Evaluating temozolomide for pediatric adamantinomatous craniopharyngiomas using microspheroid-based drug screening

Pediatric adamantinomatous craniopharyngioma (ACP) is the most common tumor of the diencephalic-pituitary axis in children. Although histologically benign, pediatric ACP is frequently associated with substantial endocrine dysfunction and neurological complications. The gold-standard treatment is complete surgical resection; however, because of the tumor's location, total removal is often not feasible. Consequently, several authors recommend radiotherapy as an adjuvant option. Nevertheless, partial resections are frequently followed by recurrence, and repeated surgical interventions increase morbidity and impair quality of life. Thus, adjuvant therapeutic strategies capable of controlling this tumor should be encouraged.

We analyzed seven fresh tumor specimens ACP from patients < 18 years of age using a chemoresistance platform (Bioverso Test, Ziel Biosciences, São Paulo, Brazil). These cases demonstrated widespread resistance to most chemotherapeutic agents tested. Temozolomide (500 µM) was the only drug that showed consistent and significant sensitivity.

Based on these findings, we initiated treatment in a 14-year-old patient with recurrent ACP who had previously undergone multiple surgical procedures and radiotherapy. The tumor involved the left cavernous sinus and extended into the sphenoid sinus. Clinically, the patient was amaurotic and presented with panhypopituitarism. The patient received temozolomide (200 mg/m²/day for 5 consecutive days in 28-day cycles). After completing 12 cycles of chemotherapy, there was a notable regression of the lesion, with approximately 50% reduction in total tumor volume.

These findings suggest that temozolomide may represent a promising therapeutic option for controlling ACP.