Aggressive cancer therapy places patients at greater risk for oral complications and treatment-related consequences. Unfortunately, prevention and/or treatment of such oral sequelae have become often overlooked priorities of the treatment team.
Aggressive cancer therapy places patients at greater risk for oral complications and treatment-related consequences. Unfortunately, prevention and/or treatment of such oral sequelae have become often overlooked priorities of the treatment team. We describe a philosophy of management of the cancer patient that specifically emphasizes the prevention and treatment of oral complications associated with cancer therapy. These concepts and principles are based on treatment protocols and ongoing clinical practices at The University of Texas M.D. Anderson Cancer Center in Houston, Texas.
In 1995, a projected 1.2 million people in the United States (excluding those with skin cancers) will be diagnosed with cancer; most of these individuals will undergo some form of potentially curative chemotherapy, surgery, radiotherapy, or combinations thereof . These therapies can be even more effective when accompanied by supportive care aimed at (1) preventing preexisting or treatment-associated pathologies from compromising treatment outcome and (2) maintaining patients' quality of life.
Almost all patients treated for cancer need some measure of rehabilitation, specifically delivered through a team effort focused on the whole person rather than on a cancer at a specific site. Consequently, the past several decades have seen the evolution of multidisciplinary teams that offer maximal therapy with minimal morbidity and optimal functional recovery. The dental oncologist is an important member of such teams.
In this article, we aim to help practitioners better understand how diverse dental oncology concepts are unified and used in the multidisciplinary treatment of cancer patients. Thus, we will discuss, in terms of a practical approach developed at our institution, general and specific considerations related to minimizing the oral complications of chemotherapy, radiotherapy, and surgery. We will also explore the integration of dental and oral treatment into specific oncologic therapy.
The status of the oral cavity in the cancer patient is no different from that found in the general population: poorly maintained dentition, moderate to advanced periodontal disease, ill-fitting denture prostheses, and related soft-tissue pathologies associated with tobacco and alcohol use and nutritional and/or general hygiene neglect [2,3]. The overall treatment outcome in cancer patients can be influenced by preexisting oral/dental pathologies that could be easily diagnosed with appropriately timed oral examination and minimized or eliminated with the implementation of preventive or treatment measures.
In addition, patients being treated aggressively with anticancer regimens often develop preventable or treatable oral mucosal and dental sequelae that can produce morbid events . This treatment-associated oral morbidity may vary, depending on the interaction of each patient's oral/dental status with the type of malignancy and the combination of therapies used, ie, surgery, radiation, and/or chemotherapy . Also, treatment-limiting toxicities that can lead to possible dose reduction or termination of therapy, such as mucositis, infection, and bleeding, can be minimized, and in some cases eliminated, by means of early evaluation and treatment by a dental oncology team.
Pretreatment Oral Examination
It is most important for the oncologist to ensure that patients who have head and neck surgery and associated radiotherapy or who receive chemotherapy undergo a thorough pretreatment oral examination. Several general types of oral complications are associated with cancer therapy: stomatitis, infection, bleeding, mucositis, pain, loss of function, and xerostomia . Most of these are related to preexisting conditions that cause the complication's initiation, intensification, or persistence. The three sites in the oral cavity that are the focus of these complications and at which preventive or therapeutic measures can be directed are the mucosa, periodontium, and teeth.
At the initial dental oncology visit, a patient undergoes a head and neck evaluation, oral and dental clinical examination, and an intraoral radiologic evaluation. This initial visit is directed at documenting and removing preexisting acute and chronic conditions that could produce obvious complications: dental abscesses, teeth with advanced periodontal disease, dental calculus that could cause gingivitis, partially erupted teeth with the potential for pericoronitis, and soft-tissue tooth trauma. Even if the cancer treatment is nontoxic to the mucosa or nonmyelosuppressive, the potential for oral infection is still present and could develop into a painful condition even under usual circumstances. Thus, with the possibility of cancer progression necessitating prompt and aggressive therapy, evaluation of the oral/dental status and treatment of any pathologies will minimize these predictable complications.
