Relapse Patterns and Subsequent Outcomes of Patients Treated on the NCIC CTG HD.6 (ECOG JHD06) Randomized Trial Evaluating ABVD Alone in Patients with Limited Stage Hodgkin Lymphoma (HL).

Abstract Background: We completed a randomized trial comparing ABVD alone with treatment that included extended field (EF) radiation therapy (RT) in 399 patients with limited stage HL. Patients allocated to EF RT received this as a single modality if categorized as favourable risk or preceded by 2 cycles of ABVD if unfavourable risk. The 5-year FFP was superior in patients receiving RT but no difference in overall survival was detected as the difference in FFP has been offset by deaths due to other causes (Meyer, J Clin Oncol2005; 23: 4634 42). Overall, 34 patients had progressive disease (PD) and 15 patients died (4 from HL, 2 from treatment-related toxicity and 9 from other causes). To better understand the implications of treatment with ABVD alone, we compared the patterns of PD and outcomes with secondary therapy of the two randomized groups. We were particularly interested in assessing how frequently sites of PD observed in patients assigned to ABVD alone occurred within the EF of RT that was prescribed in the HD.6 trial, or within a hypothetical involved field (IF) of RT that constitutes an accepted current practice. Methods: Two expert reviewers, blinded to treatment allocation, were provided a list of disease sites at diagnosis and at PD. Sites of PD were categorized as ’within field only’, ’out of field only’ and ’in + out of field’. Two analyses were performed by considering both EF and IF RT fields. A third blinded reviewer adjudicated disagreements. Results: Inter-observer agreement was excellent for both the EF (kappa 0.87) and IF (kappa = 1.0) analyses. More cases of PD were observed in patients allocated to ABVD alone (24 vs. 10). More within field only PD was observed in patients allocated to ABVD alone when assessed according to both the EF (88% vs 30%; P = 0.002) and IF (71% vs. 20%; P = 0.01) analyses. Individual investigators determined the actual choice of therapy for PD; among patients allocated to ABVD alone, secondary therapy included chemotherapy alone (2), RT alone (8), combined modality therapy (6) and autologous stem cell transplantation (8). No difference in the proportion of patients alive without second progression was detected between patients allocated to ABVD alone (18 /24; 75%) or treatment that included RT (8 /10; 80%) (P = 1.0). Conclusion: For patients with limited stage HL, treatment with ABVD alone is associated with a greater risk of PD at disease sites that would be included in an IF of RT. Secondary therapy is often successful and further testing is required to determine the optimum choice of therapy for these patients.