What is the treatment for Hodgkin's lymphoma by stage?

Treatment of Hodgkin's Lymphoma by Stage

Treatment for Hodgkin's lymphoma is stratified into three risk categories—limited-stage, intermediate-stage, and advanced-stage disease—with combined-modality therapy (chemotherapy plus radiotherapy) for early stages and chemotherapy alone for advanced stages, with treatment intensity modified by interim PET-CT response. 1

Limited-Stage Disease (Early Favorable)

Standard treatment consists of 2-3 cycles of ABVD followed by involved-site radiotherapy (ISRT) at 20-30 Gy. 1

• This combined-modality approach achieves superior tumor control compared to radiotherapy alone, with cure rates exceeding 90%. 1, 2
• ISRT is now recommended over involved-field radiotherapy (IFRT) after chemotherapy to minimize radiation exposure and late toxicity. 1
• Chemotherapy alone may be considered when the late risks of radiotherapy (secondary malignancies, cardiovascular disease) outweigh the short-term benefit of improved disease control. 1

Intermediate-Stage Disease (Early Unfavorable)

Four cycles of ABVD followed by 30 Gy ISRT represents the standard of care for intermediate-stage Hodgkin's lymphoma. 1, 3

• For patients ≤60 years eligible for more intensive treatment, an alternative regimen of 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD and 30 Gy ISRT can be offered, which has demonstrated superior freedom from treatment failure. 1
• Patients with positive interim PET after 2 cycles of ABVD should be switched to 2 cycles of BEACOPPescalated before completing ISRT. 1
• ISRT is recommended over IFRT to reduce radiation field size and late effects. 1
• Extranodal involvement (such as an isolated abdominal mass) automatically upgrades patients to intermediate-stage unfavorable disease requiring this more intensive approach. 3

Advanced-Stage Disease (Stage III-IV)

Advanced-stage Hodgkin's lymphoma is treated with chemotherapy alone, with radiotherapy confined to patients with residual disease after chemotherapy. 1

For Patients ≤60 Years:

• Either 6 cycles of ABVD or 4-6 cycles of BEACOPPescalated, optionally followed by localized radiotherapy. 1
• BEACOPPescalated demonstrates superior tumor control and overall survival (10% improvement at 5 years) compared to ABVD, but carries significant acute toxicity requiring appropriate surveillance and supportive care. 1
• After 2 cycles of ABVD, bleomycin should be omitted in cycles 3-6 if interim PET is negative, especially in elderly patients and those at increased risk for lung toxicity. 1
• Patients with positive interim PET after 2 cycles of ABVD should switch to BEACOPPescalated. 1
• After 2 cycles of BEACOPPescalated, PET-negative patients require only 2 more cycles (total 4), while PET-positive patients need 4 more cycles (total 6). 1
• Radiotherapy is restricted to patients with PET-positive residual lymphoma >2.5 cm after BEACOPPescalated. 1

For Patients >60 Years:

• ABVD-based chemotherapy (6-8 cycles) represents the standard of care; BEACOPP should NOT be given due to increased treatment-related mortality. 1
• Bleomycin must be discontinued after the second cycle in this age group due to increased pulmonary toxicity risk. 1, 4

Relapsed or Refractory Disease

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the treatment of choice for most patients with relapsed or refractory Hodgkin's lymphoma. 1, 5

• Salvage regimens (DHAP, IGEV, or ICE) are administered before HDCT and ASCT to reduce tumor burden and mobilize stem cells. 1, 5
• Achieving a negative PET should be the goal of salvage therapy irrespective of the protocol used. 1
• Consolidating treatment with brentuximab vedotin following HDCT and ASCT is recommended in patients with defined poor-risk factors. 1
• High-risk patients may benefit from tandem ASCT. 1
• Single-agent brentuximab vedotin may be sufficient as salvage therapy before HDCT and ASCT in selected patients. 1

Critical Treatment Modifications and Pitfalls

Age-Related Considerations:

• Never administer BEACOPP to patients >60 years due to excessive treatment-related mortality. 1
• Always discontinue bleomycin after 2 cycles in patients >60 years. 1, 4

PET-Adapted Therapy:

• Interim PET-CT after 2 cycles guides treatment intensification or de-escalation, using the Deauville scoring system. 1, 5
• PET-negative patients (Deauville 1-3) can safely de-escalate therapy, while PET-positive patients (Deauville 4-5) require treatment intensification. 4, 5

Pre-Treatment Requirements:

• Cardiac and pulmonary function tests must be performed before starting treatment. 1
• Reproductive counseling and fertility preservation (sperm banking, oocyte collection, ovarian tissue cryopreservation) should be offered to all patients of reproductive age before treatment initiation. 1, 5
• Screening for HBV, HCV, and HIV is compulsory. 1

Radiation Field Planning:

• ISRT has replaced IFRT as the standard to minimize radiation exposure while maintaining disease control. 1
• For abdominal wall involvement, ensure adequate radiation field planning with appropriate margins. 4

Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

• Stage IA without risk factors: 30 Gy IFRT alone is standard treatment. 1
• All other stages: Treated identically to classical Hodgkin's lymphoma. 1
• A renewed biopsy should be obtained before salvage therapy in suspected NLPHL relapse, as transformation to aggressive disease may occur. 1