Superior outcome but high incidence of pseudoprogression and unfavorable neurocognitive outcome in children with embryonal tumor with multylayered rosettes treated with radiation and high-dose chemotherapy with tandem autologous stem cell rescue

Objective

Embryonal tumor with multilayered rosettes (ETMR) is a rare and highly aggressive embryonal brain tumor in young children. Treatment of this tumor often includes maximal safe resection, radiotherapy, and high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT). Early radiation has been recommended according to recent outcome results. The combination of this multimodal treatment may provoke radiographic changes that can mimic tumor progression. This phenomenon is known as pseudoprogression.

Methods

We report four consecutive patients under 5 years old with ETMR, treated according to CCG 99703 protocol (which includes conventional chemotherapy and HDCT with ASCT). Off protocol, radiation was given before (three patients) or after (one patient) high-dose chemotherapy.

Results

All patients developed pseudoprogression. All patients but one presented symptoms such as irritability, hypotonia, headache and vomiting. Severe neurocognitive impairment was evident in all patients. At a median follow-up of 50.5 months (range, 37–64), three of the patients are alive. Patients who are alive, continue to require significant multidisciplinary support to address treatment sequelae.

Conclusion

This case series demonstrates that, while survival rates appear encouraging, combining radiation therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) in the treatment of embryonal tumors with multilayered rosettes may carry a substantial risk of pseudoprogression and notable neurological damage.