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Oral Complications of Chemotherapy and Head/Neck Radiation (PDQ®)

  • Last Modified: 04/10/2014

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Oral and Dental Management Before Cancer Therapy

Chemotherapy Patients
Assessment of Hematopoietic Stem Cell Transplant Patients

Poor oral health has been associated with increased incidence and severity of oral complications in cancer patients, hence the adoption of an aggressive approach to stabilizing oral care before treatment.[1,2] Primary preventive measures such as appropriate nutritional intake, effective oral hygiene practices, and early detection of oral lesions are important pretreatment interventions.

There is no universally accepted pre–cancer therapy dental protocol because of the lack of clinical trials evaluating the efficacy of a specific protocol. A systematic review of the literature revealed two articles on oral care protocols prior to cancer therapy.[3] One study examined the benefits of a minimal intervention pre–cancer therapy (mostly chemotherapy) dental protocol, and the other examined the impact of an intensive preventive protocol on patients undergoing chemotherapy. Both studies had several flaws, including small sample size or the lack of comparison groups.[3]

The involvement of a dental team experienced with oral oncology may reduce the risk of oral complications via either direct examination of the patient or in consultation with the community-based dentist. The evaluation should occur as early as possible before treatment.[4,5] The examination allows the dentist to determine the status of the oral cavity before cancer treatment begins and to initiate necessary interventions that may reduce oral complications during and after that therapy. Ideally, this examination should be performed at least 1 month before the start of cancer treatment to permit adequate healing from any required invasive oral procedures. A program of oral hygiene should be initiated, with emphasis on maximizing patient compliance on a continuing basis.

Chemotherapy Patients

Oral evaluation and management of patients scheduled to undergo myeloablative chemotherapy should occur as early as possible before initiation of therapy (refer to the list on Oral Disease Stabilization Before Chemotherapy and/or Hematopoietic Stem Cell Transplantation). To maximize outcomes, the oncology team should clearly advise the dentist as to the patient’s medical status and oncology treatment plan. In turn, the dental team should delineate and communicate a plan of care for oral disease management before, during, and after cancer therapy.[5]

Oral Disease Stabilization Before Chemotherapy and/or Hematopoietic Stem Cell Transplantation

  • Data provided by oncology team to dental providers:
    • Underlying disease:
      • Cancer: type, stage, prognosis.
      • Aplastic anemia status, complete blood count (CBC).
      • Other.
    • Type of transplant:
      • Autologous.
      • Allogeneic donor types:
        • Matched related and unrelated.
        • Mismatched related.
      • Mismatched unrelated.
      • Syngeneic.
    • Hematopoietic stem cell source:
      • Bone marrow.
      • Peripheral stem cells.
      • Cord blood stem cells.
    • Conditioning regimen:
      • Myeloablative.
      • Reduced-intensity conditioning (including nonmyeloablative regimens).
    • Planned date of transplant.
    • Conditioning regimen:
      • Chemotherapy.
      • Total-body irradiation.
      • Radioactive antibodies.
    • Current hematologic status and immunologic status.
    • Present medications.
    • Other medical considerations:
      • Cardiac disease (including murmurs).
      • Pulmonary disease.
      • Indwelling venous access line.
      • Coagulation status.
      • Splenectomy.

  • Data provided by dental providers to oncology team:
    • Dental caries (number of teeth and severity, including designation of number of teeth that should be treated before cancer treatment begins).
    • Endodontic disease:
      • Teeth with pulpal infection.
      • Teeth with periapical infection.
    • Periodontal disease status.
    • Number of teeth requiring extraction.
    • Other urgent care required.
    • Time necessary to complete stabilization of oral disease.

The overall goal is to complete a comprehensive oral care plan that eliminates or stabilizes oral disease that could otherwise produce complications during or following chemotherapy. Achieving this goal will most likely reduce risk of oral toxicities with resultant reduced risk for systemic sequelae, reduced cost of patient care, and enhanced quality of life. If the patient is unable to receive the medically necessary oral care in the community, the oncology team should assume responsibility for oral management.

It is important to realize that dental treatment plans need to be realistic relative to type and extent of dental disease and how long it could be before resumption of routine dental care. For example, teeth with minor caries may not need restoration before cancer treatment begins, especially if more conservative disease stabilization strategies can be used (e.g., aggressive topical fluoride protocols, temporary restorations, or dental sealants).

Specific interventions are directed to:

  • Mucosal lesions.
  • Dental caries and endodontic disease.
  • Periodontal disease.
  • Ill-fitting dentures.
  • Orthodontic appliances.
  • Temporomandibular dysfunction.
  • Salivary abnormalities.

Guidelines for dental extractions, endodontic management, and related interventions (see Table 3) can be used as appropriate.[6,7] Antibiotic prophylaxis prior to invasive oral procedures may be warranted in the context of central venous catheters; the current American Heart Association (AHA) protocol for infective endocarditis and oral procedures is frequently used for these patients.

