What is the best management approach for a patient with a history of Ewing sarcoma (ES) of the leg, treated with chemotherapy (chemo) and radiation 7 years ago, who developed recurrence with lower limb paraplegia and now complains of burning sensation from the lower back to the limbs after decompression spinal cord surgery?

Management of Neuropathic Pain in Recurrent Ewing Sarcoma with Persistent Paraplegia

This patient requires immediate initiation of neuropathic pain medication, specifically pregabalin 150-600 mg/day, combined with palliative radiotherapy to the symptomatic spinal sites, while acknowledging that the overall prognosis remains poor with recurrent disease and the focus should shift toward quality of life rather than cure.

Understanding the Clinical Context

This patient presents with recurrent Ewing sarcoma 7 years post-treatment, which carries an extremely poor prognosis. Recurrent disease is associated with poor outcomes, with patients relapsing systemically or locally generally considered to be in a palliative situation 1. The burning sensation from lower back to limbs represents neuropathic pain secondary to spinal cord involvement and surgical intervention, requiring specific management distinct from oncologic treatment.

Primary Management: Neuropathic Pain Control

First-Line Pharmacologic Therapy

Pregabalin should be initiated as first-line treatment for neuropathic pain associated with spinal cord injury, starting at 150 mg/day with flexible dose titration up to 600 mg/day based on response and tolerability 2. The FDA label demonstrates that:

• Treatment with pregabalin 150-600 mg/day statistically significantly improved pain scores in spinal cord injury-associated neuropathic pain 2
• Some patients experienced pain decrease as early as week 1, which persisted throughout studies 2
• The regimen consists of a 3-4 week dose adjustment phase followed by maintenance dosing 2

Patients can continue opioids, non-opioid analgesics, antiepileptic drugs, muscle relaxants, and antidepressant drugs if doses are stable 2.

Oncologic Management: Palliative Approach

Local Palliative Radiotherapy

Radiotherapy should be considered for palliation of the symptomatic spinal recurrence sites 1. While the guidelines emphasize that local control with radiotherapy and/or surgery may help palliate local symptoms in recurrent disease, the contribution to long-term disease control has not been robustly evaluated 1.

• Radiotherapy may palliate inoperable sites in recurrent disease 1
• Supplemental irradiation of symptomatic bone sites is usually indicated in metastatic/recurrent settings 1

Systemic Therapy Considerations

For recurrent Ewing sarcoma, the rEECur trial established the following hierarchy of chemotherapy regimens in order of decreasing efficacy: high-dose ifosfamide, topotecan and cyclophosphamide, irinotecan and temozolomide, and gemcitabine and docetaxel 1. However, with the exception of patients with limited relapse after a long disease-free interval, patients relapsing systemically or locally should be considered to be in a palliative situation 1.

Given this patient's 7-year disease-free interval and isolated spinal recurrence, chemotherapy options include:

• High-dose ifosfamide (highest efficacy but significant myelotoxicity and risk of encephalopathy/renal toxicity) 1
• Topotecan and cyclophosphamide (preponderance of myelotoxicity and neutropenic fever) 1
• Irinotecan and temozolomide (gastrointestinal toxicity profile) 1

Multi-targeted tyrosine kinase inhibitors (pazopanib, cabozantinib, regorafenib) have shown single-agent activity in relapsed Ewing sarcoma 1. However, decision-making must be balanced with potential toxicity and need for repeated hospital visits in a disease setting where median overall survival is approximately one year 1.

Critical Decision Algorithm

Step 1: Immediate Symptom Management

• Start pregabalin 150 mg/day, titrate over 3-4 weeks to 300-600 mg/day based on pain response 2
• Continue or add opioids for breakthrough pain as needed 2

Step 2: Assess Disease Burden and Patient Goals

• Obtain restaging imaging (MRI spine, CT chest, bone scan) to define extent of recurrence 3
• Have explicit goals-of-care discussion acknowledging poor prognosis 1

Step 3: Local Control Decision

• If patient desires aggressive treatment and has isolated spinal recurrence: Consider palliative radiotherapy to symptomatic sites 1
• If widespread disease or patient prioritizes quality of life: Focus on symptom management alone

Step 4: Systemic Therapy Decision

• If disease-free interval >2 years AND isolated recurrence AND patient accepts toxicity: Consider chemotherapy (high-dose ifosfamide or topotecan/cyclophosphamide) 1
• If patient declines intensive chemotherapy: Consider tyrosine kinase inhibitor trial or supportive care only 1
• Enroll in clinical trials if available 1

Common Pitfalls and Caveats

The most critical pitfall is pursuing aggressive oncologic treatment without addressing the neuropathic pain, which significantly impacts quality of life. The burning sensation will not resolve with chemotherapy or radiotherapy to the tumor alone—it requires specific neuropathic pain management 2.

Another common error is offering false hope about cure. Recurrent Ewing sarcoma, particularly with spinal involvement causing paraplegia, has extremely poor outcomes with 5-year survival of 10-45% 1. The paraplegia did not resolve after decompression surgery and is unlikely to improve, representing permanent neurologic deficit 1.

Avoid incomplete surgery followed by radiotherapy in recurrent disease, as this approach is not superior to radiotherapy alone and should be avoided 1.

Do not delay pain management while pursuing oncologic workup—pregabalin can be started immediately and titrated while staging studies are completed 2.

Quality of Life Focus

Given the poor prognosis of recurrent disease, supportive care should be incorporated into treatment from the beginning 1. This includes:

• Aggressive neuropathic pain management with pregabalin as first-line 2
• Physical therapy and rehabilitation for paraplegia management
• Psychological support for patient and family
• Palliative care consultation early in the disease course 1

The median overall survival for recurrent Ewing sarcoma is approximately one year, making quality of life the paramount consideration over aggressive treatment that may cause significant toxicity without meaningful survival benefit 1.