This article is divided into three time periods according to the different phases of cancer treatment: pre, inter, and postcancer therapy. The purpose of dental protocols prior to cancer therapy and the incidence and management of acute and long term oral complications from cancer therapy in the pediatric population are discussed.
Cancer is the second most common cause of fatalities in children in the United States, after accidents. The incidence of childhood malignancy is greatest in the first year of life, with a second peak at 2 to 3 years of age. The rate of childhood malignancies has remained relatively constant, with approximately 7300 children between 0 and 14 years of age diagnosed with cancer annually. Acute leukemias, lymphomas, brain tumors, soft tissue tumors, and renal tumors are the more common malignancies in children. Early diagnosis and advances in medicine have significantly improved outcomes of treatment resulting in higher survival rates ; however, this progress comes at the expense of a higher incidence of adverse side effects because of more aggressive antineoplastic treatment strategies.
The oral cavity, a trauma-prone environment, is extremely sensitive to toxicities from antineoplastic agents. Mucositis, parotitis, taste changes, xerostomia, opportunistic infections, pain, and bleeding are common acute oral complications associated with chemotherapy and radiation therapy. The incidence of oral sequelae in children varies considerably in the literature and ranges between 30% and 100% . These complications, if severe, frequently require supportive therapy and may delay, or be a dose-limiting factor in, the delivery of optimal treatment.
Oral health care specialists, including pediatric and hospital dentists can support the oncology team by providing basic oral care, implementating oral care protocols, delivering emergency dental treatment, and assisting and/or managing oral complications from cancer therapy.
This chapter covers the considerations in the dental management of pediatric patients undergoing cancer treatment, specifically chemotherapy, radiotherapy, and hematopoietic stem cell transplantation (HSCT). Because of the limited amount of published materials directly addressing oral complications and management in pediatric patients, the bulk of the recommendations were adapted and modified from the adult literature.
Oral and dental management before initiation of cancer therapy
The diagnosis of cancer is overwhelming for families of affected children and many parents naturally focus on the medical aspects of treatment, overlooking the significance of oral health. Hematologic malignancies and most cancer treatment protocols are associated with immunosuppression, and the oral cavity, which is naturally colonized by and serves as a reservoir for a large number and variety of microorganisms, is a potential portal of entry for opportunistic infections . It is thus essential to educate both patients and parents about the importance of a thorough pre–cancer therapy dental evaluation, maintenance of good oral hygiene, adherence to a noncariogenic diet, and the benefits of preventive oral care to avoid oral problems during and after cancer therapy . The delayed effects of antineoplastic treatment on the developing dentition and craniofacial complex should also be discussed.
Initial dental evaluation
Review medical and dental history
A review of the medical history should include the following information on type of malignancy: goal of treatment (curative versus palliative); treatment protocols (single modality therapy versus multimodality therapy); schedule, dosage, and class of chemotherapeutic agents; field, dosage, and site of radiation; use of indwelling central venous catheter; current status of immune system; secondary medical diagnoses; medications and allergies . For patients undergoing HSCT, information on type of transplant (allogeneic versus autologous), human leukocyte antigen (HLA) compatibility, conditioning protocol, and graft-versus-host disease (GVHD) prophylaxis should also be elicited .
The dental history should include date of last dental visit, dietary habits, history of dental trauma, elicited or spontaneous dental pain, and oral hygiene practices.
Poor underlying oral health has been linked to an increased incidence of intertherapy complications; hence, the rationale for precancer dental evaluation . However, no single precancer dental protocol has enjoyed universal acceptance because of few outcome-oriented clinical trials conducted to measure the efficacy of a particular protocol .
Precancer dental protocols typically involve a thorough extraoral and intraoral examination including radiographs, preferably completed before commencement of antineoplastic therapy. The goals of precancer dental protocols include the following:
Removal of any active and potential sources of infection in the oral cavity. Acute and chronic odontogenic infections such as caries and periodontal disease, and teeth with questionable/poor prognosis must be definitively treated. The justification for this aggressive approach is that any minor odontogenic infection in a profoundly immunosuppressed individual may develop into a systemic infection; occasionally resulting in a life-threatening event.
