Manifestations of radiation toxicity in the head, neck, and spine: An image-based review

Abstract

Background and purpose

Radiation therapy is an important component of treatment in patients with malignancies of the head, neck, and spine. However, radiation to these regions has well-known potential side effects, many of which can be encountered on imaging. In this manuscript, we review selected radiographic manifestations of therapeutic radiation to the head, neck, and spine that may be encountered in the practice of radiology.

Methods

We conducted an extensive literature review of known complications of radiation therapy in the head, neck, and spine. We excluded intracranial and pulmonary radiation effects from our search. We selected complications that had salient, recognizable imaging findings. We searched our imaging database for illustrative examples of these complications.

Results

Based on our initial literature search and imaging database review, we selected cases of radiation-induced tumors, radiation tissue necrosis (osteoradionecrosis and soft tissue necrosis), carotid stenosis and blowout secondary to radiation, enlarging thyroglossal duct cysts, radiation myelopathy, and radiation-induced vertebral compression fractures.

Conclusions

We describe the clinical and imaging features of selected sequelae of radiation therapy to the head, neck, and spine, with a focus on those with characteristic imaging findings that can be instrumental in helping to make the diagnosis. Knowledge of these entities and their imaging findings is crucial for accurate diagnosis. Not only do radiologists play a key role in early detection of these entities, but many of these entities can be misinterpreted if one is not familiar with them.

Introduction

Radiation therapy (RT) plays a continuously increasing role in the management of patients with a wide variety of malignancies. However, like many medical therapies, it can have a range of potential side effects. Many of the adverse sequelae of RT, particularly delayed side effects, are apparent on imaging. ¹ In this manuscript, we review selected radiographic manifestations of therapeutic radiation that may be encountered in the practice of radiology, focusing on complications involving the extracranial head, neck, and spine. While some are readily characterized on imaging, others have important imaging differential considerations, which are also discussed where appropriate. The selected entities were included due to their characteristic imaging features and clinical importance. We start with a brief background discussion of the mechanism of therapeutic radiation, followed by selected cases organized by anatomic region.

Radiation mechanism of action

The primary mechanism of action for RT is through damaging cancer cell DNA. For standard radiation treatments involving X-rays (photons) or protons, this DNA damage occurs through either indirect ionization of water, forming free radicals which then damage the DNA, or through direct interactions with DNA. Multiple factors influence tissue sensitivity to RT, including rate of replication, cell cycle phase, and oxygenation status. ¹

Clinical manifestations of RT are separated into acute effects, happening within weeks of treatment, and late reactions, occurring many months after treatment. Acute effects such as dermatitis and mucositis tend to occur in tissues with rapid cell turnover. Late effects are diverse and include effects such as tissue fibrosis, vascular changes, and atrophy. Both acute and late effects are related to radiation dose. ² The radiation sensitivity of normal tissues varies depending on tissue structure. Structures with functional units in-line with each other (serial architecture), such as the spinal cord, experience significant compromise when a single functional unit fails, while structures with independent functional units (parallel architecture), such as salivary glands, experience functional decline proportional to the number of exposed functional units. Regardless of structure, the adverse sequelae of radiation therapy are often apparent on imaging. This is particularly true of various delayed radiation sequelae in the head, neck, and spine.

Radiation effects on the head and neck

Radiation-induced malignancy

Radiation-induced malignancy (RIM) was formally defined by Cahan et al. in 1948, ³ and modifications of Cahan’s criteria are still in use to date. ⁴ The following four primary elements are necessary to diagnose RIM:

• 1. A tumor must arise within previously irradiated tissue.

• 2. A sufficient latent period, at least several years, must have elapsed between radiation and development of the secondary tumor.

• 3. Both the originally treated tumor and the subsequent radiation-induced tumor must have been biopsied and shown to histologically differ in order to distinguish RIM from late recurrence of the primary malignancy.

• 4. The tissue in which the secondary tumor arose must have been normal at the time of RT, including lack of a generic tumor predisposition syndrome in the exposed patient.