Table 3. Management Guidelines Relative to Invasive Dental Procedures
Medical Status  Guideline  Comments 
Patients with chronic indwelling venous access lines (e.g., Hickman).AHA prophylactic antibiotic recommendations (low risk).There is no clear scientific proof detailing infectious risk for these lines following dental procedures. This recommendation is empiric.
Neutrophils Order CBC with differential.
>2,000/mm3No prophylactic antibiotics.
1,000–2,000/mm3AHA prophylactic antibiotic recommendations (low risk).Clinical judgment is critical. If infection is present or unclear, more aggressive antibiotic therapy may be indicated.
<1,000/mm3Amikacin 150 mg/m2 1 h presurgery; ticarcillin 75 mg/kg IV ½ h presurgery. Repeat both 6 h postoperatively.If organisms are known or suspected, appropriate adjustments should be based on sensitivities.
Plateletsa Order platelet count and coagulation tests.
>60,000/mm3No additional support needed.
30,000–60,000/mm3Platelet transfusions are optional for noninvasive treatment; consider administering preoperatively and 24 h later for surgical treatment (e.g., dental extractions). Additional transfusions are based on clinical course.Utilize techniques to promote establishing and maintaining control of bleeding (i.e., sutures, pressure packs, minimize trauma).
<30,000/mm3Platelets should be transfused 1 h before procedure; obtain an immediate postinfusion platelet count; transfuse regularly to maintain counts >30,000–40,000/mm3 until initial healing has occurred. In some instances, platelet counts >60,000/mm3 may be required.In addition to above, consider using hemostatic agents (i.e., microfibrillar collagen, topical thrombin). Aminocaproic acid may help stabilize nondurable clots. Monitor sites carefully.

CBC = complete blood cell count; IV = intravenous.
aAssumes that all other 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.

Assessment of Hematopoietic Stem Cell Transplant Patients

Stages of assessment have been described relative to the hematopoietic stem cell transplant patient (see Table 4).[5] This model provides a useful classification for neutropenic cancer patients in general. Type, timing, and severity of oral complications represent the interaction of local and systemic factors that culminate in clinical expression of disease. Correlating oral status with systemic condition of the patient is thus critically important.

Selected conditioning regimens characterized by reduced intensity for myelosuppression have been used in patients. These regimens have generally been noted to significantly reduce the severity of oral complications early posttransplant, especially for mucositis and infection risk. The guidelines listed in Table 4 can be adjusted to reflect these varying degrees of risk, based on the specific conditioning regimen to be used.

Table 4. Oral Complications of Hematopoietic Stem Cell Transplantation
Transplant Phase Oral Complication 
GVHD = graft-versus-host disease.
Phase I: PreconditioningOral infections: dental caries, endodontic infections, periodontal disease (gingivitis, periodontitis), mucosal infections (i.e., viral, fungal, bacterial).
Gingival leukemic infiltrates.
Metastatic cancer.
Oral bleeding.
Oral ulceration: aphthous ulcers, erythema multiforme.
Temporomandibular dysfunction.
Phase II: Conditioning Neutropenic PhaseOropharyngeal mucositis.
Oral infections: mucosal infections (i.e., viral, fungal, bacterial), periodontal infections.
Hemorrhage.
Xerostomia.
Taste dysfunction.
Neurotoxicity: dental pain, muscle tremor (e.g., jaws, tongue).
Temporomandibular dysfunction: jaw pain, headache, joint pain.
Phase III: Engraftment Hematopoietic RecoveryOral infections: mucosal infections (i.e., viral, fungal, bacterial).
Acute GVHD.
Xerostomia.
Hemorrhage.
Neurotoxicity: dental pain, muscle tremor (e.g., jaws, tongue).
Temporomandibular dysfunction: jaw pain, headache, joint pain.
Granulomas/papillomas.
Phase IV: Immune Reconstitution Late PosttransplantOral infections: mucosal infections (i.e., viral, fungal, bacterial).
Chronic GVHD.
Dental/skeletal growth and development alterations (pediatric patients).
Xerostomia.
Relapse-related oral lesions.
Second malignancies.
Phase V: Long-term SurvivalRelapse or second malignancies.
Dental/skeletal growth and development alterations.

Phase I: Before Chemotherapy

Oral complications are related to current systemic and oral health, oral manifestations of underlying disease, and oral complications of recent cancer or other medical therapy. During this period, oral trauma and clinically significant infections, including dental caries, periodontal disease, and pulpal infection, should be eliminated. Additionally, patients should be educated relative to the range and management of oral complications that may occur during subsequent phases. Baseline oral hygiene instructions should be provided. It is especially important to note whether patients have been treated with bisphosphonates (e.g., patients with multiple myeloma) and to plan their care accordingly.

Phase II: Neutropenic Phase

Oral complications arise primarily from direct and indirect stomatotoxicities associated with high-dose chemotherapy or chemoradiotherapy and their sequelae. Mucositis, xerostomia, and those lesions related to myelosuppression, thrombocytopenia, and anemia predominate. This phase is typically the period of high prevalence and severity of oral complications.