Ensure that the oral cavity is free of all possible sources of local irritation such as a sharp tooth cusp or a rough area on a restoration.
Evaluate for evidence of involvement of the oral cavity by the malignancy (such as leukemia or metastatic tumor).
Educate the patient regarding the necessity of dental treatment before cancer therapy starts, what to expect during cancer treatment, and long-term side effects of cancer treatment.
Dental treatment should ideally be completed before the child is immunocompromised, which may not be feasible in all situations. Some patients may be immunosuppressed by virtue of their malignancy, while others have depressed bone marrow function because they have already begun cancer therapy. The patient’s blood count typically declines 5 to 7 days after a dose of chemotherapy and remains depressed for 2 to 3 weeks before recovering to near normal levels, although this may vary depending on the specific cytotoxic treatment regimen. Discussion with the child’s physician to coordinate the timing of dental treatment and to discuss the need for additional medical interventions is warranted.
When all treatment cannot be completed before the immune status is compromised, prioritizing dental procedures is vital. Removal of sources of tissue irritation, addressing periodontal disease, treating symptomatic oral infections, and instituting endodontic treatment of asymptomatic permanent teeth precede restoration of asymptomatic teeth with shallow caries and replacement of non-ideal restorations.
Fluoride varnish may be applied to incipient and small carious lesions. Larger asymptomatic cavities may be temporarily restored with interim restorative material or glass ionomer cement, or ideally, permanent restorations. These may be performed when the patient is immunologically stable or during the window period between chemotherapy doses where their blood counts have recovered to near normal levels.
The safety and risks of performing pulp therapy on primary teeth before cancer therapy are not known. Despite the high success rates of pulp therapy in primary teeth , many clinicians often elect to extract the teeth because of the risk of failure and subsequent infection. Clinically asymptomatic teeth with small apical pathoses that have previously been endodontically treated may be left as they are, with no re-treatment . However, signs and symptoms of inflammation and infection may be diminished in immunocompromised patients and suspicious periapical lesions need to be investigated further.
Endodontic therapy for symptomatic permanent teeth should be completed at least 1 week before initiation of cancer therapy to ensure adequate time for managing lingering symptoms. Extraction of the tooth should be strongly considered if resolution of infection cannot be established. Symptomatic teeth requiring more than one visit for completion of the root canal therapy are often extracted because of the need to begin cancer therapy as soon as possible.
The guidelines for extractions before cancer therapy are largely anecdotal. Soft tissue impacted teeth; nonrestorable teeth; root tips; and teeth with significant bone loss, furcation involvement, and periodontal pockets of more than 6 mm should be removed. Atraumatic extractions with primary closure are desirable and ideally completed 2 weeks before initiation of cancer therapy to allow for adequate healing . Patients should return for a follow-up visit after extractions to ensure that there are no postoperative complications. Mobile deciduous teeth may be left to exfoliate passively in most circumstances. Patients are advised not to attempt to hasten the exfoliation process as this may cause bleeding and increase the risk for bacteremia.
Because poor periodontal health has been thought to increase the risk of infection during periods of immunosuppression, a thorough periodontal evaluation, and any necessary treatment, is recommended for all patients scheduled to receive cancer therapy . A dental prophylaxis should be performed on all patients within 6 months before beginning cancer therapy.
Partially erupted molars are a source of infection because of food accumulation and poor plaque removal under the operculum, which is a risk for the development of pericoronitis . The overlying gingival tissue may be excised if the practitioner deems it a potential source of infection.
It is often difficult to maintain optimal oral hygiene around orthodontic brackets and wires because of the propensity of these appliances to accumulate plaque. In addition, most orthodontic appliances, with the exception of well-fitting smooth appliances such as band and loops and fixed lower lingual arches, irritate the mucosa, and may exacerbate oral mucositis during chemotherapy or radiation therapy . Therefore, removal of orthodontic appliances before cancer therapy is frequently recommended. This is especially important when the cancer treatment protocol carries a high risk for the development of moderate to severe mucositis.
