A. Different therapeutics modalities:

Fig 2: Different therapeutic modalities.

• Therapeutic management of nasopharyngeal carcinoma relies on radiotherapy, given the tumor's high sensitivity to radiation.
• Exclusive radiotherapy, long considered the standard treatment, achieves local control rates of approximately 50–75% for T3–T4 stages. However, intensity-modulated radiotherapy (IMRT) offers excellent dosimetric coverage while providing better protection to at-risk organs, making it the preferred approach.
• Chemotherapy is an adjuvant treatment to IMRT in advanced stages, improving overall survival rates of 75% or higher at five years.
• Meanwhile, surgery plays a limited role due to the anatomical inaccessibility of this region and is generally reserved for cases of recurrence in advanced stages.

B. Surveillance and Protocol :

The primary goal of surveillance is early detection of tumor recurrence and monitoring of post-therapeutic complications. Imaging plays a major role in this process, relying mainly on MRI and PET-CT.

     I/ Surveillance rhythm:

• MRI should be performed 3 months after the end of treatment.
• Subsequent imaging should occur every 6 months or when there is a clinical symptom.

     II/ Imaging Modalities:

1. CT-Scan: 
   • Sensitive to detect bone complications.
   • Limited in differentiating residual tumor, recurrence, and post-radiation changes.
2. MRI: 
   • MRI is superior to  CT in assessing tumor extension, skull base involvement, spinal cord evaluation, and detecting bone metastases.
   • Limitations: Claustrophobia, metallic implants.
3. PET-SCAN: 
   • Detection of tumor residues and recurrences → sensitivity and specificity > CT and MRI.
4. Flexible Endoscopy :

• • The most sensitive modality to confirm mucosal recurrence, but could miss submucosal recurrences or residual tumors.
  • Post-radiation mucositis, crusts, and limited mouth opening may hinder the examination.

     III/ MRI protocol:

Fig 3: MRI protocol.

C. Post-therapeutic aspects:

• • Complete remission: Complete remission is defined as the disappearance of the entire nasopharyngeal process as well as cervical lymphadenopathies, with no evidence of residual tumor.
    

    Fig 4: 43-year-old patient treated for nasopharyngeal carcinoma classified as T2N1M0. Notice that, following radiotherapy, the thickening of the posterior and lateral walls, predominantly on the right side, which showed diffusion restriction and enhancement after contrast injection, has completely resolved.

• • Residual tumor: Defined as the persistence of the tumor after the treatment.
    

    Fig 5: A 16-year-old patient under follow-up for UCNT of the nasopharynx (yellow arrow) was treated with concurrent chemoradiotherapy (CCR). After treatment, a subtotal regression of the extensive nasopharyngeal. Thickening was observed, with residual thickening persisting only at the level of the left posterolateral wall (green arrow), corresponding to a residual tumor.
  • Recurrence: Differentiating between tumor recurrence and post-therapeutic changes remains challenging, as both can present with contrast enhancement. PET scans are particularly valuable for distinguishing between these two possibilities, as they provide metabolic information that can help confirm or rule out active tumor recurrence. MRI with advanced sequence can also help.
    

    Fig 6: A 30-year-old patient, monitored for nasopharyngeal undifferentiated carcinoma (UCNT), underwent radiochemotherapy. Post-treatment, the thickening had resolved; however, a follow-up MRI at one year revealed an extensive local recurrence and lymph node involvement.
    Recurrence may also manifest exclusively as the development of lymphadenopathies.
    

    Fig 7: A 23-year-old patient, monitored for nasopharyngeal undifferentiated carcinoma (UCNT), underwent radiotherapy. Post-treatment MRI showed complete remission, but the follow-up MRI revealed the appearance of retropharyngeal lymphadenopathy with strong contrast enhancement.
  • Post-therapeutic aspects:
    • In addition to assessing these types of responses, It is crucial to assess adjacent structures for radiotherapy-related side effects, including subcutaneous tissues, glands, bones, sinuses, blood vessels, muscles, and brain regions, to avoid missing complications.
    • We can distinguish between early and late effects.
      

      Fig 8: Post-radiation effects.

