A 57-year-old lady with no comorbidities presented in May 2019 with a mass on the left side of the palate extending from the third molar to the junction of the soft palate and up to the midline. She had a history of prior tooth extraction; biopsy showed high-grade adenocarcinoma. Baseline computed tomography (CT) scan showed involvement of the high infratemporal fossa and positron emission tomography (PET)-CT revealed no evidence of distant metastases [Figure 1a–c]. The disease was staged as cT4bN1M0. Magnetic resonance imaging (MRI) showed no perineural spread. The patient underwent surgery (left total maxillectomy with neck dissection and tracheostomy with free flap reconstruction). The postoperative histopathological report showed a high-grade malignant tumor with basaloid and focal glandular morphology involving the hard palate with no lymphovascular or perineural invasion; all the cut margins were free of tumor. The patient was planned for postoperative radiotherapy with intensity-modulated radiation therapy and received a dose of 64 Gy/32 fractions, over 50 days, completed on Sept 9, 2019. Follow-up PET-CT on Nov 26, 2019 showed no evidence of recurrence [Figure 1d-f].
A year later in Jan 2021, the CT scan showed an ill-defined soft tissue mass in the bilateral ethmoid and sphenoid sinuses, eroding the lamina papyracea, extending to the retro-orbital soft tissue, involving the left superior orbital fissure, extending to the anterior and middle cranial fossae, and involving the left cavernous sinus. This lesion was biopsied and showed recurrence of poorly differentiated carcinoma; hence, the patient was treated with chemotherapy (8 cycles of paclitaxel and carboplatin weekly). Post chemotherapy scan showed response to therapy, and an additional 8 cycles of chemotherapy were planned.
At 6 months post chemotherapy, the CT scan done on Jun 28, 2021, showed new onset soft tissue in the supraorbital region with extradural intracranial extension, left optic nerve involvement, bone erosion, and abnormal hypodensity in the overlying left frontal lobe and bony expansion with lucent pattern of trabecular changes in the frontal and sphenoid bones and the ethmoid sinuses bilaterally. As the patient had platinum refractory progressive disease, oral metronomic chemotherapy was started on Jul 02, 2021. A chemotherapy assessment CT scan done 3 months later on Sept 13, 2021 showed a significant increase in the soft tissue lesion in the supraorbital region with extradural intracranial extension and bony expansion with lucent trabecular loss in the frontal and sphenoid bones and the ethmoid sinuses bilaterally. These bony changes had significantly increased in extent as compared to the previous scan [Figure 1g-i]
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DIFFERENTIAL DIAGNOSIS AND FURTHER MANAGEMENT
The findings on the CT scan were reported to be suspicious for sphenoid osteoradionecrosis [Figure 1g-i]. The other differential diagnoses were osteomyelitis, radiation-induced meningioma, and fibrous dysplasia. Fibrous dysplasia was ruled out as the baseline CT showed no bone changes. Moreover, craniofacial fibrous dysplasia commonly presents with sclerotic changes since most patients do not report in the initial phase of the disease.
Osteomyelitis was ruled out as there was an absence of intraosseous gas which is considered the pathognomonic feature of osteomyelitis; in addition, there was no gross suppuration and no obvious soft tissue abscess formation. The possibility of radiation-induced meningioma was considered highly unlikely as the usual latency period for this is long (measured approximately in decades), and the disease typically presents as a well-defined extra axial soft tissue mass with or without the dural tail sign. Bony changes in the form of hyperostosis are seen. The patient progressed on standard therapies and was subsequently lost to follow-up.
Sphenoid osteoradionecrosis in a patient treated with radical radiation for hard palate adenocarcinoma.