Modification of Oral Care and Hygiene
The patient's oral care and hygiene techniques are modified, if possible, to minimize mucosal and gingival complications that could arise from the specific treatment(s) being given. One major objective is to reduce and control plaque formation on teeth and soft tissue. Plaque is a proteinaceous, adherent, bacteria-laden debris material that can be colonized by normal flora as well as opportunistic pathogens; plaque accumulation can lead to several harmful conditions, such as superinfection of mucositis, gingivitis, periodontal disease, or caries .
Calculus can eventually form from plaque, resulting in the pathologic loss of supporting soft tissue and bone and thus creating a sanctuary for bacteria or sites of gingival bleeding . It must be mentioned that, contrary to popular belief, rinsing with salt or baking soda does not remove the potential septic foci of plaque and calculus; rather, they must be professionally removed.
Removal of Infected Tissue
Oral surgery, definitive or intermediate restorations, and oral prophylaxis may be performed quickly and safely under local dental anesthesia and/or intravenous sedation/general anesthesia to expeditiously remove acutely and chronically infected tissue. However, because communication and teamwork are critical in maximizing therapy, the medical and hematologic status of the patient must be reviewed and discussed with the primary-care physician before such dental treatment is initiated.
It has been estimated that up to 60% of patients with cancer will receive chemotherapy as one component of their treatment . If oral complications develop during therapy, they can potentially lead to systemic involvement [9,10]. Specific interceptive and therapeutic guidelines have been established to correct or modify potential clinical or radiographic oral/dental pathology before such problems occur [4,11,12].
Stomatitis vs Mucositis
Much confusion exists with regard to the soft-tissue mucosal reactions seen during chemotherapy. In order to achieve a clear understanding about what is going on in the oral cavity and to provide the appropriate treatment, the clinician must be able to determine whether these changes should be diagnosed as stomatitis or mucositis [4,11,13].
The term "stomatitis" can be generally applied when mucosal integrity has been lost due to local trauma, ie, biting, denture irritation, or even infection (Figure 1) . Treatment usually consists of identifying (by culture) and/or correcting local causes, ie, smoothing rough teeth, prescribing mucosal toothguards, or stressing the importance of a soft diet in order to decrease functional irritation and trauma [4,11].
Denture prostheses promote as well as augment stomatitis in several ways: They can produce traumatic wounds (Figure 2) while providing a sanctuary for microorganisms by shielding the mucosa from oral hygiene or appropriate topical medication rinses . In addition, not only can dentures hold the infectious agents in close proximity to any ulceration that may develop under them, they can hinder proper mucosal assessment. Stomatitis, then, can be prevented and/or corrected with dental or antimicrobial treatment.
In contrast, the term "mucositis" denotes the cytotoxic effect chemotherapy has on the oral mucosal tissues. Before a diagnosis of mucositis is made, however, all other factors must be ruled out, ie, trauma, factitious injury, and/or infection. If incorrectly identified, mucosal reactions could cause effective therapy to be delayed, chemotherapy dosage to be reduced, or chemotherapy/radiotherapy to be discontinued. Hence, an essential aspect of oral care is culturing for microorganisms to evaluate the incidence of mucositis vs infection [4,11]. To aid in early diagnosis, the patient must be counseled to report any mucosal changes or increased sensitivity.
Diagnosis of Mucositis
Mucositis is the most common acute complication of chemotherapy, and usually begins as erythema and increased sensitivity resulting from thinning of the mucosa [2,11]. As tissue changes continue, small ulcerations begin to develop, which can lead to large areas of mucosal denudation (Figure 3). Use of a grading score of severity for mucosal reactions during each course of therapy allows clinicians to take appropriate preventive or therapeutic measures during current and future treatment courses (Table 1).
Patients vary greatly in their tolerance of chemotherapy regimens and their proclivity for developing mucositis. Several classes of chemotherapeutic agents are known to produce mucositis, depending on the dosage and duration of treatment; these include antimetabolites, antibiotics, and, to a lesser degree, alkylating agents and vinca alkaloids. However, from what we have observed clinically, any agent given at an intensified dose or for a sufficient duration can produce mucosal toxicities leading to dose limitation [12,13].