Preventive dentistry and education
Basic oral care
Patients should perform routine oral hygiene measures such as brushing and flossing and use fluoride therapy even before cancer therapy. Chlorhexidine mouth rinse may be prescribed for patients with poor oral hygiene and/or periodontal disease. Systemic fluoride supplements (in case the patient is not drinking optimally fluoridated water) and neutral fluoride rinses or gels are recommended for high caries risk patients during all phases of cancer treatment.
Informing parents about the need to adhere to a noncariogenic diet is essential. However, this is often difficult because many children are on highly cariogenic carbohydrate-rich dietary supplements for weight maintenance or are taking oral sucrose-rich medications. Furthermore, caretakers tend to indulge their sick child with sweets, juices, carbonated beverages, and sport drinks, which increase the child’s risk for caries. They must be educated about these issues to prevent more oral health problems.
Antibiotic prophylaxis for nonvalvular cardiovascular devices
It is evident from the literature that the bulk of infections of nonvalvular cardiovascular devices are caused by staphylococci species, with only a minority of cases caused by other gram-positive cocci, gram-negative bacilli, and fungi . The American Heart Association (AHA) does not recommend antibiotic prophylaxis for patients with nonvalvular cardiovascular devices undergoing dental, respiratory, gastrointestinal, or genitourinary procedures because of the lack of robust evidence to suggest that microorganisms associated with these procedures are the cause of device infections . Immunosuppression is not an independent risk factor for infection of nonvalvular cardiovascular devices and the AHA proposes that these individuals may “receive primary and secondary antibiotic prophylaxis as advocated for immunocompetent hosts” .
Indwelling central venous catheters are often placed in patients undergoing chemotherapy for drawing blood, administration of intravenous medications, and sometimes parenteral nutrition. Although staphylococci species are the main organisms shown to infect such catheters and there is insufficient evidence to support the effectiveness of antibiotic prophylaxis, many health care professionals continue to prescribe antibiotics for patients undergoing invasive dental procedures with these devices. Interestingly, Lockhart and colleagues found that 24% of infectious disease specialists recommended antibiotic prophylaxis because of medico-legal rather than for scientific reasons.
Antibiotic prophylaxis to prevent infections in immunosuppressed patients
Oral microbial flora is cited frequently as a source of systemic infections during periods of immunosuppression . While, it is common practice to prescribe prophylactic antibiotics in neutropenic patients prior to invasive dental procedures (because of the concerns for bacteremia), the evidence to support this practice is weak .
The National Cancer Institute (NCI) recommends that patients with an absolute neutrophil count (ANC) between 1000 and 2000/mm 3 be prescribed antibiotic prophylaxis before invasive dental treatment using the agents and doses in the guidelines provided by the American Heart Association (AHA) . For patients with ANC below 1000/mm 3 , the NCI recommends prescribing amikacin 150 mg/m 2 1 hour and ticarcillin 75 mg/kg intravenously (IV) 30 minutes before the procedure and repeating both medications 6 hours postoperatively. The American Academy of Pediatric Dentistry (AAPD) recommendations also suggest providing antibiotic coverage according to the prophylactic antibiotic guidelines set out by the AHA, but only for patients whose ANC is below 1000/mm 3 . The lack of consensus regarding the use and dosages of antibiotic prophylaxis in preventing infection for varying levels of immunosuppression is unlikely to be resolved because of ethical concerns involved in not providing antibiotics to profoundly neutropenic patients and placing them at risk for septicemia.
Hematologic malignancies and chemotherapy cause bone marrow suppression resulting in leukopenia, anemia, and thrombocytopenia. The extent and severity of these conditions should be evaluated before dental treatment is initiated.
Most transfusion decisions are dependent on the patient’s clinical condition, and it is often difficult to assign an absolute hemoglobin (Hgb) level at which transfusion is indicated . In general, transfusion is warranted for children whose Hgb levels are between 6 and 7 g/dL. For patients with Hgb levels between 7 and 10 g/dL, transfusion is indicated only if they are symptomatic. Consultation with physicians to assess need for preoperative red blood cell transfusions prior to patients undergoing general anesthesia for dental rehabilitation is recommended if their hemoglobin levels are below 10 g/dL . As with red blood cell transfusions, platelet levels at which replacement is indicated is not absolute and opinions vary among hematologists. Table 1 illustrates the guideline recommended by NCI for platelet replacement therapy. The guidelines are only suggestions and the definition of “invasive dental procedures” and the need for platelet transfusion are left to the clinicians’ discretion. For example, post operative bleeding from an extraction of a deciduous tooth or a simple extraction of a permanent tooth may be managed easily with local hemostatic measures and do not require replacement even when platelet counts are below 40,000mm 3 . Prophylactic platelet transfusions for dental procedures should be requested only in situations where hemostasis cannot be achieved by local measures. This will decrease the frequency of recipient’s exposure to donor platelets and lower patient’s risk of developing alloimmunization against donor platelets .
