Postradiation dental extractions without hyperbaric oxygen W, G. Maxymiw, DDSn R. E. Wood, DDS, MSc, Dip Oral Rad, IURCDC,~ and F.-F. Liu, MD, FRCPC,” Toronto, Ontario, Canada PRINCESS MARGARET

HOSPITAL

This study examined the incidence of osteoradionecrosis after tooth extraction with low-epinephrine or epinephrine-free, nonlidocaine local anesthetics and conservative surgical techniques. Estimates of the absorbed radiation dose on irradiated alveolar bone were made by reviewing radiotherapy records. This investigation included 72 patients ranging in age from 22 to 80 years (median 57.4 years). We removed 449 teeth. Analysis of radiotherapy check films revealed that only 198 teeth (44%) were included within the treatment volume. The median prescribed tumor dose was 50 Gy (range 25 to 84 Gy) in 20 fractions (range 10 to 37) with a median dose per fraction of 2.5 Gy (range 1.88 to 3.14 Gy). Follow-up time ranged from 88 days to 19.3 years (median 4.8 years). No instances of osteoradionecrosis occurred as a result of dental extraction with this conservative method. (ORAL SURC ORAL MED ORAL PATHOL 1991;72:270-4)

(ORN) of the mandible is a se0rioussteoradionecrosis complication after radiotherapy for head and neck malignancies.’ It is defined as the presence of exposed bone for a minimum of 6 months.2 The risk of ORN developing is greatest in the first 12 months after radiation but can continue for years thereafter.3 The reported incidence of ORN in irradiated jaws after tooth extraction is up to 61 .I’%.‘~ 4-7 However, no method of estimation of absorbed radiation dose to affected alveolar bone has been specified. Several conditions may predispose a patient to ORN, including inadequate postextraction healing before commencement of radiotherapy, brachytherapy radiation in close proximity to bone, high total doses of radiation (260 Gy), high dose per fraction (>2 Gy), alcohol and tobacco abuse, poor compliance with oral hygiene, surgical procedures after radiotherapy, trauma to irradiated bone, and nutritional factors.’ Radiation damage to the cellular and vascular components of bone and its soft tissue envelope has been emphasized as the most important factor in the development of ORN.* ORN is considered to be a ra-

Whief, Department of Dentistry. bDepartment of Dentistry. cDepartment of Radiation Oncology. 7/12/26013 270

diation-induced, nonhealing hypoxic wound with loss of osteocytes and osteoblasts in the direct path of the radiation beam, in the lacunae of both the outer lamellar and the haversian bone.5 A traumatic incident such as a tooth extraction produces a demand for protein synthesis that requires activity of both the cellular elements capable of protein synthesis (mainly fibroblasts) and an intact vascular network capable of nutrient delivery to the wound (i.e., a functioning capillary bed).3 It is claimed that approaches without hyperbaric oxygen (HBO) are incapable of improving ORN consistently and that only HBO is capable of arresting ORN but may not totally resolve it.9, lo The successful treatment of advanced ORN with surgical principles and HBO can be attributed to improvement of the existing hypoxia, hypocellularity, and hypovascularity. Tissue oxygen tensions are dramatically elevated during HBO treatment,“’ l2 which can stimulate collagen synthesis and fibroblastic proliferation9v I2 There is no evidence of regression of tissue angiogenesis resulting from HBO. The positive results of HBO in terms of wound healing and improved repair response in irradiated tissue could be expected to last at least 3 years.13 The purpose of this investigation was to assess the impact of careful surgical techniques with specific local anesthetic and antibiotic coverage, instead of

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i :

L-------------_----------------------------------~

Fig. 1. Check film of lateral parallel pair field of radiation for cancerof oropharynx.

Fig. 2. Isodosedistribution for samepatient. A, Presumedinner cortex of mandible;B, outer cortex. Prescribed tumor doseof 5200 cGy wasat 195%line.

