What is the treatment approach for adamantinomatous craniopharyngioma?

Treatment Approach for Adamantinomatous Craniopharyngioma

For unresectable or postoperative persistent adamantinomatous craniopharyngioma, proton beam therapy is recommended as postoperative radiotherapy, providing equivalent local control and survival outcomes to conventional X-ray therapy with similar therapeutic efficacy. 1

Primary Treatment Strategy

Surgical Resection

• Gross total resection (GTR) or near-total resection (NTR) should be the initial goal when technically feasible, as residual tumor volume directly correlates with recurrence rates 1
• GTR achieves recurrence rates of approximately 3.8%, compared to 9.4% for NTR and 27.6% for subtotal resection (STR) 1
• However, the lower recurrence risk with GTR must be weighed against higher risks of facial nerve dysfunction and lower hearing preservation rates in large tumors 1
• For large tumors where complete resection risks significant morbidity, intentional NTR or STR followed by radiotherapy is an acceptable strategy 1

Surgical Considerations

• The surgical procedure should be designed to resect all gross tumor with adequate tumor-free surgical margins 1
• En bloc resection should be attempted whenever feasible 1
• Median time to recurrence after GTR is 16.3 months versus 11.7 months for subtotal resections 2
• Subtotal resection is associated with less mortality/morbidity but higher recurrence rates 2

Adjuvant Radiotherapy

Proton Beam Therapy (PBT)

• PBT is weakly recommended as postoperative radiotherapy for unresectable/postoperative persistent craniopharyngioma based on level C evidence 1
• Local control, progression-free survival, and overall survival rates with PBT are similar to conventional X-ray therapy 1
• No adverse events specific to PBT or increased by PBT have been reported 1
• Long-term follow-up is needed for full evaluation of PBT benefits, though it may potentially decrease adverse events compared to conventional radiotherapy 1

Radiotherapy Timing and Indications

• Radiotherapy is indicated for unresectable tumors or postoperative persistent disease 1
• After intentional NTR or STR, a watch-and-scan policy is warranted as only a minority of remnants progress 1
• The risk of progression increases with the size of the residual tumor 1

Long-Term Monitoring and Complications

Surveillance Protocol

• MRI surveillance is recommended at 3 and 6 months, and at 1,2,3, and 5 years after surgery 3
• Close monitoring for tumor recurrence is essential throughout follow-up 3

Endocrine Complications

• Hypopituitarism develops in up to 80% of patients by 10-15 years after radiotherapy 1, 3
• Follow-up for hypopituitarism needs to be lifelong with planned transition to specialist adult services 1
• Hormonal testing abnormalities are more common in younger patients 2

Secondary Malignancy Risk

• Radiotherapy carries significant long-term risks, particularly when administered at younger ages 1, 3
• Risk of malignant brain tumors increases 2.4-fold for every 10 years of younger age at treatment 1, 3
• Standardized incidence ratio for meningiomas after cranial radiotherapy is 658 1, 3
• The incidence rate ratio for malignant brain tumors is 3.34 and for meningiomas is 4.06 in patients who underwent radiotherapy versus no radiotherapy 1

Other Complications

• Visual field defects are common, with formal visual field testing recommended in all patients 2
• Neurocognitive sequelae and cerebrovascular events are concerns, particularly in children 1

Emerging Targeted Therapies

Molecular Pathogenesis

• Adamantinomatous craniopharyngioma harbors CTNNB1/Wnt pathway alterations 4, 5
• These tumors develop from epithelial remnants of Rathke's pouch according to the embryonic theory 6
• Clusters of cells with upregulated Wnt/β-catenin signaling may induce tumor formation in a paracrine manner 5

Investigational Approaches

• CTNNB1/Wnt pathway inhibitors have shown promising results in pre-clinical studies and are under continued investigation 4
• Tocilizumab (IL-6R antibody) has been studied in phase 0 trials, with evidence that adamantinomatous craniopharyngioma does not reside behind an intact blood-brain barrier 7
• This finding dramatically broadens the range of potential systemic antitumor therapies 7

Critical Pitfalls to Avoid

• Do not modify surgical procedures based on response to preoperative therapy except in cases of tumor progression requiring more extensive resection 1
• Avoid using radiotherapy as sole primary treatment without attempting maximal safe resection first 1
• Do not assume all visual defects are symptomatic—formal visual field testing reveals "silent" defects in many patients 2
• Balance the low recurrence risk of GTR against the higher functional risks, especially for large tumors 1