The treatment of osteoradionecrosis of the mandible

The FRANK

Treatment of Osteoradionecrosis of the Mandible

W. MASTERS,

M.D., ROBERT L. KLAUS, M.D. AND DAVID W. ROBINSON, M.D., Kansas City, Kansas

From tbe Department of Surgery, Division of Plastic Surgery-, University qf Kansas Medical Center, Kansas Ci tt; Kansas.

STEORADIONECROSIS of the mandibIe is a compIex compIication of radiation therapy for intraoral disease. Characterized by severe pain, trismus, fetor, Aeration and gradual sequestration, radionecrosis pursues a sIowIy progressive, indoIent course and if untreated may produce drug addiction or chronic alcohol&. Unfortunately, this disease process is frequentIy associated with recurrent also malignancy, and both the cIinica1 picture and prognosis become confused by the addition of a second major disease entity. In some published series [r~r] osteonecrosis of the mandibIe is associated with a high mortaIity rate. When analyzed, however, the mortality rate more often reflects the termination of an advanced malignancy rather than the end result of therapy for primary osteonecrosis aIone. Seventeen patients with primary radiation necrosis of the mandible not associated with recurrent malignant disease have been treated, without mortaIity, at the University of Kansas Medical Center since 1948. Study of the eitology, symptomatoIogy and complications presents a picture of a progressive morbid disthe therapy of which can be ease process, individualized to provide a maximum of symptom relief and a minimum of serious complication.

0

ETIOLOGY Since the time of Regaud [6], most authors [z--4,7-g] agree that the mandibIe is peculiarly susceptibIe to osteoradionecrosis. The thin, flat, anatomica structure with a singIe eccentric artery, the compact nature, the high caIcium content which increases radiosensitivity [?I,

and the superficial Iocation in the path of externa1 radiation predispose to radiation injury. In 1922 Regaud [6] first noted that osteoradionecrosis differed from osteomyelitis of infectious or traumatic origin. He believed that in bone injured by radiation, there was no distinct Iine of demarcation between dead and living bone, and that no invoIucrum formed until the disease process reached the limits of the radiated fieId where sequestrectomg and heaIing occured. This, he believed, was the resuIt of a decreased vascular reserve which Iowered the ability of bone to combat bacterial invasion. Ewing [7], in 1926, stated that “complete death of bone of a peculiar type appears to occur in some cases after heavy external radiation by x-ra.? or radium” and that the necrosis, characterrzed by eburnation of bone, resuIted from vascular scIerosis in the haversian system, the periosteum ancl surrounding soft trssues. There is concomitant death of the bone ceIIs and intrinsic change in the lamellar substance due to secondary radiation effect which increased brittleness and predisposed to spontaneous fracture. Warren [8], in review, emphasized four major points in the pathogenesis of osteoradionecrosis: (I) Radiation injury can occur beneath intact skin and mucous membrane. (2) The macroscopic integrity of bone is maintained even after heavy radiation due to amorphous minera foundation. (3) Infection or trauma superimposed upon radiation damage produces marked necrosis. (4) Sequestration in radionecrosis is sIower than necrosis due to infection or trauma alone. Osteoradionecrosis of bone is thus the end result of the combination of radiation, infection

Masters,

KIaus

and Robinson soft tissue to form a persistent draining orocutaneous fistula. Fetor, too, is a constant companion of the ora uIceration, and the foul odor is an unending source of annoyance and discomfort to the patient. Roentgen examination varies with the stage and extent of the disease process. The Hurst evidence of radiation necrosis is periostea1 thickening, followed by mottIed areas of absorption and osteoporosis which may, in advanced cases, continue to pathoIogic fracture [I I]. Involucrum formation and discrete sequestration is uncommon [6]. In addition, irritabiIity, personality change, chronic alcohoiism and drug addiction are frequentIy seen in patients with radionecrosis. The unremitting pain, oraI fetor and inability to eat create a demand for relief which can, in be managed only by the many instances, continuous use of aIcoho1 or narcotics.

and trauma. The unique structure of the mandibIe and its anatomica position as an obstruction in the pathway of radiation therapy for oraI carcinoma are the major factors in the frequency of this particular comphcation. Necrosis on the basis of radiation alone seldom occurs. Although radiation damage may take pIace beneath intact skin or mucous membrane, the macroscopic integrity of bone persists even after extensive radiation, and sequestration occurs onIy with the addition of infection or trauma. The notoriousIy poor oraI hygiene and high incidence of dental caries associated with intraora1 malignancy provide a fertiIe ground for the bacteria1 invasion of a radioIogicaIIy damaged mandibIe. Dental caries, per se, may be a primary source of bacteria1 invasion or a cause of a deIayed or “Iate” necrosis [8]. Tooth decay foIIowing radiation therapy may result from both radioIogic injury to the puIp and decrease in the amount and pH of sahva [IO]. This is a slow process which may provide the mechanism for osteoradionecrosis months or years foIIowing the primary radiation therapy. CLINICAL