The most common RIM in the head and neck is squamous cell carcinoma (SCC). While the exact risk varies depending on initial tumor type and anatomic location, one study found that the risk of radiation-induced SCC in the oral cavity ranges from 1 to 5% at a median of 9 years after radiation treatment; similar numbers are seen for other head and neck radiation-induced SCC. ⁵ Sarcomas, in aggregate, represent the second most common RIM in the head and neck, followed by thyroid carcinoma and major/minor salivary gland tumors.^6–8 Radiation-induced sarcomas occur in 0.035–0.2% of all irradiated patients. ⁹ While over two-thirds of radiation-induced sarcomas in one series were osteosarcoma, a broad spectrum of sarcoma types can be seen.^8,9 When RIM is suspected, care must be taken to exclude recurrence of the original lesion before concluding a subsequent cancer is radiation-induced.^6,10 This is because radiation-induced head and neck cancers typically do not respond to chemoradiation as well as de novo tumors.

The imaging appearance of radiation-induced head and neck malignancies varies with tumor type. SCC typically appears as an ulcerated mass and frequently demonstrates avid contrast enhancement (Figures 1(a) and (b)). Osteosarcomas should be intimately associated with bone and can cause lytic change and an adjacent soft tissue mass, often with characteristic osteoid matrix (Figures 1(c) to (e)). Other soft tissue sarcomas may have a less specific appearance, although enhancement and central necrosis are common (Figure 1 (f)-(h)). Overall, since RIM does not generally have distinct imaging features from de novo tumors, knowledge of patient history and comparison with prior imaging is critical. Cahan’s criteria are especially helpful in this regard. Ultimately, a combination of clinical suspicion for RIM, early detection on imaging, and tissue biopsy can guide treatment for these patients.

Figure 1.

Radiation-induced malignancies of the head and neck. (a–b): A 78-year-old woman presenting 60 years after right parotidectomy and radiation therapy for reported malignancy of unknown type. Coronal post-gadolinium T1-WI demonstrates an enhancing right auricular mass (a, arrows). Photograph of the lesions demonstrates a necrotic mass (b), representing squamous cell carcinoma on biopsy. (c–e): A 28-year-old woman with history of radiation for Hodgkin’s lymphoma 12 years earlier. Axial (c) and coronal (d) CT images demonstrate a mixed lytic/sclerotic mass (arrows). Photograph of the lesions shows a resected low grade osteosarcoma (e–h): A 59-year-old woman with history of right tongue SCC with nodal metastases who underwent resection and adjuvant chemoradiation 2 years earlier. Axial (f) and coronal (g) contrast enhanced CT demonstrates a large lingual mass (arrows), representing pleomorphic sarcoma on resection. This was successfully treated with surgical resection and chemoradiation. Axial T1W postcontrast image 2 years later shows a large recurrent sarcoma occupying the left parotid space.

Osteoradionecrosis and radiation-induced soft tissue necrosis

Osteoradionecrosis (ORN) refers to radiation-induced injury to bone within an irradiated field, which can occur early (<2 years following treatment) or late (>2 years following treatment). It generally involves osseous necrosis, sometimes with involvement of soft tissues as well. ¹¹ Early ORN is believed to be related to higher radiation doses (>70 Gy). Late ORN is multifactorial, involving radiation-related cellular injury and impaired osteoblast function, as well as vascular damage resulting in a chronically hypoxic microenvironment.^{12, 13} The mandible is the most common bone involved by ORN, affected in 5%–22% of cases, with the relatively tenuous blood supply of the mandible believed to be the most important pathogenic factor based on pathologic studies. ¹⁴ Importantly, ORN may be complicated by concurrent osteomyelitis. ¹⁵

ORN results in heterogeneous bone density, irregularity, and coarse trabeculations, potentially with fracture through areas of structural weakness. These osseous changes are best demonstrated by CT, with ORN often demonstrating a permeative pattern of trabecular loss and areas of bony sclerosis (Figure 2). Prominent FDG-activity at sites of ORN is often demonstrated on PET/CT and may mimic recurrent tumor in cases of treated malignancy. ¹⁵ Typical MRI findings include altered marrow signal with decreased T1 signal, variable T2 signal, and intense enhancement (Figure 2). Variability in T2 signal is believed to be related to changes within the marrow space, with decreased T2 signal related to fibrosis and increased T2 signal related to ongoing inflammatory changes. ¹⁶

Figure 2.

Osteoradionecrosis. (a): A 60 year-old female with a history of oral cavity SCC treated with surgical resection and adjuvant radiation presenting with new pain. Axial CT image windowed for bone demonstrates a permeative pattern of trabecular loss involving the right mandible and erosive changes involving the buccal cortex (arrows) without associated soft tissue component. (b and c): A 69-year-old male with a history of nasopharyngeal carcinoma treated with chemoradiation presented for routine follow-up imaging. Sagittal T1W (b) and axial T2W (c) images demonstrate T1 hypointense signal in the clivus (b, arrow) with corresponding T2 hyperintensity (c, arrow), compatible with osteoradionecrosis.

