Surgery, Chemotherapy, and Radiation Therapy (Multimodality Therapy)

Of the 42 patients in the AT/RT Registry, 13 (31%) received radiation therapy in addition to chemotherapy as part of their primary therapy.[1] The radiation field was to the primary tumor bed in nine children, and the radiation field was to the tumor bed and the craniospinal axis in four children.

Of the 42 patients in the AT/RT Registry, 13 (31%) received radiation therapy in addition to chemotherapy as part of their primary therapy.[1] The radiation field was to the primary tumor bed in nine children, and the radiation field was to the tumor bed and the craniospinal axis in four children.

The median survival of these patients was 48 months, compared with 16.75 months for all patients in the registry.

In a retrospective series of 31 patients with AT/RT from the St. Jude Children's Research Hospital, the following results were reported:[12]

In a retrospective series of 31 patients with AT/RT from the St. Jude Children's Research Hospital, the following results were reported:[12]

The 2-year EFS rate was 78% for patients older than 3 years, which was considerably better than the EFS rate of 11% for patients younger than 3 years.

In a retrospective series of 31 patients with AT/RT from the St. Jude Children's Research Hospital, the following results were reported:[12]

All but one of the surviving patients (seven of eight) in the older group received craniospinal irradiation and intensive chemotherapy with hematopoietic stem cell transplant.

In a retrospective series of 31 patients with AT/RT from the St. Jude Children's Research Hospital, the following results were reported:[12]

Only 3 of the 22 younger patients received any form of radiation therapy, 2 of whom were disease free.

In a Surveillance, Epidemiology, and End Results (SEER) Program registry review, radiation therapy was associated with improved survival in children younger than 3 years.[13]

In the European Registry for rhabdoid tumors series, the following results were observed:[14][Level of evidence C1]

In the European Registry for rhabdoid tumors series, the following results were observed:[14][Level of evidence C1]

Radiation therapy was also associated with improved survival, with a 6-year OS rate of 66% (± 0.1%) in patients who received this treatment.

In the European Registry for rhabdoid tumors series, the following results were observed:[14][Level of evidence C1]

The significant benefit of radiation therapy was corroborated in an extension of this series.[15]

The IRS-III study used radiation therapy, intrathecal methotrexate, cytarabine, hydrocortisone, and systemic multiagent chemotherapy. The results of this small retrospective series were encouraging,[16,17] leading to the first prospective study of multimodality treatment in this group of patients.

On the basis of the previous pilot series, a prospective multi-institutional trial was conducted for children with newly diagnosed CNS AT/RT. Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy was either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on the child's age and extent of disease at diagnosis.[7]

On the basis of the previous pilot series, a prospective multi-institutional trial was conducted for children with newly diagnosed CNS AT/RT. Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy was either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on the child's age and extent of disease at diagnosis.[7]

The 2-year PFS rate was 53% (± 13%), and the 2-year OS rate was 70% (± 10%).

On the basis of the previous pilot series, a prospective multi-institutional trial was conducted for children with newly diagnosed CNS AT/RT. Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy was either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on the child's age and extent of disease at diagnosis.[7]

Results were most favorable for children who were older, had a gross-total resection, and had no metastatic disease at presentation.

On the basis of the previous pilot series, a prospective multi-institutional trial was conducted for children with newly diagnosed CNS AT/RT. Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy was either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on the child's age and extent of disease at diagnosis.[7]

Six of the eight children without progressive disease at the time of the report had received conformal radiation therapy, and two children had received craniospinal radiation therapy. Seven children had a gross-total resection, and only one child had metastatic disease (this child had persistent, stable disease 1.5 years from diagnosis).

The COG performed a prospective single-arm study of 65 children. Fifty-four of the children were younger than 36 months and received two courses of methotrexate, cyclophosphamide, cisplatin, and etoposide followed by three courses of high-dose carboplatin and thiotepa supported by peripheral stem cell rescue. For patients with nondisseminated disease, focal involved-field radiation therapy was mandated after either induction or consolidation, depending on age. For patients with disseminated disease, craniospinal radiation at the end of therapy was recommended but not mandated.[8]

The COG performed a prospective single-arm study of 65 children. Fifty-four of the children were younger than 36 months and received two courses of methotrexate, cyclophosphamide, cisplatin, and etoposide followed by three courses of high-dose carboplatin and thiotepa supported by peripheral stem cell rescue. For patients with nondisseminated disease, focal involved-field radiation therapy was mandated after either induction or consolidation, depending on age. For patients with disseminated disease, craniospinal radiation at the end of therapy was recommended but not mandated.[8]

For all patients, the 4-year EFS rate was 37%, and the 4-year OS rate was 43%.

The COG performed a prospective single-arm study of 65 children. Fifty-four of the children were younger than 36 months and received two courses of methotrexate, cyclophosphamide, cisplatin, and etoposide followed by three courses of high-dose carboplatin and thiotepa supported by peripheral stem cell rescue. For patients with nondisseminated disease, focal involved-field radiation therapy was mandated after either induction or consolidation, depending on age. For patients with disseminated disease, craniospinal radiation at the end of therapy was recommended but not mandated.[8]

For children younger than 36 months at diagnosis, the 4-year EFS rate was 35%, compared with 6.4% in a historical cohort of patients who received chemotherapy alone (P < .0005).

The COG performed a prospective single-arm study of 65 children. Fifty-four of the children were younger than 36 months and received two courses of methotrexate, cyclophosphamide, cisplatin, and etoposide followed by three courses of high-dose carboplatin and thiotepa supported by peripheral stem cell rescue. For patients with nondisseminated disease, focal involved-field radiation therapy was mandated after either induction or consolidation, depending on age. For patients with disseminated disease, craniospinal radiation at the end of therapy was recommended but not mandated.[8]

For the 11 children aged 36 months or older at diagnosis, the 4-year EFS rate was 48%, and the 4-year OS rate was 57%.

The COG performed a prospective single-arm study of 65 children. Fifty-four of the children were younger than 36 months and received two courses of methotrexate, cyclophosphamide, cisplatin, and etoposide followed by three courses of high-dose carboplatin and thiotepa supported by peripheral stem cell rescue. For patients with nondisseminated disease, focal involved-field radiation therapy was mandated after either induction or consolidation, depending on age. For patients with disseminated disease, craniospinal radiation at the end of therapy was recommended but not mandated.[8]

Toxicity from this regimen was significant. Four treatment-related deaths (6% of the patients) resulting from sepsis, respiratory failure, or CNS necrosis were reported.