Abstract
The continual advances in research and improvements in technology are resulting in a much higher incidence of detecting cancer in the beginning stages. Early diagnosis coupled with the growth of the aging population is resulting in an increase in the number of cancer patients treated each year. Therefore, oral health professionals are increasingly likely to encounter patients dealing with the oral side effects of cancer therapy. Oral complications from cancer therapies are common and can substantially impair the comfort and function of patients during and after treatment for cancer. In addition, these complications may affect a patient's willingness to adhere to or ability to complete the prescribed therapies. Management of oral complications is best accomplished with an interdisciplinary approach between dentistry and medicine. Communication between the disciplines is crucial to a positive outcome for the patient.

In 1999, the National Institute of Dental and Craniofacial Research (NIDCR) projected that of the 1.2 million Americans diagnosed with cancer each year, approximately 400,000 would develop oral complications from their treatments.¹ More recent statistics show that projection was accurate. More than 1.3 million people were diagnosed with cancer in 2003.²

With the outpatient management of health care increasing, including cancer therapy, every health care professional is a potential and integral part of the cancer treatment team that once existed solely within the hospital setting.²It is more important now than ever before that the oral health care team take an aggressive role in the supervision of cancer patients' oral health before, during, and after cancer therapy.

Most cancer patients do not know that visiting a dentist can make a difference in their cancer therapy, but evidence shows that pretherapy intervention can help reduce the incidence and severity of oral complications.³ Oral complications from cancer therapy can seriously compromise patients' health and quality of life as well as the cancer treatment itself. These conditions can be so debilitating that patients may tolerate only lower, less effective doses of anticancer drugs, may postpone scheduled treatments, or may have to discontinue treatment entirely.⁴

Oral complications also can lead to potentially fatal systemic infections, such as disseminated candidiasis. Oral candidosis is the most common op­portunistic fungal infection encountered in dentistry. Normally a benign inhabitant of mucous membranes, the fungal organism Candida albicans may present serious, even life-threatening infection in specific patient populations. As an opportunistic organism, C albicans is extremely responsive to any process resulting in immunosuppression.⁵ The frequency of invasive mycoses caused by opportunistic path­gens has increased significantly over the past 2 decades. This increase in infections is associated with excessive morbidity, and mortality is directly related to the increase in patient populations at risk for developing serious fungal infections.⁶

Systemic candidiasis has a mortality rate as high as 77% depending on the underlying illness leading to compromised immune status. Systemic candidiasis is the cause of more case fatalities than any other systemic mycosis. Candidiasis can spread from a local infection to one affecting almost any organ system. Prompt treatment should be instituted to decrease the chance of a systemic and possibly fatal complication.⁷ Between 25% and 54% of septicemia cases in neutropenic cancer patients may originate from oral infection. Infections in the oral cavity are associated with oral ulcers, periodontal disease, pulpal disease, pericoronal disease, and sinus infections.²Therefore, it is important that oral health professionals be diligent when performing oral examinations on patients undergoing cancer therapy, and promptly inform the patient and the oncologist if any signs of oral infection are present.

A 1989 National Institutes of Health (NIH) Consensus Development Conference targeted oral mucositis research as one of the key areas for investigation relative to causation, clinical impact, and potential links with other complications in cancer patients.⁸ Ten years later, many oral health professionals and oncologists were still unaware of the correct steps to prevent or manage potentially serious problems. In an effort to change this, the NIDCR launched a campaign in 1999 to educate health care practitioners.¹The NIDCR created informational publications for oncology and oral health professionals detailing their roles in the prevention and management of oral complications of cancer therapy. Table 1 lists these publications as well as the NIDCR's informational publications for patients on the oral complications of cancer therapy, including wallet-sized cards to help patients keep track of every health care professional involved in their treatment as well as personal contact information. These cards have a reminder printed on the back informing the oncology team of what information they should send to the oral health care team for patients' pretreatment exams.

This ongoing campaign also emphasizes the critical importance of communication and cooperation between medicine and dentistry.¹The oral health care team should contact their patient's oncology team as soon as possible. Comprehensive dental consultation forms enhance and encourage communication with other members of the patient's cancer care team. These are 2-part forms. The first section details the patient's cancer diagnoses (disease and stage) and past and planned treatments. The second section details the patient's present oral health conditions, current treatments, and planned treatments. A sample form, can be viewed and printed by clicking here.