Oral mucositis usually begins 7 to 10 days after initiation of cytotoxic therapy and remains present for approximately 2 weeks after cessation of that therapy. Viral, fungal, and bacterial infections may arise, with incidence dependent on the use of prophylactic regimens, oral status prior to chemotherapy, and duration/severity of neutropenia. Frequency of infection declines upon resolution of mucositis and regeneration of neutrophils. This phenomenon appears to be more a temporal relation than a causative one, based on the predominant evidence. Despite the initial marrow recovery, however, the patient may remain at risk for infection, depending on status of overall immune reconstitution.

Salivary gland hypofunction/xerostomia secondary to anticholinergic drugs and taste dysfunction is initially detected in this phase; the toxicity typically resolves within 2 to 3 months.

In allogeneic transplant patients, while uncommon, hyperacute graft-versus-host disease (GVHD) can occur and can result in significant oral mucosal inflammation and breakdown that can complicate the oral course for patients. Clinical presentation will often not be sufficiently distinct to diagnosis this lesion. The clinical assessment is typically based on the patient experiencing more-severe-than-expected mucositis that will often not heal within the time line for mucosal recovery associated with oral mucositis caused by chemotherapy.

Phase III: Hematopoietic Recovery

Frequency and severity of acute oral complications typically begin to decrease approximately 3 to 4 weeks after cessation of chemotherapy. Healing of ulcerative oral mucositis in the setting of marrow regeneration contributes to this dynamic. Although immune reconstitution is developing, oral mucosal immune defenses may not be optimal. Generally stated, immune reconstitution will take between 6 and 9 months for autologous transplant patients and between 9 and 12 months for allogeneic transplant patients not developing chronic GVHD. Thus, the patient remains at risk for selected infection, including candidal and herpes simplex virus infections.

Mucosal bacterial infections during this phase occur less frequently unless engraftment is delayed or the patient has acute GVHD or is receiving GVHD therapy. Most centers will use systemic infection prophylaxis throughout this period (and, in many instances, longer) to reduce the risk of infections in general, a practice that positively influences the rate and severity of both systemic and local oral infections.

The hematopoietic stem cell transplant patient represents a unique cohort at this point. For example, risk for acute oral GVHD typically emerges during this time in allogeneic graft recipients.

Phase IV: Immune Reconstitution/Recovery from Systemic Toxicity

Oral lesions are principally related to chronic conditioning regimen–associated (chemotherapy with or without radiation therapy) toxicity and, in the allogeneic patient, GVHD. Late viral infections and xerostomia predominate. Mucosal bacterial infections are infrequent unless the patient remains neutropenic or has severe chronic GVHD.

Risk exists for graft failure, cancer relapse, and second malignancies. The hematopoietic stem cell transplant patient may develop oral manifestations of chronic GVHD during this period.

Phase V: Long-term Survival

Long-term survivors of cancer treated with high-dose chemotherapy alone or chemoradiotherapy will generally have few significant permanent oral complications.

Risk for radiation-induced chronic complications is related to the total dose and schedule of radiation therapy. Regimens that incorporate total body irradiation may result in permanent salivary gland hypofunction/xerostomia,[8] which is the most frequently reported late oral complication. Permanent salivary gland dysfunction can occur in autologous transplant patients in addition to nonautologous recipients. Other significant complications include craniofacial growth and developmental abnormalities in pediatric patients, and emergence of second malignancies of the head/neck region.

References
  1. Sonis ST, Woods PD, White BA: Oral complications of cancer therapies. Pretreatment oral assessment. NCI Monogr (9): 29-32, 1990.  [PUBMED Abstract]

  2. Epstein JB: Infection prevention in bone marrow transplantation and radiation patients. NCI Monogr (9): 73-85, 1990.  [PUBMED Abstract]

  3. Hong CH, Napeñas JJ, Hodgson BD, et al.: A systematic review of dental disease in patients undergoing cancer therapy. Support Care Cancer 18 (8): 1007-21, 2010.  [PUBMED Abstract]

  4. Lalla RV, Brennan MT, Schubert MM: Oral complications of cancer therapy. In: Yagiela JA, Dowd FJ, Johnson BS, et al., eds.: Pharmacology and Therapeutics for Dentistry. 6th ed. St. Louis, Mo: Mosby Elsevier, 2011, pp 782-98. 

  5. Schubert MM, Peterson DE: Oral complications of hematopoietic cell transplantation. In: Appelbaum FR, Forman SJ, Negrin RS, et al., eds.: Thomas' Hematopoietic Cell Transplantation: Stem Cell Transplantation. 4th ed. Oxford, UK: Wiley-Blackwell, 2009, pp 1589-1607. 

  6. Williford SK, Salisbury PL 3rd, Peacock JE Jr, et al.: The safety of dental extractions in patients with hematologic malignancies. J Clin Oncol 7 (6): 798-802, 1989.  [PUBMED Abstract]

  7. Overholser CD, Peterson DE, Bergman SA, et al.: Dental extractions in patients with acute nonlymphocytic leukemia. J Oral Maxillofac Surg 40 (5): 296-8, 1982.  [PUBMED Abstract]

  8. Jensen SB, Pedersen AM, Vissink A, et al.: A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer 18 (8): 1039-60, 2010.  [PUBMED Abstract]