Temporal bone osteoradionecrosis: an 18-year, single-institution experience

Abstract

Objectives

To report the largest single-institution review of temporal bone osteoradionecrosis (TBORN), and characterize the disease’s natural history, prognostic factors, management, and outcomes.

Methods

Retrospective review was conducted to identify patients with TBORN. Pertinent data were extracted. Descriptive statistics were used to summarize patient, tumor, and treatment characteristics. Multivariable analyses were conducted to explore associations between these characteristics and time to TBORN diagnosis and risk of developing diffuse disease.

Results

TBORN was identified in 145 temporal bones from 128 patients. Mean age at diagnosis was 62 years, and mean time to diagnosis after radiotherapy was 10 years. Age greater than 50 years was associated with earlier diagnosis. According to the Ramsden criteria, 76% of TBs had localized and 24% had diffuse disease at initial diagnosis; 37% had diffuse disease at last follow-up. On multivariable analysis, diabetes, 3-dimensional conformal radiotherapy (3D-CRT), and periauricular skin malignancy were significant risk factors for developing diffuse disease. Localized disease was successfully managed with conservative measures, whereas surgery was often necessary for diffuse disease. When TBORN spread outside the mastoid or infratemporal fossa, conservative measures were always unsuccessful.

Conclusion

TBORN occurs earlier in older patients. While diffuse disease is less common than localized disease, it occurs more frequently in patients with diabetes, history of 3D-CRT, and periauricular skin malignancies. Conservative management is appropriate for localized disease, while surgery is often necessary for diffuse disease. The prognostic factors identified helped propose a TBORN staging system and treatment guidelines which may improve patient risk stratification and disease management.

Introduction

Radiotherapy for head and neck (H&N) malignancies can produce a variety of sequelae. Temporal bone (TB) complications include otitis externa, serous otitis media, sensorineural hearing loss, and osteoradionecrosis (ORN), of which ORN is among the most devastating. ORN is a fibroatrophic process in which irradiated bone becomes exposed and devitalized without healing in the absence of cancer recurrence^1–3.

Temporal bone osteoradionecrosis (TBORN)⁴ is typically diagnosed when exposed bone in the external auditory canal (EAC) develops after H&N radiotherapy. TBORN can be confined to the tympanic portion of the TB (localized TBORN) or extend beyond this region (diffuse TBORN), as classified by Ramsden et al.⁵ Because diffuse disease can lead to serious sequelae if left untreated,⁶ early diagnosis and effective treatment are imperative. Most cases of TBORN improve with conservative treatment, but diffuse disease is often an indication for surgical management.⁷ The Ramsden classification can be clinically relevant in predicting responses to conservative treatment,⁸ yet prognostic factors for progression to diffuse disease have never been evaluated.

Studies have estimated that TBORN occurs in 8.5% of all H&N radiation patients⁹ and 1.9% of patients who underwent parotidectomy and radiotherapy.^7,10 Given TBORN’s rarity, descriptive statistics and treatment recommendations are currently based on variably described case reports and case series. Therefore, we conducted this review to characterize the disease’s natural history, prognostic factors, management, and outcomes and better predict which patients with TBORN may benefit from surgery.

Materials and methods

Search methodology

This study was approved by The University of Texas MD Anderson Cancer Center’s institutional review board (PA19-0106). We searched the records of MD Anderson Cancer Center’s Department of Head and Neck Surgery to identify patients treated between January 2002 and March 2020 for International Classification of Disease codes 733.40 (9th edition) and M87 (10th edition). Medical records were then retrospectively reviewed. The inclusion criterion was TBORN diagnosis, confirmed by reviewing physical examination findings and imaging data. There were no exclusion criteria. Data extracted were patient demographics and histories; oncologic treatments; and TBORN characteristics, treatments, and outcomes.