These forms foster interdisciplinary communication between health care team members. As importantly, they enable patients to participate more actively in their own cancer therapy program by knowing who is on their team and what roles they play in their treatment. In 1999, Dr. Harold Slavkin noted that "preventing and managing oral complications provides an excellent example of how dentistry and medicine can work together in partnership—and the winner is the patient." ¹

Oral Complications of Cancer Therapy
Oral complications are present in all 4 major types of cancer therapy²:

• Head and neck surgery
– surgical removal of anatomical structures of the head and neck

• Chemotherapy
– cytotoxic effects on the cells lining the oral cavity

• Head and neck irradiation
– tissue changes associated with total body radiation and therapeutic radiation to the head and neck

• Blood and bone marrow transplant
– the body's response to allogeneic bone marrow transplant and adjunctive pharmacological pre­parations (other than antineoplastic drugs)

The most common oral complications related to cancer therapies are mucositis; bacterial, viral, and/or fungal infections; salivary gland dysfunction; dysgeusia; and pain. These manifestations can lead to secondary sequela such as dehydration, malnutrition, fatigue, and as noted earlier, potentially fatal systemic infections. Radiation of the head and neck can irreversibly injure oral mucosa, vasculature, muscle, and bone. This can result in permanent xerostomia, rampant caries, trismus, soft-tissue necrosis, and osteoradionecrosis (ORN) of the jaw, another potentially deadly complication of cancer therapy.⁹

ORN is defined as "bone death secondary to radiotherapy."¹⁰ The mandible is among the bones most frequently affected by irradiation, with ORN the most severe postradiation injury. Although ORN typically occurs within 3 years after radiotherapy, patients probably remain at risk indefinitely. The diagnosis of ORN is principally based on the clinical picture of chronically exposed bone. In recent years, the incidence of ORN has decreased because of the introduction of preventative oral hygiene measures and meticulous dental evaluations before and after irradiation; the improvement in radiotherapy techniques,¹¹ such as intensity-modulated radiation therapy, which uses computer generated images to plan and then deliver tightly focused radiation beams to cancerous tumors;¹² and the development of reliable diagnostic and therapeutic procedures. Nevertheless, given the severe impact of ORN on patient quality of life, research should be continued to further ameliorate this problem.¹¹

With the advent of new treatments for cancer comes new side effects. There are now reports of osteonecrosis of the jaws (ONJ) in the absence of radiation. Jawbone necrosis is a clinical condition associated with defects in vascularization of the maxilla or the mandibular bone, which usually presents after head and neck radiotherapy and/or oral surgical intervention. However, over the last 10 years, cases of ONJ have been associated with bisphosphonate (BP) therapy.¹³ BPs are bone resorption inhibitors used in the treatment of multiple myeloma, bone metastasis, and malignant hypercalcemia (tumor-induced hypercalcemia). They are also widely used to prevent and treat osteoporosis and certain bone disorders, such as Paget's disease. These drugs are used worldwide, with clear and clinically contrasted benefits—particularly in application to malignancies.¹⁴ Accordingly, in September 2002, a group of experts in multiple myeloma developed a clinical guide for the administration of BPs, including the use of 2 potent intravenous (IV) agents: Pamidronate disodium (Aredia, Novartis Pharmaceuticals, East Hanover, NJ, www.pharma.us.novartis.com) and zoledronic acid (Zometa, Novartis Pharmaceuicals).¹⁴

In a recent study, 4 cases of ONJ were reported in patients taking pamidronate disodium and zoledronic acid without having undergone any kind of radiotherapy or dental surgery.¹³ These side effects had not been detected in the clinical trials before marketing and, in September 2004, in the face of increasing reports, the manufacturer included a warning communication and modified the recommendations for use of the 2 agents. As a result, osteonecrosis was included among the potential side effects and studies were initiated to further explore the relationship between BPs and ONJ.¹⁴

A review of 63 cases of osteonecrosis associated with BPs between 2001 and 2003 conducted a the Long Island Jewish Medical Center resulted in the following conclusion: "In view of the current trend of increasing and widespread use of chronic bisphosphonate therapy, our observation of an associated risk of osteonecrosis of the jaw should alert practitioners to monitor for this previously unrecognized potential complication. An early diagnosis might prevent or reduce the morbidity resulting from advanced destructive lesions of the jaw bone."¹⁵

Novartis sent out packets of information to oral health professionals in May 2005. These packets included: "Expert Panel Recommendation for the Prevention, Diagnosis, and Treatment of Osteo­necrosis of the Jaw,"¹⁶ revised package inserts on complete prescribing information for both Aredia and Zometa, a patient brochure, "Taking Care of Yourself While Living with Cancer: Dental Health and Osteonecrosis of the Jaw,"¹⁷ and a letter titled, "Important Drug Precautions for Dental Health Professionals with Patients Being Treated for Cancer," which requests that they report any serious adverse events of IV BP treatment to the US Food and Drug Administration (FDA) MedWatch Adverse Event Reporting Program (www.fda.gov/MedWatch/report.htm). Novartis included a copy of the letter, specifically requesting the dentist "to share with other dental health professionals in your practice, including dental hygienists [author emphasis]."¹⁸

