacy remains unclear. These agents include palliative rinses such as MuGard (AMAG Pharmaceuticals Inc, Waltham, MA), Episil (Camurus
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