What is the management plan for a post-menopausal female with a history of endometrial cancer, who received radiation therapy (20 Gy in 5 fractions) to the base of skull structures and calvaria bones 6 months ago, and now presents with diplopia and consistent radiology findings?

Management of Recurrent Skull Base Metastasis from Endometrial Cancer

This patient requires systemic chemotherapy with carboplatin and paclitaxel as the primary treatment, with consideration for additional palliative radiation if symptomatic progression occurs despite prior radiotherapy to the same site.

Clinical Context and Disease Classification

This presentation represents Stage IVB endometrial cancer (distant metastases to skull base/calvaria) with disease progression after palliative radiotherapy 1. The recurrence of diplopia with identical radiology 6 months post-radiation indicates either:

• Radioresistant disease that failed to respond adequately to the initial 20 Gy in 5 fractions
• Progressive metastatic disease requiring systemic therapy 2

The prior radiation dose (20 Gy/5 fractions) was palliative in intent, and re-irradiation to the same site carries significant risk of toxicity to critical skull base structures 1.

Primary Management Strategy: Systemic Chemotherapy

Initiate combination chemotherapy immediately as this addresses both the symptomatic skull base disease and potential occult metastases elsewhere 1, 2:

• Carboplatin (AUC 5-6) plus paclitaxel (175 mg/m²) every 3 weeks is the standard regimen for Stage IV endometrial cancer 1, 2
• This combination demonstrates significant single-agent objective response rates in metastatic disease 1
• Alternative regimen: Doxorubicin with cisplatin and paclitaxel (with bone marrow support) significantly improves progression-free survival and overall survival, though at the cost of higher toxicity 1

The carboplatin-paclitaxel combination is preferred due to better tolerability while maintaining efficacy 1.

Role of Additional Radiation Therapy

Re-irradiation should be approached cautiously given the recent prior treatment to the same anatomic site 1:

• The patient received 20 Gy in 5 fractions only 6 months ago to skull base structures
• Re-irradiation carries substantial risk of late complications including cranial neuropathies, brainstem injury, and temporal lobe necrosis 1
• If diplopia worsens acutely despite chemotherapy, palliative re-irradiation with stereotactic techniques may be considered for focal symptomatic control, but cumulative dose constraints must be respected 1

Symptomatic Management of Diplopia

While systemic therapy takes effect:

• Ophthalmology consultation to assess cranial nerve involvement (likely CN VI palsy given skull base location)
• Prism glasses or eye patching for temporary diplopia relief
• Corticosteroids (dexamethasone 4-8 mg daily) may provide temporary symptom relief by reducing perimetastatic edema, though evidence is limited in this specific context

Monitoring and Follow-Up Strategy

Close surveillance during chemotherapy is essential 1:

• Clinical assessment every 3-4 weeks during active chemotherapy to evaluate diplopia progression and treatment response 1
• MRI brain/skull base after 2-3 cycles of chemotherapy to assess radiographic response
• Monitor for chemotherapy-related neuropathy, which occurs in 15-40% of patients receiving taxanes and may compound neurologic symptoms 1

Prognosis and Treatment Goals

Stage IVB endometrial cancer has poor prognosis, with treatment focused on:

• Palliation of symptoms (diplopia in this case) 1
• Prolonging survival where possible with systemic therapy 1, 2
• Maintaining quality of life as the primary outcome measure 1

The combination of doxorubicin with cisplatin and paclitaxel significantly improves progression-free survival and overall survival compared with radiotherapy alone in Stage IV disease, though toxicity must be carefully weighed 1.

Critical Pitfalls to Avoid

• Do not delay systemic therapy while pursuing additional local treatments—metastatic disease requires systemic control 1, 2
• Avoid re-irradiation without careful dosimetric planning and multidisciplinary discussion given recent prior treatment 1
• Do not overlook performance status assessment—maximal surgical cytoreduction or aggressive therapy is only appropriate in patients with good performance status 1, 2
• Monitor for platinum-induced neuropathy which could worsen diplopia or cause additional neurologic symptoms 1