Pediatr Blood Cancer 2014;61:1479–1480

BRIEF REPORTMandibular Condyle Erosion and Sclerosis in Pediatric Patients Treated

With Radiotherapy to the Head and Neck Region

Catherine E. Mercado, BA,1 Stephen B. Little, MD,2 Claire Mazewski, MD,3

Frederick P. Schwaibold, MD,4 and Natia Esiashvili, MD1*

INTRODUCTION

Pediatric patients who are long-term survivors treated with

radiotherapy (RT) to the head and neck area have a substantial risk

of late radiation effects, including those in the musculoskeletal

system [1,2]. Trismus and temporomandibular joint dysfunction are

well described in children receiving RT doses above 40Gy to the

pterygoid muscles, masseter muscles, and temporomandibular

joints [3,4]. Themandibular ramus is at risk of osteoradionecrosis in

adults due to its limited blood supply and RT doses as high as 70Gy

delivered in its proximity [5]. However, frank bone erosion in

pediatric patients receiving 60Gy or less is rare and erosion of the

mandibular condyle is not well described in the current pediatric

literature. In this report, we present three cases of erosion of

the mandibular condyle amongst pediatric patients treated with

radiotherapy at a single institution for Ewing’s sarcoma, Nasopha-

ryngeal Rhabdomyosarcoma, and Medulloblastoma.

Patient 1

This 17-year-old male presented with a painful right-sided

ulcerating mass of his hard palate increasing in size for several

months causing congestion of his right nares and intermittent

episodes of epistaxis. Head CT scan revealed amass originating from

the right posteriormedial maxilla. The diagnosis of Ewing’s sarcoma

was confirmed histologically via biopsy. After six cycles of induction

chemotherapy, the patient was referred to radiation oncology for

definitive radiotherapy, which was delivered with the Intensity

Modulated Radiation Treatment (IMRT) technique to a total dose of

55.8Gy. As a result of its proximity to the planned target volume

(PTV), the right temporomandibular joint (TMJ) received 30–45Gy,

while the contralateral TMJ received <30Gy (Fig. 1). A significant

degree ofmucosal acute toxicitieswas observed during treatment and

the patient required prolonged total parenteral nutrition. He then

went on to receive the remaining chemotherapy treatments.

Following completion of therapy, the patient experienced

intermittent jaw pain without significant trismus; chewing and

swallowing function was preserved. Two years after radiotherapy

was completed, a CT scan of the maxillofacial structures revealed

erosion of the articulating surface of the mandibular condyles

bilaterally (Fig. 1b). He did not experience further symptoms from

the TMJ area and did not require any intervention.

Patient 2

This 10-year-old male presented with a painful swollen left jaw.

Biopsy and imaging studies confirmed a diagnosis of group III

nasopharyngeal rhabdomyosarcoma. The patient was treated with

multi-agent chemotherapy according to a cooperative group

protocol and underwent radiation therapy as his primary local

control modality. Utilizing the IMRT technique, he received

50.4Gy of total radiation dose to the tumor. The TMJ area

bilaterally received <40Gy.

Four years post-radiation treatment, patient 2 experienced

a decrease in temporomandibular joint mobility and trismus.

Maxillofacial CT imaging revealed asymmetry of the TMJs as a

result of degenerative changes in the right temporomandibular joint.

Imaging illustrated evidence of a small bony spur, mild widening of

the lateral TMJ space and mild narrowing medially. In addition to

condylar erosion, patient 2 has suffered from significant craniofa-

cial hypoplasia, and growth hormone deficiency. After 10 years

post-treatment, the patient continues to have a moderate degree of

TMJ symptoms.

Patient 3

This 15-year-old female presented with intermittent severe

headaches associated with vomiting, vertigo, and blurred vision.

Brain MRI revealed a highly cellular mass of the posterior fossa

arising from the left cerebellar hemisphere and obstructing the

fourth ventricle resulting in hydrocephalus. The patient underwent

surgical resection of the tumor with pathology confirming the

diagnosis of Medulloblastoma. After surgery, the patient was

Head and neck radiotherapy in children is associated withsignificant acute and late morbidities. Temporomandibular jointdysfunction and trismus has been widely reported in patientsreceiving radiotherapy for sarcomas and nasopharyngeal carcinoma;however, erosion of the mandibular condyle is a rare sequela of

modern radiotherapy techniques. In this report, we present threecases of erosion of the temporomandibular joint amongst pediatricpatients treated with radiotherapy for distinct head, neck and brainmalignancies. Pediatr Blood Cancer 2014;61:1479–1480.# 2014 Wiley Periodicals, Inc.

