Chemotherapy with or without radiation therapy

ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for three to six cycles.[1]

ABVD for two to four cycles plus involved-field radiation therapy (IFRT) (20 Gy or 30 Gy).

Radiation therapy alone in certain circumstances (such as for older adults with absolute contraindications for using chemotherapy).[2,3]

A randomized, prospective trial from the National Cancer Institute of Canada involving 123 patients with early favorable classic HL compared ABVD for four to six cycles with subtotal nodal radiation.[9][Level of evidence A1]

A randomized, prospective trial from the National Cancer Institute of Canada involving 123 patients with early favorable classic HL compared ABVD for four to six cycles with subtotal nodal radiation.[9][Level of evidence A1]

With a median follow-up of 11.3 years, no difference was observed in event-free survival rates (89% vs. 86%; P = .64) or in overall survival rates (OS) (98% vs. 98%; P = .95).

A randomized study from the Milan Cancer Institute of patients with clinical early-stage HL compared 4 months of ABVD followed by IFRT with 4 months of ABVD followed by extended-field radiation therapy (EFRT).[10][Level of evidence B1]

A randomized study from the Milan Cancer Institute of patients with clinical early-stage HL compared 4 months of ABVD followed by IFRT with 4 months of ABVD followed by extended-field radiation therapy (EFRT).[10][Level of evidence B1]

The results showed similar OS and freedom from progression of disease with a 10-year median follow-up, but the study had inadequate statistical power to determine noninferiority of IFRT versus EFRT.

In the HD10 trial, the German Hodgkin Study Group (GHSG) randomly assigned 1,190 patients with early favorable HL to receive one of the following:[11,12][Level of evidence A1]The following results were observed for the trial:

In the HD10 trial, the German Hodgkin Study Group (GHSG) randomly assigned 1,190 patients with early favorable HL to receive one of the following:[11,12][Level of evidence A1]The following results were observed for the trial:

Two cycles of ABVD plus 30 Gy of IFRT.

In the HD10 trial, the German Hodgkin Study Group (GHSG) randomly assigned 1,190 patients with early favorable HL to receive one of the following:[11,12][Level of evidence A1]The following results were observed for the trial:

Two cycles of ABVD plus 20 Gy of IFRT.

In the HD10 trial, the German Hodgkin Study Group (GHSG) randomly assigned 1,190 patients with early favorable HL to receive one of the following:[11,12][Level of evidence A1]The following results were observed for the trial:

Four cycles of ABVD plus 30 Gy of IFRT.

In the HD10 trial, the German Hodgkin Study Group (GHSG) randomly assigned 1,190 patients with early favorable HL to receive one of the following:[11,12][Level of evidence A1]The following results were observed for the trial:

Four cycles of ABVD plus 20 Gy of IFRT.

In the HD10 trial, the German Hodgkin Study Group (GHSG) randomly assigned 1,190 patients with early favorable HL to receive one of the following:[11,12][Level of evidence A1]The following results were observed for the trial:

With an 8.2-year median follow-up, no differences were observed (hazard ratio [HR], 1.0; 95% confidence interval [CI], 0.6–1.5) in 10-year progression-free survival (PFS) rates (87%) or OS rates (94%) for all four groups.

A follow-up study by the GHSG (HD13 trial) compared modified versions of ABVD with elimination of dacarbazine, bleomycin, or both in combination with 30 Gy of radiation therapy in 1,502 patients with early favorable HL.[13]

A follow-up study by the GHSG (HD13 trial) compared modified versions of ABVD with elimination of dacarbazine, bleomycin, or both in combination with 30 Gy of radiation therapy in 1,502 patients with early favorable HL.[13]

After 5 years, freedom from treatment failure was significantly worse when dacarbazine, bleomycin, or both were omitted.

A follow-up study by the GHSG (HD13 trial) compared modified versions of ABVD with elimination of dacarbazine, bleomycin, or both in combination with 30 Gy of radiation therapy in 1,502 patients with early favorable HL.[13]

This trial suggests that ABVD remains the standard chemotherapy regimen.