HBO therapy, on tooth extraction in patients who previously received head and neck radiation. MATERIAL AND METHODS Radiation therapy

All patients were immobilized with individually customized masks and received radiation with highenergy photons or electrons. Beam-modifying devices such as wedges or compensators were used to achieve dose homogeneity of + 5%, abiding by the guidelines of the International Commission on Radiation Units and Measurements.14 A wedge is a device of graduated thickness that causes a gradual decline in the dose rate across a beam. It is often used when differences are present across the width of a target volume, such as in irradiation of the larynx. A compensator is a device that modifies the dose distribution, accounting for changes in the shape or obliquity of the target volume with respect to the beam. The most common indication for a compensator is irradiation of a nasopharyngeal or oropharyngeal neoplasm, whereby a major contour change results because of the mandible. Dental extraction

protocol

Since December 1982 a precise regimen for postradiation extractions has been followed at the Princess Margaret Hospital. This consisted of prophylactic antibiotic coverage with 2.0 gm penicillin V potassium orally 1 hour before any surgical procedure and then 600 mg four times a day for 1 week. Low-concentration epinephrine-containing (~1:200,000), nonlidocaine local anesthetic (prilocaine plain or

Fig. 3. Worksheetdiagramwith superimpositionof field of radiation, indicating teeth removedinsideand outside treatment volume.

prilocaine forte) and an atraumatic surgical technique that avoided periosteal elevation were employed. In cases where multiple extractions were required, a single tooth or at most two teeth were extracted at one appointment in the same quadrant. Further extractions were performed by alternating quadrants at subsequent appointments. These patients were closely followed, and detailed instructions were given regarding the use of irrigators to maintain socket hygiene. Determination of ORN

Patients were regularly followed in both otolaryngology and dental clinics. This enabled assessment of both tumor control and presence of ORN. The incidence of ORN was determined as a function of total

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ORAL SURG ORAL MED ORAL PATHOL September 199 1

Table I. Primary

cancer sites of 72 patients requiring postradiation extractions Site

Oral cavity Larynx Oropharynx Nasopharynx Hypopharynx Salivary gland Paranasal sinuses Skin Unknown primary site with neck node Other Total

Table II. Dose delivered to each segment of jaws for

72 patients requiring postradiation

No. of cases

16 14 16 11 2 5

1 2 4

extractions

Dose (Gy) Site

I

Maxilla Right Left Mandible Right Left

Range

24-84

17.82-84 25.48-84.76 25.48-62.74

I

Median

49.58 48.7 49.65 49.58

1 72

follow-up period was 4.8 years, with a range from 68 days to 19.3 years. number of teeth removed either inside or outside the radiation field for the respective jaws and as a function of the total number of patients treated. Radiatlon dose estimation

The charts and obtainable check films (Fig. 1) were reviewed for all patients. The dose, fractionation, technique of radiation, and energy chosen were all collected from the radiation therapy treatment record. A computerized dose distribution was available for the majority of patients. The outer surface of the mandible and maxilla were assumed to start at 1 cm from skin; thickness of these bones was assumed to be 1.5 cm. Range in maxillary and mandibular doses was calculated by concomitantly examining the patient’s isodose distribution and check films (Fig. 2). The field of radiation was also superimposed on an accompanying worksheet diagram (Fig. 3). If check films were not available, the absorbed bone dose was estimated with a depth-dose chart and by assuming the patient’s face was 10 cm wide. Teeth removed were classified into one of four categories: (1) maxillary teeth removed in radiation field, (2) maxillary teeth removed outside radiation field, (3) mandibular teeth removed in radiation field, or (4) mandibular teeth removed outside radiation field. RESULTS

Seventy-two patients who had extractions at Princess Margaret Hospital after head and neck radiation therapy were treated and examined according to the previous protocol, with the study period ending June 1990. Of these patients, one had an implant and five received additional chemotherapy. Their ages ranged from 22 to 80 years, with a median age of 57.4 years. Disease sites are summarized in Table I. The median

