1. Diagnostic Imaging Findings After Radiation Therapy for Skull Base Region Tumors
Daniel Thomas Ginat MD, MS Department of Radiology
James M. Melotek MD
Department of Radiation Oncology
Daniel Haraf MD
EdE-57

2. Disclosures
None
Please Daniel Ginat at with questions or comments.

3. Introduction
Radiation oncology plays an important role in the treatment of nasopharynx and skull base carcinomas.
Expected findings and complications will be reviewed, including recurrent tumor and metastases, radiation-induced necrosis, radiation-induced neoplasms, optic neuropathy, and Eustachian tube dysfunction.
In addition, the role of diffusion weighted imaging and perfusion MRI, as well as PET will be discussed.

4. Critical Anatomic Landmarks for Radiation Treatment Planning
Brainstem: Sagittal T1-weighted MRI shows a squamous cell carcinoma with skull base invasion (*) and epidural extension abutting the brainstem.
Optic Nerve: Coronal fat suppressed post-contrast T1-weighted MRI shows a squamous cell carcinoma in proximity to the left optic nerve (arrow).
Carotid Artery: Coronal T2-weighted MRI shows a squamous cell carcinoma with skull base invasion that encases the left internal carotid artery (arrow).

5. Critical Anatomic Landmarks for Radiation Treatment Planning
Radiation dose limits for selected critical structures in the skull base region:
Brainstem: Up to 54 Gy
Optic Apparatus: Up to 54 Gy
Temporal Lobes: Up to 60 Gy
In general, MRI is the best modality for the assessment of these structures.
Radiation therapy isodose lines in a patient with T4 nasopharyngeal carcinoma illustrate planning difficulties.

6. Locoregional Failure versus Success
Axial fat-suppressed post-contrast T1 MRI show an mass in the right lateral nasopharyngeal recess at the site of a treated nasopharyngeal carcinoma treated 10 years before.
Follow up axial fat-suppressed post-contrast T1 MRI shows development of necrosis in the tumor following radiation therapy.

7. Locoregional Failure versus Success
Locoregional failure is the predominant pattern of relapse following non-surgical treatment and includes in-field and marginal recurrence patterns.
This may relate to intrinsic radioresistance or factors such as tumor hypoxia.
Methods to intensify locoregional treatment include chemotherapy, biological therapies, radiosensitizers, altered fractionation, and dose escalation.
Diffusion-weighted imaging, perfusion-weighted imaging, and FDG-PET may be useful for characterizing post-treatment status.

8. Diffusion Weighted Imaging
Treatment Response
Adenoid cystic carcinoma
Before and after treatment.
Tumor Progression

9. Diffusion Weighted Imaging
Water molecules within intact cell membranes of viable tumor cells are characterized by a relatively small mean free-path length, which results in restricted diffusion and low ADC values.
On the other hand, tumor necrosis is characterized by increased membrane permeability and breakdown of the cell membrane, resulting in free diffusion and increased mean free-path length of diffusing molecules.
These changes result in decreased restriction and thereby increased diffusion of water molecules in the necrotic regions.
DWI can potentially assist in selecting the site for biopsy.

10. Perfusion Weighted Imaging
Treated Tumor
Versus
Viable Tumor
Enhancing tissue in the treated left nasopharyngeal region does not show corresponding high blood volume, consistent with non-viable tumor (arrows).
Enhancing mass in the central skull base shows corresponding high blood volume, consistent with viable tumor (arrows).

11. Perfusion Weighted Imaging
Dynamic contrast-enhanced (DCE) MRI is a non-invasive technique that can provide anatomical and physiological information about tumors.
Areas of persistent enhancement in the treatment bed can mimic tumor.
The presence of low blood volume suggests treatment effects, while elevated blood volume suggests persistent tumor.

12. Adenoid cystic carcinoma
18FDG-PET
“False Negative”
Adenoid cystic carcinoma
“True Positive”
Tumor Recurrence
“False Positive”
Inflammation

13. 18FDG-PET
Although very useful for staging and cases with unknown primaries, 18FDG-PET has several limitations, particularly in the first 3 months after treatment.
False positive results: Inflammation and infection in particular can mimic tumor.
False negative results: Small tumors may have inconspicuous hypermetabolism and certain tumors, such as adenoid cystic carcinoma and highly necrotic tumors, may have inherently low metabolic activity.

14. Perineural Tumor Spread
The patient has a history of right submandibular adenoid cystic carcinoma. Axial CT shows widening of the right foramen ovale (arrow). Axial and coronal fat-suppressed post-contrast MR images show expansion and enhancement of the right trigeminal nerve (arrows).