Consequently, it is of the utmost importance for the clinician to be aware of the relationship between the timing of administration of chemotherapy and any mucosal reactions. One would expect mucosal toxicity, or mucositis, to develop shortly after the start of chemotherapy. However, mucosal herpes simplex virus infections also can occur early in the chemotherapy cycle. There is significant misdiagnosis of such infections as mucositis, which results in nontreatment of the infectious process . Also, mucosal reactions that occur in association with a hematologic nadir could be related to infectious stomatitis. Culturing is essential in these situations to differentiate chemotherapy-induced mucosal toxicity from mucosal neutropenic infections caused by bacteria, fungi, or viruses (Figure 4). The loss of mucosal integrity can produce bacteremic episodes that could be life threatening to immunocompromised patients .
Prevention and Treatment of Mucositis
Effective approaches for the prevention or treatment of oral mucositis have not been standardized, and vary considerably among institutions. Comprehensive care should focus on the prevention of complications by eliminating known and predictable factors that initiate mucosal pathology and by promoting good hygiene and nutrition, thereby minimizing the risks of infection, bleeding, and pain.
In addition to these measures, oral rinses containing antidotal concoctions of antibiotics, antifungals, and narcotic analgesics in a coating suspension can be administered for treatment palliation [16-19]. Other agents, such as allopurinol, leucovorin, vitamins, cryotherapy, and growth factors, have been tried for the prevention of chemotherapy-induced mucositis [20-25]. Use of a capsaicin-containing candy has also been advocated to desensitize pain receptors in the mouth . To date, none of these approaches has shown a significant impact.
Oral Hygiene-Chemotherapy-induced sequelae can include pancytopenia, nausea, mucositis, and infection [11,27]. To avoid such sequelae, the patient should be advised of the importance of brushing with a soft toothbrush, keeping the oral mucosa moist and clean, and selecting and maintaining an appropriate diet following chemotherapy.
The fear that brushing will increase the chances of oral complications has always been a concern among practitioners, and yet the benefits of brushing outweigh the drawbacks. Even in healthy mouths, a certain degree of bacteremia can be associated with normal function (eg, eating) . However, any threat of persistent bacteremia in a compromised host is cause for concern [29,30]. Thus, the benefits of controlling bacteremia-promoting plaque through appropriate hygiene-swishing fluids is a poor substitute for thorough oral care by brushing-far exceeds the drawback of a potential increase in oral complications (Figure 5). Indeed, with careful oral care that includes brushing, chemotherapy-induced sequelae can be kept to a minimum or even eradicated.
Fortunately, for those practitioners who still worry about the harmful side effects of brushing, there are warning signs that indicate when a change to a softer brush is needed. If a patient's platelet count falls below 40,000/mm³ if his or her oral tissue becomes more sensitive, or if a coagulopathy exists, the patient should be switched to an ultrasoft "chemobrush" (Ultra Suave; Periodontal Health Brushes, Osseo, Wisconsin). The use of a foam brush is highly discouraged . However, if the patient is maintaining good oral care and oral lesions still develop, the microorganism concentration in the oral cavity should still be low enough that any superinfection potential would have a minimal influence on the intensity of the patient's discomfort and on wound healing .
Oral Rinses-Compliance with oral care procedures is a major factor in maintaining the relative health of the mucosal tissues and the effectiveness of locally applied topical oral agents. These topical medications should be nonirritating and nondehydrating. Mouth rinses are frequently recommended as therapy for mucositis in both dentate and edentulous patients. Such rinses not only cleanse the mouth of loose debris and thick mucus but also hydrate the mucosa and treat mucositis.
Most commercial mouth rinses contain alcohol- or phenol-like substances that should be avoided, since they can irritate and desiccate inflamed, compromised xerostomic tissues . Furthermore, these rinses can further compromise the mucosa by prolonging the healing of oral wounds.
Our experience has shown that a diluted hydrogen peroxide solution (1 part 3% hydrogen peroxide to 4 parts water) adequately cleanses the tissues of debris, bacteria, and mucus [4,12]. This cleansing should be immediately followed by a rinse of water. When oral lesions exist, rinsing with the diluted hydrogen peroxide solution is recommended only to decrease wound contamination and colonization. The hydrogen peroxide rinse should not be used if there are any blood clots or bleeding, since it would only foster more bleeding.
Topical coating agents can be most effective in promoting mucosal wound healing, yet the sequence of delivery of these agents to the compromised oral soft tissues is important [2,11]. The tissue must be cleaned of mucoid debris before the application of the agents. Next, a troche or lozenge form of the oral medication should be taken, as it provides a longer and more constant application of the medicine to the tissue . An oral liquid suspension can be used if the mouth is dry, even though it will be in contact with the tissue and any organisms for only a limited time. All prostheses should be removed during the oral-mucosal treatment .
