Oralmedicinepacific.com

Oral and Dental Management Related to
Radiation Therapy for Head and Neck Cancer
• Pamela J. Hancock, BSc, DMD •
• Joel B. Epstein, DMD, MSD, FRCD(C) •
• Georgia Robins Sadler, BSN, MBA, PhD •
The clinical management of squamous cell carcinoma of the head and neck causes oral sequelae that can compro-mise patients’ quality of life and necessitate abandonment or reduction of optimal therapeutic regimens, which inturn reduces the odds of long-term survival. Such sequelae can be prevented or at least better managed if dentaland medical health care providers work together. It is therefore essential that dentists have an understanding ofcancer therapy and a sound working knowledge of the prevention and management options for the oral sequelaeof cancer treatment. This paper offers the dental team an overview of the consequences associated with radiother-apy, as well as a systematic overview of preventing or managing acute and chronic conditions before and duringradiotherapy. In addition, it reviews considerations for continued treatment needs during the patient’s lifetime. MeSH Key Words: cranial irradiation/adverse effects; osteoradionecrosis/prevention & control; stomatitis/prevention & control;
xerostomia/prevention & control
J Can Dent Assoc 2003; 69(9):585–90 This article has been peer reviewed. Surgery, chemotherapy and radiotherapy are the to remodel and may be at increased risk of infection and options for treatment of head and neck cancers. Each modality is associated with a number of considera- A consultation with a dental team experienced in caring tions related to treatment of the cancer and quality of life for patients undergoing treatment for head and neck cancer of the patient. When the oral cavity and salivary glands are should be completed before the start of therapy.3,4 Many exposed to high doses of radiation, there can be dramatic oral conditions, such as poor oral hygiene, broken teeth, effects on the patient’s oral health. This paper offers the defective restorations and periodontal disease, are likely to dental team an overview of the consequences associated precipitate complications during and after a course of with radiotherapy to facilitate collaboration with the radiation therapy (Table 1).
patient’s medical team1,2 (summarized in Table 1).
In addition to the clinical examination, a thorough ra- Oral Assessment before Treatment
diographic examination is crucial to determine the presence To a significant degree, the oral problems associated with of inflammatory periapical abnormalities, periodontal radiation therapy can be prevented or minimized through status, other dental disease and tumour invasion of bone. optimal management. The acute effects of radiation ther- A panoramic radiograph plus selective periapical or apy include mucositis, altered salivary gland function and bitewing films (or both) should be available for preradio- risk of mucosal infection. The long-term effects are due to therapy dental assessments. Consultation with the patient’s changes in the vascularity and cellularity of soft tissue and physician on the timing, nature (external beam radiother- bone, damage to the salivary glands and increased collagen apy or radioactive implant) and features (location and size synthesis resulting in fibrosis. These changes lead to of treatment fields, radiotherapy fractionation and total hypovascularity, hypocellularity and hypoxia of the tissues.
dose) of the radiotherapy is essential for overall risk assess- The affected bone and soft tissue have a reduced capacity ment and scheduling of any required dental intervention.
Journal of the Canadian Dental Association Table 1 Strategies for oral and dental management in relation to radiotherapy for head and
neck cancer
Component of care
Before radiotherapy
Resting (> 0.1 mL/minute), stimulated (> 1.0 mL/minute) Pulp tests, specific cultures (fungal, viral, bacterial) Prognosis (cure or palliation)Proposed radiation therapy During radiotherapy
Brushing 2 to 4 times daily with soft-bristled brush; flossing daily Custom trays, brush-on prescription-strength fluoride Frequent saline rinsesLip moisturizer (non-petroleum based)Passive jaw-opening exercises to reduce trismus After radiotherapy
Complete dental work that was deferred during radiotherapyMaintain integrity of teeth Check for oral hygiene, xerostomia, decalcification, decay, ORN, metastatic disease, recurrent disease, new malignant disease TMJ = temporomandibular joint, ORN = osteoradionecrosis Table 2 Criteria for preradiotherapy extractions
therapy (cure or palliation). A more aggressive dentalmanagement strategy should be considered for patients with limited previous dental care, poor oral hygiene and Active periapical disease (symptomatic teeth)Moderate to severe periodontal disease evidence of past dental or periodontal disease (Table 2).
