What is the recommended treatment regimen for atypical teratoid rhabdoid tumors (AT/RT)?

Treatment Regimen for Atypical Teratoid Rhabdoid Tumors (AT/RT)

AT/RT requires maximal safe surgical resection followed by intensive multimodal chemotherapy with delayed radiotherapy, using regimens that include high-dose alkylating agents, platinum compounds, and anthracyclines, with treatment intensity and timing stratified by patient age.

Surgical Management

• Maximal safe resection with the goal of image-verified complete resection is the first-line treatment 1
• Document extent of resection with postoperative MRI within 72 hours 1
• Second-look surgery should be considered if initial resection is incomplete 2
• When complete resection is not feasible, subtotal resection for tissue diagnosis and debulking should be performed, especially if mass effect symptoms are present 1

Age-Stratified Chemotherapy Approach

Children < 3 Years of Age

Intensive chemotherapy without immediate radiotherapy is recommended to avoid neurotoxic effects of radiation in developing brains 1, 3

Preferred regimen components include:

• Cyclophosphamide, vincristine, cisplatin, and etoposide as the backbone 4
• High-dose methotrexate added to each induction cycle significantly improves outcomes 4
• Doxorubicin, ifosfamide incorporated in dose-dense schedules 5
• Intrathecal chemotherapy augmentation 5, 2

Specific protocol structure:

• Five cycles of induction chemotherapy with cisplatin, vincristine, cyclophosphamide, and etoposide 4
• High-dose methotrexate should be added to each of the five induction courses 4
• Consolidation with myeloablative chemotherapy (carboplatin, thiotepa, etoposide) followed by autologous hematopoietic progenitor cell rescue 4
• Alternative intensive regimen: Three 9-week courses of dose-dense therapy including doxorubicin, cyclophosphamide, vincristine, ifosfamide, cisplatin, etoposide, and methotrexate with intrathecal therapy, followed by high-dose chemotherapy 5

Children ≥ 3 Years of Age

Radiation therapy combined with high-dose alkylator-based chemotherapy is the standard of care and achieves significantly superior outcomes 3

Treatment sequence:

• Maximal surgical resection 3
• Craniospinal radiation therapy (dose and timing per institutional protocols) 3
• High-dose alkylating chemotherapy 3
• Local radiotherapy boost to primary site 5

Key outcome data: Children ≥3 years treated with radiation and high-dose alkylating therapy achieve 2-year event-free survival of 78% and overall survival of 89%, compared to only 11% and 17% respectively in younger children 3

Radiation Therapy Timing and Approach

• Radiotherapy should be delayed until after high-dose chemotherapy and stem cell rescue in young children to allow for intensive systemic therapy first 5
• For children ≥3 years, postoperative craniospinal radiation is the standard approach 3
• Local radiotherapy to the primary tumor bed is completed after systemic therapy 5
• Intensity-modulated radiation therapy is preferred when radiation is indicated 1

Management of Metastatic Disease (M1-M3 Stage)

• The intensive multimodal regimen with delayed radiotherapy is effective in preventing early relapses even in patients with metastatic disease at diagnosis 5
• Intrathecal chemotherapy is particularly important for patients with leptomeningeal dissemination 5, 2

Salvage Therapy for Progressive/Recurrent Disease

For patients ≥3 years with progressive disease, ifosfamide, carboplatin, and etoposide (ICE) chemotherapy can achieve successful salvage 3

• Three of four patients ≥3 years with progressive disease were successfully rescued with ICE therapy 3
• Two long-term survivors after relapse have been reported using modified Intergroup Rhabdomyosarcoma Study Group (IRS III) parameningeal protocol 2

Critical Treatment Principles

• Correct initial diagnosis is essential - misdiagnosis and treatment according to incorrect protocols significantly worsens outcomes 5
• Multi-agent intravenous and intrathecal chemotherapy is required 2
• The drug combination and sequence are critical for preventing early relapses 5
• Treatment must be disease-specific rather than using generic embryonal tumor protocols 5

Prognostic Factors

• Age ≥3 years at diagnosis is the single most important favorable prognostic factor 3
• Supratentoral location appears more favorable than posterior fossa 6
• Complete surgical resection improves outcomes 6
• Absence of metastatic disease at diagnosis is favorable 3
• Younger children (<3 years) have dismal prognosis with median survival historically of 7-8.5 months without intensive protocols 2, 4

Common Pitfalls to Avoid

• Do not use standard embryonal tumor protocols - AT/RT requires disease-specific intensive therapy 5
• Do not give early radiation to children <3 years - delay until after intensive chemotherapy and stem cell rescue 5, 4
• Do not undertreat based on poor historical outcomes - modern intensive protocols achieve long-term survival in select patients 5, 4, 3
• Avoid directing young patients or those with recurrent disease to comfort care without attempting curative intensive therapy 2