The main differential considerations for ORN include recurrent tumor and osteomyelitis. All three entities can cause interruption of cortical margins. A measurable solid soft tissue mass or presence of a cystic mass is much more suggestive of tumor recurrence. ¹⁵ Some studies suggest that diffusion imaging may help to differentiate ORN from residual/recurrent tumor, with recurrent tumor demonstrating lower mean ADC values. ¹⁷ ORN can appear identical to osteomyelitis, and sometimes there can even be overlap in clinical findings. Treatment of ORN varies depending on clinical features but may include hyperbaric oxygen treatment, antibiotics, and surgical debridement, with the latter two being especially important if there is any suspicion for superimposed infection.

RT can also cause soft tissue necrosis, specifically manifesting as ulceration and cavitation. This, too, could potentially be mistaken for recurrent tumor. Necrotic tissue usually has a peripheral enhancement pattern without central or nodular enhancement (Figure 3(a)).^{18, 19} FDG uptake is often seen in soft tissue necrosis due to associated granulation tissue, although typically with less radiotracer avidity compared to recurrent tumor. Increased T2 signal and high ADC values are more common in soft tissue necrosis than carcinoma recurrence. Ultimately, while it is often possible to suggest soft tissue necrosis over recurrent tumor, close imaging follow-up or biopsy may be needed to exclude the latter.

Figure 3.

Soft tissue necrosis and carotid blowout. A 64-year-old-man with history of definitive chemoradiation (70 Gy) for p16-positive SCC 5 months earlier. Axial contrast enhanced CT (a) shows a partially air-filled necrotic cavity in the left parapharyngeal space communicating with the oral cavity (a, arrow), compatible with soft tissue necrosis. Ulceration extends laterally (arrow head), which is not uncommon with soft tissue necrosis. Left common carotid angiogram (b) obtained when the patient later presented with massive transoral hemorrhage demonstrates internal carotid stenosis (b, arrow) and pseudoaneurysm (b, arrowhead). Pathology specimens during subsequent surgical treatment (not shown) demonstrated necrosis with no viable tumor.

Carotid stenosis and blowout secondary to radiation

Carotid stenosis is a well-described complication of RT. The incidence of asymptomatic carotid artery stenosis after RT has been described as high as 33.7% at 8 years, with smoking, hyperlipidemia, and diabetes being contributing factors. ²⁰ This is greater than the prevalence in high risk groups without radiation therapy, for example, 7.5% of men older than 80 years of age had asymptomatic moderate carotid stenosis in one study. ²¹ Radiation therapy concomitantly increases the risk of stroke, specifically in patients under 55 years of age. ²² One study demonstrated a hazard ratio of 1.70 for development of ischemic stroke after radiation for head and neck malignancy compared to surgery alone. ²³ The mechanism of radiation-induced carotid stenosis after radiation therapy is complex. Radiation causes endotheliopathy of the vasa vasorum, producing presumptive transmural ischemia, intima-media fibrosis, endothelial cell loss, and decreased thrombomodulin expression in radiated carotid stenosis. ²⁴ These changes, when severe, can even lead to carotid artery rupture, also known as carotid blowout.

Carotid stenosis related to RT has a nonspecific imaging appearance, with combinations of soft and calcified plaque being seen depending on other patient risk factors. Nonetheless, it is important to identify progressive stenosis on serial imaging to guide appropriate stroke prevention measures, as well as potential intervention such as stenting or endarterectomy. Imaging in patients with carotid blowout may show focal pseudoaneurysm formation or luminal disruption (Figure 3(b)). ²⁵ Fortunately, carotid blowout is an uncommon RT complication; a recent study showed a small risk (2.7%) of carotid blowout in reirradiated patients with recurrent head and neck cancer, even when complete carotid encasement was present. ²⁶ While the mortality rate of carotid blowout can be as high as 30%, endovascular stenting has been shown to reduce this, highlighting the importance of early recognition on imaging. ²⁷

Enlarging thyroglossal duct cysts

Thryoglossal duct cysts are the most common congenital neck cyst. They usually occur in the midline and can exist anywhere between the foramen cecum and thyroid gland. Enlargement and increased contrast enhancement of thyroglossal duct cysts can occur after RT, presumably on an inflammatory basis. ²⁸ Radiation can also result in the apparently de novo development of these cysts. ²⁹ After enlarging, these cysts will typically eventually decrease in size (Figure 4).

