Radiation treatment of heterotopic bone formation in the temporomandibular joint articulation

Inl. J. Radialron Oncology BIO/ Phvv.. Vol. 21. Pnnted in the U.S.A. All r&is reserved.

pp.

863-869

Copyright

0X0-3016/93 $6.00 + .W 0 1993 Pergamon Press Ltd.

??Clinical Original Contribution

RADIATION

TREATMENT OF HETEROTOPIC BONE FORMATION TEMPOROMANDIBULAR JOINT ARTICULATION

E.DOLORES DURR, M.D.,*EASTWOOD

G. TURLINGTON, AND ROBERT L. FOOTE, M.D.*

Mayo Clinic and Mayo Foundation,

Rochester,

IN THE

D.D.S.+

MN

Purpose: The efficacy and toxicity of radiation therapy used for preventing re-formation of heterotopic bone involving the temporomandibular joint are assessed. Methods and Materials: Ten patients (15 TMJs) with bony ankylosis of the TMJ were referred after reconstruction with costochondral graft, gap arthroplasty, or debridement of heterotopic bone. Treatment consisting of 10 Gy was delivered early postoperatively to a field encompassing the TMJ with adequate margin. Response to therapy was assessed by comparison of routine roentgenograms obtained preoperatively, immediately postoperatively, and at last follow-up; the Turlington-Durr grading system was used. Median duration of postoperative follow-up was 19 months. Results: Radiation therapy prevented ectopic bone re-formation in 10 (69%) of 15 TMJs with prior bony ankylosis. Of the 15 TMJs, 13 (87%) had improvement in their Turlington-Durr scores compared with the preoperative scores. Development of ectopic bone formation was prevented in 9 (90%) of 10 TMJs rendered Turlington-Durr grade 0 postoperatively. Eight of the 10 patients have remained asymptomatic. Treatment was well tolerated. The only complication experienced was parotitis in three patients. Conclusion: Radiation therapy is useful for prevention of heterotopic bone redevelopment after TMJ operation. We recommend 10 Gy in 5 fractions beginning early postoperatively for high-risk patients. This strategy appears beneficial in this young patient population, who suffer significant pain and functional impairment in the TMJ articulation. Heterotopic bone, Radiation therapy, Temporomandibular joint. INTRODUCI’ION

bone formation when radiation therapy was begun by postoperative day 4. Our success in preventing ectopic bone formation in the hip joint led us to consider the use of radiation therapy to prevent heterotopic ossification in other locations. Since 1976, we have been irradiating other joints (shoulders, elbows, knees, ankles) at risk for development of ectopic bone after operation. In 1989, we began irradiating the temporomandibular joint (TMJ) in high-risk patients who underwent TMJ procedures. These patients had bony ankylosis of the TMJ as a result of heterotopic bone formation and were referred after a revision surgical procedure or debridement of heterotopic bone. There are few reports of bony ankylosis of the zygomatic arch with the coronoid process of the mandible. It has been reported after facial trauma and orthognathic surgical procedures (12, 19, 45). In 1979, Schwartz and Kagan (40) described a 5 1-year-old black man who had a large mass of heterotopic bone in the left TMJ that caused bony

Heterotopic ossification is a significant complication after total hip arthroplasty or traumatic acetabular fracture. The reported frequency in high-risk patients ranges from 58% to 90% (1, 2, 8, 23, 41, 42). Numerous published series have shown the benefit of postoperative radiation therapy in preventing formation of heterotopic bone. The earliest series, reported by Coventry and Scanlon from the Mayo Clinic (15), showed that 20 Gy given early after operation prevented re-formation of massive ectopic bone. Subsequent studies reported that 10 Gy is as effective (1, 2, 8, 23, 24, 41, 42) and that single or divided doses as low as 5 Gy (14), 7 Gy (7, 29), or 8 Gy (7, 26, 35) can prevent ectopic ossification. Radiation therapy is most effective when given early postoperatively (7, 15, 2 1, 30, 42). Blount et al. (7) suggested that treatment be initiated before postoperative day 5. Sylvester et al. (42) found no significant heterotopic

Accepted

*Division of Radiation Oncology. ‘Department of Dentistry. Reprint requests to: Robert L. Foote, M.D., Mayo Clinic, 200 First St. SW, Rochester, MN 55905.