|Platelets a||Recommendations||Local measures|
|>75,000/mm 3||No additional support needed.|
|40,000–75,000/mm 3||Platelet transfusions are optional; consider administering preoperatively and 24 hours later. Additional transfusions are based on clinical course.||Use techniques to promote establishing and maintaining control of bleeding (ie, sutures, pressure packs, minimizing trauma).|
|<40,000/mm 3||Platelets should be transfused 1 hour before procedure; immediately obtain platelet count, transfuse regularly to maintain counts above 30,000–40,000/mm 3 until initial healing has occurred.||In addition to above, consider using hemostatic agents (ie, microfibrillar collagen, topical thrombin). Monitor sites carefully.|
a Assumes that all other bleeding and coagulation parameters are within normal limits and that platelet counts will be maintained at or above the specified level until initial stabilization/healing has occurred.
Dental management during therapy
In light of the risk of bacteremia and bleeding because of the patient’s immunocompromised status during antineoplastic therapy, elective or nonemergency dental treatment should be deferred until after the completion of cancer therapy or recovery of the immune system.
If an acute odontogenic infection occurs in the midst of cancer therapy, discussion with the patient’s physician is advisable before dental treatment is performed. Depending on the extent of the patient’s bone marrow depression, blood product and antibiotic prophylaxis may be indicated. An expert panel in 2001 reviewed evidence for platelet transfusion for patients who have cancer and concluded that major invasive procedures including craniotomies, tooth extractions, and so forth may be performed safely at platelet count levels of between 40,000 to 50,000mm 3 if there are no other existing coagulopathies .
Myelosuppression alone is not a contraindication for toothbrushing, flossing and the use of fluoride therapy. Patients may continue their daily oral hygiene practices during cancer therapy; this should be done judiciously if the patient is thrombocytopenic . Use of a soft bristle toothbrush to prevent plaque accumulation is important, as plaque serves as a nidus for bacterial growth and increases the risk for local inflammation and infection. Young children should be supervised by their parents or caregivers to ensure toothbrushing is effective and atraumatic. Air drying the toothbrush after use, soaking them in chlorhexidine solution and replacing toothbrushes regularly are recommended as they become colonized with oral bacteria as quickly as within 2 weeks of use and may be a potential source of infection .
The use of extra-soft brushes, sponge toothbrushes, or toothettes is recommended by some health professionals because they are believed to be gentler on the ulcerated oral mucosa. These oral hygiene aids are less effective than soft nylon-bristled toothbrushes for plaque removal and caries prevention and should only be used during episodes of severe mucositis when the patient absolutely cannot tolerate a regular toothbrush. During this period, toothpaste may cause burning and irritation and its use may be discontinued until mucosal inflammation has resolved. Flossing may be continued if it is an existing component of the patient’s daily oral hygiene routine; however, flossing is discouraged if the patient is not skilled at it, because he or she may cause trauma and bleeding. Use of toothpicks and water irrigation devices are discouraged during periods of pancytopenia because of their potential to cause mucosal injury and the subsequent risk of bacteremia . The incidence of significant oral bleeding or life-threatening septicemia arising from flossing or the use of toothpicks and water irrigation devices has not been well investigated.
Despite weak evidence to support their use, bland mouth rinses such as baking soda and water or 0.9% saline solution may help with oral pain palliation and debris removal . Chlorhexidine mouth rinse is discontinued during active antineoplastic treatment because of its high alcohol content (11.6%), which may irritate and dehydrate the oral mucosa, and may be poorly tolerated by the patient. Petrolatum-based products such as Aquaphor (Beiersdorf, Wilton, CT) may be applied to the lips on an as needed basis to keep them from cracking.