Demographics

Patients’ date of TBORN diagnosis at MD Anderson, age at TBORN diagnosis, sex, race, comorbidities, tobacco use history (past use: cessation > 1 year before TBORN diagnosis), and ipsilateral otologic surgery history were recorded.

Oncologic history and treatment

The primary tumor’s anatomic site, stage, and histopathologic characteristics were recorded. Primary cutaneous malignancies with parotid nodal metastases were recorded under “periauricular skin.” The stage was recorded using the American Joint Committee on Cancer TNM classification (7th edition for tumors diagnosed before 2017 and 8th edition for those diagnosed in 2017 or later). T3 and T4 tumors were considered advanced. Additionally, other malignancies and their associated treatments were reviewed. Reirradiation was defined as multiple rounds of H&N radiotherapy. The total radiation dose was that delivered to the primary tumor site during the initial round of radiation, regardless of reirradiation. Patients with no specified technique who completed irradiation before 2005 were included in the 3-dimensional conformal radiotherapy (3D-CRT) group because intensity-modulated radiation therapy (IMRT) was less common for H&N tumors until 2005.¹¹ Patients with reirradiation were included in the IMRT group only if all radiotherapy was delivered using IMRT. Finally, systemic therapy was defined as any chemotherapy, immunotherapy, or hormonal therapy.

TBORN characteristics

For bilateral TBORN, each TB was reported and characterized separately. Time to TBORN diagnosis was calculated from the date of radiotherapy completion. For patients with reirradiation, time to diagnosis was based on the radiation event closest to diagnosis. Based on physical examination and imaging findings TBORN was classified according to Ramsden classification. For example, features such as synovial fluid otorrhea and canal-mastoid fistula were indicative of diffuse disease. Similarly, full-thickness EAC cortical erosion extending past the tympanic bone was defined as diffuse disease. TBORN-related symptoms and location of exposed bone at diagnosis were recorded. Finally, initial location of bony EAC erosion was determined using the computed tomography (CT) images temporally closest to TBORN diagnosis. If there were no CT data within 2 years before or after diagnosis, no initial radiographic data were collected.

TBORN treatments

Localized disease was mostly managed conservatively with routine ear cleaning and office debridements, otic drops, and oral antibiotics based on clinical presentation, while diffuse disease was treated on the basis of patient symptoms and disease severity. Conservative management was defined as nonsurgical treatments. Any ablative and reconstructive surgical procedures and the use of pentoxifylline and tocopherol (PENTO), hyperbaric oxygen (HBO), and hearing rehabilitation procedures were recorded.

TBORN outcomes

Follow-up duration was calculated from date of TBORN diagnosis to date of last follow-up for TBORN. Treatment success was defined as resolution of otalgia, aural fullness, and otorrhea at the last follow-up. Disease resolution was defined as skin coverage over all previously exposed bone. Disease resolution was not described for TB resection or mastoid obliteration (MO), as these procedures preclude otoscopic examination. Finally, radiation-induced TBORN-associated outcomes and complications were termed “TBORN associations” and “TBORN complications,” respectively. Death was only attributed to TBORN if it directly resulted from a TBORN complication.

Statistical analysis

Patients with diffuse disease by last follow-up were considered to have diffuse disease for statistical analysis. Assessments unique to the ear were conducted at the ear level; all other assessments were conducted at the patient level. Descriptive statistics were used to summarize patient, tumor, and treatment characteristics. Mean and standard deviation were used to summarize continuous variables; frequencies and percentages were used to summarize categorical variables. Bivariate analyses were conducted to explore the associations between patient characteristics and diffuse disease; chi-square tests were used for categorical variables and t-tests for continuous variables. Univariable logistic regression was used to assess the association between patient characteristics and diffuse disease independently. Statistically significant associations were included in a multivariable logistic regression model to obtain adjusted estimates. Comparisons between patient characteristics and time to TBORN diagnosis were explored visually using cumulative incidence plots and statistically using log-rank tests. P-values < 0.05 were considered statistically significant, and all analyses were conducted using Stata software (StataCorp, College Station, Texas).