Lack of opposing teeth, compromised hygienePartial impaction or incomplete eruption During Therapy
Extensive periapical lesions (if not chronic or well localized) Monitoring of the oral cavity should be increased during radiation therapy in an effort to decrease the severity of side All teeth, but especially those located within the radia- effects. Systematically applied oral hygiene protocols may tion fields, should be closely evaluated. A UK study found reduce the incidence, severity and duration of oral compli- that only 11.2% of patients who reported regular visits with cations.7 This, in turn, reduces the odds that patients’ a general dentist before a diagnosis of oral cancer were optimal therapeutic course will need to be modified, which considered to have no dental conditions that required treat- thereby increases patients’ odds of survival. Therefore, it is ment before radiation therapy.5 The criteria used for dental imperative that patients continue their oral hygiene extractions before radiation therapy are not universally regimen throughout their course of cancer therapy.8 The accepted and are subject to clinical judgement. However, patient’s self-care procedures should include frequent teeth in the high-dose radiation field should be considered brushing with a soft-bristled toothbrush and fluoride tooth- for extraction before radiotherapy if they are nonrestorable; paste or gel to help prevent plaque accumulation and if they require significant restorative, periodontal or demineralization or caries of the teeth.3 endodontic intervention or if they have moderate to severeperiodontal disease (pockets of 5 mm or more).6 Side Effects of Radiation
Factors to consider when assessing preradiotherapy The oral tissues directly affected by head and neck dental status include the overall condition of the patient’s radiation therapy include the salivary glands, the mucosal dentition (caries, periapical status, inflammatory periapical membranes, the jaw muscles and bone. Dry mouth abnormalities), previous dental care, current oral hygiene, (xerostomia) is a common and significant consequence of the urgency of the cancer treatment, the planned therapy head and neck radiotherapy. Because of the loss of saliva, (radiation fields and dose) and the prognosis of the cancer patients with xerostomia are more susceptible to Journal of the Canadian Dental Association Oral and Dental Management Related to Radiation Therapy for Head and Neck Cancer periodontal disease, rampant caries, and oral fungal and fitted vinyl tray if possible.3,11,17 This practice may be started bacterial infections. Mucositis, characterized by inflamma- on the first day of radiation therapy and continued daily as tion and ulceration of the oral mucosa, is the most signifi- long as salivary flow rates are low and the mouth remains dry.
cant acute side effect reported by patients and is a potential High-potency fluoride brush-on gels and dentifrices may be source of life-threatening infection. Almost all patients considered in those who are unable or unwilling to comply undergoing head and neck radiation therapy experience confluent mucositis by approximately the third week of Another potential consequence of radiotherapy to the Health care providers should be concerned about oral cavity is fibrosis around the muscles of mastication, preventing local and systemic infections in addition to leading to trismus. It is believed that jaw exercises may limit managing oral symptoms. Treating infections as soon as the severity of trismus, but they will not mobilize fibrosis they are detected will help to reduce pain, as well as the once it has occurred.11,12 Bone exposed to high levels of spread of infection. A fungal, bacterial or viral culture is radiation undergoes irreversible physiologic changes recommended if infection is suspected.
including narrowing of the vascular channels (endarteritis), In patients undergoing head and neck radiotherapy, which diminishes blood flow to the area, and loss of Candida colonization tends to increase throughout the osteocytes. The bone essentially becomes nonvital, which course of treatment and remains increased if xerostomia leads to limited remodelling of bone and limited healing occurs.18,19 Nystatin rinses are the most widely prescribed treatment for oral fungal infections, despite a lack of provenefficacy. Nystatin has an unpleasant flavour and may cause nausea and vomiting,17 and its high sucrose content is a Systemic sialagogues may increase the production of major concern in dentate patients. For more severe natural saliva from functional glands. There is no optimal infections, the use of a systemic antifungal medication substitute for saliva that can be used when glands are such as fluconazole (Diflucan) or amphotericin B is recom- nonfunctional. Pilocarpine (Salagen) has shown promising mended.3 Systemic amphotericin B must be used with effects in increasing saliva but is only effective for salivary caution because of its potential to cause liver toxicity4 glands with residual function.13 Cevimeline (Evoxac), a (Table 3). Topical antifungals to consider include clotrima-
new sialagogue approved for use in the United States for zole, ketoconazole and chlorhexidine.
