Oral Complications

chemotherapy (CT) radiation therapy (RT), hematopoietic stem cell transplantation

(HSCT)

1. CT- and RT-related stomatitis 2. oropharyngeal pain3. xerostomia4. oral infection 5. oral chronic graft-versus-host disease

(cGVHD).

Oral complications

Stomatitis is an inflammation of the mucous membranes of the oral cavity and oropharynx characterized by tissue erythema, edema, and atrophy, often progressing to ulceration.

The clinical significance of CT- and RT-

related stomatitis as a dose- and treatment-limiting side effect is well appreciated.

Stomatitis

PATIENT-RELATEDAge older than 65 y or younger than 20 yGenderInadequate oral health and hygiene practicesPeriodontal diseasesMicrobial floraChronic low-grade mouth infectionsSalivary gland secretory dysfunctionHerpes simplex virus infectionInborn inability to metabolize chemotherapeutic agents effectivelyInadequate nutritional statusExposure to oral stressors including alcohol and smokingIll-fitting dental prostheses

Cancer Treatment- and Patient-Related Risk Factors for Stomatitis

TREATMENT-RELATEDRadiation therapy: dose, scheduleChemotherapy: agent; dose, scheduleMyelosuppressionNeutropeniaImmunosuppressionReduced secretory immunoglobulin AInadequate oral care during treatmentInfections of bacterial, viral, fungal originUse of antidepressants, opiates, antihypertensives, antihistamines, diuretics, and sedativesImpairment of renal and/or hepatic functionProtein or calorie malnutrition, and dehydrationXerostomia

Risk factors for CT-related stomatitis are complex, and study results are conflicting.

continuous CT infusion therapy for breast and colon cancer [5-FU and leucovorin ]

selected anthracyclines alkylating agents taxanes vinca alkaloids Antimetabolites antitumor antibiotics myeloablative conditioning regimens for HSCT; RT to the head and neck.

Known risk factors include

Children are 3 times more likely than adults to develop stomatitis because of a higher proliferating fraction of basal cells.

Individual drug metabolism affects stomatitis incidence and severity, as seen with patients who are unable to adequately metabolize certain CT

40% of CT patients develop stomatitis, Half requiring parenteral analgesia that may

lead to treatment modification. 60% are seen in the HSCT setting, Oral infection, herpes simplex virus (HSV) in

particular, may increase stomatitis severity a 4 times greater relative risk of septicemia

Chemotherapy-Induced Stomatitis

asymptomatic erythema and progresses from solitary, white, elevated desquamative patches that are slightly painful to large, contiguous, pseudomembranous, painful lesions.

Stomatitis presents

Area Type of ionizing radiation volume of irradiated tissue daily and cumulative dose duration of RT

Radiation-Induced Stomatitis

Stomatitis is a dose- and rate-limiting toxicity of RT for head and neck cancer, and of hyperfractionated RT and CT that is designed to improve survival time.

COX-2 plays an amplifying role in RT-related stomatitis.

Atrophic changes in the oral epithelium usually occur at total doses of 1,600 to 2,200 cGy, administered at a rate of 200 cGy per day. Doses higher than 6,000 cGy place the patient at risk for permanent changes in the salivary glands.

depend primarily on salivary changes rather than on direct irradiation of the teeth.

Direct irradiation of teeth may alter the organic or inorganic components making them more susceptible to decalcification or hypocalcification.

daily fluoride application is necessary

RT-induced dental effects

Long-term effects of head and neck RT 1. Soft tissue fibrosis2. Obliterative endoarteritis3. Trismus4. Nonhealing or slow-healing mucosal

ulcerations5. slow healing of dental extraction sites.

Radiation Therapy-Related Complications

RT-induced fibrotic changes up to 1 year post-therapy, becoming more

serious over time.

Higher incidences are seen after total doses to the bone exceed 65 Gy.

The risk of ORN actually increases over time following RT.

pathologic fracture, infection of surrounding soft tissues, and severe pain.

time to allow adequate extraction site healing is 10 to 14 days before start of RT.

Osteoradionecrosis (ORN)

Long use :bisphosphonate therapy majority required surgical procedures to

remove the involved bone.

Osteonecrosis of the jaw bone

Oral candidiasis angular cheilitis, may appear as white and removable chronic hyperplastic (nonremovable)chronic erythematous (diffuse patchy

erythema).