Key words: bone erosion; pediatrics; radiation therapy; temporomandibular joint

1Department of Radiation Oncology, Emory University School of

Medicine, Atlanta, Georgia; 2Department of Radiology, Children’s

Healthcare of Atlanta, Atlanta, Georgia; 3Aflac Cancer and Blood

Disorder Center of Children’s Healthcare of Atlanta, Atlanta, Georgia;4Department of Radiation Oncology, Piedmont Hospital, Atlanta,

Georgia

Conflict of interest: Nothing to declare.

�Correspondence to: Natia Esiashvili, Department of Radiation

Oncology, Winship Cancer Institute of Emory University, 1365 Clifton

Road NE, Atlanta, GA 30322. E-mail: nesiash@emory.edu

Received 8 November 2013; Accepted 19 December 2013

�C 2014 Wiley Periodicals, Inc.DOI 10.1002/pbc.24941Published online 17 January 2014 in Wiley Online Library(wileyonlinelibrary.com).

treated with cranio-spinal irradiation followed by a conformal

tumor bed boost with IMRT to a cumulative dose of 54Gy.

The bilateral TMJ received approximately 35Gy. The patient

was treated with concurrent daily carboplatin chemotherapy and

radiotherapy. She then subsequently received maintenance multi-

agent chemotherapy. Acute toxicities were within the expected

range. During follow-up evaluation, the patient was noted to have

neuroendocrine dysfunction, including low somatomedin C levels

but normal bone mineral density. She also developed progressive

symptoms of TMJ pain. On maxillofacial CT scan 4 years post-

radiation treatment, patient 3 was found to have severe erosive

changes of eachmandibular condylewith joint space narrowing and

associated retrognathia. The patient continues to have significant

TMJ symptoms secondary to her extensive mandibular condyle

erosion and sclerosis.

DISCUSSION

Radiation induced late effects are common in pediatric patients

treated to the head and neck region, with the most common being

facial asymmetry, neuroendocrine, and ocular dysfunction [1,2]. In

addition, the alteration in function of the oral cavity and the bony

facial structures caused by radiation therapy can lead to a

substantial deterioration of the patient’s quality of life. Trismus

is a commonly reported late toxicity of the TMJ area in adults and

children treated for head and neck malignancies due to fibrotic

changes of the pterygoid muscles, masseter muscles, and

temporomandibular joints [3,4]. Destructive bone changes, like

osteoradionecrosis, usually are associated with high radiation doses

(60–70Gy) delivered to the mandibular ramus [5,6]. This particular

anatomic area is thought to be more susceptible to radiation

damage as a result of poor blood supply resulting in a fibroatrophic

process.

Radiation therapy has significant effects on cartilaginous growth

centers in children experiencing growth and maturation of skeletal

structures which includes the region of the mandibular condyles.

However, to our knowledge, erosion of the cartilaginous surface

of the mandibular condyle has not been reported as a direct

complication of radiotherapy. We recognized this toxicity in

children receiving moderate dose (30–40Gy) to the mandibular

condyles as part of definitive radiotherapy for sarcomas and a brain

tumor.While pathogenesis of this late toxicity is hard to elucidate, it

is necessary to take into account that radiosensitization from

chemotherapy agents may play a role.

It is important to further investigate the prevalence of this quality

of life limiting complication to develop strategies for its diagnosis

and possible prevention. We suspect that mandibular condyle

erosion is an under-recognized complication of radiotherapy for

head and neck tumors and could be far more under-recognized in

posterior fossa brain tumors. It is very difficult to assess the

prevalence of this condition in patients treated for sarcomas or

posterior fossa brain tumors who undergo MRI for routine

surveillance due to the fact that these findings are more difficult

to recognize on MRI. Only patients undergoing routine sinus or

facial CT scans can be diagnosed with mandibular condyle erosion,

but this form of imaging is rarely performed. In addition,

symptomatology as demonstrated in our cases can at times be

subtle and non-specific. As modern radiotherapy techniques like

IMRTand proton beam therapy may allow more dose sparing to the

TMJ area [7]. More research is needed to determine radiotherapy

dose limits to avoid this significant late sequela in children.

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Fig. 1. Patient 1: (a) Intensity Modulated Radiation Therapy (IMRT) dose plan; (b) three-dimensional image reconstruction of computer

tomography images demonstrating bilateral mandibular condyle erosions of the articulating surfaces.

Pediatr Blood Cancer DOI 10.1002/pbc

1480 Mercado et al.