15. Perineural Tumor Spread
Can be a manifestation of out-of-field treatment failure.
Adenoid cystic carcinoma has a strong tendency for perineural tumor spread at presentation, but is most commonly encountered with cutaneous squamous cell carcinomas.
The facial and trigeminal nerves are most commonly involved.
Imaging findings: thickened nerves with abnormal enhancement, foraminal widening, and obliteration of surrounding fat.

16. Leptomeningeal Carcinomatosis
The patient has a history of small cell neuroendocrine carcinoma of the nasopharynx with extension into the skull base, treated with cisplatin/etoposide and concurrent radiotherapy. Axial post-contrast T1-weighted MR images show scattered areas of leptomeningeal enhancement, including along the cranial nerves.

17. Leptomeningeal Carcinomatosis
Rare form of metastatic disease that can manifest even after treatment of certain head and neck carcinomas, such as those of neuroendocrine origin.
May be overlooked or inapparent on routine post-treatment head and neck CTs.
Entire neuraxis MRI with contrast and cerebrospinal fluid analysis is necessary for diagnosis.
Portends a poor prognosis.

18. Radiation-Induced Neoplasms
The patient has a history of right maxillary sinus squamous cell carcinoma in treated with radiation therapy (61.2 gray in 1.9 gray fractions) 20 years earlier and presents with right vision loss. MRI depicts an enhancing right skull base mass (arrows), including within the cavernous sinus and optic canal. The tumor proved to be a spindle cell sarcoma.

19. Radiation-Induced Neoplasms
Radiation-induced tumors most commonly arise at the margins of the radiation field, where the dose is not high enough to decimate tissues, but high enough to be carcinogenic.
The most common types of neoplasms include soft tissue sarcomas, squamous cell carcinomas, and salivary gland tumors.
The development of radiation-induced neoplasms is delayed, with a mean duration from radiotherapy until the diagnosis of cancer is 13 years; therefore, long-term follow up is warranted.

20. Dural Reaction
Axial and coronal post-contrast fat-suppressed T1-weigheted MR images show an esthesioneuroblastoma with orbital and epidural extension. There is also diffuse mild right cerebral convexity dural thickening and enhancement (arrows).

21. Dural Reaction
Should not be confused with actual neoplastic involvement and lead to an unnecessarily high radiation field.
“Dural tail” presumed to represent hypervascular tumor reaction.
Criteria:
Should be identified on two successive sections through the tumor.
Should taper smoothly away from the tumor.
Must enhance more than the tumor itself.

22. Skull Base Remineralization
Int J Radiat Oncol Biol Phys May 1;44(2):305-9.
Computed tomography findings of bony regeneration after radiotherapy for nasopharyngeal carcinoma with skull base destruction: implications for local control.
Fang FM1, Leung SW, Wang CJ, Su CY, Lui CC, Chen HC, Sun M, Lin TM.
Author information
Abstract
PURPOSE:
To evaluate the response of bony destruction (BD) of the skull base following radiotherapy in nasopharyngeal carcinoma (NPC) and investigate the implications of bony regeneration (BR) on local control and its related factors.
METHODS AND MATERIALS:
Ninety patients with NPC with skull base destruction clearly demonstrated on computed tomography (CT) were reviewed. These patients have completed the prescribed treatment and received regular CT follow-up. A total of 338 sets of CT images of the head and neck were reviewed. The tumor response and the appearance of BR in the previous destructive part of the skull base were recorded and analyzed. The tumor response was divided into complete, partial, or no response. BR was defined as recalcification or sclerotic change with partial or complete healing in the previous osteolytic bony defect. Local failure was confirmed either by pathological or merely by imaging studies showing progression of tumor in consecutive radiological pictures.
RESULTS:
The distribution of specific sites of bony destruction (BD) in these patients included the sphenoid bone (68%), paracavernous sinus area (48%), petrous apex (47%), clivus (44%), pterygoid plates (20%), and others (7%). The CT showed 57 patients (63%) had BR. All were observed within 1 year after treatment. Sixty-two patients (69%) had complete tumor response after treatment. Analyzed by logistic regression method, tumor response after treatment was found to have a statistically significant correlation with BR (p = ). Most BR (55/57) was demonstrated in patients with complete tumor response. The 3-year actuarial local control rate was 54 % in these patients. The local control was quite different in the comparison of patients with BR versus those with persistent BD (77% vs. 21%, p < ). Multivariate analysis showed that patients with complete tumor response or with BR on imaging had statistically better local control than those without either of the two findings (p < 0.05).
CONCLUSION:
Appearance of BR at previous destructive skull base following radiotherapy for NPC patients could be clearly demonstrated on CT. Bony regeneration significantly correlated with treatment response and local control. Although the underlying significance of BR was unknown, to predict the outcome after treatment, the appearance of BR shown on CT may imply the complete eradication of tumor in this area.
Initial scan
One year later
Axial CT image shows extensive skull base erosions associated with a nasopharyngeal carcinoma.
Follow up axial CT image shows near-anatomical remineralization of the previously affected skull base.