Management of Oral Complications
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. This care should be both preventive and therapeutic as indicated to minimize risk for oral and associated systemic complications.⁹

Pretreatment Phase
Optimum management for the patient receiving chemotherapy requires that the patient be seen by the dental practitioner before chemotherapy begins. In general, oral care should be completed at least 1 week before chemotherapy starts, leaving approximately 2 weeks before the patient will be at the greatest risk of oral complications. Coordination of oral care will require close consultation with the patient's medical oncologist.² Open communication is essential to ensure that each provider has the information necessary to deliver the best possible care.⁴ An example of a patient communication form, which allows each provider to share patient information, can be viewed and printed by clicking here. Table 2 lists the information each health care team should provide.

A medical clearance form can be sent with the communication form to provide additional information regarding contraindications to any dental treatment, anesthetic, anxiolysis medication, and any medications the patient may need to hold for a particular procedure as well as the recommended prescription for prophylactic antibiotics, if necessary. An example form can be viewed and printed by clicking here. Copies should be sent to the patient's primary physician as well as any other consulting health care providers.

Time is of the utmost importance when treating a patient undergoing cancer therapy. If circumstances allow, the pretreatment period is the optimal time to institute an oral hygiene regimen, restore or remove diseased dentition, and eliminate potential sources of infection and trauma.²Severity of oral complications is reduced significantly when an aggressive approach to stabilizing oral care is initiated before treatment.⁹Table 3 lists the oral health care team's pretreatment objectives.

As early as 1965, Silverman and Chierici stated that meticulous care must be taken in evaluating the periodontal status before, during, and after radiation treatment.¹⁹ Mechanical oral hygiene procedures (calculus removal, root planing, soft-tissue curettage, tooth surface polishing, and daily plaque removal) must be used to remove the local etiologic factors of inflammatory diseases of the periodontium. The overall effect of the use of mechanical procedures is the reversal or control of inflammation, and there is no controversy that these positive effects on the periodontium are beneficial as pretreatment intervention.¹⁰

The recommended oral hygiene treatment will depend on the oral health of the individual and should be the most efficient and effective method of reducing the oral bacterial load in the time available before initiation of cancer therapy.⁷If the patient has a healthy periodontium, a prophylaxis should be performed before initiation of cancer therapy even if it is sooner than their previously scheduled 3-, 4-, or 6-month time frame. If the patient's periodontal disease is stable or in remission, an individualized periodontal maintenance appointment is appropriate at their previously determined 3-, 4-, or 6-month interval, or more often as determined by their home care routine and amount of build up they acquire. If the patient is diagnosed with acute active periodontal disease and cannot tolerate the long appointment needed to perform a full mouth disinfection and/or there is not sufficient time before the initiation of cancer therapy for an individualized course of nonsurgical periodontal therapy, with or without localized antibiotic placement, then a gross debridement for the purpose of decreasing the bacterial load before cancer therapy is recommended.

Preventive Therapies
Preventive therapies are critical to counteract the effects of xerostomia caused by both chemotherapy and radiation.³ Rampant caries increase secondary to a number of factors including shifts to cariogenic flora, reduced concentrations of salivary antimicrobial proteins, and loss of salivary mineralizing components.⁷ Ideally, the patient should be started on neutral fluoride therapy before radiation treatment. This may take the form of fluoride gel carriers, brush-on gels, fluoride rinses, and/or professionally applied fluoride varnishes.²Unflavored or lightly flavored products can increase compliance.

In addition to traditional fluoride treatments, there is a myriad of products available that work individually and/or synergistically with fluoride to minimize the effects of the chemical and biological processes attacking the oral cavity during cancer therapy. These products counteract the effects of xerostomia by stimulating saliva flow, buffering plaque acid, and providing bioavailable sources of calcium and phosphate minerals that can be incorporated into tooth enamel. These products help to restore the oral cavity to homeostasis and replenish lost minerals while providing an environment that allows for increased uptake of fluoride by the teeth. There are also numerous palliative products to introduce to the patient before the initiation of therapy. A table listing preventive, therapeutic, and palliative products can be viewed by clicking here.

Trismus is another oral complication that can be reduced by preventive therapy. Trismus tends to develop slowly. Treatment that begins early in the progression of the condition is likely to be more effective and easier on the patient.²⁰Because of this, it is important to be proactive in looking for the early signs of trismus. One simple test is the "3 finger test." Ask the patient to insert 3 fingers into his or her mouth. If all 3 fingers fit between the central incisors, the mouth opening is considered functional. If less than 3 fingers can be inserted, restriction is likely. To help prevent and decrease future trismus complications, suggest initiating a prophylactic exercise program for the jaw muscles.