PROPHYLAXIS

The prevention of radionecrosis of the mandibIe faIIs primarily into the province of the radiotherapist. Modern technics which incIude the use of intraora1 cones, cobalt bomb therapy, careful shielding of uninvolved areas and in particuIar the fractionation of dosage may reduce the incidence of radiation injury. Shultz [12], however, has shown that supervoItage therapy does not protect the mandible from damage when it lies directly in the path of proposed treatment for an intraoral lesion. Wildermuth [j] also advocated the use of radium when possible for he believed that by virtue of the short range effect of radium, pIus direct application to a primary tumor, the amount of effective radiation to the mandible was Iessened. In this series of 104 patients with intraora1 malignancy, necrosis did not deveIop in any of those treated with radium. This experience, however, has not been paralleled by others [I] and is not borne out by the three patients with osteonecrosis presented herein who were treated by radium therapy aIone (Cases 2, 3 and 5). Since infection is an important etiologic agent and denta caries a constant companion of radiotherapy, prophylactic denta extraction has been wideIy advocated as an important measure to prevent radionecrosis [2,1o]. Warren 181 has shown that external radiation causes ceIIuIar change which aImost inevitabIy leads to caries in the pulp and cementum of normal

PICTURE

Unremitting pain in the mandibIe is the most constant cIinica1 finding in osteoradionecrosis whether primary or associated with recurrent malignancy. In earIy stages, the pain is associated with hypersensitivity of the remaining teeth and persists as a continuous toothache with associated alteration of taste. As the disease process progresses, the discomfort increases, characteristicahy, the patient complains of a deep, boring, persisting type of pain Iimited to the jaw which is not reIieved by ordinary anaIgesics and is increased by the norma motion of taIking or eating. Secondary trismus may be caused by pain, an intraoral uIcer or a pathologic fracture, or may be the result of muscular fibrosis caused by radiation and infection. UIceration with exposure of necrotic bone aIso occurs. CharacteristicaIIy, the uIcer crater is deep, ragged and exquisitely tender, and there is marked inflammatory induration of the surrounding soft tissue. This may be extremeIy diffrcuIt to differentiate clinicahy from a recurrent maIignant process which has secondariIy invoived bone. MuItipIe regional biopsies may be necessary for adequate pathoIogic differentiation. The uIceration may extend through

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Osteoradionecrosis teeth. This fact, combined

with the usual poor ora hygiene so frequently seen in intraoral carcinoma, has led to prophyIactic extractions to reduce the portals of entry of infection. Wildermuth [?I, however, has demonstrated convincingly that such extraction of teeth either immediately before or during radiotherapy promotes rather than prevents radionecrosis. The small spicules of bone which remain in the surrounding soft tissue of the alveolus following extraction form a nidus for infIammation and foreign hod:\- reaction and may well scrvc as a starting pomt for necrosis. In R’ildermuth’s series, all cases of radionecrosis occurred in the group who had prophylactic extraction either shortly before or at the beginning of radiation. Tooth extraction, if carefully performed under conditions of good ora hygiene with antibiotic therapy, has not resulted in osteonecrosis. If intraoral malignancy exists in the presence of severe dental caries and poor ora hygiene, surgical treatment of the primary lesion wouId obviate the dangers of radiation therapy and concomitant denta extraction.

of Mandible extraoral mandibulectomy and subsequent reconstruction of orocutaneous fistula if present. The following cases are representative. CASE REPORTS CASE 1. H. D. (KUMC No. 59-999), a sixtyseven year old white man, received 6,220 r of intra- and extraoral radiation for a squamous cel1 carcinoma of the floor of the mouth three days following full mouth extraction. Tfle alveolar mucous membrane did not heal and graduaIIy receded from the underlying mandible. (Figs. IA and B.) X-rayl:examination’ revealed destruction of the mandible. (Fig. IC.) Intraoral scquestrectomy was performed with preservation of the mandibular rim. (Fig. ID.) CompIete healing occurred with maintenance of contour. (Figs. IE and F.) CASE II. S. M. (KUMC NO. 5o-2718), a seventy-two year old white man, received 5,408 mg. hours of radium to a squamous cell carcinoma of the lip with marked Iocal reaction. (Fig. zA.) Three years following therapy, pain, ulceration and fetor devcIoped, with exposure of the mandible. IntraoraI sequcstrcctomy to bleeding bone was foIlowed by prompt healing and preservation of facial contour. (Fig.. zB.)

