What is the first-line treatment for Hodgkin's lymphoma nodular sclerosis?

First-Line Treatment for Hodgkin's Lymphoma Nodular Sclerosis

The first-line treatment for Hodgkin's lymphoma nodular sclerosis depends on disease stage and risk stratification, with ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) forming the backbone of therapy across all stages, combined with involved-site radiotherapy for limited and intermediate stages. 1

Risk Stratification Framework

Before determining treatment, patients must be allocated to one of three risk groups based on Ann Arbor staging and specific risk factors 1:

Risk factors include:

• Large mediastinal mass (>1/3 horizontal chest diameter) 1
• Extranodal disease 1
• High ESR (>50 with B symptoms; >30 without B symptoms) 1
• Three or more involved lymph node areas 1

Risk group categories:

• Early favorable: Stage I-II without risk factors 1
• Early unfavorable (intermediate): Stage I-II with risk factors 1
• Advanced: Stage III-IV, or stage IIB with large mediastinal mass or extranodal involvement 1

Treatment by Stage

Limited-Stage Disease (Early Favorable)

Standard treatment is 2 cycles of ABVD followed by 30 Gy involved-site radiotherapy (ISRT). 1

• This combined modality approach is based on German Hodgkin Study Group (GHSG) HD7 and HD10 trials, as well as EORTC H7F and H8F trials 1
• Two cycles of ABVD is non-inferior to four cycles when combined with 30 Gy radiotherapy 1
• ISRT is now recommended instead of involved-field radiotherapy (IFRT) to minimize long-term toxicity 1
• Chemotherapy alone (4-6 cycles ABVD) may be offered when late radiotherapy risks outweigh short-term disease control benefits, though prospective data supporting this approach remains limited 1

Intermediate-Stage Disease (Early Unfavorable)

Standard treatment is 4 cycles of ABVD followed by 30 Gy ISRT. 1

• This achieves tumor control and overall survival exceeding 85-90% at 5 years 1
• For patients ≤60 years eligible for intensive treatment, an alternative is 2 cycles of escalated BEACOPP followed by 2 cycles of ABVD and 30 Gy radiotherapy 1
• PET-adapted approach: Patients with positive interim PET after 2 cycles of ABVD should switch to 2 cycles of escalated BEACOPP before ISRT 1

Advanced-Stage Disease

For patients ≤60 years, standard treatment is either 6 cycles of ABVD or 4-6 cycles of escalated BEACOPP. 1

ABVD approach:

• Six cycles of ABVD is the international standard 1
• After 2 cycles, if interim PET is negative, bleomycin should be omitted in cycles 3-6, especially in elderly patients or those at increased risk for lung toxicity 1
• If interim PET is positive after 2 cycles of ABVD, consider switching to escalated BEACOPP 1

Escalated BEACOPP approach:

• Escalated BEACOPP demonstrates superior disease-free survival (88%) and overall survival (92%) at 5 years compared to ABVD 1
• After 2 cycles of escalated BEACOPP, PET-negative patients require only 2 more cycles (total 4), while PET-positive patients need 4 more cycles (total 6) 1
• Critical caveat: BEACOPP should NOT be given to patients >60 years due to excessive toxicity 1

Radiotherapy in advanced disease:

• Radiotherapy is confined to patients with PET-positive residual lymphoma ≥2.5 cm after chemotherapy 1
• Additional radiotherapy of initial tumor bulks or residual disease <2.5 cm is not generally recommended 1

Age-Specific Considerations

For patients >60 years:

• ABVD-based chemotherapy is the standard of care 1
• Bleomycin should be discontinued after the second cycle due to increased pulmonary toxicity risk 1
• Six to eight cycles of ABVD should be used; escalated BEACOPP is contraindicated 1

Critical Pre-Treatment Requirements

Mandatory baseline assessments include: 1

• Cardiac function (bidimensional ultrasound evaluation of left ventricular ejection fraction) 1
• Pulmonary function tests 1
• Baseline PET-CT for response-adapted therapy 1
• HBV, HCV, and HIV screening 1
• Reproductive counseling and fertility preservation options (sperm banking, oocyte collection, ovarian tissue cryopreservation) for patients of reproductive age 1, 2
• Thyroid function assessment (TSH, FT3, FT4) and dental care for patients requiring neck irradiation 1

Common Pitfalls to Avoid

• Do not use MOPP-based regimens: MOPP has higher rates of second malignancies (particularly acute leukemia) and infertility compared to ABVD 3
• Do not exceed bleomycin beyond 2 cycles in elderly patients: This significantly increases pulmonary toxicity risk 1
• Do not give escalated BEACOPP to patients >60 years: The toxicity profile is unacceptable in this age group 1
• Do not routinely irradiate small residual masses: Radiotherapy should be restricted to PET-positive residual disease ≥2.5 cm after chemotherapy in advanced stages 1