H &N RT

Acute GVHD occurs within the first 100 days after allogeneic HSCT.

Chronic GVHD begins as early as 70 days or as late as 15 months after allogeneic transplant.

80% of patients with extensive cGVHD have some type of oral involvement

Oral infection in cGVHD patients is a risk factor for systemic infections that are the primary cause of death in this population

Chronic Graft-Versus-Host Disease Oral Manifestations

stomatitis-related pain Immunocompromised cancer patients with

HSV infections have larger, more painful lesions as compared with noncancer patients

cGVHD

Oropharyngeal Pain

The effect on the patient's psychological well-being:

medication usage, decreased oral intake use of analgesics and opioids.

individual's thought process, self-perception, reported pain relief, the personal meaning of the pain.

Cognitive dimension of pain

The sociocultural dimension includes demographic characteristics, cultural background, and family and work roles.

age and pain perception, intraethnic differences in pain perception Gender

Multidimensional oral pain

Pain control is critical to accomplish to avoid suffering and psychological distress.

Effective oral pain management is promoted through open, consistent communication between and among patient, physician, nurse, and caregiver.

A comprehensive pain assessment tool?

Xerostomia Severity dependent on the radiation dosage and

location, and volume of exposed salivary glands. Significant xerostomia has not been reported in

patients treated with CT alone. Xerostomia can affect oral comfort, fit of

prostheses, speech, and swallowing. Xerostomia-associated enzymes contribute to

the growth of caries (decay)-producing organisms, and the decrease in quantity and quality of saliva can be very harmful to dentition

Xerostomia

Pretherapy Dental Evaluation and Intervention

Assessment of the Oral Mucosa

Strategies for Prevention and Treatment of Oral Complications

an experienced dental team Many health care institution-specific

policies and preventive approaches exist for oral care for CT and RT patients.

Pretherapy Dental Evaluation and Intervention

dental screening at least 2 weeks before therapy

Oral hygiene

Patients scheduled for CT and/or head and neck RT:

related to several important factors, including radiation exposure, type, portal field, fractionization, total dosage tumor prognosis, expediency of control of the cancer.

The decision to extract asymptomatic teeth

Careful examination of extraction sites must be performed before RT commences.

Dental extractions following RT require collaborations between dental and radiation oncology team members to minimize the risk of ORN.

A low incidence of ORN is seen when pre-RT dental consultation and appropriate treatment (e.g., extractions) are rendered.

Follow-up

Assessment of the Oral Mucosa

The optimal treatment ? mainly empirical The only standard forms of care are

pretreatment oral/dental stabilization, saline mouthwashes, and oropharyngeal pain management.

oral hygiene

Treatment Strategies

unreliable evidence for the effectiveness of1. allopurinol mouthwash,2. vitamin E, 3. immunoglobulin, 4. human placental extract no single agent completely prevented

stomatitis, suggesting that combined strategies may be necessary

stomatitis treatment.

A standardized approach for the prevention and treatment of CT- and RT-induced stomatitis is essential.

Chlorhexidine gluconate (Peridex), Saline rinses, Sodium bicarbonate rinses, Acyclovir Amphotericin B Ice

prophylactic measures

a local anesthetic such as lidocaine or dyclonine hydrochloride, magnesium-based antacids (Maalox, Mylanta), diphenhydramine hydrochloride (Benadryl), nystatin, or sucralfate

These agents are used either alone or in various combinations as a mouthwash formulation.

opioids

Treatment of stomatitis and related pain

used less commonly include kaolin-pectin (Kaopectate), allopurinol, vitamin E, beta-carotene, chamomile (Kamillosan) liquid, aspirin, antiprostaglandins, prostaglandins, MGI 209 (marketed as Oratect Gel), silver nitrate, and antibiotics

Other agents

has shown efficacy in the treatment of gastrointestinal (GI) ulceration

has been tested as a mouthwash for the prevention and treatment of stomatitis?

CT? Sucralfate has also been tested in the head

and neck RT population?

Direct CytoprotectantsSucralfate

Gelclair is a concentrated, bioadherent gel that has received for the management of stomatitis-related oral pain.

Gelclair

Benzydamine is a nonsteroidal anti-inflammatory drug with reported analgesic, anesthetic, anti-inflammatory, and antimicrobial properties.

