Consolidation Radiotherapy Is Associated with Improved Outcomes after Chemotherapy for Advanced Hodgkin Lymphoma: Analysis of Results from the UKLG LY09 Trial (ISRCTN97144519)

Introduction: This international randomised controlled trial compared ABVD with two multi-drug regimens (MDR) for the initial treatment of advanced Hodgkin Lymphoma (HL). The effects of radiotherapy (RT) given to patients (pts) in complete or partial remission after chemotherapy have been analysed.

Methods: Pts with advanced HL (stage IIAX-IV) were randomised between standard therapy with ABVD and one of two prespecified MDRs: Alternating ChlVPP/PABlOE or Hybrid ChlVPP/EVA. Six cycles were planned, plus two extra for slow responses. Involved field RT was recommended for incomplete response or bulk disease (over 1/3 transthoracic ratio or 10cm outside the chest) at presentation. The primary outcome measure was event-free survival (EFS).

Results: 807 pts were randomised from Apr-1997 to Sep-2001; 406 allocated ABVD and 401 MDRs. 702 pts achieved either PR, CR(u) or CR, and RT was reported for consolidation at the completion of chemotherapy in 300 (43%). Among these pts, the maximum dose of radiotherapy was up to 30Gy in 87 (29%), 31–39Gy in 165 (55%) and over 39Gy in 48 (16%). Of these pts, 48 were reported in PR, 40 in CRu, 88 had initial bulk but reached CR, 102 had both initial bulk and residual disease, and 22 had RT despite no bulk and CR. At 6.5 years median follow-up, 161 PFS events were reported, and 83 pts had died. The allocated chemotherapy regimen had no effect upon response rate, PFS or OS. The baseline characteristics showed that more pts reported to have RT had bulk disease (190, 63% vs 111, 28%), were younger (median 31 vs 36 years), and had better International Prognostic Score (IPS 0–3)(253, 84% vs 318, 79%). There was no good evidence of a difference in gender, baseline WHO performance status (PS) or allocated chemotherapy. More RT pts were reported as in PR after chemotherapy (150, 50% vs 36, 9%). EFS from the end of chemotherapy was superior for pts who had RT (hazard ratio (HR) 0·43, 95% CI 0·30, 0·60) with 5-year EFS 71% in pts without RT and 86% with RT. An advantage was also seen for overall survival (HR 0·47, 95% CI 0·29, 0·77) with 5-year survival 87% in pts without RT and 93% in pts with RT. A similar magnitude of effect was seen for RT irrespective of subgroups divided by bulk, baseline IPS, or chemotherapy. For pts in CR the HR was 0.44 (CI 0.24, 0.78) for CR(u) 0.33 (CI 0.19, 0.58) and for PR 0.25 (CI 0.11, 0.59). A multivariate analysis including baseline IPS, PS, bulk, allocated chemotherapy, choice of MDR chemotherapy and RT showed that the dominant effects upon EFS were RT (HR 0·44) and IPS (HR 1·41).

Strengths: Systematically collected, prospective data from a large randomised controlled trial. Use of RT was advised but not mandated and no dose was specified if RT was to be given: this provides a dataset that reflects practice.

Limitations: A non-randomised comparison with exploratory outcome measures; limited long-term toxicity data.

Conclusion: Pts who received consolidation RT apparently had better outcomes, a finding which is consistent across all prognostic groups. The use of newer techniques such as FDG-PET scanning might be more reliable at identifying pts for whom radiation can safely be omitted, and prospective studies are underway to address this question.