Sphenoid wing osteoradionecrosis is a very rare condition that can occur following the treatment of head-and-neck malignancies. It can have lethal implications. Osteoradionecrosis represents severe delayed radiation-induced injury that typically occurs 6–12 months after the completion of radiation and is characterized pathologically by bone tissue necrosis due to microvascular damage. The altered blood supply does not allow the normal tissue repair to occur, thus resulting in continuous tissue breakdown. Postoperative radiotherapy is an essential component in the management of carcinoma of the palate, and it lowers the risk of postoperative recurrence. However, despite being the cornerstone of management, radiotherapy can lead to severe complications, including osteoradionecrosis. Osteoradionecrosis is rare if the dose of radiation delivered is below 60 Gy. The other risk factors for osteoradionecrosis include close proximity of the tumor to the bone, higher T stage of disease, the use of concomitant chemotherapy, and trauma.
Daoudi et al. reported a case series of seven patients with a mean age of 54 years; most cases were of nasopharyngeal carcinoma, followed by chordoma, and lastly olfactory neuroblastoma. The mean time from the last course of radiotherapy to the diagnosis of osteoradionecrosis was 7 years. The authors reported that the extent of the disease in sphenoid osteoradionecrosis decided the management strategies, which could consist of medical therapy only, endovascular intervention, or surgery. At a mean follow up of 24 months, the survival rate was 57%; three patients died after progression of the osteoradionecrosis. The possibility of severe complications was high in patients who received more than one course of radiotherapy or doses >72 Gy. In another study by Han et al., the incidence of osteoradionecrosis of the skull base in nasopharyngeal carcinoma was 1.04% after one course of radiotherapy with an average latent period of 45.57 months. Clinically, osteoradionecrosis presents with non-specific symptoms and signs; however, the treating radiation oncologist should be watchful for the occurrence of chronic pain, cranial nerve palsies, and asthenia in a patient who has previously received radiotherapy, which should raise the clinical suspicion of osteoradionecrosis, and may help to pick up clinically occult cases prior to clinical bone exposure. Since the findings are mostly non-specific, patients are usually diagnosed in the advanced stage with acute symptoms such as carotid blowout and meningitis. On imaging, the plain radiograph shows ill-defined cortical destruction with or without sequestration with associated osteopenic changes and heterogeneous bone density. Cross-sectional imaging is usually obtained to determine the exact extent, associated complications, evaluate the bone integrity, the risk of pathological fracture, and to rule out recurrent malignancy. Cone beam CT or multidetector CT are preferred as cortical destruction and other bony changes are better depicted. On the CT images, although a permeative pattern is typical of osteoradionecrosis, a lucent pattern of trabecular loss has also been reported in the literature.
At the time of performing the scan, contrast is usually given in cases when there is a high clinical suspicion of recurrence rather than osteoradionecrosis; however, PET- CT is preferred to rule out recurrence. MRI shows a heterogeneous signal intensity within the marrow of the radiation exposed region and can be helpful to differentiate recurrent tumor and second primaries such as osteogenic sarcoma. A carotid angiogram is usually ordered in cases with suspected carotid blowout to plan further endovascular interventions such as occlusion with coils and placement of stents. Close differentials of sphenoid wing osteoradionecrosis are osteomyelitis and radiation-induced meningioma.
Treatment strategies for sphenoid wing osteoradionecrosis are controversial and depend upon the extent of involvement and clinical symptoms. For uncomplicated cases, the conservative approach is the first line of treatment and surgery is usually preferred in patients with secondary complication due to osteoradionecrosis.
Prevention of osteoradionecrosis is an important task for every radiation oncologist, wherein the appropriate dental treatment plan prior to radiation therapy, prophylactic Hyperbaric Oxygen Therapy, and the use of systemic steroids have shown promising results. Management of osteoradionecrosis is a multidisciplinary team effort and involves conservative approaches, oral hygiene, antibiotic coverage, and in advanced diseases, surgical interventions like sequestrectomy or saucerization are performed. In cases where response to standard treatment is poor, antifibrotics, antioxidants, and antibiotics help in symptomatic treatment and surgical debulking may be performed in poor responders.
Osteoradionecrosis is an important long-term sequela of high-dose radiotherapy, and a high degree of clinical suspicion should be maintained during the follow-up of these cases. Early imaging plays an important role in the diagnosis and prompt management and thus may optimize outcomes and prevent complications.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
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