Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study

Abstract

Purpose: Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes.

Patients and methods: Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS).

Results: High PET score was associated with inferior EFS, before (P < .001) and after adjustment (P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P > .4).

Conclusion: In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.

Trial registration: ClinicalTrials.gov NCT00943423.

Figures

FIG 1.

CONSORT diagram. ABVD, doxorubicin, bleomycin, vinblastine, and dacarbazine; CMR, complete metabolic response; IFRT, involved-field radiotherapy; NFT, no further treatment; PET, positron emission tomography.

FIG 2.

Kaplan-Meier curves of (A) event-free survival (EFS), (B) progression-free survival (PFS), and (C) overall survival (OS) by positron emission tomography (PET) score.

FIG 3.

Kaplan-Meier curves of event-free survival (EFS) by (A) European Organisation for Research and Treatment of Cancer (EORTC) and (B) German Hodgkin Study Group (GHSG) risk group.

FIG A1.

Kaplan-Meier curves of event-free survival (EFS) by positron emission tomography score (PET) of 1 to 4 versus 5 for (A) EORTC favorable risk, (B) EORTC unfavorable risk, (C) GHSG favorable risk, and (D) GHSG unfavorable risk.