Results

Demographics

Since 2002, 128 patients were diagnosed with TBORN. The mean age was 62 ± 14 years (range, 24–91 years), 57% were male, and 70% were White (Table 1). Most common comorbidities were hypothyroidism (35%), dyslipidemia (27%), mandibular ORN (14%), and diabetes mellitus (13%). Furthermore, 27% of patients were former and 16% were current tobacco users. Finally, 27% had prior ipsilateral otologic surgery.

Table 1.

Demographic characteristics, oncologic histories, and treatments of 128 patients with temporal bone osteoradionecrosis (TBORN).

Characteristic	N=128 (%)
TBORN cases	145
Bilateral TBORN	17 (13)
Sex
Male	73 (57)
Female	55 (43)
Mean age ± SD (range), y	62 ± 14 (24-91)
Race
White	89 (70)
Asian	15 (12)
Hispanic	10 (8)
Black	7 (5)
Other	7 (5)
Comorbidities
Hypothyroidism	45 (35)
Dyslipidemia	35 (27)
Mandibular ORN	18 (14)
Diabetes mellitus	16 (13)
Maxillary ORN	5 (4)
History of tobacco use
Never	74 (58)
Past	34 (27)
Current	20 (16)
Prior otologic surgeryb	39 (27)
Pressure equalization tube	21 (16)
Mastoidectomy	11 (9)
EAC surgery	5 (4)
LTBR	3 (2)
Tympanoplasty	2 (2)
Primary malignant site
Periauricular skin	31 (24)
Parotid	28 (22)
Nasopharynx	25 (20)
Oral cavity	13 (10)
Oropharynx	8 (6)
Sinonasal	4 (3)
Other	19 (15)
Primary pathology
Squamous cell carcinoma	40 (31)
Nasopharyngeal carcinoma	22 (17)
Adenoid cystic carcinoma	12 (9)
Sarcoma	6 (5)
Basal cell carcinoma	6 (5)
Melanoma	5 (4)
Mucoepidermoid carcinoma	5 (4)
Other	32 (25)
Advanced T stage of primary malignancy	48 (38)
Surgery for primary malignancy	92 (72)
Mean radiation dose to primary tumor ± SD (Gray)	61.8 ± 9.8
Received 3D-CRT	62 (48)
Received systemic therapy	76 (59)
Recurrence of primary malignancy	45 (35)
Second H&N malignancy	24 (19)
H&N reirradiation	21 (16)

^aUnless otherwise indicated.

^bNo. (%) of temporal bones (N = 145).

Abbreviations: ORN, osteoradionecrosis; EAC, external auditory canal; LTBR, lateral temporal bone resection; 3D-CRT, 3-dimensional conformal radiotherapy; H&N, head and neck.

Oncologic history and treatment

The most common primary malignancy sites were periauricular skin (24%), parotid (22%), and nasopharynx (20%) (Table 1). The most frequent primary tumor types were squamous cell carcinoma (31%), nasopharyngeal carcinoma (17%), and adenoid cystic carcinoma (9%). Of primary malignancies, 38% were advanced stage. Nearly half of patients (48%) received 3D-CRT, and mean dose to primary site was 61.8 ± 9.8 Gy.

TBORN characteristics

Of the 128 patients, 17 had bilateral disease, resulting in 145 cases of TBORN (Table 1). Mean time to diagnosis after radiation completion was 10 ± 9.4 years (range, < 1–56 years) (Figure 1A). Age 50 years or older at radiation completion was significantly associated with earlier diagnosis (p < 0.001) (Figure 1B). Time to TBORN diagnosis did not differ among malignancy sites (p = 0.896) (Figure 1C). The most common symptoms were hearing loss (84%), otorrhea (49%), and otalgia (37%) (Table 2). Exposed bone on physical examination and bony erosion on CT were most frequently seen in the inferior and anterior EAC. Of all TBs, 76% had localized and 24% had diffuse disease at initial diagnosis. The most frequent regions of diffuse ORN were the mastoid (22%), infratemporal fossa (19%), and tegmen (8%).