Prostaglandins, Antiprostaglandins, and Nonsteroidal Agents?

+ اب بتامتازون + + + دیفن تتراسایکلین نیستاتین هیدروکورتیزون

هیدرامین

Corticosteroids

Vitamin E + vitamins C and E and glutathione ? Azelastine may be useful to prevent CT-

induced stomatitis

Vitamins and Other Antioxidants

Silver Nitrate + Laser? Miscellaneous Agents?diphenhydramine hydrochlor-ide (Benadryl),

saline, sodium bicarbonate, and gentian violet

Cryotherapy used to induce vasoconstriction should be considered for patients receiving 5-FU or melphalan when these agents are administered during short infusion times.

Cryotherapy

Hematopoietic Growth Factors? Keratinocyte Growth Factors Antimicrobials Pharmacologic Modulation

Indirect Cytoprotectants

Recently, palifermin, which is a recombinant human keratinocyte growth factor, has shown efficacy in the reduction of oral mucosal injury related to cytotoxic therapy

Keratinocyte Growth Factors

Treatment approaches for oral candidiasis include Mycostatin (troches), nystatin (liquid or ointment), or clotrimazole.

Pseudomembranous candidiasis is successfully treated topically.

Chronic candidiases usually requires much longer treatment, and it may be necessary to use oral ketoconazole, fluconazole, or intravenous amphotericin B.

chlorhexidine mouthwash ?

Antimicrobials

Allopurinol mouthwash for the prevention and treatment of 5-FU-related stomatitis

positive results have led to allopurinol becoming routine practice.

no protective effect of allopurinol against 5-FU-induced stomatitis was seen in a randomized, double-blind clinical trial conducted by the NCCTG and the Mayo Clinic.

Pharmacologic Modulation

RT-induced fibrosis of the masticatory muscles and/or the temporal mandibular joint may be prevented or attenuated through early exercises with trismus appliances posttherapy. Fibrosis of the masticatory muscles may occur up to 1 year postradiation; therefore, jaw-opening exercises should start after oral mucosal healing and continue for more than 1 year following RT. Effective exercises in reducing trismus include the use of tongue depressors taped together 10 to 15 times a day for 10-minute sets.

Exercises for Radiation Therapy-Induced Complications

1. Antibiotics and surgical debridement and curettage.

2. Hyperbaric oxygen ?

Treatment Strategies for Osteonecrosis

conservative debridement and antibiotic therapy.

surgical procedures to remove the involved bone.

Early diagnosis pretherapy dental care

Osteonecrosis of the jaw related to bisphosphonate therapy

Stomatitis is the principal etiology of most pain experienced during the 3-week post-BMT time period.

Stomatitis-related oropharyngeal pain is multidimensional.

Immunocompromised patients with cancer who are also HIV develop larger, more painful lesions

Oral pain associated with cGVHD has been described as severe, with symptoms of burning, irritation, dryness, and loss of taste has been reported.

Symptom ManagementOropharyngeal Pain

viscous lidocaine (Xylocaine) or dyclonine hydrochloride

temporary pain relief kaolin-pectin, diphenhydramine, Orabase,

and Oratect Gel.

Anesthetic Cocktails

One large clinical research center uses a topical formulation that contains lidocaine viscous 2% (40 mL), diphenhydramine 12.5 mg/5mL (40 mL), and Maalox 10 mg (40 mL) and prescribes its use every 3 to 4 hours as needed.

Severe stomatitis-related oropharyngeal pain may interfere with hydration and nutritional intake and affect quality of life. Management of this oropharyngeal pain may require use of opioids,

oral transmucosal fentanyl was more effective than morphine sulfate immediate release in treating breakthrough pain

At present, no standard treatment has been defined for the prevention or treatment of stomatitis-related oral pain; therefore, it is essential to continue studies of the treatments already available and to develop promising new approaches.

Capsaicin?

Oral hygiene regimens that include the use of water/saline and daily fluoride application along with brushing teeth at least 3 times daily may reduce colonization and proliferation of oral pathogens.

Xerostomia

pilocarpine, 5- and 10-mg doses amifostine (Ethyol), administered at 200

mg/m2 as a 3-minute intravenous infusion 15 to 30 minutes before each fraction of radiation.

Artificial saliva, which usually uses carboxymethylcellulose as a base?

sugarless gum and hard candy

Xerostomia

Conclusion