Figure 4.

Enlarging thyroglossal duct cyst. A 68-year-old man presenting with p16-positive squamous cell carcinoma of the tongue base and right neck metastasis who underwent transoral resection, neck dissection, and adjuvant chemoradiation including 36 Gy. Pretreatment contrast enhanced CT (a) demonstrates a midline presumptive thyroglossal duct cyst which has enlarged on the contrast enhanced CT performed 4 months posttreatment (b). Regression in size and absence of FDG avidity are seen on the 1-year posttreatment PET/CT (c).

Imaging typically shows a midline cystic neck lesion with peripheral enhancement. Caution should be exercised to not mistake thryoglossoal duct cysts for new or progressive cystic nodal metastasis. Location is the most important distinguishing feature between thyroglossal duct cysts and cystic metastases because both entities can demonstrate wall enhancement and even FDG avidity. Radiologists must be aware of the history of RT, scrutinize prior imaging for subtle preexisting thyroglossal duct cysts, and use their knowledge of the embryologic course of the thyroglossal duct to differentiate the development of a thyroglossal duct cyst from new metastatic disease. ³⁰ In uncertain cases, aspiration or wall biopsy of the cyst can be done.

Radiation effects on the spine

Radiation-induced spinal tumors

RT to the spine can cause secondary tumors, either benign or malignant. Diagnosis can be challenging, and differential diagnosis includes recurrence of the original primary tumor, metastatic disease, osteomyelitis, and ORN. Clinically, patients may present with pain, swelling, pathologic fracture, or a new palpable mass. One study reviewed 30 cases of radiation-induced spinal malignancy from 23 articles. ³¹ The mean latency to diagnosis was 16.6 (+/-9.73) years. Mean survival after diagnosis was 11 months. Surgery is the mainstay of therapy for radiation-induced malignancies in the spine, largely because they tend to respond poorly to radiation and chemotherapy.

Sarcoma is the most common spinal RIM, typically occurring within bone (Figure 5). Post-radiation sarcomas comprise 1–2% of all bone sarcomas. ³² One estimate of the overall incidence in patients who received RT and survived at least 5 years is 0.2%. ³³ An estimated 1/3 of radiation-induced sarcomas arise in pre-existing lesions including lymphoma, osteosarcoma, giant cell tumor, or round cells tumors. ³⁴ Radiation-induced sarcomas tend not to occur in the most heavily irradiated and damaged areas of bone; rather, they tend to be found in the periphery of the radiation field. Histopathologically, osteosarcomas and spindle cell sarcomas predominate with fewer than 10% of cases being chondrosarcomas. ³⁵

Figure 5.

Radiation-induced osteosarcoma. A 59-year-old male presenting 7.5 years after radiation for tonsillar squamous cell carcinoma metastatic to lymph nodes in the neck. Axial T1W pre (a) and postcontrast (b) images at the level of C1 demonstrate marrow-replacing T1 hypointensity in the left C1 ring with an associated soft tissue mass (a, arrow) and corresponding enhancement (b, arrow). Axial CTat the level of C1 (c) demonstrates sclerosis within the left C1 ring and cloud-like osteoid matrix within the surrounding soft tissues (c, arrow). Finally, axial18 F-FDG PET/CT fused image (d) demonstrates that the lesion is markedly FDG avid. CT-guided biopsy (not shown) yielded high-grade osteoblastic osteosarcoma.

Typical imaging features of RIM of bone include destructive, enhancing lytic lesions with an associated soft tissue mass.^13,36,37 Lesions may also be mixed lytic-sclerotic or sclerotic. Expansion of the bone, periosteal reaction, osteoid matrix, and pathologic fractures may or may not be present. Adjacent bone not involved by the tumor may demonstrate radiation osteitis. When comparison films are lacking, MRI can be extremely valuable and allows for the evaluation of soft tissue extension. Biopsy is often required for diagnosis, especially to differentiate primary tumor recurrence. ¹³

Fortunately, the majority of radiation-induced spinal tumors are not malignant. Osteochondromas are the most common benign radiation-induced secondary bone tumor. Most cases of radiation-induced osteochondromas have been reported in children with prior radiotherapy for Wilm’s tumor or neuroblastoma, the majority of whom were likely treated before 6 years of age. ³⁴ The incidence of radiotherapy-induced osteochondromas in children is approximately 5–12%. ³⁸ The latency between radiotherapy and diagnosis is highly variable and impacted by lesion site, associated pressure/mass effect, and if discovery is incidental on follow-up imaging. ³⁴ The behavior and treatment are similar to spontaneous osteochondromas, with malignant degeneration only rarely reported. On imaging, radiation-induced osteochondromas are indistinguishable from those arising spontaneously, typically appearing as an exostosis with corticomedullary continuity (Figure 6). ¹³

Figure 6.

