J.Sales-Llopis

Neurosurgery Department, General University Hospital Alicante, Spain

Craniopharyngiomas, especially their cystic forms, pose unique management challenges due to their proximity to critical neurovascular structures. Intracystic therapies offer a minimally invasive alternative to repeated surgical interventions. Over the past decade, interferon-alfa-2a/2b emerged as a viable intracystic treatment due to its anti-proliferative and immune-modulating properties, coupled with low toxicity. However, discontinuation of commercial availability prompted the search for alternatives.

Hedrich et al. describes a retrospective case series, including five patients with intracystic peginterferon alfa-2a for cystic craniopharyngioma treatment according to an innovative care protocol. After initial CP cyst aspiration, peginterferon alfa-2a was injected once per week via an Ommaya reservoir for 6 weeks followed by response assessment with MRI.

Patients' age ranged from 4 to 54 years (four patients <12 years, one adult patient). Intracystic therapy with peginterferon alfa-2a was tolerated well by all five individuals without any major toxicities and resulted in cyst shrinkage in all of the five patients. The importance of a permeability study prior to commencing intracystic therapy became apparent in one patient who suffered from cyst leakage.

Intracystic treatment with peginterferon alfa-2a was found to be a tolerable and efficacious treatment modality in patients with cystic craniopharyngioma. This experience warrants further research with a larger number of patients with measurement of long-term efficacy and safety outcomes ¹⁾.

The authors propose peginterferon alfa-2a, a pegylated form with extended half-life and established safety profile in other indications, as a substitute, presenting a retrospective case series evaluating its feasibility and safety.

Study Design and Methodology

- Design: Retrospective case series

- Sample: 5 patients (age 4–54; 4 children, 1 adult)

- Protocol: After initial cyst aspiration, peginterferon alfa-2a was administered weekly for 6 weeks via an Ommaya reservoir.

- Follow-up: MRI for response assessment

- Pre-treatment: Permeability study was highlighted as essential following one adverse case of leakage.

🔎 Strengths:

- Innovative use of peginterferon alfa-2a to fill a therapeutic gap.

- Uniform protocol across cases.

- Clear documentation of safety and early efficacy.

- Broad age range increases generalizability.

⚠️ Limitations:

- Very small sample size (n=5) limits statistical validity.

- Retrospective nature introduces potential bias and lacks standardized outcome metrics.

- Short-term follow-up; no data on recurrence, endocrine impact, or long-term survival.

- No comparator group (e.g., standard interferon alfa-2a or surgery-only) limits interpretation of relative efficacy.

Results

- Safety: No major toxicities reported in any patient.

- Efficacy: Cyst shrinkage achieved in all five patients.

- Complication: One patient experienced leakage, underscoring the need for a permeability test.

The data supports the hypothesis that peginterferon alfa-2a is a safe and potentially effective intracystic agent in this context.

Discussion and Clinical Relevance

This study provides preliminary real-world evidence that peginterferon alfa-2a can serve as an effective intracystic treatment option for cystic craniopharyngiomas, particularly important in the wake of discontinued access to interferon alfa-2a. The lack of significant toxicity is encouraging, especially in pediatric patients.

However, due to the small number of cases and lack of long-term outcome data, the findings should be interpreted as hypothesis-generating rather than practice-changing. Further research in prospective, multi-institutional trials with larger cohorts is warranted.

Conclusion Hedrich et al. offer a promising alternative approach for managing cystic craniopharyngiomas using peginterferon alfa-2a. The treatment appears feasible, safe, and effective in the short term. Yet, the study's limitations — particularly its size and retrospective design — mean that broader validation is essential before widespread clinical adoption.

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🧠 Flowchart Logic

Is the patient under 5 years old?

  → Yes → ❌ Avoid radioisotopes

  → No → ✅ Radioisotopes may be considered

Is radiation facility & radiopharmacy available?

  → Yes → Consider radioisotopes

  → No → Proceed to next

Is cyst accessible with Ommaya and permeability confirmed?

  → No → ❌ Intracystic therapy not recommended

  → Yes → Proceed to next

Is neurotoxicity a major concern (e.g., very young child, hypothalamic proximity)?

  → Yes → ✅ Prefer Peginterferon alfa-2a

  → No → Proceed to next

Institutional experience with bleomycin?

  → Yes → Consider bleomycin

  → No → Consider peginterferon alfa-2a

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This case report is an 8-year-old child presenting with a sellar/suprasellar cystic lesion suggestive of craniopharyngioma. Following transfer from a referring hospital, the patient underwent a comprehensive diagnostic and stabilization process including mechanical ventilation, anticonvulsant and steroid therapy, and preparation for potential neurosurgical intervention. This case highlights the early multidisciplinary approach to pediatric intracranial cystic masses, focusing on timely imaging, supportive care, and surgical planning.

An 8-year-old school-aged child (30 kg) was transferred from a Hospital after brain MRI revealed a sellar/suprasellar cystic lesion suggestive of a craniopharyngioma.

On admission (24/03), the patient was sedated with propofol following discontinuation of midazolam the night before.

He remained under conventional analgesia.

Neurological exam: isochoric, reactive pupils.

Treatment ongoing with levetiracetam and dexamethasone.

An EEG was scheduled and was pending at the time of assessment.

🫁 Respiratory:

• Mechanical ventilation (FiO₂ 0.4)
• O₂ saturation: 100%
• VBG: pH 7.36, pCO₂ 39 mmHg, lactate 0.8 mmol/L, base excess –3, HCO₃⁻ 21.6 mmol/L

❤️ Cardiopulmonary:

• Regular rhythm, no murmurs
• Preserved vesicular breath sounds

🌡️ Temperature & Infection:

• Afebrile in past 24h
• Receiving cefuroxime