Nausea and vomiting are other significant side effects of chemotherapy . Acidic contents from the stomach may cause severe erosion of the teeth and increase their susceptibility to dental decay. Patients are encouraged to rinse their mouth with water thoroughly after each emesis episode.
Oral mucosal complications and management
Children are reported to be three times more likely than adults to develop oral complications with incidence as high as 100% . Acute oral manifestations include (1) mucositis, (2) opportunistic infections, (3) bleeding, (4) xerostomia, (5) pain, (6) taste changes, (7) neuropathies, and (8) trismus ( Table 2 ).
|Oral complication||Treatment goals||Method|
|1. Oral mucositis||Prevention||Palifermin (not approved in children), cryotherapy, oral care protocols|
|Palliative||Topical anesthetics (eg, viscous lidocaine), mucosal coating agents (eg, Kaopectate, [Chattem, Chattanooga, Tennessee] other topical agents (eg, diphenhydramine, benzydamine, bicarbonate soda and water), systemic analgesics (especially patient-controlled analgesia)|
|2. Fungal infection||Prevention||Fully or partially systemically absorbed antifungals (eg, fluconazole, ketconazole, clotrimazole)|
|Treatment||Topical (eg, nystatin, clotrimazole) and systemic agents (eg, fluconazole, ketoconazole)|
|3. Viral infection (HSV, VZV a )||Prevention||Systemic antivirals (eg, acyclovir, valcyclovir) for seropositive individuals|
|Treatment||Systemic antivirals (eg, acyclovir, valcyclovir)|
|4. Bacterial infection||Prevention||Meticulous oral hygiene|
|Treatment||Topical and systemic antibiotics|
|5. Oral bleeding||Prevention||Maintain good oral hygiene, removal of potential sources of irritation|
|Treatment||Local measures with pressure packs, topical hemostatic agents (eg, thrombin, antifibrinolytic agents)|
|Systemic measures (eg, platelet transfusion)|
|6. Xerostomia||Prevention||Amifostine (Not approved for use in children)|
|Protective shielding of major salivary glands during radiotherapy|
|Palliation||Muscarinic agonists (Not approved for use in children)|
|Saliva substitutes, oral lubricants, frequent sips of water, salivary gland stimulants (eg, sugarless lemon drops, fresh acidic fruits), humidifier by bedside|
|7. Acute odontogenic infection||Prevention||Pre–cancer therapy dental examination and treatment|
|Treatment||Consult with physician for requirement of antibiotic prophylaxis and blood products before dental procedure|
The severity of oral mucositis ranges from localized to generalized erythema, and in severe cases, frank ulceration and hemorrhage, and is considered by many patients to be the most distressing sequelae of cancer therapy ( Fig. 1 ) . An increase in severity of oral mucositis is associated with an increased risk of infection, additional days of total parenteral nutrition, longer hospital stays, additional hospital charges, and an increased risk of mortality within 100 days . Airway compromise because of severe oral mucositis resulting in anoxia-induced brain injury and even death has also been reported in children .
The incidence of oral mucositis in children undergoing antineoplastic treatment ranges from 10% to 100%, and is higher in patients who receive myeloablative chemotherapy before HSCT and/or in those receiving radiation to the head and neck region . The diverse range in reported prevalence and incidence of mucositis may be attributed to the lack of a universally agreed instrument for assessing mucositis in children .
Several host- and treatment-related factors have been associated with the development of oral mucositis such as (1) age, (2) female gender, (3) low body mass index, (4) poor nutritional status, (5) decreased renal function, (6) previous cancer treatment, (7) smoking, (8) reduced salivary function, (9) poor oral hygiene, (10) allogeneic bone marrow transplantation, (11) type and dosage of certain chemotherapy agents, (12) head and neck radiation, and (13) use of combined modality therapy . Evidence to support the association of many of these factors has been conflicting . For example, age, although often significant in univariate analysis, drops out of significance when multivariate analysis is used . In comparison with the other risk factors, cancer treatment variables such as the dosage and schedule of certain specific antineoplastic agents, radiation to the head and neck region, use of total body irradiation (TBI), and the diagnosis of hematologic malignancies seem to consistently influence the development and severity of oral mucositis .