Three prospective randomized trials (EORTC/LYSA/FIL H10 [NCT00433433][14,15]; RAPID [NCT00943423][16,17]; and GHSG HD16 [NCT00736320][18]) of 2,889 patients with early-stage disease investigated the use of PET‒computed tomography (CT) scans to modify therapy.[14-18]

Three prospective randomized trials (EORTC/LYSA/FIL H10 [NCT00433433][14,15]; RAPID [NCT00943423][16,17]; and GHSG HD16 [NCT00736320][18]) of 2,889 patients with early-stage disease investigated the use of PET‒computed tomography (CT) scans to modify therapy.[14-18]

Among patients with early favorable HL who had negative PET-CT scan results (Deauville score of 1 or 2) after two or three cycles of ABVD, radiation therapy could be omitted with no significant loss of OS in all three trials.[14,16,18][Level of evidence B1]However, two of the trials showed an increased risk of relapse when radiation therapy was omitted. In the GHSG HD16 trial, for the 628 patients with PET2-negative disease (PET after two cycles of ABVD), the 5-year PFS rate was 93.4% (95% CI, 90.4%–96.5%) with combined modality therapy and 86.1% (95% CI, 81.4%–90.0%) with ABVD alone (HR, 1.78; 95% CI, 1.02–3.12).[18] A subsequent analysis of the GHSG HD16 trial showed that most of the recurrences occurred in the proposed radiation field.[15] In the EORTC/LYSA/FIL H10 trial, the 10-year PFS rate was 98.8% with three cycles of ABVD plus radiation therapy and 85.4% with four cycles of ABVD without radiation therapy (HR, 13.2; 95% CI, 3.1–55.8; P < .001).[17]In summary, this 7% to 13% difference in PFS without a difference in OS can be seen either as a mandate to combine radiation therapy with ABVD to avoid recurrences or as a rationale to give four or more cycles of ABVD when omitting radiation therapy.

Three prospective randomized trials (EORTC/LYSA/FIL H10 [NCT00433433][14,15]; RAPID [NCT00943423][16,17]; and GHSG HD16 [NCT00736320][18]) of 2,889 patients with early-stage disease investigated the use of PET‒computed tomography (CT) scans to modify therapy.[14-18]

ABVD was given for three cycles (six doses) in the RAPID study,[16] for four cycles (eight doses) in the EORTC/LYSA/FIL H10 study,[14] and for two cycles (four doses) in the GHSG HD16 study [18] when applied without radiation therapy.

Three prospective randomized trials (EORTC/LYSA/FIL H10 [NCT00433433][14,15]; RAPID [NCT00943423][16,17]; and GHSG HD16 [NCT00736320][18]) of 2,889 patients with early-stage disease investigated the use of PET‒computed tomography (CT) scans to modify therapy.[14-18]

None of the studies randomly assigned therapy for positive results from an interim PET-CT scan (Deauville score of 3, 4, or 5) after two or three cycles of ABVD because this occurred in only 15% to 25% of the patients studied. One of the studies (RAPID) added an extra cycle of ABVD and IFRT to 30 Gy,[16] another study (EORTC H10F) switched to BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)–escalated therapy for two cycles plus involved nodal radiation therapy to 30 Gy,[14] and the other study (GHSG HD16) added IFRT to 30 Gy.[18]In the RAPID study (NCT00943423), patients with postchemotherapy PET-CT Deauville scores of 5 (uptake ≥3 times maximum liver uptake) had inferior 5-year PFS rates (61.9%; 95% CI, 41.1%–82.7%) and 5-year OS rates (85.2%; 95% CI, 69.7%–100%) (P = .002) when compared with patients with Deauville scores of 1 to 4 (P < .001).[19]

In 287 patients older than 60 years or with early favorable disease, a retrospective review of pulmonary toxicity in the HD10 and HD13 trials showed the following:[20]

In 287 patients older than 60 years or with early favorable disease, a retrospective review of pulmonary toxicity in the HD10 and HD13 trials showed the following:[20]

Two cycles of ABVD plus IFRT (137 patients): 2% pulmonary toxicity.

In 287 patients older than 60 years or with early favorable disease, a retrospective review of pulmonary toxicity in the HD10 and HD13 trials showed the following:[20]

Two cycles of AVD (omitting bleomycin) plus IFRT (82 patients): 2% pulmonary toxicity.

In 287 patients older than 60 years or with early favorable disease, a retrospective review of pulmonary toxicity in the HD10 and HD13 trials showed the following:[20]

Four cycles of ABVD plus IFRT (68 patients): 10% pulmonary toxicity.

ABVD alone for three to four cycles is recommended for patients with early favorable classical HL when the interim PET-CT scan results are negative after two or three cycles of chemotherapy.[21] These patients are also unlikely to ever have a relapse, so routine CT scans are not recommended in follow-up.

With positive interim PET-CT scan results, extra cycles of ABVD and involved nodal radiation therapy are recommended.

A combined-modality approach with two cycles of ABVD and 20 Gy of IFRT can also be used for patients with early favorable classic HL.[21] In this situation, a PET-CT scan to assess response after completion of therapy would suffice.