Figure 1.

Time from radiotherapy to diagnosis of temporal bone osteoradionecrosis.

A. All cases.

B. Stratified by patient age at time of radiation completion.

C. Stratified by primary malignancy site.

Table 2.

Characteristics of 145 cases of temporal bone osteoradionecrosis (TBORN).

Characteristic	Temporal bonesa N = 145 (%)
TBORN laterality
Left	76 (52)
Right	69 (48)
Mean time to diagnosis ± SD (range), y	10 ± 9.4 (< 1–56)
Ramsden classification at initial diagnosis
Localized	110 (76)
Diffuse	35 (24)
Ramsden classification at last follow-up
Localized	92 (63)
Diffuse	53 (37)
Symptoms
Hearing loss	122 (84)
Otorrhea	71 (49)
Otalgia	54 (37)
Tinnitus	40 (28)
Aural fullness	33 (23)
Facial weakness	30 (21)
Dizziness	28 (19)
Location of EAC exposed bone
Inferior	98 (69)
Anterior	66 (46)
Posterior	34 (24)
Superior	8 (6)
Location of EAC bony erosionb
Anterior	59 (55)
Inferior	39 (36)
Posterior	37 (34)
Superior	5 (5)
Location of extratympanic ORNb
Mastoid	24 (22)
Infratemporal fossa	20 (19)
Tegmen	9 (8)
Middle ear	7 (6)
Posterior fossa	5 (5)
Otic capsule	4 (4)

^aUnless otherwise indicated.

^bNo. (%) of available CT scans (N = 108).

Abbreviations: EAC, external auditory canal; ORN, osteoradionecrosis; CT, computed tomography.

TBORN treatment

Of all TBs, 81% were managed conservatively and 19% were managed surgically; HBO was used in 19% of cases and PENTO in 7% (Table 3). Conservative management was used for 95% of localized and 57% of diffuse cases (Table 4). Among the surgically managed TBs, the most common procedures were lateral TB resection (57%) and canal-wall-down tympanomastoidectomy with MO (14%) (Table 3). Temporalis muscle flap and free flap reconstructions were used in 48% and 52%, respectively. Osseointegrated hearing aids and cochlear implants were used for hearing rehabilitation in 12% and 1%, respectively.

Table 3.

Management and sequelae of 145 cases of temporal bone osteoradionecrosis (TBORN).

Outcome	Temporal bonesa N = 145 (%)
Total conservatively managed	117 (81)
Total surgically managed	28 (19)
Received HBO	27 (19)
Received PENTO	10 (7)
Ablative surgeryb
LTBR	16 (57)
CWD with MO	4 (14)
Canalplasty	3 (11)
Labyrinthectomy	2 (7)
Mastoidectomy without MO	2 (7)
STBR	1 (4)
Reconstructive surgeryc
Temporalis muscle flap	11 (48)
Free flap	12 (52)
Hearing rehabilitation
OIHA	17 (12)
CI	1 (1)
Mean length of follow up ± SD (range), y	3.7 ± 3.5 (< 1–14)
Associations
Chronic otorrhea	17 (12)
Non-healing TM perforation	16 (11)
Cholesteatoma	10 (7)
Complications
Temporal bone osteomyelitis	10 (7)
Wound infection	8 (6)
Facial palsy	5 (3)
Profound SNHL	5 (3)
Carotid rupture	3 (2)
Dead at last follow-up	40 (28)
Attributed to TBORN	1 (1)

^aUnless otherwise indicated.

^bNo. (%) of those surgically managed (N = 28).

^cNo. (%) of those surgically managed with additional reconstructive surgery (N = 23).