Palifermin is currently the only medication approved by the Food and Drug Administration (FDA) for prevention of oral mucositis in adults with hematologic malignancies. The benefits and risks of palifermin in children are unknown.
Management of oral mucositis in children is mostly palliative. Based on the available literature, it is difficult to recommend any evidence-based interventions for the management of oral mucositis in children ; however, some beneficial interventions proven effective in the adult population may be implemented in children because of their excellent safety profiles. Cryotherapy is recommended for pediatric patients receiving bolus of 5-fluorouracil and chemotherapy agents with a short serum half-life, eg, edatrexate, single-dose mephalan and etidronate . Instituting oral care protocols is another relatively noninvasive intervention reported to reduce the incidence and severity of oral mucositis . Although the evidence is weak, the merits of good oral hygiene are desirable because they reduce the risk for local dental complications by reduction of oral microbial load, dental plaque, gingivitis, and dental caries. The Multinational Association of Supportive Care in Cancer (MASCC) Web site ( www.mascc.org ) provides current International Society of Oral Oncology (ISOO) guidelines on mucositis care.
As mentioned previously, the signs and symptoms of inflammation and infection in the oral cavity may be diminished because of a depressed immune system. Oral health care professionals should therefore be more vigilant when performing an oral examination to detect any atypical signs of fungal, viral, and bacterial infections.
Species in the genus Candida are responsible for most opportunistic superficial and deep oral fungal infections in neutropenic patients Prompt diagnosis and treatment are crucial, as this condition may progress rapidly into a systemic infection in immunosuppressed individuals, with very high mortality rates . For these reasons, the initiation of empirical prophylactic antifungal therapy has been instituted in many oncologic treatment centers when a patient’s absolute neutrophil counts falls below a critical level or when a patient’s fever continues to persist despite antibiotic therapy .
There is sound evidence to support the benefits of partially and completely absorbed antifungal agents in the prevention and treatment of oral candidiasis, while agents that are not absorbed through the gastrointestinal tract are generally ineffective .
Nystatin and clotrimazole troches are the two most common choices for the treatment of oral candidiasis in children. The pediatric dosage for clotrimazole is similar to adult dosing and is prescribed as a dissolvable 10-mg troche to be taken orally 3 to 6 times a day. Both preparations are high in sucrose and patients should be warned of their predisposition to dental caries when using these medicines . When compliance with oral medications because of frequent dosing is an issue or when topical agents are ineffective, systemic fluconazole is an effective alternative . The suggested pediatric dose for systemic fluconazole is 6 mg/kg/day on day 1 and subsequent doses at 3 mg/kg/day for 7 to 10 days .
The most common viral oral infection in children undergoing cancer therapy is herpes simplex virus (HSV) . The infection often occurs as a result of reactivation of a dormant virus in a previously infected individual . Therefore, known HSV seropositive patients are routinely placed on prophylactic doses of acyclovir to prevent reactivation . Suggested prophylactic dose for prevention of HSV reactivation in children is 600 to 1000 mg/day of acyclovir orally in three to five divided doses during the period of risk.
Diagnosis of recrudescent HSV infection is mostly based on clinical findings. It generally occurs on the attached mucosa but is not necessarily confined to this area. The lesions present as areas of superficial necrotic and ulcerated mucosa with distinct raised borders and are much larger than the typical pinhead-sized ulcers seen in an immunocompetent patient. Diagnosing HSV infection may be difficult in some patients, as it is easily confused with oral mucositis. To confirm the diagnosis, the base of a fresh or intact lesion is swabbed with a cotton tip, placed in cold viral culture media and sent to the laboratory immediately. However, this does not distinguish between recrudescent lesion of HSV and reactivated HSV in the patient’s saliva.
In addition to maintaining adequate hydration and providing pain relief, initiation of antiviral therapy is recommended for immunosuppressed patients with active HSV infection . HSV infection in an immunocompromised child may be treated with 1000 mg of oral acyclovir in three to five divided doses for 7 to 14 days with the maximum dose not exceeding 1000 mg/day.