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zygomatico-coronoid ankylosis. The patient received 2,000 cGy postoperatively and had excellent mandibular function at 19 months of follow-up. This article presents the results of our experience with postoperative radiation therapy for the prevention of heterotopic ossification in high-risk patients who undergo TMJ operation. METHODS AND MATERIALS From May 1989 to September 1991, 10 patients (15 TMJs) were referred to the Division of Radiation Oncology at the Mayo Clinic after TMJ surgical procedures. All 10 patients were eligible for analysis. The patient population included four men (5 TMJs) and six women (10 TMJs); eight were white and two were black. Their median age was 32.5 years (range, 14 to 59 years). All patients were determined to be at high risk for the development of heterotopic ossification. In nine patients, heterotopic bone had formed afier previous operation on the TMJ; six of these had a history of trauma. The other patient had bilateral heterotopic ossification after previous trauma and had not undergone prior surgical intervention. Surgical procedures included one reconstruction with costochondral graft, eight gap arthroplasties, and six debridements of heterotopic bone. Heterotopic bone formation in the TMJ articulation was classified into 1 of 4 grades, according to the Turlington-Durr grading system (Table 1). This system was adapted from an earlier classification published by Brooker et al. (lo), which graded heterotopic bone formation around the hip. Grades 1, 2, and 3 are further classified as symptomatic (S) and asymptomatic (A). Symptomatic ossification includes severe pain, decreased interincisal opening (15 mm or less), closed locking of the jaw, or decreased lateral or protrusive movement. All patients had Turlington-Durr grade 2s or 3s heterotopic bone formation preoperatively (Figs. 1 and 2). Radiation therapy was initiated between 1 and 3 days after operation. Seven TMJs were treated with a single lateral field and the dose was calculated at a median depth of 4.0 cm (range, 1.5 to 5.0 cm). In 4 of the 5 patients who underwent bilateral TMJ procedures (eight TMJs),

Table 1. Turlington-Durr classification of heterotopic ossification in the temporomandibular joint* Grade’

Description

0 1 2 3

No bone islands visible Islands of bone visible within soft tissues around joint Periarticular bone formation Apparent bony ankylosis

* Modified from the classification of heterotopic ossification in the hips described by Brooker et al. (10). t Grades 1, 2, and 3 are subdivided: A, asymptomatic; S, symptomatic.

a

b Fig. 1. (a) Evidence of periarticular bone surrounding chondral portion (Turlington-Durr Grade 2). (b) Normal temporomandibular joint (Turlington-Durr Grade 0).

opposed lateral fields were used and the dose was calculated at mid-plane. Thirteen TMJs were irradiated with 6-MV photons and two with 16-MeV electrons. Treatment technique varied by the treating physician. In general, ipsilateral electron beam or 6-MV photons were used for unilateral treatment, and opposed lateral 6-MV photons were used for bilateral involvement. For single lateral fields, a IOO-cm source-to-skin distance was used. For opposed lateral fields, a 100-cm source-to-axis distance was used. Fields were designed to encompass the TMJ with an adequate margin (2 cm). Median field size was 39 cm2 (range, 30 to 99 cm2). A typical radiation portal is shown in Figure 3.

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Irradiation for heterotopic bone 0 E. D. DURR et al.

compared with paired t tests. Correlation coefficients were calculated between various factors (patient characteristics, trauma and surgical history, and radiation therapy techniques) and Turlington-Dun grades preoperatively, immediately postoperatively, and at last follow-up. RESULTS

Fig. 2. Massive (Turlington-Durr

ankylosis of right temporomandibular grade 3).

joint

Most of the patients (8 patients, 12 TMJs) received a total dose of 10 Gy in 5 fractions (2 Gy per fraction). This was delivered over a median of 5 days (range, 4 to 7 days). One patient (one TMJ) received 10 Gy in 4 fractions (2.5 Gy per fraction) over 6 days. The other patient (two TMJs) received a total dose of 11.25 Gy. This was given in 5 fractions (2.25 Gy per fraction) over 5 days. The response to therapy was assessed by comparison of routine roentgenograms obtained preoperatively, immediately postoperatively, and at last follow-up (minimum, 7 months). Comparison of the immediate postoperative roentgenogram with the roentgenogram obtained at final examination was the principal basis for documentation of the results. This method allowed for comparison of heterotopic bone existing immediately postoperatively (that is, not removed at operation) with any heterotopic bone that formed in the months after radiation treatment. Statistical analysis of the data was performed on a desktop computer with a standard statistical package.* Analyses included descriptive statistics for patient characteristics, trauma and surgical history, surgical procedure, radiation technique, Turlington-Durr grades, and duration of follow-up. Turlington-Durr grades preoperatively, immediately postoperatively, and at last follow-up were

*Macintosh

IIsi with StatView

II.