23. Skull Base Remineralization
After radiation for nasopharyngeal carcinoma, 23% have sclerosis or bony regeneration in the skull base
Sclerosis in 28% of these transforms into osteoporosis 1 to 5 years afterwards.
The appearance of osteolytic changes in the skull base during follow-up of patients with nasopharyngeal carcinoma who had normal skull base morphology before treatment is associated with tumor recurrence.

24. Skull Base Osteomyelitis
T1C
The patient has a history of nasopharyngeal carcinoma treated with radiation. The MR images show edema and enhancement in the bone marrow of the central skull base with relatively elevated diffusivity.
ADC
map

25. Skull Base Osteomyelitis
Patients with head and neck carcinomas may be prone to infections at the treatment sites.
The signal characteristics, enhancement, and an infiltrating pattern can be indistinguishable from neoplastic processes on MRI.
Diffusion-weighted MRI ADC values of skull base osteomyelitis are often significantly higher than with nasopharyngeal carcinoma and lymphoma.

26. Osteonecrosis
The patient has a history of recurrent nasopharyngeal carcinoma treated with chemoradiation. The patient also required dental extractions , which where complicated by osteoradionecrosis of the right mandible. Axial and coronal CT images show an irregular lytic process in the right mandible adjacent to the extraction sites (arrows).

27. Osteonecrosis
Most commonly involves the mandible, particularly following dental extractions, and may be pharmaceutical and/or radiation induced.
Appears as a lytic process sometimes associated with pathological fracture, soft tissue swelling, enhancement, and hypermetabolism on FDG-PET, which can mimic tumor.
Biopsy can exacerbate the patient symptoms.

28. Nasopharyngeal Necrosis and Carotid Blow Out Syndrome
The patient has a history of right nasopharyngeal carcinoma. The pretreatment contrast-enhanced CT image shows an enhancing mass in the right nasopharynx with extension into adjacent spaces. The patient subsequently developed hemoptysis and CT shows hemorrhage in the treatment bed (arrow). Follow up CT image shows a large defect at the site of the tumor due to extensive soft tissue necrosis.

29. Nasopharyngeal Necrosis and Carotid Blow Out Syndrome
Late complication of radiation therapy for nasopharyngeal carcinoma.
Imaging can show edematous soft tissues that can slough and then lead to soft tissue deficiencies.
Carotid blow-out refers to rupture of the carotid artery and its branches and is predisposed by vessel exposure from tumor.
Angiography may demonstrate pseudoaneurysm formation or even frank contrast extravasation, often associated with deficient soft tissue.

30. Temporal Lobe Necrosis
2 years later
History of right nasopharyngeal lymphoepithelioma. The initial axial T2-weighted MRI shows a hypointense mass in the right nasopharynx. Follow up brain FLAIR and post-contrast T1-weighted MR images show extensive anterior right temporal lobe edema and ring-enhancement.

31. Temporal Lobe Necrosis
Debilitating late complication of radiation therapy for nasopharyngeal cancer.
The location and timing are highly suggestive of brain necrosis.
However, ring enhancement and edema can mimic neoplasm.
Associated hemorrhage is occasionally observed as well.
PET and MR perfusion can help differentiate necrosis from tumor if otherwise uncertain, whereby there is decreased metabolic activity and hypoperfusion.

32. Optic Neuropathy 2 years later
The patient was treated with radiation for adenoid cystic carcinoma invading the left cavernous sinus (encircled). The left optic nerve was normal initially.
The patient subsequently developed left visual acuity deficits. MRI demonstrated hyperintensity of the left optic nerve without significant enlargement (arrow).
2 years later

33. Optic Neuropathy
Radiation optic neuropathy causes rapid deterioration over days to weeks.
Likely result from vascular endothelial injury and related to total dose and daily fractionation size.
The affected nerve may display diffuse T2 hyperintensity and/or focal enhancement and remain normal in size or become slightly enlarged.

34. Eustachian Tube Dysfunction
The patient has a history of left nasopharyngeal carcinoma treated with radiation and presented with post-treatment left hearing loss. Axial T2-weighted MRI shows effusions within the left mastoid air cells, middle ear, and part of the Eustachian tube (arrow).

35. Eustachian Tube Dysfunction
Eustachian tube edema and secretory otitis media are the main cause of conductive hearing loss in early stages and is mostly reversible.
Tumor regression following radiotherapy is the main factor leading to improvement in Eustachian tube function, but scarring can lead to persistent dysfunction after treatment.
On imaging, fluid within the involved mastoid air cells, middle ear, and a portion of the Eustachian tube is commonly observed.

36. Selected References
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