Although, bacterial infections can involve any oral mucosa surface, the gingivae are the most commonly affected site. If the localized infection is not addressed and treated in a timely fashion, it may cause febrile episodes in immunosuppressed patients and, in severe cases, result in systemic bacteremia . Localized infections may be treated with chlorhexidine mouthwash and meticulous oral hygiene. An infectious disease specialist should be consulted for advice on initiation of an appropriate systemic antibiotic regimen if there is a high risk for, or strong suspicion of, systemic spread of the oral infection.
The incidence of oral bleeding reported in children undergoing cancer therapy ranges from 6% to 42%, and is often a result of thrombocytopenia . Bleeding frequently occurs from the gingival tissues and may be exacerbated by poor oral hygiene . Other commonly reported sites are the tongue and the lips . Spontaneous bleeding is rare if platelet counts are more than 50,000/mm 3 .
Local measures such as pressure, primary closure, and use of topical measures such as gelfoam, sutures, thrombin, and topical antifibrinolytic agents (eg, tranexamic acid) may be used to control mild to moderate spontaneous oral bleeding . Platelet transfusions may be required for patients who have clinically significant oral bleeding that cannot be controlled with local measures . If there is a possibility that these supportive measures may be needed, the patient should be treated in a hospital dental clinic or in the operating room.
Xerostomia and hyposalivation
Patients undergoing chemotherapy often complain of transient xerostomia . Temporary relief of oral dryness may be provided by topical agents such as bland oral rinses, mucosal coating agents, and salivary substitutes . Other homecare regimens include use of sugar free (preferably xylitol) mints or chewing gum, frequent sipping of water, consumption of slightly acidic foods, and placement of a humidifier by the bedside at night. Patients who have significant salivary gland hypo-function are also at risk for opportunistic fungal infections, oral mucosal trauma, taste changes, and speaking difficulties.
Pain management is an important component of oncology care. Mucositis-associated discomfort is a major contributing cause of cancer treatment–related pain . The use of patient-controlled analgesia (PCA) has been found to be beneficial in relieving pain in adult and pediatric hematopoietic stem-cell transplant recipients. In addition, PCA has been shown to reduce the requirement for analgesics compared with other pain control modalities .
Unlike the established benefits of PCA, the use of topical analgesic preparations for relieving oral pain is not supported by scientific evidence . Despite the lack of robust evidence, topical analgesic preparations are extensively used in combination with systemic analgesics in an effort to alleviate pain with the safest and lowest doses of systemic pain medications. Common ingredients in topical agents include 2% viscous lidocaine alone or in various combinations (eg, sodium bicarbonate mixed with water, saline, diphenhydramine) . Use of topical preparations containing viscous lidocaine should be supervised in children because (1) rapid absorption through the ulcerated mucosa increases the risk for systemic lidocaine toxicity and (2) gargling with or swallowing mouth rinses that contain topical anesthetics may cause loss of the gag reflex, increasing the risk of aspiration.
Altered taste sensations during chemotherapy and/or radiotherapy are not uncommon . Fortunately, most patients recover their sense of taste between 1 and 3 months after treatment cessation. Although the benefits are controversial, zinc supplements may be recommended to help with the recovery of taste sensations .
Jaw pain, occurring mostly in the mandible, in the absence of odontogenic pathology is a frequent complaint from patients treated with vinca alkaloids. These agents may cause neuropathy of the trigeminal and facial nerves, which often mimics odontogenic pain . Fortunately, the pain resolves with discontinuation of the responsible agents and no treatment is required.
Children and adolescents who received radiation to the head and neck may develop trismus due to fibrosis of the masticatory apparatus . The severity of trismus is dependent on the extent of tumor invasion, surgical procedures, and dose and field of radiation . Routine oral hygiene procedures, speech, nutritional intake, and dental treatment often become very difficult when trismus is severe. Current management of trismus involves performing daily oral stretching exercises/physical therapy during radiation and continuing for 3 to 6 months after radiation . Commercial physical therapy devices such as TheraBite (Atos Medical, West Allis, WI) and Dynasplint (Dynasplint Systems, Severna Park, MD) may help patients with these jaw stretching exercises; however, their superiority over traditional mouth opening exercises (eg, passive stretching, tongue blades) have not been proven. Furthermore, compliance with these exercises may be a problem in children.