If a mucosal-coating agent, eg, sucralfate (Carafate) or kaolin-pectin, is to be used, it must be administered last so as not to block out the effects of the topical antimicrobial agents on the tissues or in the wounds. Thirty minutes should elapse between the applications of the agents.
In providing the treatment described above, an oral care schedule for patients receiving chemotherapy can be very useful to the practitioner (Table 2). Again, it must be emphasized that the clinician must maintain constant vigilance of oral mucosal wounds and order cultures when indicated to provide appropriate assessment and therapy.
Avoidance of Topical Anesthetics-An additional comment should be made with regard to the use of topical anesthetics. We routinely discourage use of anesthetic agents once mucosal discomfort develops due to their irritating nature. A more significant factor is the profound suppression of the gag-cough reflex topical anesthetics can produce, leading to possible aspiration.
Nutrition-Finally, an important, often overlooked factor for immunocompromised chemotherapy patients is nutrition. The diet for cancer patients during chemotherapy must be palatable as well as nontraumatizing to the oral mucosa. During the myelosuppressive phase of therapy or during periods of mucositis, the patient's diet should consist of soft food that will not abrade or puncture the mucous membrane or cause direct tissue trauma. Patients, family members, and dietitians can be creative in preparing foods that comply with such a diet and yet remain appetizing, tasteful, and nutritious [4,5,35].
Complications from therapeutic administration of ionizing radiation to the head and neck are generally of two kinds: acute (treatment-related mucositis, alteration of taste or smell, infectious stomatitis, and dermatitis), or chronic (xerostomia, dental decay, trismus, fibrosis, photosensitivity, and osteoradionecrosis). Treatment-related complications can also be categorized as transient or permanent. Clinically, the severity of the morbidity is related to the radiation dose, volume of tissue treated, and age of the patient . In general, a healthy oral status prior to radiotherapy reduces a patient's risk of post-radiotherapy complications.
Adverse Effects on Bone
Irradiation can adversely affect cellular elements of bone, which can limit the potential for wound maintenance and the ability to heal after a traumatic event [4,36]. Further, the risk of complications following trauma from oral surgery in an irradiated field can be highly significant, although some claim that this risk is low, up to a predetermined threshold of irradiation [37-39]. For these reasons, elective oral surgical procedures, such as extractions and soft-tissue surgery, are contraindicated within an irradiated field [4,40]. However, some nonsurgical dental procedures can be safely done, including oral prophylaxis, radiography, routine restorative procedures, and nonsurgical endodontic and prosthodontic procedures, since these procedures do not cause bony trauma.
Existing or potential problems should be eliminated prior to irradiation in order to prevent future post-radiotherapy oral trauma . For minor oral bony necrotic lesions following radiotherapy, local debridement and irrigation with an antimicrobial rinse (chlorhexidine gluconate [Peridex]) can be beneficial in treating the wound; such a procedure can be performed by a dental oncologist or an oncologic nurse practitioner under supervision.
Hyperbaric Oxygen-If surgical intervention, ie, extractions, endodontic, or periodontal surgery, is required after radiotherapy, preoperative hyperbaric oxygen treatments may increase the potential for healing while minimizing the risk for osteoradionecrosis [41-43]. Unfortunately, this form of treatment is time consuming and expensive (each treatment can last up to 3 hours and cost approximately $500). In general, 20 treatments are required prior to surgery and 10 treatments afterward . Nevertheless, when compared with post-radiation dental treatment, ie, radical debridement and reconstruction, hyperbaric oxygen treatment can be cost effective and possibly prevent jaw amputation. It is therefore beneficial to do a preradiotherapy oral examination, not only for financial reasons but also for the purpose of potentially decreasing patient morbidity.
Damage to Salivary Glands
When the salivary glands are involved in a radiation field, the daily use of a fluoride gel is necessary to prevent caries due to the decrease in salivary protection (Figure 6). This radiation-induced xerostomia is due to permanent damage to the salivary gland tissues .