CLINICAL MATERIAL Since 15~48, seventeen patients with primary osteoradionecrosis not associated with recurrent malignancy of the mandible have been treated on the Plastic Surgical Service of the University of Kansas Medical Center. In fourteen patients radionecrosis developed following therapy for intraoral malignancy; the remaining three patients had radiation for benign lesions. A11 patients were treated surgicahy by either intraora1 resection to bleeding bone or by

CASE III. F. F. (KUhllC No. 55-5920), a fiftythree year old white man, received 6,400 gamma r of radium for epidermoid carcinoma of the tongue. Two years following therapy, dental extraction was performed without prophyIactic antibiotic therapy and the aIveoIar mucous membrane did not heaI. Pain, ulceration and severe trismus occurred (Fig. 3A) with x-ray evidence of a pathologic fracture of the mandible. (Fig. 3B.) IntraoraI sequestrectomy was performed with primary soft tissue healing.

FIG. IA. Case I.

FIG. IB. Cast I. 889

FIG. ID. Case I. fistuIa occurred with exposure of the orocutaneous showed mandibIe. (Fig. 4A.) Roentgen examination tota destruction of the mandibIe from mid-body to (Fig. 4B.) mid-body. ExtraoraI mandibuIar resection was performed. fistula persisted but (Fig. 4C.) The orocutaneous the patient has refused pedicIe coverage. FIG. IC. Case I.

CASE IV.

R. M. (KUMC No. 54-734g), a fiftytwo year oId man with diabetes, received externa1 and intraora1 radiation for a carcinoma of the floor of the mouth, folIowed by biIatera1 suprahyoid dissection of the neck for metastases. Eighteen months Iater, foIIowing drainage of an abscess, a persistent

FIG. IE Case I.

FIG. zA. Case

II.

0. A. (KUMC No. 51-3453), aseventy CASEV. year oId white man, received 5,930 mg. hours of radium for a squamous cell carcinoma of the oraI commissure and ora mucous membrane. Eighteen folIowing radiation therapy, severe pain months deveIoped in the right side of the face and mandibIe, as did an orocutaneous fistuIa. (Fig. 5A.)

FIG. IF. Case I.

FIG. 2B. Case II.

Osteoradionecrosis

of Mandible

FIG. 3A. Case III.

Frc. 4A. Case IV.

FIG. 3B. Case III.

FIG. 4B. CaFe IV.

FIG. 5A. Case v. HemimandibuIectomy reconstruction closed 5B.)

the

FIG. 4C. Case IV.

FIG. 5B. Case v. mandible with bone graft for a “benign osteosarcoma” which proved on pathoIogic review to be an ossifying fibroma of the mandible. (Fig. SA.) Thirteen years folIowing therapy, radionecrosis of the bone graft occurred with pain, ulceration and formation of a fistuIa. (Fig. 6B.) Extraoral resection of the involved bone and

was performed and pedicle persistent fistuIa. (Fig.

CASE VI. J. G. (KUMC No. 5I-zo6g6), a seventeen year old white boy, received radiation therapy folIowed by subtota1 resection of the

891

Masters,

FIG. 6A. Case

VI.

KIaus

and

FIG. 6E. Case

Robinson

VI.

FE. 6C. Cast VI.

ford [I] has shown that even in the presence of hopeless maIignancy, paIIiation can be accompIished. The deep boring pain, trismus and uIceration which accompanies advanced radionecrosis often converts patients with widespread maIignancy into confirmed narcotic addicts or aIcohoIics. This symptom compIex is not a manifestation of the maIignant process and often can be reIieved totaIIy by mandibuIar resection. PaIIiation of pain may be worth whiIe even though the uItimate prognosis is hopeIess. The therapy of radio-osteonecrosis when unaccompanied by maIignancy is a unique probIem. The sparse Iiterature reveaIs a conff ict of opinion varying from conservatism to radicaIity. Kanthak [T] has stated that sequestrectomy shouId be performed when the dead bone separates or when a pathoIogic fracture occurs. Because of the avascuIarity due to the radiation injury, the mandibIe Ioses its capacity to form an invoIucrum and thus preserve continuity whiIe sequestration occurs. Once started, sequestration is a sIow but inexorable process which wiI1 continue progressiveIy but with no sharp demarcation as in osteomyelitis or trauma. This dying process often takes months or even years to occur, and the continued presence of pain, trismus, inability to eat and poor oral hygiene persists for the duration of the sequestration. Gaisford [I 1, on the other hand, advocates the immediate resection of a11 radiated bone at the onset of In using an extraora1 approach symptoms. routineIy, however, the poor heaIing quaIities of the surrounding soft tissue Ied to hemorrhage from the carotid artery in four cases. It is our beIief that the treatment of radio-

reconstruction with a tube pedicle graft produced reIief of symptomatoIogy and cIosure of the fistula. (Fig. 6C.) TREATMENT