All patients were available for review at a minimum of 7 months after the index operation. The median duration of postoperative follow-up was 19 months (range, 7 to 3 1 months). Most patients received the initial dose of radiation therapy within 36 hr of operation (on postoperative day 1 in 12 [80%] of the 15 TMJs, on postoperative day 2 in 1 [7%], and on postoperative day 3 in 2 [ 13%]). The results of treatment are shown in Table 2. Of the 15 TMJs treated, 10 (67%) were Turlington-Durr Grade 0 postoperatively, and 5 (33%) were Turlington-Durr Grade 1 (residual heterotopic bone not resected at operation). All patients were asymptomatic after operation. Because heterotopic bone formation continues to appear radiographically up to 4 months after operation (27, 28, 39,43), response to treatment was assessed by comparison of the immediate postoperative roentgenograms with those obtained at last follow-up (Table 3). Of the 15 TMJs, 5 were Turlington-Durr grade 2s and 10 were grade 3s heterotopic bone preoperatively. Immediately postoperatively, 10 TMJs had no ectopic bone (Turlington-Durr grade 0, Fig. 4). Of the five TMJs with

Fig. 3. Typical radiation

field.

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Table 2. Data on 10 patients with ectopic bone in the temporomandibular joint who had irradiation after revision surgical procedure Delivery of RT Case

Age (yr) and sex

TMJ site

Prev surg. no.

1 2 3 4 5 6 7 8 9 10

37 M 33M 43 F 32 F 34 F 26 M 27 M 59 F 29 F 14 F

Right Left Right Right Bilat Right Bilat Bilat Bilat Bilat

3 1 2 4 7 2 0 4 5 1

Index procedure

Dose, GY

Fx, no.

Gap arthro Debridement Debridement Debridement Debridement Gap arthro Gap arthro Gap arthro CC graft/debridement* Gap arthro

10 10 10 10 10 10 10 10 11.25 10

4 5 5 5 5 5 5 5 5 5

Turlington-Durr

grade*

POD

Pre

Post.

Recent

Follow-up, mo

2 1 1 :

3 s 3s 2 s 2 s 312 S 3 s 313 s 213 S 312 S 313 s

0 IA 0 0 l/l A 0 O/O Of0 l/l A O/O

0 1A 1 A 0 2/2 s+ 0 O/O O/O 212 s O/O

30 15 13 31 18 7 20 13 26 22

1 1 1 1 1

* For patients with bilateral involvement, the first number is the grade for the right jaw and the second number is the grade for the left jaw (right/left). Grades 1, 2, and 3 are subdivided: A, asymptomatic; S, symptomatic. +In this patient, symptomatic periarticular bone formation (grade 2) developed bilaterally 3 months after the index surgical procedure and radiation therapy. She underwent bilateral gap arthroplasties and at 18 months of follow-up had Turlington-Durr grade 0 heterotopic bone formation bilaterally. She was coded as a treatment failure for recent grade. * Different procedures were done on each jaw: CC (costochondral) graft on right and debridement on left. Fx = Fractions; POD = Postoperative day; Post. = Postoperative; Pre = Preoperative; Prev surg = Previous surgery; RT = Radiation therapy; TMJ = Tempor&mandibul& joint.

of grade 1A postoperatively, one remained asymptomatic with Turlington-Durr grade 1 at follow-up of 15 months; in the four other TMJs (two patients), progression to symptomatic Turlington-Durr grade 2 was noted within 14 months. Both of these patients had a history of trauma and had more prior surgical procedures (five and seven) than the other patients in this review. Of the 10 TMJs that were Turlington-Durr grade 0 postoperatively, only 1 had re-formed ectopic bone (TurlingtonDurr Grade 1A) at follow-up (13 months). There were significant differences in the TurlingtonDurr grades preoperatively compared with immediately postoperatively (p = 0.0001) and with the latest followup examination @ = 0.0001). The median TurlingtonDurr grades preoperatively, postoperatively, and at final examination were 3, 0, and 0, respectively. In addition, there was a significant difference between the immediate postoperative grades and the latest follow-up grades (p = 0.0 192). This reflects progression of residual heterotopic ossification in 2 patients (4 TMJs) and re-formation of heterotopic ossification in 1 patient (1 TMJ).