Abbreviations: HBO, hyperbaric oxygen; PENTO, pentoxifylline and tocopherol; LTBR, lateral temporal bone resection; CWD, canal wall down tympanomastoidectomy; MO, mastoid obliteration; STBR, subtotal temporal bone resection; OIHA, osseointegrated hearing aid; CI, cochlear implant; TM, tympanic membrane; SNHL, sensorineural hearing loss.

Table 4.

Outcomes of 145 cases of temporal bone osteoradionecrosis (TBORN) stratified by Ramsden classification.

	All cases (%)	Localized disease (%)	Diffuse disease (%)
Conservatively managed	81	95	57
Surgically managed	19	5	43
Successful conservative management (%)	52	75	19
HBO	44	60	17
PENTO	83	83	NA
Successful operative management (%)	86	80	87
LTBR and CWD with MO	86	66	89
Mastoidectomy without MO	100	0	100
Disease resolution after conservative management (%)	25	27	19
HBO	44	60	17
PENTO	17	17	NA
Disease resolution after operative management (%)	89	75	91
LTBR and CWD with MO	NA	NA	NA
Mastoidectomy without MO	100	100	100

Abbreviations: HBO, hyperbaric oxygen; PENTO, pentoxifylline and tocopherol; NA, not applicable; LTBR, lateral temporal bone resection; CWD, canal wall down tympanomastoidectomy; MO, mastoid obliteration.

TBORN outcomes

Mean follow-up duration was 3.7 ± 3.5 years (range, < 1–14 years). Of the 110 cases with localized TBORN at initial diagnosis, 18 progressed to diffuse disease during follow-up. Factors significantly associated with developing diffuse disease in multivariable analysis were diabetes (OR=4.02; p=0.022), 3D-CRT (OR=2.30; p=0.044), and periauricular skin primary malignancy (OR=3.52; p=0.017) (Table 5). Factors that trended towards significance were maxillary ORN (OR=6.93; p=0.088), current smoking (OR=2.55; p=0.069), prior ipsilateral mastoidectomy (OR=2.37; p=0.172), and superior EAC exposed bone (OR=4.01; p=0.066).

Table 5.

Risk factors for development of diffuse temporal bone osteoradionecrosis (TBORN).

Factor	Univariable analysis		Multivariable analysis
	OR (95% CI)	p-value	OR (95% CI)	p-value
Age	1.01 (0.98−1.03)	0.561
Sex	0.76 (0.37−1.56)	0.451
Comorbidities
Diabetes	3.12 (1.05−9.23)	0.040*	4.02 (1.22−13.2)	0.022*
Maxillary ORN	6.93 (0.75−63.96)	0.088
Hypothyroidism	1.49 (0.71−3.13)	0.292
Dyslipidemia	1.30 (0.59−2.87)	0.514
Mandibular ORN	1.35 (0.49−3.68)	0.563
Smoking history
Current	2.55 (0.93−6.97)	0.069
Past	1.46 (0.63−3.37)	0.378
Prior otologic surgery	1.39 (0.63−3.09)	0.415
Mastoidectomy	2.37 (0.69−8.20)	0.172
Primary malignancy
Periauricular skin	2.94 (0.98−8.86)	0.055	3.52 (1.25−9.92)	0.017*
Parotid	1.59 (0.52−4.91)	0.417
Surgery for primary malignancy	1.6 (0.70−3.64)	0.263
Radiation dose to primary tumor	0.98 (0.94−1.03)	0.421
Received 3D-CRT	2.32 (1.12−4.81)	0.024*	2.30 (1.02−5.15)	0.044*
Received systemic therapy	0.66 (0.32−1.35)	0.253
Recurrence of primary malignancy	1.29 (0.61−2.71)	0.500
Second H&N malignancy	0.96 (0.38−2.40)	0.930
H&N reirradiation	0.99 (0.38−2.60)	0.985
EAC exposed bone
Superior	4.01 (0.91−17.64)	0.066
Anterior	1.83 (0.87−3.84)	0.110
Inferior	0.63 (0.28−1.40)	0.256
Posterior	0.89 (0.38−2.07)	0.779

Abbreviations: OR, odds ratio; CI, confidence interval; ORN, osteoradionecrosis; 3D-CRT, 3-dimensional conformal radiotherapy; H&N, head and neck; EAC, external auditory canal.