The treatment of osteoradionecrosis of the mandibIe is surgica1. The surgical approach, however, depends not onIy upon the extent of the IocaI disease process but aIso on the concomitant surrounding radiation injury to soft tissue, symptomatology and the presence or absence of recurrent maIignancy. Since radionecrosis is aImost universaIIy accompanied by uIceration, IocaI infIammation of soft tissue and induration, the appearance of the inflammatory process may be extremeIy diffIcuIt to differentiate from recurrent malignancy. This distinction is essentia1. In the presence of malignancy, treatment shouId be directed, with rare exception, toward the eradication of cancer. In this instance, mandibuIar necrosis is of secondary importance and shouId not become a potentia1 “red herring” in the therapeutic approach. The condition of the surrounding soft tissue is an important surgica1 consideration. The notoriously poor heaIing quaIities of radiated skin are we11 known, and if cIosure becomes a probIem, some form of reconstruction such as a pedicIe graft which brings with it an intact bIood suppIy is the procedure of choice. CIosure under tension or split-thickness skin grafting frequentIy faiIs because of the aItered vascuIarity of the surrounding soft tissue. Such wounds may disrupt and, if the carotid vesseIs are thus exposed, fata hemorrhage may occur. SymptomatoIogy itself often provides a concrete indication for surgica1 therapy, Gais-

892

Osteoradionecrosis

of Mandible Radiation injuq presents a clinical picture of pain, trismus, ulceration and fetor \\hich is amenable to speciiic surgical therap!. Treatment depends upon the pathologic condition present. If malignant>- exists, therapyis directed toward the ablation of carcinoma, although surgical excision of painl’ul radiation necrosis ma\- be a valuable palliative weapon. Primary osteonecrosis not assocG~tec1 ltith malignancy, when each case is given carefully individualized attention, can bc treated so as to produce dramatic relief of symptoms, \\ith :I low mortality rate.

ostconecrosis unaccompanied by malignancy should be carefully individualized. AIthough it is diffkxlt to ascertain radiologically the extent of radiation injury, the presence of necrotic bone does not necessarily indicate mandibular resection. \%‘hen possible, the involved mandiblc should be resected to bleeding bone, n-hic*h on occasion will allow the preservation of at least a basilar rim of mandible for support to the floor of the mouth and the maintenance of contour (Cases I and 2). Although radiated mandibular periosteum may fail to regenerate the osseous continuit\of the resected bone, an intraoral approach has been used when indicated to avoid the compIications of surger? through radiated soft tissue. With careful selection, good postoperative oral hygiene and antibiotic therapy, the intraoral incisions have healed well and infection of the remaining mandible has not been a problem. If orocutaneous fistulas exist, however, wide resection associated with primary cIosure without tension, or followed by pedicIe coverage Iater, has proved to be the procedure of choice. Surgery should not he deferred once symptoms of radionecrosis have appeared. The inexorable nature of the disease militates against temporization and, perhaps, if resection to bleeding bone is performed early, partially damaged bone which is not subjected to low grade chronic infection over a long period of time ma?; survive as its nutrition may be provided bs- surrounding soft tissue, free of infection and foreign body reaction.

KEFERENCES

J. and KLECKEKT, I:. Ost~clradionccrosis of the mnndiblc. Plas!. P Recons~ruc/. Surq., 18:

I. GAISFOKD,

436 -447, ‘956. 2. \%‘hTSOX. \%‘. L. :md SCAKBOKOLGH.J. I:. Osteo-

in intraoral radionecrosis c:~ncc‘rs. Am. J. Rcentged, 40: 524-534, 1938. 3. WILDERMCTH, 0. and CANTRII., S. T. Radiation necrosis of the mandible. Radiolory, 61: 771-785, 1953. 4. LAWKE~CE, 4.

6.

7. 8. 9.

IO. SUMMARY

Osteoradionecrosis of the mandible is a common complication of radiation therapy for intraoral malignancy and results from a combination of radiation, infection and trauma.

I I.

12.

893

E. A. Osteoradionecrosis of the mnndible. Am. J. Roentgenol., 55: 733~-742, 1938. I