Sjogren’s disease, may increase salivary flow in patients Chlorhexidine gluconate (0.12%; Peridex), an antimicro- undergoing head and neck radiotherapy. Two alternative bial rinse, has both antifungal and antibacterial properties in medications that may be beneficial in stimulating salivary addition to antiplaque effects; however, its value is still glands include anethole trithione (Sialor) and bethanechol unconfirmed. Its tendency to stain teeth and its alcohol (Urecholine)14 (Table 3).
content, which can irritate inflamed tissues, are draw- Although saliva replacements such as UniMist (Westons backs.18 If chlorhexidine is used, it is important to note that Health), Mouth Kote (Parnell Pharmaceuticals) and Oral nystatin and chlorhexidine should not be used concurrently, Balance Gel (Laclede Pharmaceuticals) are poor salivary because chlorhexidine binds to nystatin, rendering both substitutes, as they primarily attempt to mimic the texture ineffective;17 furthermore, chlorhexidine should be used at of saliva but do not simulate the rheologic properties, the least 30 minutes before or after the use of any other topical antimicrobial factors (e.g., antibodies, antimicrobial proteins) and other components of saliva, patients may find For cancer patients with viral infections, such as that they offer some relief. Oral Balance Gel may be the Herpes simplex 1, acyclovir (Zovirax, GlaxoSmithKline) or best accepted by patients because of its extended duration derivatives are recommended for both prophylaxis and of effect.15,16 Sugarless gum or lozenges may stimulate treatment.3,20 Penciclovir (Denavir, GlaxoSmithKline), a salivary secretion in patients with residual salivary gland newer topical antiviral with increased tissue penetration, is function. Sugar-free popsicles, plain ice cubes or ice water may be used to keep the mouth cool and moist. Eatingfoods high in ascorbic acid, malic acid or citric acid will stimulate the glands to increase salivary flow, but this Maintaining a self-care regimen may decrease the measure is not recommended in dentate patients because incidence of mucositis.17 While many products and the acidity can further irritate oral tissues and contribute to combined product rinses have been suggested for clinical use, they have not been studied in randomized controlled For the prevention of rampant dental demineralization trials and should be used with caution. Among the and caries, patients should apply a 1.1% neutral sodium concerns with the use of combinations of rinses are the risks fluoride gel daily (for at least 5 minutes), using a custom- that some products may interfere with the action of others, Journal of the Canadian Dental Association Table 3 Therapies to deal with specific problems associated with head and neck radiotherapy
Contraindications
Systemic sialogogue
Asthma, peptic ulcer, bladder inflammation Anethole dithiolethione (Sialor),b 25 mg Antifungal agents
Systemic
Fluconazole (Diflucan), 100 mg
Liver or renal dysfunction, coumadin, warfarin Topical
Nystatin suspension, 100,000 U/mL
Hypersensitivity to drug class, liver dysfunction Mucosal coating agents
Hypersensitivity to drug class, renal dysfunction Diphenhydramine liquid (Benadryl), 12.5 mg/5 mL Asthma, glaucoma, cardiovascular disease, Hypersensitivity to drug class, renal dysfunction Topical anesthetics or analgesics
Hypersensitivity to drug class, glaucoma, Hypersensitivity to drug class, renal dysfunction aBrand names are included only as examples and not to promote any one product. The manufacturers are as follows: Salagen, Pharmacia; Urecholine, Merck;Sialor, Paladin; Evoxac, SnowBrand Pharmaceuticals; Diflucan, Pfizer; Fungizone, Bristol-Myers Squibb Canada Inc.; Peridex, Zila Pharmaceuticals; Maalox, NovartisConsumer Health; Benadryl, Pfizer Consumer Healthcare; Tantum, 3M Pharmaceuticals; Orajel, Del Laboratories.
bOver the counter; not available in the United States.
cNot available in Canada. and compounding may result in dilution of the individual rinse has potential effects on mucositis, others report no products to levels that may be ineffective.
effects,9 and no effects have been reported for radiation- The use of a common oral rinse, such as isotonic saline induced mucositis to date. Use of other oral rinses, includ- or sodium bicarbonate, is often suggested, but no studies ing commercial alcohol-based mouthwashes and hydrogen have confirmed any beneficial effect upon mucositis.3 It has peroxide rinses, should be discontinued because of their been suggested that patients begin prophylactic rinses with drying and irritating effects on the oral mucosa.