^*Statistically significant (p < 0.05)

For localized disease, conservative management was successful in 75% of cases and produced disease resolution in 27%; for diffuse disease, conservative management was successful in only 19% (Table 4). For localized disease, HBO and PENTO were successful in 60% and 83%, respectively. For diffuse disease, surgery was successful in 87% and produced disease resolution in 91%. Procedures involving EAC closure were successful in 86%, and mastoidectomy without MO was successful in 100% of cases. Furthermore, conservative management was never successful when TBORN extended beyond the mastoid or infratemporal fossa. TBORN associations were chronic otorrhea (12%), nonhealing tympanic membrane perforation (11%), and cholesteatoma (7%) (Table 3). The most frequent TBORN complications were TB osteomyelitis (7%), wound infection (6%), facial palsy (3%), and profound sensorineural hearing loss (3%). The percentage of osteomyelitis, wound infection, facial palsy, and profound sensorineural hearing loss complications prior to presentation were 70, 75, 80, and 40%, respectively. With the exception of two peri-operative wound infections, no TBORN complications occurred after operative treatment. Forty patients (28%) were dead at the time of the last follow-up, and 1 was directly attributed to TBORN.

Discussion

To our knowledge, this is the largest single-institution review of TBORN. We demonstrated that TBORN is a long-term complication after H&N radiotherapy and is most commonly seen in patients treated with lateralized H&N radiotherapy or radiotherapy for a nasopharyngeal tumor. Hearing loss, otorrhea, and otalgia are the most common symptoms, and exposed bone is most frequently seen in the anterior and inferior EAC. Furthermore, older age (≥ 50 years) was significantly associated with earlier diagnosis, corroborating previous suspicions.⁵ Finally, while TBORN is rarely fatal, radiation-associated sequelae and severe TBORN complications are not infrequent.

Many disease characteristics identified in the largest systematic review of TBORN to date⁷ are similar to the ones we identified, but some differences deserve mention. First, we identified a much higher rate of primary periauricular skin malignancies, likely because most of our patients were from the southern United States, where ultraviolet light exposure and rates of cutaneous malignancies are higher than the national average.¹² Furthermore, we grouped skin cancers with parotid metastases into the periauricular skin group. Given that the parotid lymph nodes are the sentinel nodes for a large portion of the H&N skin¹³, it is not surprising that the most frequent primary malignancies were cutaneous. Second, this study demonstrated a lower rate of diffuse disease, surgical intervention, and TBORN-complication-related deaths, which is likely related to reporting bias, as cases necessitating surgery and those with unique complications are likely overrepresented in the literature.

TBORN treatment is primarily centered on symptom control. We noted that conservative measures were largely adequate for localized disease, despite a low rate of complete disease resolution. This is unsurprising because many symptoms can be attributed to superinfection of necrotic bone, and such infection must resolve prior to reepithelialization. Furthermore, while there is an inherent risk of developing complications during conservative therapy, this appears to be low as the majority of the complications were evident prior to presentation. Regarding adjuvant treatment options, HBO increased the rate of reepithelialization yet had a lower overall rate of symptom abatement than conservative management alone. As there have been reports of HBO’s successful use in TBORN, our results may be partially attributed to selection bias, as patients with severe TBORN likely received HBO.^14,15 However, a recent systematic review highlighted the variability of HBO success in TBORN, mimicking that of the mandibular ORN literature where heterogenous study designs yield conflicting evidence.⁷ In a double-blind, randomized, placebo-controlled trial, Annane et al.¹⁶ did not find evidence that HBO benefitted patients with mandibular ORN. However, a Cochrane review¹⁷ concluded that moderate quality evidence exists for justification of HBO in select ORN patients. Further investigation is needed to determine its benefit in TBORN.

