What is the optimal treatment strategy for newly diagnosed pediatric Hodgkin lymphoma, including risk‑adapted chemotherapy and radiation?

Optimal Treatment of Pediatric Hodgkin Lymphoma

Pediatric Hodgkin lymphoma should be treated with risk-adapted, response-adapted combined modality therapy using multi-agent chemotherapy followed by low-dose involved-field radiation, with treatment intensity determined by initial disease stage and early response assessment via PET imaging. 1

Risk Stratification Framework

Treatment selection begins with classifying patients into three distinct risk groups based on Ann Arbor staging with Cotswolds modification: 1

• Low-risk (early favorable): Limited-stage disease without unfavorable features
• Intermediate-risk (early unfavorable): Limited-stage with risk factors including extranodal involvement, bulky mediastinal disease, or B symptoms 1
• Advanced-stage/high-risk: Stage III-IV disease or extensive involvement 1

Treatment by Risk Group

Low-Risk Disease

For early favorable disease, administer AVPC or OEPA chemotherapy regimens with response-adapted radiation therapy. 1

• Patients with adequate early response (AER) on interim PET receive chemotherapy alone without radiation 1
• Those with inadequate early response (IER) receive 21 Gy involved-field radiation therapy 1
• Alternative regimens include 2 cycles of ABVD followed by 20-30 Gy radiation for patients requiring more intensive therapy 1
• This approach achieves >90% overall survival while minimizing cumulative anthracycline exposure (150-200 mg/m² doxorubicin) 1

Intermediate-Risk Disease

For early unfavorable disease, use OEPA or ABVE-PC chemotherapy with response-adapted consolidation. 1

• OEPA regimen delivers 200 mg/m² doxorubicin, 60 IU/m² bleomycin, with 21 Gy radiation for inadequate responders 1
• ABVE-PC provides 160 mg/m² doxorubicin, avoiding bleomycin but including 1,500 mg/m² etoposide and 3,200 mg/m² cyclophosphamide 1
• Adequate early responders may omit radiation, while inadequate responders receive 20-35 Gy involved-field radiation 1
• This strategy achieves 85-90% tumor control at 5 years 1

Advanced-Stage/High-Risk Disease

For advanced disease, administer ABVE-PC or intensified regimens with mandatory radiation to residual masses. 1

• ABVE-PC delivers 250 mg/m² doxorubicin, 75 IU/m² bleomycin, 1,875 mg/m² etoposide, and 6,000 mg/m² cyclophosphamide 1
• Radiation (21-30 Gy) is directed to large mediastinal adenopathy or residual disease 1
• Alternative intensive approach uses BEACOPP regimens, but these carry significantly higher gonadal toxicity risk due to 2,800 mg/m² procarbazine exposure 1

Response Assessment Strategy

PET-CT imaging after 2-4 cycles of chemotherapy determines whether radiation can be safely omitted. 1

• Response assessment uses FDG-PET/CT, PET/MRI, or contrast-enhanced diagnostic CT/MRI of original disease sites 1
• Adequate early response (negative PET) allows radiation omission in low and intermediate-risk patients 1
• Inadequate early response mandates consolidative involved-field radiation therapy 1

Critical Treatment Principles

Avoid procarbazine-containing regimens (BEACOPP) in male patients whenever possible due to severe infertility risk. 1

• Procarbazine causes high-risk gonadal toxicity (≥4 Gy equivalent to testes) 1
• OEPA and ABVE-PC regimens preserve fertility in most patients by avoiding procarbazine 1

Minimize radiation exposure, particularly to breast tissue in female patients and mediastinal structures in all patients. 1

• Limit radiation to involved-site or involved-node fields rather than extended-field approaches 1
• Keep mean thyroid radiation dose <10 Gy to avoid high-risk thyroid dysfunction 1
• Restrict chest radiation to <15 Gy when possible to reduce cardiomyopathy risk 1
• Any breast radiation exposure creates high risk for subsequent breast neoplasms requiring lifelong surveillance 1

Long-Term Surveillance Requirements

Implement risk-stratified surveillance based on cumulative treatment exposures. 1

• Cardiomyopathy screening: Every 2 years for high-risk patients (≥15 Gy chest radiation), every 5 years for intermediate-risk 1
• Thyroid surveillance: Yearly if mean thyroid radiation dose >10 Gy 1
• Breast cancer screening: Yearly beginning at age 25 and 8 years post-radiation for any breast radiation exposure 1
• Pulmonary toxicity: Assessment at entry into long-term follow-up and as clinically indicated if bleomycin or chest radiation received 1
• Colorectal cancer screening: Every 5 years beginning at age 30 and 5 years post-radiation for abdomen/pelvis radiation 1

Common Pitfalls to Avoid

Do not use adult treatment protocols for adolescents aged 17-21 years, as this results in approximately 10% reduction in progression-free survival. 1

Do not omit radiation in patients with inadequate early PET response, as this compromises disease control. 1

Do not use chemotherapy-only approaches without response-adapted assessment, as this requires higher cumulative alkylator doses with increased late toxicity risk. 1, 2

Ensure fertility preservation counseling occurs before treatment initiation, particularly for patients receiving BEACOPP or high-dose alkylator regimens. 1