chlorhexidine to prevent the onset of microbial infection, The discomfort of mucositis can be reduced with coat- gum inflammation and bleeding, and to reduce the risk of ing agents, topical anesthetics and analgesics, although caries. While some authors report that a chlorhexidine oral systemic analgesics are frequently needed.3 Aluminum Journal of the Canadian Dental Association Oral and Dental Management Related to Radiation Therapy for Head and Neck Cancer hydroxide/magnesium hydroxide (milk of magnesia- detect signs of recurrence or new primary malignant lesions Maalox) and sucralfate have been suggested as coating is essential. Close follow-up will facilitate the management agents for the oral mucosa. Sucralfate suspension may also of any chronic complications that may occur, such as be helpful in the treatment of oral pain, although the xerostomia, mucosal sensitivity, increased risk of cavities, effect on mucositis has not been clearly documented21–25 candidiasis and persisting risk of osteoradionecrosis (Table 3).
Topical anesthetics used in rinse form may result in The period after completion of cancer therapy is an intense but short-term anesthesia. However, the localized excellent time for patients to resolve any oral concerns that anesthesia can increase the risk of aspiration, and their were previously deemed not medically necessary and for systemic absorption can cause cardiac effects. When oral which care had been deferred. Since patients with cancer mucosal pain is present, benzydamine hydrochloride are more likely to experience a recurrence or a new cancer (Tantum), doxepin suspension 0.5% or an antihistamine and require further therapy, resolution of any deferred such as diphenhydramine can be prescribed.10,26 dental care should be a top priority.
Benzydamine is the only medication available that has beenshown in multicentre, double-blind controlled studies to Osteoradionecrosis
reduce mucositis and pain in patients with head and neck ORN is irreversible, progressive devitalization of irradi- cancer.10,26 Topical anesthetics, such as benzocaine, viscous ated bone. The condition is characterized by necrotic soft lidocaine and topical benzocaine can be applied locally to tissue and bone that fails to heal spontaneously. Most cases sites of pain with a swab or a soft vinyl mouth guard3 of ORN occur in the mandible, where vascularization is (Table 3).
poor and bone density is high. Clinical manifestations of Of all available mouth rinses that can be used as treat- ORN may include pain, orofacial fistulas, exposed necrotic ments for mucositis, the least costly and easiest for patients bone, pathologic fracture and suppuration.28–30 One-third to prepare is a simple mouthwash comprising a teaspoon of ORN cases occur spontaneously. Among cases where (10 mL) of salt and a teaspoon (10 mL) of baking soda ORN has been initiated by trauma the majority result from (sodium bicarbonate) in 8 ounces (250 mL) of water.
extraction of teeth. The incidence of ORN is twice as A comparison among salt and soda mouthwashes, mouth- high in dentate patients as it is among edentulous patients.
washes prepared from lidocaine and diphenhydramine with Poor oral hygiene and continued use of alcohol and tobacco Maalox, and mouthwashes of 0.12% chlorhexidine gluconate found that the 3 options were equally effective Over the years, ORN has been treated by numerous in the treatment of chemotherapy-induced mucositis.27 methods with variable success.28 Hyperbaric oxygen ther- Although chlorhexidine may also decrease oral Candida apy is considered an adjunctive treatment for ORN, often counts and bacterial levels, studies on radiotherapy patients used in conjunction with surgery, and has been associated have shown no effect on mucositis. According to the current with better success rates than surgery alone.29,30,32,33 literature, good oral hygiene, topical fluorides for caries Conclusions
prevention and benzydamine offer the greatest benefits.