     I. Early effects:

1. Glandular changes: 
   • Glandular involvement primarily manifests as salivary gland dysfunction. Most patients after radiation therapy will present with dry mouth or xerostomia.
   • On MRI, at an early stage, this appears as oedematous infiltration with heterogeneous signal intensity and enhancement of the salivary gland.
     

     Fig 9: MRI in axial T2W and axial T1W after injection sequences showed different morphological changes in the salivary glands after radiation therapy. In the early stage, there is an oedematous infiltration with heterogeneous signal intensity and enhancement of the salivary glands. At a late stage, there is a fatty infiltration and atrophy of the glands.
   • At the late stage, it may present as atrophy or fatty infiltration, either unilateral or bilateral, with compensatory hypertrophy.
     

     Fig 10: MRI in axial T2W, axial and coronal T1W after injection sequences showed fatty infiltration of the left parotid gland with atrophy and compensatory hypertrophy of the right gland.
2. Sinus : 

   There is reactive mucosal edema leading to meatal obstruction after radiotherapy, which can result in sinusitis or otomastoiditis, progressing to chronicity.

   On MRI, this presents as a sinus or mastoid cavity filling with T2 hyperintensity fluid, with or without marginal contrast enhancement.

   

   Fig 11: MRI in axial and coronal T2W sequences showed bilateral mastoid air cells completely occupied by T2 hyperintense fluid (A and B), but also maxillary sinus (A and C) and frontal sinus (C).

   Other findings: Choanal atresia, paranasal sinus mucoceles, or polyps.

   

   Fig 12: MRI through the paranasal sinus in axial DWI (A), axial T2W (B), sagittal T1 (C), and axial T1W after injection (D), showing complete opacification of the left maxillary antrum. The content is isointense on T1, intermediate signal centrally, and high signal peripherally on T2 and demonstrates only peripheral enhancement. The sinus is expanded slightly compared to the left one.

   In the case of nasopharyngeal tumors invading the nasosinus system, tumor recurrence can occur exclusively in the sinus, without involving the nasopharyngeal mucosa.

3. Musculoskeletal :
   • Radiation-induced fatty replacement of the bone marrow is a common finding at the boundaries of the irradiation field, particularly in the sphenoid bone at the skull base and the proximal cervical spine. In some cases, bone lysis may occur, leading to a bucco-sinusal communication.
     

     Fig 13: A: Brain CT scan in axial bone window showing a mottled aspect of the right sphenoid bone. B: Cervical MRI in sagittal T1W sequence showing fatty replacement of the bone marrow. C: Cervical MRI in coronal T2W sequence showing bucco-sinusal communication.
     Over time, progression to osteoradionecrosis is possible.
   • The muscles are not spare. Limited mouth opening is frequently observed, secondary to the involvement of the muscles of mastication,
     

     Fig 14: MRI in axial and coronal T2W sequences shows atrophy and masticatory muscle signal change.
     the mandibular nerve (rare), or the bone. MRI may appear normal in 1/3 of cases.
4. Nasopharyngeal mucosa:

• The mucosa of the nasopharynx tends to thicken, indicating post-radiation edema, fibrosis (mature or immature), or telangiectasia.
  

  Fig 15: MRI aspect of the nasopharyngeal mucosa after radiotherapy.
• MRI is crucial in differentiating between mature fibrosis and tumor recurrence. However, the real diagnostic challenge lies in distinguishing immature fibrosis from recurrence.
• Any enlarging post-treatment soft-tissue mass, new deep lesion, or intracranial enhancement should raise concern for recurrent disease.
• Early Stage: Thickening and mucosal enhancement can be observed, which is difficult to distinguish from recurrence.
• Late Stage: This progresses to mature fibrosis or mucosal atrophy, often accompanied by necrosis and/or ulceration, which makes distinguishing it from malignant lesions challenging.
  

  Fig 16: Late-stage aspect of nasopharyngeal mucosa: atrophy.
   