Fluoride Gels-Either a 1.0% sodium fluoride gel or an acidic 0.4% stannous fluoride gel is used for the prophylaxis of dental caries. Most patients apply the gel in a custom-fabricated polypropylene applicator that completely covers and extends slightly beyond the tooth surface . The applicators are worn for 10 minutes daily. Patients who receive low doses of radiation, whose compliance is good, and who are expected to have a slight degree of xerostomia can apply fluoride gel by toothbrush.
We must mention that sodium fluoride, due to its lower acidity, has a lesser degree of uptake by the tooth structure and always necessitates the use of custom applicators . On the other hand, sensitivity and pain can be a problem with the use of the more acidic stannous fluoride, and may require a change to the sodium fluoride preparation. Despite these problems, a properly utilized daily fluoride program can protect the teeth from profound radiation-induced xerostomic decay [4,5,45].
Permanent Xerostomia-In most cases, transient decreases in salivary flow caused by radiation therapy can become permanent, as illustrated by a study that followed patients for up to 25 years after radiotherapy . In that study, Liu et al found that patients who received bilateral ionizing radiotherapy involving the major salivary gland tissues exhibited, over time, decreases of 80% in stimulated salivary flow and 78% in unstimulated salivary flow, when compared with a nonirradiated group. Patients who underwent unilateral irradiation involving only one parotid and one submaxillary gland experienced comparable 60% and 51% decreases in stimulated and unstimulated mean salivary flow, respectively. Patients who underwent neck irradiation, ie, mantle field treatment, likewise experienced decreases of 43% and 32% in stimulated and unstimulated flow rates.
Oral Rinses-Changes in salivary flow induced by radiation are worrisome because saliva protects the oral mucosa from dehydration and assists in the mechanical lavage of food and microbial debris from the oral cavity . To avoid oral infections that may arise from radiation therapy, the patient must frequently rinse the oral cavity to reduce the number of oral microorganisms and to maintain mucosal hydration . Such oral lavage can be done with a solution of 1 teaspoon of sodium bicarbonate in 1 quart of water. This solution should be used frequently each day. It has been our clinical experience that this patient-prepared solution is better accepted than the commercially available salivary substitutes. Also, a specially prepared oral suspension of sucralfate, which has been tested and proven at our institution, can be used to soothe mucosal reactions during radiotherapy [4,5].
If these guidelines are followed, oral tissues can be maintained in a healthy state following radiotherapy. However, the cooperation and compliance of the patient, which includes scheduled professional evaluations and treatment, are essential, and are considered the result of education and motivation.
It is estimated that in 1995, 68,000 individuals will develop head and neck cancer (excluding superficial skin cancer) [1,47]. Most of these cancers are treated with surgery, radiation, or the two modalities combined. Chemotherapy has been of little benefit to patients with head and neck malignancies, except those with sarcoma .
The choice of treatment depends primarily on the anatomic site, extent and histologic grading of the tumor, and infection. Primary tumors of the head and neck area are specified by the site of occurrence: 40% occur in the oral cavity, 25% in the larynx, 15% in the oropharynx/hypopharynx, 17% in the major salivary glands, and 13% in the remaining head and neck sites .
The dental oncologist has become an integral member of the rehabilitative team that treats head and neck cancer patients. Modern reconstructive techniques permit cancer patients, especially those with head and neck malignancies, to undergo more immediate reconstruction and thereby achieve better functional outcomes while still progressing through multimodality treatment in a timely manner.
As mentioned above, infections in the oral cavity can lengthen postoperative recovery time, significantly compromise any reconstructive graft to the point of failure, and delay effective adjunctive therapy, such as radiation or chemotherapy . However, if a thorough oral and dental examination is done prior to surgery, compromising dental situations can be eliminated by coordinating oral surgery with the primary ablative oncologic procedure [11,35]. Patients usually appreciate this approach as it avoids stressful treatment in a clinical setting under routine local dental anesthesia.
Removable prostheses are sometimes needed to replace surgically removed anatomy in head and neck cancer patients; the maxillofacial prosthodontist is ultimately responsible for coordinating fabrication of such devices [2,34,48]. Prostheses can be of several types. Extraoral (facial) prostheses, such as orbital, auricular, and nasal prostheses, cover obvious surgical ablative tumor defects and help the patient adapt or achieve a more "normal" lifestyle . Intraoral prostheses (maxillary obturator, palatal augmentation device, or mandibular resection denture) reproduce preoperative oral contours important in aiding and maintaining speech and deglutition .
