Chemotherapy for Atypical Teratoid Rhabdoid Tumors in Children

Treatment

• Survival dependent on extent of resection: Patients with gross total resection had a better survival rate than those who did not have a gross total resection (2-year overall survival rate of 60±12.6% versus 21.7±8.5%, p=0.03) (30).
• Chemotherapy plus radiation: A multicenter study reported using chemotherapy and focal radiation for children under the age of 3 years and craniospinal radiation with chemotherapy for children 3 years and older (46). The chemotherapy regimen consisted of vincristine, dactinomycin, cyclophosphamide, cisplatin, doxorubicin, and temozolomide, and was coupled with intrathecal treatments according to the extent of the disease. Children without metastatic disease received intrathecal methotrexate, cytarabine, and hydrocortisone, coinciding with each cycle of chemotherapy. Those with metastatic disease received intrathecal chemotherapy weekly until two consecutive CSF samples were negative for malignant cells. Once two consecutive CSF samples were negative for malignant cells, patients received intrathecal therapy as scheduled for patients with M0 disease. The intrathecal chemotherapy alternated between the intralumbar and intraventricular routes. The 2-year PFS rate was 53%.
• High-dose chemotherapy may improve outcome: A study reported a better outcome for children who received high-dose chemotherapy compared to those who received standard chemotherapy regimens and/or radiation (2-year overall survival rate of 47.9±12.1% versus 27.3±9.5%, p=0.036). The same report found that upfront radiation did not provide survival benefit. Six of the 12 survivors did not receive radiation (30).

Adjuvant Therapy

• Radiation despite age: Due to the aggressive nature of AT/RTs, which occur most commonly in infancy, many favor the use of radiation in combination with chemotherapy. However, even if this combination results in a cure, the morbidity risk of radiation needs to be carefully considered.

Complications

• 5–10% mortality rate associated with treatment: Mortality secondary to toxicity of high-dose chemotherapy and related sepsis and multi-organ failure has been reported as high as 5–10% in some centers. The highest risk is mortality due to aggressive progressive malignant disease.
• Long-term morbidity risk of radiation: The morbidity risk of radiation needs to be continually reevaluated and documented, with improvement in the precision of techniques when focal radiation is a consideration in the young developing brain.

Outcome

• Prognosis very poor: Despite these promising reports on multimodality therapy, most patients die within a year of diagnosis. A few survivors have been reported in the context of a gross total resection and intensive chemotherapy with or without radiation.