evidence

Table 3. Results of irradiation for heterotopic bone formation in 15 temporomandibular joints No. of joints Turlington-Durr grade 0 1 2 3 Total

Final grade

Preop

Postop

0

1

2

3

0 0 5 10 15

10 5 0 0 15

9 0 0 0 9

1 1 0 0 2

0 4 0 0 4

0 0 0 0 0

There was no correlation between Turlington-Durr grades (preoperatively, postoperatively, or at last followup) and patient characteristics (age, sex, race, right versus left TMJ), history of trauma, number of prior operations, type of surgical procedure, or radiation therapy technique (number of fields, field size, total dose, number of fractions, dose per fraction, or energy). There were no systemic or local wound complications attributable to radiation therapy. Parotitis developed in three patients at 1.5 to 3 months after irradiation. No xerostomia or osteoradionecrosis had developed. Only one patient (case 5) had required reoperation for heterotopic bone (grade 2/2) after radiation therapy. She remained asymptomatic (grade O/O) 15 months after reoperation. DISCUSSION The pathogenesis of heterotopic bone formation has been previously reviewed. It is suggested that immediately postoperatively pluripotential mesenchymal cells are stimulated to differentiate into osteoblastic and chondroblastic stem cells (4, 13, 16, 20, 32, 33, 36, 44). The mechanism of this stimulation is unknown, but a factor in the bone matrix is the most likely agent (17, 36, 37, 47). Other theories have also been reported (11, 2 1, 32, 33,46), and the causes may be multifactorial. The mechanism by which radiation prevents ectopic bone formation has been studied. Rat studies conducted by Kantorowitz et al. (22) showed that radiation may inhibit subsequent proliferation or differentiation of multipotential cells. It is evident that radiation therapy delivered early postoperatively plays a role in preventing ectopic bone formation in the hip joint (1, 2, 7, 8, 14, 15, 21, 23, 24, 26, 29, 35,

Irradiation for heterotopic hone 0 E. D. DURR et al.

a

b

(a) Patient with prior gap arthroplasty who had ensuing development of heterotopic bone and reankylosis. (b) No evidence of heterotopic bone 7 months after operation and radiation treatment. Fig. 4.

4 1, 42). No data are available regarding the time course for the development of heterotopic ossification in the TMJ. Thus, we used heterotopic ossification of the hips as a model and thought it was reasonable to assume there is no major difference between the time course for its development and that in other joints. Thus, it is reasonable to assume that radiation would have similar results in other sites predisposed to the development of ectopic bone. There are few reports of ectopic bone formation in the mandible and maxillofacial region (12, 19, 3 I, 40, 45). Nwoku (3 I) reported two cases of extensive bone regeneration in the mandible after mandibular resection. Reports of bony ankylosis of the zygomatic arch with the coronoid process of the mandible are less common. In 1979, Schwartz and Kagan (40) described a 5 l-year-old black man who had trismus after reduction of a depressed