Another adjuvant protocol, pentoxifylline, tocopherol, and clodronate (PENTOCLO), inhibits radiation-induced fibrosis and ongoing osteolysis and promotes new bone formation.¹⁸ For mandibular ORN previously unresponsive to local surgery and HBO, PENTOCLO demonstrated complete mucosal disease resolution.¹⁹ However, given the risk of bisphosphonate-induced osteonecrosis and the unavailability of clodronate in the United States, PENTO alone has been evaluated, with a recent meta-analysis supporting its use in mandibular ORN.²⁰ The largest report of PENTO in TBORN evaluated 5 cases and concluded that it may be beneficial for symptom control and coverage of exposed bone.²¹ In the present study, PENTO controlled symptoms better than conservative management alone, but given our low number of cases, definitive conclusions cannot be made.

Most diffuse cases did not respond well to conservative treatment as diffuse disease represents a more serious radiation injury, and that most conservative therapies are directed towards the EAC, which is not the only site of disease in diffuse cases.⁵ On the other hand, surgery demonstrated high rates of symptom abatement and bone coverage with a low rate of peri- or post-operative TBORN complications. Although mastoidectomy without MO demonstrated a higher rate of treatment success than did procedures with EAC closure, only a small number of patients underwent mastoidectomy without MO, so it is unlikely that this variance represents a true difference. In fact, Yuhan et al.⁷ reported that the success rates for lateral TB resection and mastoidectomy were 91% and 60%, respectively. This finding is supported by our findings of a high rate of infratemporal fossa involvement in diffuse TBORN, an area not addressed in mastoidectomy. Regarding reconstruction, free flaps had a higher rate of postoperative wound infection than temporalis muscle flaps, but this is likely because free flaps are used in patients with severe disease and extensive defects. Kadakia et al.²² demonstrated a lower rate of wound breakdown with regional or free flaps than with local flaps after TBORN resection. Thus, we recommend at least lateral TB resection with regional or free flap reconstruction for diffuse TBORN who undergo surgery. When diffuse disease spread outside of the mastoid or infratemporal fossa, conservative management always failed. Thus, we consider the mastoid and infratemporal fossa “favorable locations” as diffuse disease in these locations may be more likely successfully controlled with conservative management.

A previous study⁸ demonstrated that patients with localized disease were more likely to become symptom free after conservative therapy, which was confirmed in our larger analysis. Given this finding, predicting which patients will develop diffuse disease is critical. We demonstrated that diabetes, 3D-CRT, and periauricular skin primary malignancy were significant factors for developing diffuse disease. Diabetes causes microvascular disease that can perpetuate the hypovascular and hypoxic state of ORN and inhibit healing. Diabetes is also a known risk factor for developing medication-related mandibular osteonecrosis.²³ Compared to IMRT, 3D-CRT has been associated with higher rates of mandibular ORN as 3D-CRT does not take advantage of steep dose gradients and dose-reduction protocols.²⁴ Despite this, no statistical differences in dose-volume histograms have been found between mandibular ORN grades in patients with oropharyngeal cancer.²⁵ Although incidence rates predicated on radiation techniques or doses have never been studied for TBORN, Sharon et al.²⁶ demonstrated that tympanic bones with ORN received a mean dose of 65 Gy and those without ORN received a mean dose of 32 Gy. Techniques and doses are clearly determinates of radiation injury and have an impact on both ORN development and progression. Thus, it is not surprising that having a primary periauricular malignancy was the final determinant predictive of disease progression given the thin temporal soft tissue envelope. Given the thin skin and soft tissue envelope, radiation to the temporal skin will cause substantial damage to the adjacent TB.