Radiation dose

All patients received radiation once daily. Analysis of prescribed tumor dose revealed a range from 25 to 84 Gy, with a median of 50 Gy. The median fraction number was 20 (range 10 to 37) delivered during a median period of 28.5 days (range 13 to 105 days). The median dose per fraction was 2.5 Gy, with a range from 1.88 to 3.14 Gy. As can be seen in Table II, the range in the absorbed maxillary and mandibular doses was wide, from 17.82 to 84.76 Gy. The median doses, however, were much more closely clustered, from 48.70 to 49.58 Gy. Isodose distribution and check films were available in 65 of 72 patients. Patient outcome

Local control of the tumor was obtained in 52 patients with radiation alone, with an additional 13 patients requiring subsequent surgery to attain control. Thirty-two patients had complete xerostomia as a result of treatment, 35 had partial xerostomia, one was not affected, and four were not examined for this. Fifty-eight patients are alive with no evidence of disease, five are alive with disease, and four died without evidence of disease. Five patients died of their disease. Dental extractions

A total of 449 teeth were removed in patients treated with radiation therapy for head and neck malignancy. However, analysis of the dose-distribution data revealed that only 196 teeth (44%) were extracted in osseous zones that had been directly irradiated. In the maxilla 197 teeth were extracted, 73 (37%) of which were directly in the field. In the mandible 123 of 252 teeth extracted (49%) were encompassed within the radiation field. Among these 72 patients, ORN developed in none; this includes teeth

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extracted directly in, and those outside, the irradiated volume. DISCUSSION

Recently HBO has been suggested as a prophylactic procedure to avoid ORN when extractions are required after radiation therapy.15 Kraut16 reported three cases where HBO with prophylactic antibiotics and conservative surgical techniques were used successfully to remove teeth. However, with this approach it is difficult to determine which component accounted for the favorable response. Marx et a1.13attempted to answer this question by randomly assigning radiation-treated patients undergoing dental extractions to either prophylactic antibiotics or HBO treatment. Of 37 patients, ORN developed in 11 (29.9%) when they were treated with antibiotics alone, whereas ORN developed in only 2 of 37 patients (5.4%) with prophylactic HBO. This advantage for HBO was attributed to the selection of teeth contained in a segment of the mandible receiving high-dose radiation (tumor dose ~68 Gy). The authors did not provide any details as to how alveolar bone dose was estimated. Although this analysis implies that prophylactic HBO is effective in preventing ORN after dental extractions, it may not be universally applicable in that many patients will refuse this approach because of time commitment and financial considerations. Some patients may be ineligible because of their medical conditions (e.g., chronic obstructive pulmonary disease). 17 Finally, accessibility is limited because it is not available in every community. This study was undertaken to evaluate the incidence of ORN after radiotherapy for head and neck malignancies, with dental extractions performed in a specific manner. A preponderance of patients with oral cavity and oropharynx tumors were in our study, primarily because of the proximity of these sites to the teeth. This is the first study in the literature to have documented in detail the method of estimating the absorbed alveolar bone dose. Interestingly, there is clearly a broad range in the absorbed bone dose and thus one cannot automatically assume that the prescribed tumor dose represents absorbed bone dose. We recognize that this method of dose estimation has limitations, because it is assumed that photons and electrons behave the same way in bone, which clearly may be incorrect. In addition, there is attenuation of absorbed energy in bone, which was not accounted for in our estimation. These limitations may result in an error of +- lo%, which is well below the range of es-