     II. Late effects:

1. Temporal radio-necrosis: 
   • The nervous system is most commonly affected in the temporal lobe due to its proximity to the irradiation field. Temporal lobe necrosis, a severe and disabling condition, typically occurs 1.5 to 13 years after treatment and is primarily dependent on the radiation dose.
   • It is often asymptomatic, leading to a radio-clinical mismatch.
   • MRI can reveal signal abnormalities in the white or gray matter,
     

     Fig 17: Brain MRI revealing white and grey matter signal abnormalities.
      most frequently in the infero-medial part of the temporal lobe, which may be unilateral or bilateral. Over time, this may progress to temporal lobe atrophy, leading to clinical symptoms.
     

     Fig 18: Brain MRI showing signal abnormalities of the right temporal lobe, evolving towards atrophy.
   • Another aspect can be found such as a necrotic or cystic lesion which may become hemorrhagic, and either progress or resolve over time.
     

     Fig 19: Left temporal lobe radionecrosis.
     In severe cases, this can lead to macrocystic encephalomalacia.
     

     Fig 20: MRI showing intracranial extension of the tumor (yellow arrow) with cystic lesion with fluid content and fluid/blood level, surrounded by a hypointense rim on all sequences consistent with hemosiderin deposition. (green arrow) This lesion presents peripheral enhancement and is surrounded by extensive edema, with a mass effect on the ipsilateral lateral ventricle, causing a midline shift. (blue arrow).
     

     Fig 21: The patient was treated with steroids. Notice the reduction in size, bleeding, then parenchymal atrophy.
   • In cases of extensive white matter involvement, a mass effect can also occur.
2. Nerve palsy: 
   • Cranial nerves are radioresistant, so post-radiation paralysis remains uncommon. It can occur 2 to 7 years after the end of treatment. It may be due to either direct or indirect damage caused by vascular injury to the vasa nevorum or by nerve compression resulting from radiation-induced perineural fibrosis.
   • Hypoglossal nerve is the most frequently affected, followed by the vagus nerve and the recurrent laryngeal nerve.
   • On imaging, this may present as perineural fibrosis or signal abnormalities in the nerve itself. However, more commonly, signs of muscle denervation are observed, such as asymmetry of the hemilingual muscles or atrophy of the sternocleidomastoid (SCM) and trapezius muscles.
     

     Fig 22: MRI aspect of hypoglossal (up) and spinal accessory (down) nerve injury.
3. Osteoradionecrosis: 
   • This most commonly appears one year after radiotherapy and is typically located at the skull base, cervical spine, or mandible. It results from post-radiation fibrosis, which leads to bone destruction accompanied by vascular damage. This process causes tissue degradation, necrosis, and bone sequestration.
   • On CT, it manifests as areas of mixed osteolysis and sclerosis at the irradiation site. Fragmented appearance and exfoliation of necrotic bone may also be observed. Peri-lesional soft tissue inflammation can mimic osteomyelitis or tumor recurrence.
     

     Fig 23: A facial CT scan of the bone window showed mandibular bone destruction: osteoradionecrosis.
   • MRI findings include low-to-intermediate heterogeneous T1 signal and intermediate-to-high T2 medullary signal. Adjacent soft tissue mass can also mimic tumor recurrence or concomitant osteomyelitis, making the differential diagnosis challenging.
4. Radiation-induced tumor: 
   • Rare tumors, with poor prognosis. They frequently occur around the maxillary region, including the palate, maxillary sinus, alveolar process, and nasal cavity. The most common histological types are:
     • Radiation-induced sarcomas:  5 to 10 years after irradiation, developing in high-dose radiation areas such as the maxillary bone or the skull base. Imaging findings can vary, but a characteristic destructive, rapidly progressing mass with a heterogeneous signal, with or without calcifications, is often noted.
     • Squamous cell carcinoma: Commonly arises in the temporal bone and external auditory canal, occurring 10 to 15 years after irradiation. It can also develop in low-dose irradiation areas and may affect peripheral regions like the temporal bone.
   • Diagnostic criteria for tumor associated with irradiation:
     

     Fig 24: Radiation-induced tumor.
5. Vessel involvement: Rare (including the exacerbation of atherosclerosis, dissection, or a pseudoaneurysm).
   

   Fig 25: Vessel involvement.