Although not statistically significant, current tobacco use, prior mastoidectomy, maxillary ORN, and superior EAC exposed bone were associated with an elevated risk for progression to diffuse disease. Both tobacco use and pre-radiation surgery (marginal mandibulectomies and dental extractions) are risk factors for the development of mandibular ORN, so their association with diffuse TBORN is predictable.^27,28 Furthermore, maxillary ORN and exposed bone on the superior EAC are rare. Their presence likely denotes severe radiation injury and, therefore, a propensity to developing advanced disease, as previously discussed. Interestingly, H&N reirradiation did not significantly predict progression, but this may reflect the low number of such patients in our study. Also, unmeasured factors, such as the interval between radiation doses, dose fractionation, and location of reirradiation, may have contributed to this outcome.

Based on this study, we now classify patients according to the MD Anderson TBORN index (Table 6). The stratification of patients based of their risk of developing diffuse disease and response to treatment is imperative to ensure adequate disease management and reduce unnecessary surgeries. If the patient’s symptoms are severe or worsening, a re-evaluation of risk factors and repeat imaging to evaluate the location of diffuse ORN, if applicable, should be performed. The importance of ongoing evaluation of modifiable risk factors has been documented in mandibular ORN.²⁹ Finally, any patient with protracted treatment failure, as defined by persistent or progressive symptoms after reassessment, should be moved to the next higher class, and the corresponding treatment initiated.

Table 6.

MD Anderson temporal bone osteoradionecrosis (TBORN) index.

MD Anderson TBORN index	Criteria	Treatment
Class I	Localized disease with fewer than 3 poor prognostic factors	Conservative ± PENTO
Class II	Localized disease with 3 or more poor prognostic factors Diffuse disease with:  -fewer than 3 poor prognostic factors AND  -disease limited to favorable locations	Conservative ± PENTO, HBO, IV antibiotics with close follow-up
Class III	Diffuse disease with:  -3 or more poor prognostic factors OR  -disease outside of favorable locations	Surgery

Abbreviations: PENTO, pentoxifylline and tocopherol; HBO, hyperbaric oxygen; IV, intravenous.

Conservative: otic drops and routine aural cleaning

Poor prognostic factors: diabetes, maxillary osteoradionecrosis (ORN), 3-dimensional conformal radiotherapy, periauricular skin primary malignancy, current smoker, prior ipsilateral mastoidectomy, exposed bone on the superior external auditory canal.

Favorable locations of diffuse ORN: mastoid, infratemporal fossa.

Although this study’s homogeneity allowed for consistent data collection across a large time span, it also limited the external validity and generalizability of the study. Second, this study’s retrospective nature precluded collection of other potentially important data, such as the severity of symptoms, nature of otorrhea, and TB radiation dose parameters. Third, the low number of cases managed with HBO, PENTO, and mastoidectomy without MO precluded an accurate determination of the true benefits of these modalities. Finally, assessment of the incidence and prevalence of TBORN and the risk factors associated with developing the disease would allow for better patient counseling before radiotherapy. Despite these shortcomings, the large number and longitudinal approach of this study make it unique and provide statistical power to a growing body of literature.

Conclusion

TBORN can be a devastating, late complication of H&N radiotherapy and is most frequently seen in patients who have received lateralized radiotherapy. Older age is associated with an earlier onset of disease. Localized disease is more common than diffuse disease. Risk factors for developing diffuse disease include diabetes, 3D-CRT, and a primary malignancy of the periauricular skin, although maxillary ORN, current tobacco use, prior mastoidectomy, and exposed bone in the superior aspect of the EAC are likely also important. Conservative management provides good outcomes for localized disease, whereas surgery is often necessary for diffuse disease. Risk stratification with the MD Anderson TBORN index may better identify patients with aggressive disease, thereby reducing unnecessary surgeries and preventing sequelae from inappropriate treatment.