Management of long-term oral complications from radiotherapy and chemotherapy
Delayed effects on the dental and craniofacial complex
Long-term effects of antineoplastic therapy on the developing dentition are well documented in childhood cancer survivors ( Table 3 ) . Although radiotherapy and chemotherapy are designed to specifically target tumor cells, both modalities invariably affect normal proliferating cells. Possible dental developmental defects include 1) microdontia, 2) root stunting, 3) delayed or arrested dental development, 4) enamel hypoplasia, 5) pulp chamber size abnormalities, and 6) hypodontia ( Fig. 2 ). Attributing the occurrence, extent, and severity of a particular dental defect to either radiation or chemotherapy is often difficult because of multimodality treatment strategies. More studies are needed in this area.
|Oral complication||Chemotherapy a||Head and neck radiotherapy a including TBI||Autologous HSCT a||Allogeneic HSCT a|
|Dental anomalies||Yes (Dose dependent)||Yes (Dose dependent)||Yes||Yes|
|Anomalies in craniofacial development||Unlikely||Yes b (Severity is dose- and site-specific)||Yes b||Yes b|
|Persistent xerostomia and hyposalivation||No||Yes (If major salivary glands are in radiated field)||No c||No c /Yes as complication of cGVHD|
|Trismus||No||Yes (if muscles of mastication are in radiation field)||No c||No c /Yes as complication of cGVHD|
|Postradiation osteonecrosis||No||Yes if >60 Gy directly to jaw||No c||No c|
|Chronic GVHD||No||No||No||Yes d|
|Secondary malignancies||Unlikely||Yes||Yes e||Yes e|
b Irradiation to the cranium often results in ipsilateral mandibular hypoplasia, and growth hormone, gonadotropin, and sometimes thyrotropin deficiency causing general growth retardation, indirectly affecting craniofacial development.
Dental anomalies occur when tooth development is occurring in or near the vicinity of the radiation beam. Direct high-dose radiation to the dentoalveolar complex during very early phases of tooth development may destroy nonproliferating odontogenic precursor cells and result in complete agenesis of the tooth . Radiation at a later stage of dental development, or at a lower dose, results in less drastic defects ranging from microdontia, enamel hypoplasia, and incomplete calcification to arrested root development ( Fig. 3 ). When crown formation has completed, defects are typically localized to the roots. Localized dental defects in humans have been demonstrated with radiation doses as low as 4 Grays . However, the threshold level of radiation dose to the head and neck region at which cell damage versus cell death occurs in humans is still unknown.
Unlike radiotherapy, which damages or destroys cells in the path of the radiation beam, most chemotherapeutic agents target rapidly dividing cells in the whole body . Cells that are in nonproliferative germinal stage (eg, second and third molars in an infant) remain unaffected by chemotherapy and should develop normally. Dental defects from chemotherapy range from crown hypoplasia, microdontia, enlarged pulp chamber, and disturbed root formation to complete tooth agenesis. Most defects are localized and complete tooth agenesis is rare because of the short half-life of chemotherapeutic agents except when intensive and repetitive chemotherapy is used. Chronologic eruption of permanent teeth has not been shown to be affected by chemotherapy .
The extent and location of dental anomalies are dependent on the child’s age at initiation of antineoplastic treatment and the specific cancer regimen. Children younger than 5 or 6 at time of treatment and chemotherapy combined with head and neck radiation and/or TBI have a higher incidence of dental anomalies compared with older patients or patients who undergo only chemotherapy .
Abnormalities in craniofacial development are often reported in patients who received radiotherapy for the treatment of primary tumors in the head and neck region . Higher radiation dose, longer radiation schedules, and younger age at time of treatment are associated with more pronounced defects and significant facial asymmetry because of damage to the growing bones (in particular the growth center in the mandibular condyle) ( Fig. 4 ) . Damage to the thyroid gland and pituitary axis also indirectly exacerbates the severity of skeletal discrepancy because of overall growth retardation . The road to reconstruction is often arduous, consisting of countless surgeries, and the success is often unpredictable because of poor healing of radiated tissue.