What is the recommended treatment approach for a 2-year 4-month-old baby diagnosed with Atypical Teratoid/Rhabdoid Tumor (ATRT), specifically regarding chemotherapy and radiation therapy?

Treatment Approach for 2-Year 4-Month-Old with ATRT

For a 2-year 4-month-old child with ATRT, initiate intensive multiagent chemotherapy immediately after maximal safe surgical resection, then defer radiation therapy until the child reaches 3 years of age to minimize devastating neurocognitive and neuroendocrine sequelae while maintaining curative intent. 1, 2

Immediate Management: Surgery and Chemotherapy

Surgical Resection

• Pursue maximal safe surgical resection as the first intervention, though gross total resection is often difficult due to large tumor size, location, and young patient age 1
• Obtain craniospinal MRI with contrast and CSF cytology 2-3 weeks post-surgery to assess for leptomeningeal spread, which occurs in 15-30% of ATRT patients 1

Intensive Chemotherapy Regimen

The Head Start II protocol is the preferred chemotherapy approach for this age group, as it has achieved long-term remissions in young children with ATRT without radiation therapy. 3

The regimen consists of:

• Five cycles of induction chemotherapy including cisplatin, vincristine, cyclophosphamide, etoposide, AND high-dose methotrexate in each cycle 3
• Consolidation with high-dose chemotherapy: carboplatin, thiotepa, and etoposide with autologous hematopoietic progenitor cell rescue (AHPCR) 3
• This approach achieved 3 of 7 long-term survivors (42+, 54+, and 67+ months) without radiation therapy in children with median age 28 months 3

Radiation Therapy Timing: Critical Decision Point

Defer Until Age 3 Years

Cranial radiation should be deferred until the child reaches 3 years of age due to severe developmental consequences in younger children. 4, 5, 1

The evidence supporting deferral includes:

• Cranial radiation results in developmental impairments in young children, with even doses <20 Gy to supratentorial brain causing measurable IQ decline 5
• Growth hormone deficiency is universal by 5 years post-radiation, and hypopituitarism with multiple hormone deficiencies reaches 80% incidence at 10-15 years 5
• The young brain is more vulnerable to radiation injury than the adult brain despite greater neuroplasticity 5
• Children aged 3 years or older with ATRT have dramatically superior outcomes: 2-year event-free survival of 78% and overall survival of 89%, compared to only 11% and 17% respectively in younger children 2

Radiation Protocol When Child Reaches Age 3

Once the child turns 3 years old, implement radiation therapy:

• Craniospinal irradiation is standard due to 15-30% leptomeningeal spread risk 1
• Use proton therapy if available, as it provides superior sparing of cerebrum, temporal lobes, cochlea, and hypothalamus—critical structures for development 6
• Proton therapy demonstrated favorable initial outcomes with 9 of 10 patients alive without disease at median follow-up of 27.3 months 6
• Standard dosing: craniospinal irradiation followed by boost to tumor bed 1

Alternative Consideration: Focal Radiation in Younger Children

If disease progression occurs before age 3 despite intensive chemotherapy:

• Focal radiation therapy may be a pragmatic approach rather than full craniospinal irradiation to limit neurocognitive and neuroendocrine sequelae 1
• This represents a balance between disease control and long-term quality of life in very young children 1

Critical Monitoring During Treatment

Chemotherapy Toxicity

• Monitor for significant treatment-related morbidity and mortality associated with high-dose chemotherapy and AHPCR 1
• Watch for infection risk, particularly during neutropenic periods 3

Disease Surveillance

• Perform serial MRI imaging to detect early progression that might necessitate earlier radiation intervention 1
• Monitor for distant relapse, which can sometimes be successfully salvaged with involved field irradiation and additional chemotherapy 6

Common Pitfalls to Avoid

• Do not use standard-dose chemotherapy alone, as historical outcomes with surgery and standard chemotherapy resulted in median survival of only 8.5 months 3
• Do not omit high-dose methotrexate from the regimen, as the Head Start I protocol (without methotrexate) had only 0 of 6 long-term survivors, while Head Start II (with methotrexate) achieved 3 of 7 survivors 3
• Do not delay chemotherapy initiation while waiting for the child to reach radiation age—intensive chemotherapy must begin immediately post-surgery 3, 2
• Do not assume radiation can be permanently avoided—most long-term ATRT survivors ultimately receive radiation therapy as part of upfront or salvage therapy 7

Salvage Options if Progression Occurs

If disease progresses during chemotherapy:

• Consider ifosfamide, carboplatin, and etoposide (ICE) chemotherapy, which successfully rescued 3 of 4 patients aged 3 years or older with progressive ATRT 2
• Re-evaluate timing of radiation therapy, as earlier sequencing may improve outcomes even in younger children facing progression 7