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timated absorbed bone dose. Nonetheless, this exercise underscores the importance of analysis of the radiation fields and isodose curves before recommendation of any preventive measures. The total radiation dose used in our investigation appears to be lower than in other studies, but the dose per fraction is actually more important in determining the extent of late tissue damage.‘* Although our dose per fraction (median 2.50 Gy) is higher than the conventional 2 Gy/fraction, this has not predisposed these patients to ORN. Notably, even with the addition of chemotherapy (five patients), the incidence of ORN is still nil. Local control with radiation alone was obtained in 73% of patients (52/72), with successful surgical salvage in the remaining 65% (13/ 20). These numbers clearly represent a selected population, but our objective was not to evaluate tumor control rate but to evaluate incidence of ORN in this group of patients. A total of 44% of teeth were encompassed in the actual treatment volume; 37% of maxillary (73/197) and 49% of mandibular teeth (123/252). It is to be expected that patients whose extractions lie outside the zone of irradiation would definitely not require HBO, because their tissues were not directly affected by radiation. However, one cannot rule out vascular damage to proximal vessels, which may occur with radiation, In addition, 62% (32/72) and 49% (35/52) of our patients had complete and partial xerostomia, respectively. Despite the high incidence of xerostomia in this group of patients, dental extractions performed with this technique resulted in no untoward sequelae. The choice of local anesthetic is important in this technique. The rationale of using 2% lidocaine with l:lOO,OOO epinephrine in an environment that is already hypovascular and hypocellular is questionable. Lidocaine has been shown to retard wound healing. lgS2’ In vitro and in vivo studies have demonstrated that lidocaine inhibits the synthesis of major structural macromolecules, collagen, and glycosaminoglycans. Lidocaine also reduces the breaking strength of skin wounds in rats.ig Collagen synthesis is significantly inhibited at low concentrations of lidocaine, whereas at higher concentrations collagen synthesis is completely arrested.22 Prilocaine, the anesthetic used in this investigation, is less toxic than lidocaine.23 This may well be an important factor to which we can attribute the success of our technique. The advantage of using epinephrine is related to its vasoconstrictive properties, which can maintain a high local concentration of anesthetic. This leads to a prolonged exposure of the agent on the tissues. Epinephrine alone has not been shown to retard wound

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healing,24 but injection of 0.5 ml of l:lOO,OOO epinephrine solution under traumatized tissues prolonged the reaction to the traumatic episode.20 To prevent further vascular compromise, nonlidocaine local anesthetic solutions containing minimal concentrations of vasoconstricting agents should be used.25 In our opinion, extractions after radiation should not be performed for at least 6 months after radiotherapya Antibiotic coverage is used to prevent infections, which may further compromise wound healing.5, 1‘3 25-29The surgical technique used should be atraumatic, and periosteal elevation should be avoided. After extraction the surgical site should be approximated with sutures and postsurgical recall evaluation visits should be frequent.25 Possibly, one of the three factors used in the dental extraction technique is responsible for our favorable results. It is possible to instigate studies to analyze the influence of antibiotic coverage or local anesthetic in isolation, although studies with traumatic surgical techniques on human subjects is clearly unethical. A prospectively randomized trial evaluating the relative contribution of antibiotic coverage or choice of local anesthetic to the low incidence of ORN is possible, but both maneuvers are so easily performed, with low risk and cost to patients, that the necessity of such a trial becomes questionable. CONCLUSIONS

Postradiation dental extractions may be carried out with antibiotic coverage, lidocaine-free low-epinephrine local anesthetics, and conservative surgical techniques, resulting in zero incidence of ORN. Analysis of the dose-distribution data and actual dose delivered to potential extraction sites is mandatory before definitive recommendations of preventive regimens can be made. We thank Mr. K. Oxley, Mr. A. Connor, and Ms. K. Hahn for their assistance in preparingthe illustrations;Ms. J. Pattersonfor her secretarialassistance; andMs. C. Morrison and Mr. J. Jacksonfor library services. REFERENCES

I. Kluth EV, Jain PR, Stuchell RN, Frich JC. A study of factors contributing to the development of osteoradionecrosis of the jaw. J Prosthet Dent 1988;59:194-201. 2. Marx RE. Osteoradionecrosis of the jaws: review and update. Hyperbaric Oxygen Rev 1984;5:78-128. 3. Daum RE, Negus TW. Hyperbaric oxygen in osteoradionecrosis of the mandible. J R Nav Med Serv 1988;74:51-4. 4. Marciani RD, Ownby HE. Osteoradionecrosis of the jaw. J Oral Maxillofac Surg 1986;1986:218-23. 5. Makkonen TA, Kiminki A, Kakkonen TK, Nordman E. Dental extractions in relation to radiation therapy of 224 patients. Int J Oral Maxillofac Implants 1987;16:56-64. 6. Epstein JB, Wong FL, Stevenson-Moore P. Osteonecrosis:

ORAL SURG ORAL MED ORAL PATHOL September 1991 study of the relationship of dental extractions in patients receiving radiotherapy. Head Neck Surg 1987; 10:48-54. 7. Morrish RB. Chan E, Silverman S, Meyer J, Fu KK, Greenspan D. Osteonecrosis in patients irradiated for head and neck cancer. Cancer 198 1;47: 1980-3. 8. Marx RE, Johnson RP. Studies in the radiobiology of osteoradionecrosis and their clinical significance. ORAL SURGORAL MED

ORAL PATHOL

1987;64:379-90.

9. Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg 1983;41:351-7. 10. Myers RAM, Marzella L. Hyperbaric medicine: what is it; how is it used? Md Med J 1988;37:559-64. 11. Fattore L, Strauss RA. Hyperbaric oxygen in the treatment of osteoradionecrosis: a review of its use &I efficacy.ORAL SURG ORAL MED ORAL PATHOL 1987:63:280-6. 12. Touhey JE, Davis JC, Workman WT. Hyperbaric oxygen therapy. Orthop Rev 1987; 16:829-33. 13. Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc 1985;111:49-54. 14. Dose specification for reporting external beam therapy with photons and electrons [Report 291. International Commission on Radiation Units and Measurements: Washington, DC; 1978. 15. Holmes H, Cousins G, Gullane PJ. Osteoradionecrosis: its pathophysiology and treatment. Oral Health 1989;79:17-23. 16. Kraut RA. Prophylactic hyperbaric oxygen to avoid osteoradionecrosis when extractions follow radiation therapy. Clin Prevent Dent 1985;7:17-20. 17. O’Quigley S. Hyperbaric oxygen therapy. Ir Med J 1983; 76:193-4. 18. Thames HD, Hendry JH. Fractionation in radiotherapy. London: Taylor & Francis, 1987:64-82. 19. Kanta J, Kopacova L, Patockova M, Bartos F. Effect of carbanilate local anesthetic on granulation tissue formation. Pol J Pharmacol Pharm 1984;36:659-63. 20. Passy V, d’Ablaing G, Turnbull FM, von Leden H. Cryosurgery: a comparison of the clinical and histological response to epinephrine. Laryngoscope 197 I ;8 1:1917-25. 21. Sveen K. Effect of the addition of a vasoconstrictor to local anesthetic solution on operative and postoperative bleeding, analgesia and wound healing. Int J Oral Surg 1979;8:301-6. 22. Chvapii M, Hameroff SR, O’Dea K, Peacock EE. Local anaesthetics and wound healing. J Surg Res l979;27:367-7 1. 23. Churchill-Davidson HC. Davidson’s: a practice of anaesthesia. Chicago: Year Book, 1984849. 24. Ohlsen L, Evers H, Segerstrom K, Hagelqvist E, Graffman S. Local anaesthetics modifying the dermal response of irradiation. Acta Oncol 1987;26:467-76. 25. Macdonald R. Effects of ionizing radiation on facial bones and developing dental tissues. Ann R Aust Coil Dent Surg 1986; 9:143-9. 26. Morton ME, Simpson W. The management of osteoradionecrosis of the jaw. Br J Oral Maxillofac Surg 1986;24:332-41. 27. Coffin F. The incidence and management of osteoradionecrosis of the jaws following head and neck radiotherapy. Br J Radio] 1983;56:851-7. 28. Starcke EN, Shannon IL. How critical is the interval between extractions and irradiation in patients with head and neck malignancy? ORAL SURG ORAL MED ORAL PATHOL 1977;43: 333-7. 29. Carl W, Schaaf NG, Sako K. Oral surgery and the patient who has had radiation therapy for head and neck cancer. ORAL SURG ORAL MED ORAL PATHOL 1973;36:651-7. Reprint

requesrs:

W. G. Maxymiw, DDS Ontario Cancer Institute Incorporating The Princess Margaret Hospital 500 Sherbourne St. Toronto, Ontario Canada M4X 1K9