The complications of radiotherapy must be considered After Therapy
thoroughly so that every effort is undertaken to minimize After the completion of radiation therapy, acute oral the oral morbidity of these patients before, during and after complications usually begin to resolve. Patients should cancer treatment and throughout the patient’s lifetime. C continue to follow an oral health self-care regimen to keepthe teeth and gums healthy and to facilitate repair of any Dr. Hancock is a resident in the department of oral medicine,
residual oral damage. Oral exercises should be continued or University of Washington, Seattle, WA; and dentist in the departmentof dentistry, Fraser Valley Cancer Centre, Surrey, B.C., and the introduced to reduce the risk and severity of trismus.
department of dentistry, Vancouver Hospital and Health Sciences Additional dietary counselling sessions may be appropriate for patients who must make long-term dietary adaptations Dr. Epstein is professor, department of oral medicine and diagnostic
to accommodate permanent changes to their oral cavity sciences, director, interdisciplinary program in oral cancer, College ofDentistry and College of Medicine, University of Illinois, Chicago, produced by surgery and radiation. The referral of patients Illinois; head of the department of dentistry, Vancouver Hospital and to support groups may also be a useful adjunct to patients’ Health Sciences Centre, Vancouver, BC; and staff, British Columbia Cancer Agency, Vancouver, B.C.
Dr. Sadler is associate clinical professor of surgery, University of
Long-term management and close follow-up of patients California San Diego School of Medicine, and associate director for after radiation therapy is mandatory. It is critical to community outreach, Moores UCSD Cancer Center, La Jolla, remember that patients at highest risk for a new or recur- rent cancer are those previously treated for cancer of the Correspondence to: Dr. J. Epstein, Department of Oral Medicine
and Diagnostic Sciences, MC 838 – 801 South Paulina St.,
upper aerodigestive tract. Therefore, careful examination to Chicago, IL 60612. E-mail: jepstein@uic.edu. Journal of the Canadian Dental Association The authors have no declared financial interests in any company 22. Allison RR, Vongtama V, Vaughan J, Shin KH. Symptomatic acute manufacturing the types of products mentioned in this article. mucositis can be minimized or prophylaxed by the combination of sucralfate and fluconazole. Cancer Invest 1995; 13(1):16–22.
23. Franzen L, Henriksson R, Littbrand B, Zackrisson B. Effects of References
sucralfate on mucositis during and following radiotherapy of malignan- 1. Sadler GR, Oberle-Edwards L, Farooqui A, Hryniuk WM. Oral seque- cies in the head and neck region. A double-blind placebo-controlled lae of chemotherapy: an important teaching opportunity for oncology study. Acta Oncol 1995; 34(2):219–23.
health care providers and their patients. Support Care Cancer 2000; 24. Meredith R, Salter M, Kim R, Spencer S, Weppelmann B, Rodu B, and others. Sucralfate for radiation mucositis: results of a double-blind 2. Sadler GR, Stoudt A, Fullerton JT, Oberle-Edwards LK, Nguyen Q, randomized trial. Int J Radiat Oncol Biol Phys 1997; 37(2):275–9.
Epstein JB. Nurses’ role in managing the oral sequelae associated with 25. Carter DL, Hebert ME, Smink K, Leopold KA, Clough RL, Brizel chemotherapy. Medsurg Nurs 2003; 12(1):28–36.
DM. Double blind randomized trial of sucralfate vs. placebo during 3. Carl W. Local radiation and systemic chemotherapy: preventing and radical radiotherapy for head and neck cancers. Head Neck 1999; managing the oral complications. J Am Dent Assoc 1993; 124(3):119–23.
4. Simon AR, Roberts MW. Management of oral complications associated 26. Epstein JB, Truelove EL, Oien H, Allison C, Le ND, Epstein MS.
with cancer therapy in pediatric patients. ASDC J Dent Child 1991; Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain due to cancer or cancer therapy. Oral Oncol 2001; 37(8):632–7.
5. Lizi EC. A case for a dental surgeon at regional radiotherapy centres.
27. Dodd MJ, Miaskowdki C, Dibble SL, Paul SM, MacPhail L, Brit Dent J 1992; 173(1):24–6.
Greenspan D, and other. Factors influencing oral mucositis in patientsreceiving chemotherapy. Cancer Pract 2000; 8(6):291–7.
6. Epstein JB, Stevenson-Moore P. Periodontal disease and periodontalmanagement in patients with cancer. Oral Oncol 2001; 37(8):613–9.
28. Brown DH, Evans AW, Sandor GK. Hyperbaric oxygen therapy in the management of osteoradionecrosis of the mandible.
7. Turhal NS, Erdal S, Karacay S. Efficacy of treatment to relieve Adv Otorhinolaryngol 1998; 54:14–32.
mucositis-induced discomfort. Support Care Cancer 2000; 8(1):55–8.