A good starting point is the "7-7-7" exercise regimen. The patient opens and closes his or her mouth with assisted opening 7 times, and holds the open position at the maximum opening that can be sustained without pain for 7 seconds. The exercises should be performed 7 times per day. The Oral Cancer Foundation also recommends a passive motion device to aid in these exercises, the TheraBite (Atos Medical Inc, Milwaukee, Wisc, www.atosmedical.com) jaw motion rehabilitation system.²⁰ Researchers have found that early use of this device helps to improve mobility of the mandible and to improve speech and swallowing in a patient population that is at risk of having difficulties with these functions. One of the benefits of the TheraBite system is that it not only stretches the connective tissue that causes trismus, but also allows for proper mobilization of the temporomandibular joint, thus addressing a secondary cause of pain and tightness.^21,22

It is very important that the oral health care team support the oncology team by impressing on the patient that adequate nutrition; alcohol and tobacco avoidance; optimal oral hygiene, with frequent office visits, if necessary; and meticulous home care, before, during, and after treatment can prevent or minimize oral complications.

Assess the nutritional status of the patient and provide counseling and referrals, if needed, to enable the patient to avoid debilitation, delayed wound healing, and increased susceptibility to caries secondary to malnutrition.³Have the patient start planning a menu that will be tolerated during therapy. Additional information from nursing staff or dietary aides may be needed. Shopping can be done in advance so nutritional items will be available when the patient is not feeling well. Also, suggest beginning to reduce sugar and acidic foods from the diet and increase water intake as much as possible.

Provide patients with support information on quitting smoking. The American Dental Hygienists' Association (ADHA) and the University of California, San Francisco (UCSF) are working together to promote tobacco cessation. "Quit Now" cards, designed by the UCSF, are available through ADHA's national Smoking Cessation Initiative (SCI) and Ask.Advise.Refer. (AAR) programs.²³These programs provide numerous support options.

Alcohol use has been identified as a major risk factor for cancers of the upper aerodigestive tract. In studies controlled for smoking, moderate-to-heavy drinkers have been shown to have a 3 to 9 times greater risk of developing oral cancer.²⁴ For those patients who may have a problem abstaining from alcohol, there are many resources available.²⁵

Instructions for the Patient
Patient education is an integral part of the pretreatment therapy. It is very important that patients recognize that they can prevent or minimize oral complications by changing their behaviors. Most of the pretreatment as well as treatment protocols aimed at preventing or ameliorating oral complications of cancer therapy require patient adherence to prescribed oral hygiene procedures. Patients must be cognizant of the potential side effects of the anticancer regimen. The rationale for pretreatment strategies must be explained to encourage adherence to the therapy.³

Assess the patient's oral health awareness as well as his or her motivation and ability to perform oral hygiene procedures. To ensure that the patient fully understands what is required, provide detailed written instructions on specific oral care practices, such as how and when to brush and floss, how to recognize signs of oral complications, and other instructions appropriate for the individual. For example, remind patients with prosthodontic appliances to remove their dentures or partials when brushing, to brush after every meal and before bed, and to leave the appliances out overnight.⁴

Advise patients to begin incorporating their recommended daily oral hygiene home care routine as soon as possible. It will be easier to maintain if they start before the initiation of cancer therapy. Recommend purchasing specific toothbrushes, oral hygiene adjuncts, and preventive and palliative products in advance of cancer therapy. (A table listing these products can be viewed by clicking here.)

Supportive care including education and symptom management are important for patients experiencing complications related to cancer therapy. It is important to closely monitor each patient's level of distress, ability to cope, and response to treatment. This approach provides a setting for the health professional to demonstrate concern for the patient's complications and to educate the patient and family caregivers. Comprehensive supportive care from staff and family can enhance the patient's ability to cope with cancer and its complications.³Most importantly, emphasize the importance of immediately reporting any oral complications to both the oral health care and oncology teams to prevent the worsening of symptoms and/or the development of secondary complications that could compromise cancer therapy outcome.

Conclusion
It is our obligation to our patients as health care providers to continue to educate ourselves, the other members of our oral health care team, and our colleagues in other health care disciplines. We must be aware of the latest research, be knowledgeable in currently accepted treatment protocols, and be up-to-date on the newest products and implements available. To fulfill this obligation, it is imperative that we appropriately refer patients to other providers when necessary and maintain constant communication with the patients' cancer treatment team.

An interdisciplinary approach to patient treatment is the most comprehensive and effective way to make a significant difference in a patients' cancer therapy experiences. Increased communication between the patients' oral health teams and oncology teams will lead to enhanced treatment of oral complications by providing patients with the tools and information necessary for their active participation in managing these complications.

Dedication
In memory of Fran. Her light will continue to shine in those of us lucky to have been touched by her while she was here.

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