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fracture of the left zygomatic arch. At 14 months after injury, coronoidectomy was required for zygomaticocoronoid fibrosis. Seven months postoperatively, radiographs revealed a large mass of heterotopic bone in the left TMJ causing bony zygomatico-coronoid ankylosis. The interincisal distance was 4 mm. The patient underwent a modification of the interpositional gap arthroplasty procedure. One week postoperatively, the patient received 20 Gy in 10 fractions. At 19 months of follow-up, mandibular function was excellent and the interincisal opening was 40 mm. No mention was made of radiographs obtained after radiation therapy or whether new bone formation was present. It is unknown what percentage of patients who undergo TMJ surgical procedures will exhibit radiographic evidence of heterotopic bone formation and what percentage of patients will suffer functional impairment in the form of decreased interincisal opening or TMJ pain. In recent years, 10 patients presented to the oral surgery department at the Mayo Clinic with high-risk factors for the development of heterotopic bone postoperatively. All had existing ectopic bone, and 70% had a history of trauma. Other risk factors reported in the literature but not included in our patient population are hypertrophic osteoarthritis, diffuse idiopathic skeletal hyperostosis, and ankylosing spondylitis (2, 5, 6, 15, 17, 21, 34, 38, 39, 43). On the basis of their review of six published series, Sylvester and colleagues (42) reported that the frequency of heterotopic ossification in high-risk patients after hip operation was 60%. However, in patients with existing heterotopic bone, it is believed that 90% will have ectopic bone re-form postoperatively (2, 17, 32). In 23 patients with existing ectopic bone, Ritter and Vaughan (39) found that all had development of ectopic bone after total hip replacement. Of the 10 patients in our review, 9 had a history of surgical procedures (median, 2.5; range, 0 to 7). Brooker et al. (IO) reported a higher incidence of ossification in patients who had had previous hip operation than in patients without prior operation. Treatment consisting of 10 Gy was delivered early postoperatively and prevented ectopic bone re-formation in 10 (67%) of the 15 TMJs with prior bony ankylosis. Comparison of the preoperative and postoperative Turlington-Durr scores showed that 13 (87%) of the 15 TMJs were improved. Radiation therapy prevented the development of ectopic bone formation in 9 (90%) of the 10 TMJs that were Turlington-Durr grade 0 postoperatively. Eight of the 10 patients were asymptomatic at latest follow-up. Two patients (four TMJs) with Turlington-Durr grade 2s ectopic bone may have been at higher risk for bone re-formation because of a history of trauma and numerous prior bilateral TMJ procedures (five procedures in one and seven in the other). In addition, both had grade 1 ectopic bone bilaterally after the index procedure, which may serve as a nidus for eventual formation of high-grade heterotopic ossification. In these patients, removal of existing ectopic bone may have been less aggressive than in

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patients who had grade 0 ectopic bone immediately postoperatively. One of these patients had undergone subsequent bilateral gap arthroplasties and had no evidence of heterotopic bone formation in either TMJ at 18 months of follow-up (14 months after the second operation), One patient had Turlington-Durr grade 1A ectopic bone immediately postoperatively but had no progression at 15 months of follow-up. One patient had Turlington-Durr grade 1A ectopic bone at final examination which had not been present on postoperative films. The treatment technique is straightforward and timeefficient. An important aspect of planning treatment fields is to identify the target volume at risk for recurrent ectopic bone formation. In most of our patients, the treatment fields were reviewed by the oral surgeon before initiating radiation treatments. In contrast to irradiation of the hip joint, in which it may be necessary to shield the trochanteric osteotomy to allow osseous ingrowth into the prosthesis (2, 3, 7,27,28), shielding is not required for reconstructions with costochondral grafts. Treatment was well tolerated. The only complication experienced was parotitis in three patients. This was characterized as swelling and discomfort without systemic symptoms. The duration of symptoms was 1 month. The time of onset was 1 to 3 months after radiation therapy. To date, no patient has had osteoradionecrosis or other chronic complications. None of the patients in this study have been followed for a sufficient time to ascertain whether malignancy will develop within the radiation field. Radiation-induced malignancies are of concern because the patient population presenting with TMJ problems is often young. In the

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current review, the median age was 32.5 years (range, 14 to 59 years). Several authors have suggested that cancer induction is unlikely with low radiation doses. No patient had development of a radiation-induced sarcoma (radiation doses less than 30 Gy in 3 weeks) during a 50-year period at Memorial-Sloan Kettering (25). In a review of the literature in 1979, Brady (9) found no cases of sarcomas arising from bone or soft tissue when the radiation dose was less than 30 Gy in 3 weeks. Recently, Ftirst et al. (18) identified 18,030 children with previously irradiated hemangiomas. The frequency of all cancers combined was 1.53% in the irradiated group and 1.26% in the nonirradiated group. These results indicate that radiation therapy is useful for deterring heterotopic bone redevelopment in the TMJ articulation after gap arthroplasty, reconstruction with costochondral graft, or debridement of ectopic bone. We recommend 10 Gy in 5 fractions beginning early postoperatively to a field encompassing the surgical bed with adequate margin surrounding the TMJ. Treatment should be limited to patients at significantly higher risk of ectopic bone development. At the Mayo Clinic, high-risk patients are defined as those with preexisting heterotopic bone in the TMJ. Patients who have had five or more previous TMJ procedures may be less likely to benefit from radiation treatment unless very aggressive debridement is performed. For optimal functional results, radiation therapy should be considered early in the surgical management of patients with ectopic bone in the TMJ. This therapeutic strategy seems beneficial in the young patient population, who suffer significant pain and fimctional impairment in the TMJ articulation.

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