29. Aitasalo K, Grenman R, Virolaine E, Niinikoski J, Klossner J. A 8. Barasch A, Safford MM. Management of oral pain in patients with modified protocol to treat early osteoradionecrosis of the mandible.
malignant diseases. Compendium 1993; 14(11):1376, 1378–82, 1384.
Undersea Hyperb Med 1995; 22(2):161–70.
9. Foote RL, Loprinizi CL, Frank AR, O’Fallon JR, Gulavita S, Twefik 30. McKenzie MR, Wong FL, Epstein JB, Lepawsky M. Hyperbaric HH, and others. Randomized trial of a chlorhexidine mouthwash for oxygen and postradiation osteonecrosis of the mandible. Eur J Cancer B alleviation of radiation-induced mucositis. J Clin Oncol 1994; Oral Oncol 1993; 29B(3):201–7.
31. Curi MM, Dib LL. Osteoradionecrosis of the jaws: a retrospective 10. Epstein JB, Silverman S Jr, Paggiarino DA, Crocket S, Schubert MM, study of the background factors and treatment in 104 cases.
Senzer NN, and others. Benzydamine HCl for prophylaxis of radiation- J Oral Maxillofac Surg 1997; 55(6):540–4.
induced oral mucositis: results from a multicenter, randomized, double- 32. van Merkesteyn JP, Bakker DJ, Borgmeijer-Hoelen AM. Hyperbaric blind, placebo-controlled clinical trial. Cancer 2001; 92(4):875–85.
oxygen treatment of osteoradionecrosis of the mandible. Experience in 11. Whitmyer CC, Waskowski JC, Iffland HA. Radiotherapy and oral 29 patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995; sequelae: preventive and management protocols. J Dent Hyg 1997; 33. David LA, Sandor GK, Evans AW, Brown DH. Hyperbaric oxygen 12. Cremonese G, Bryden G, Bottcher C. A multidisciplinary team therapy and mandibular osteoradionecrosis: a retrospective study and approach to preservation of quality of life for patients following oral analysis of treatment outcomes. J Can Dent Assoc 2001; 67(7):384.
cancer surgery. OHL Head Neck Nurs 2000; 18(2):6–11.
13. Hawthorne M, Sullivan K. Pilocarpine for radiation-induced xerosto-mia in head and neck cancer. Int J Palliat Nurs 2000; 6(5):228–32.
14. Nusair S, Rubinow A. The use of oral pilocarpine in xerostomia andSjogren’s syndrome. Semin Arthritis Rheum 1999; 28(6):360–7.
15. Furumoto EK, Barker GJ, Carter-Hanson C, Barker BF. Subjectiveand clinical evaluation of oral lubricants in xerostomic patients. Spec CareDentist 1998, 18(3):113–8.
16. Epstein JB, Emerton S, Le ND, Stevenson-Moore P. A double-blindcrossover trial of Oral Balance gel and Biotene toothpaste versus placeboin patients with xerostomia following radiation therapy. Oral Oncol 1999;35(2):132–7.
17. Feber T. Mouth care for patients receiving oral irradiation. Prof Nurse1995; 10(10):666–70.
18. Epstein JB, Chin EA, Jacobson JJ, Rishiraj B, Le N. The relationshipsamong fluoride, cariogenic oral flora, and salivary flow rate during radiation therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod1998; 86(3):286–92.
19. Ramirez-Amador V, Silverman S Jr, Mayer P, Tyler M, Quivey J.
Candidal colonization and oral candidiasis in patients undergoing oraland pharyngeal radiation therapy. Oral Surg Oral Med Oral Path OralRadiol Endod 1997; 84(2):149–53.
20. Epstein JB, Sherlock CH, Wolber RA. Oral manifestations ofcytomegalovirus infection. Oral Surg Oral Med Oral Pathol 1993;75(4):443–51.
21. Makkonen TA, Bostrom P, Vilja P, Joensuu H. Sucralfate mouthwashing in the prevention of radiation-induced mucositis: a placebo-controlled double-blind randomized study. Int J Radiat Oncol Biol Phys1994; 30(1):177–82.
Journal of the Canadian Dental Association

Source: http://www.oralmedicinepacific.com/docs/whats-new/Oral-Cancer-Care-JCDA-2003.pdf