Radiation-induced osteochondroma. An 18-year-old male presenting nearly 10 years after spinal radiation for medulloblastoma for routine follow-up imaging. Sagittal T2W fat suppressed (a), sagittal T1W (b), and axial T2W (c) from a thoracic spine MRI demonstrate an expansile osseous excrescence at the inferior aspect of the T7 spinous process (a–c, arrows) with surrounding T2 hyperintensity representing a thin cartilage cap. The lesion signals similarly to the adjacent bone on all sequences. Coronal non-contrast CT image (d) confirms that this lesion has corticomedullary continuity.

Radiation myelopathy

Radiation-induced myelopathy refers to injury to the spinal cord from radiation and can be transient or chronic. Transient radiation myelopathy, also called early injury, is a self-limiting phenomenon diagnosed clinically by development of Lhermitte’s sign after radiation.^39–41 It is most commonly associated with head/neck cancer RT or mantle radiation.^39–41 Although symptomatic, it typically resolves within 6 months and is not definitively associated with chronic sequelae. In these cases, MRI is normal but can help exclude other more sinister pathologies. ³⁹

Chronic radiation myelopathy, also referred to as delayed radiation myelopathy, is the more clinically relevant syndrome, as it can have long-term sequelae that do not spontaneously resolve.^42–44 Usually, chronic radiation myelopathy starts 9–18 months after radiation and progresses over months.^{42, 45} Symptom progression varies, ranging from minor neurologic deficits to more severe manifestations such as spastic paraplegia or complete Brown-Sequard syndrome. ⁴⁶ The risk and severity of cord injury depend on radiation dose and radiotherapy type. Pathology studies have shown that these patients have damage to white matter tracts and vasculature with glial reaction. White matter lesions result from demyelination and nerve fiber destruction with subsequent coagulative or liquefactive necrosis and Wallerian degeneration. Vascular lesions tend to develop later than white matter lesions and can have various appearances including hyaline degeneration, perivascular edema, and telangiectasia, which could be related to VEGF expression alteration.^47–49

MRI is the most commonly used and helpful imaging tool. The affected segment of the cord shows T2 hyperintensity and T1 hypointensity with variable amounts of cord expansion, thought to be due to edema and white matter necrosis (Figure 7). ⁴² Although white matter is affected more than gray in pathologic evaluation, T2 hyperintensity tends to involve the central cord. Less commonly, dorsal-predominant and holocord appearances can be seen. ⁴⁴ Lesions are often longitudinally extensive, although this depends on the size of the radiation field. Vascular damage and glial reaction result in patchy cord enhancement in about half of the cases. ⁴⁴ On follow-up imaging, cord edema and enhancement tend to improve, with some cases developing cord atrophy. ⁴⁴ Given the high radiation dose needed to cause radiation myelopathy, fatty marrow signal changes should be present at the vertebral bodies spanning the cord signal abnormality. Although the appearance could mimic other longitudinally extensive lesions such as sarcoidosis, neuromyelitis optica spectrum disorder, spinal dural arteriovenous fistula, or cord infarction, patient history and temporal evolution of the findings can increase diagnostic certainty.

Figure 7.

Radiation myelopathy. A 67 year-old male presenting 8 years after radiation for esophageal adenocarcinoma with stepwise progressive thoracic myelopathy and sensory loss up to a T4-T6 level. Sagittal and axial T2W images (a and c) and post contrast sagittal T1W image (b) demonstrate multiple T2 hyperintense lesions throughout the thoracic cord (a and c, arrows) with patchy enhancement (b, arrows). Symptoms stabilized and cord abnormalities resolved with high dose steroid treatment (not shown).