Surgical prostheses are used to immediately restore function after a maxillectomy and mandibulectomy (Figure 7). Various appliances are used to fix skin grafts and to properly align the maxilla and mandible prior to reconstructive procedures [34,49,50]. Regardless of the type of prosthesis used, however, it is of the utmost importance to discuss the preoperative and postoperative care of the prosthesis and surgical site, as well as oral hygiene and postoperative physical therapy procedures that will facilitate the immediate surgical, interim, and long-term definitive prosthodontic rehabilitative phases. Patients and family members can adjust more easily to postoperative functional losses and to rehabilitative prostheses if they know about these beforehand.
Postoperative Oral Care
Oral care during the postoperative period should include the care of the maxillary surgical defect and, when applicable, the skin graft (Figure 8). The surgical site should be evaluated for skin graft viability when the surgical prosthesis is removed . At this time, the patient is instructed in the care of the surgical site and the removal of dried crust and mucoid debris from the defect.
One approach to care is gentle irrigation and rinsing with a diluted hydrogen peroxide solution (equal parts of 3% hydrogen peroxide and water) followed by a salt and baking soda rinse (1/2 teaspoon of salt plus 1/2 teaspoon of baking soda per 1 quart of warm water) [4,5]. The patient is instructed to rinse three to four times daily and to clean the prosthesis with hand soap and water several times daily.
Soon after the surgery, a dental hygiene regimen, ie, toothbrushing, can be instituted. As the skin graft integrates with adjacent tissues, usually within 3 to 6 weeks, a mechanical pump with a multiorifice tip may be used for gentle, guided irrigation. In addition to using the irrigation system, the patient can use a 4 x´4-inch gauze or clean washcloth soaked with 3% hydrogen peroxide and placed around the finger to gently clean the surgical site and remove crusting debris. The patient should be advised not to use commercial mouthwashes since they all contain some alcohol or phenol, which can delay healing and irritate the wound .
Oral opening exercises should be initiated as soon as the patient can tolerate them . Such exercises can include the use of tongue blades to counteract a decreased oral opening by placing the blades between the posterior teeth to stretch the scar tissue and create a new maximum opening.
Other exercises include the use of mechanical devices that are custom-made and stretch the postsurgical scar tissue. One such device is a threaded screw-type instrument known as the Therabite Mouth Opener (Therabite Co., Bryn Mawr, Pennsylvania), which works like a car jack to open the mouth. Users of these devices must take care to ensure that teeth do not incur orthodontic movement or damage. The edentulous patient can simply place the thumb and index finger between the maxillary and mandibular ridges in a crossed position to push open the mouth.
In addition, more advanced means of physical therapy can be instituted by a trained physical therapist, eg, auriculotherapy, electrotherapy, ultrasound therapy, and isometric exercises . Such therapy will maintain the oral opening and give the patient better access to the defect as well as the rest of the oral cavity [51-53]. Oral opening measurements should be recorded to help both the clinician and patient not only assess the progress of these exercises but also detect any insidious decrease in opening.
Even when results are excellent, patient exercises should be continued for at least 1 year and, possibly, indefinitely [51-53]. Furthermore, even with physical therapy, patients may only regain oral opening of less than 10 mm anteriorly. If a patient complains of a sudden loss of oral opening ability, one should immediately suspect and rule out disease recurrence. Infection can also cause a loss of oral opening.
In all cases, head and neck surgery patients should be followed closely by the health-care team. Regularly scheduled appointments with the dental oncologist are essential for monitoring oral and dental hygiene, ensuring proper fit of prostheses, and most important, assessing for disease recurrence [27,53]. Teams of specially trained medical and surgical personnel can then provide expert judgment and skill for patients with advanced disease.
Patients diagnosed with cancer or undergoing myelosuppressive therapy should receive a thorough oral/dental assessment. Prompt recognition of primary and secondary mucosal insults and institution of appropriate preventive or therapeutic measures can decrease the incidence of such complications or ameliorate their morbid sequelae. By encouraging collaboration and communi- cation with other members of the multidisciplinary team, the dental oncologist can have a significant influence on the treatment and prevention of cancer complications in the oral cavity.