Vertebral compression fractures following radiation treatment

Vertebral compression fractures (VCFs) occur or progress in radiated vertebral bodies due to a combination of tumor erosion and radiation effects in the bone. Pre-existing VCF, posterior cortex erosion, lytic disease, and high Spine Instability Neoplastic Scores suggest a higher rate of vertebral erosion from the tumor and are associated with a greater risk of post-radiation fracture.^50,51 Higher dose per fraction has been correlated with a higher rate of VCF, suggesting a negative effect of radiation on vertebral structural integrity. This is supported by animal and pathologic studies showing cortical thinning and an antiangiogenic effect from radiation.^52–54

Reported rates of VCF following RT vary, ranging from 6 to 39%, ⁵⁰ which may be due to their typically asymptomatic nature. However, due to the high rate of progressive compression, vertebral augmentation may be prudent even in asymptomatic cases if there is a concern for vertebral canal compromise with further collapse (Figure 8).

Figure 8.

Radiation-induced vertebral compression fracture. A 61 year-old male presenting with acute back pain 1 year after radiation to an L2 renal cell carcinoma metastasis. T1W sagittal MRI image (a) shows an irregular fracture plane without substantial height loss (a). Postcontrast sagittal T1W image (b) shows treated tumor with mild peripheral enhancement (b) with a patent spinal canal on T2W imaging (c). This was managed conservatively. Three years after radiation treatment, the patient developed worsening low back and leg pain. MRI shows progression of the L2 VCF with increased marrow edema on sagittal T1W imaging (d), edema-related enhancement on post contrast T1W imaging with fat saturation (e), and severe spinal canal narrowing due to retropulsion of inferior L2 vertebral body on T2W imaging (f). Patient underwent decompression and posterior instrumented fusion, with concurrent L2 biopsy that was negative for tumor. Note the post-radiation fatty marrow signal changes in L1–L3 vertebral bodies in T1W imaging (a, d).

For imaging evaluation of post-radiation VCF, CT and MRI are complementary. Osseous destruction, fracture planes, and distinguishing lytic/blastic/mixed nature of the tumor are best demonstrated by CT; MRI better demonstrates the degree of spinal canal narrowing and fatty marrow changes in previously radiated vertebrae. Additionally, MRI is especially helpful in assessing the extent of residual tumor in the bone and surrounding soft tissue. Variable radiotracer uptake along the fracture plane can be seen with F-18 FDG PET/CT, which can be helpful when assessing for recurrent disease.

The primary differential consideration for post-radiation VCF is tumor progression causing pathologic fracture. In this regard, MRI is more sensitive than CT, ⁵⁵ but in the setting of new or progressive compression fracture, the reactive marrow edema and enhancement can confound assessment of potential tumor margin (Figure 8). Moreover, response to RT is not immediate and varies depending on tumor type, ^55-57 typically taking several months. Therefore, seeing a component of tumor at any time post treatment does not correlate to treatment failure unless prior imaging is available for comparison. PET/CT can help assess response in cases where the original tumor had avid radiotracer uptake, but reactive uptake in the fracture may confound evaluation if no prior imaging is available. PET/CT can be particularly helpful in cases where the MRI is markedly degraded by hardware artifact from prior fusion.

Treatment depends on symptomatology, degree of bony erosion, and the risk of fracture progression, which are assessed using the Spine Instability Neoplastic Score. In addition, the degree and risk of progressive spinal canal narrowing from the progressive VCF need to be evaluated. Patients with severe narrowing may undergo surgical decompression, but select patients with pain, high instability scores, or high risk of spinal canal narrowing can be referred for vertebral augmentation, which has been shown to improve pain and quality of life. ⁵⁸ In the setting of recent radiation treatment, thermal ablation immediately prior to augmentation can prevent displacement of the tumor volume into the epidural or paravertebral space, which is a major complication that could result in spinal canal narrowing and complicate future treatments. ⁵⁹

Conclusion

Radiation therapy has advanced cancer survival in recent decades. However, radiation therapy continues to have a wide variety of potential complications, ranging from mild to severe. A strong understanding of these potential manifestations, their typical clinical presentation, and their imaging findings will allow radiologists to appropriately diagnose these conditions in the setting of prior RT. Prompt recognition of these complications is important because many affect patient management or can be potentially mistaken for alternative diagnoses.

Appendix

Abbreviations

ORN

osteoradionecrosis

RIM

radiation-induced malignancy

RT

radiation therapy

SCC

squamous cell carcinoma

VCF

vertebral compression fractures

ORCID iDs

John C Benson https://orcid.org/0000-0002-4038-5422

Ajay A Madhavan https://orcid.org/0000-0003-1794-4502

Derek R Johnson https://orcid.org/0000-0002-4217-5517