Long-Term Follow-Up of Contemporary Treatment in Early-Stage Hodgkin Lymphoma: Updated Analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 Trials

Abstract

Purpose Combined-modality treatment is widely considered the standard of care in early-stage Hodgkin lymphoma (HL), and treatment intensity has been reduced over the last years. Long-term follow-up is important to judge both efficacy and safety of the different therapies used. Patients and Methods We analyzed updated follow-up data on 4,276 patients treated within the German Hodgkin Study Group trials HD7 and HD10 for early-stage favorable HL and HD8 and HD11 for early-stage unfavorable HL between 1993 and 2003. Results In HD7 (N = 627; median follow-up, 120 months), combined-modality treatment was superior to extended-field radiotherapy (RT), with 15-year progression-free survival (PFS) of 73% versus 52% (hazard ratio [HR], 0.5; 95% CI, 0.3 to 0.6; P < .001), without differences in overall survival (OS). In HD10 (N = 1,190; median follow-up, 98 months), noninferiority of two cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) plus 20 Gy involved-field (IF)-RT to more intensive four cycles of ABVD plus 30 Gy IF-RT was confirmed with 10-year PFS of 87% each (HR, 1.0; 95%, 0.6 to 1.5) and OS of 94% each (HR, 0.9; 95% CI, 0.5 to 1.6), respectively. In both trials, no differences in second neoplasias were observed. In HD8 (N = 1,064; median follow-up, 153 months), noninferiority of involved-field RT to extended-field RT regarding PFS was confirmed (HR, 1.0; 95% CI, 0.8 to 1.2). In HD11 (N = 1,395; median follow-up, 106 months), superiority of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone at baseline over ABVD was not observed. After BEACOPP, 20 Gy IF-RT was noninferior to 30 Gy (10-year PFS, 84% v 84%; HR, 1.0; 95% CI, 0.7 to 1.5). In contrast, PFS was inferior in ABVD-treated patients receiving 20 Gy instead of 30 Gy IF-RT (10-year PFS, 76% v 84%; HR, 1.5; 95% CI, 1.0 to 2.1). No differences in OS or second neoplasias were observed in in both trials. Conclusion Long-term follow-up data of the four randomized trials largely support the current risk-adapted therapeutic strategies in early-stage HL. Nevertheless, continued follow-up is necessary to assess the long-term safety of currently applied therapeutic strategies.

The treatment of older Hodgkin lymphoma patients

“…In young early‐favourable‐stage patients, commonly defined as stages I–II without risk factors, two cycles of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) followed by 20 Gy involved‐field radiotherapy (IF‐RT) is internationally accepted as standard of care based on results of the GHSG HD10 trial (Engert et al , ; Sasse et al , ). Recently, some groups have advocated the use of FDG‐PET after chemotherapy as a means to omit radiotherapy in early‐favourable stage HL with PET‐negative restaging after ABVD (André et al , ).…”

Second cancers in Hodgkin's lymphoma long-term survivals: A 60-year single institutional experience with real-life cohort of 871 patients

“…With these new approaches, comparing to some older techniques as mantel filed technique or inverted‐Y irradiation, one may expect reduced risk of radiotherapy induced SC in the future . Reduced dose to 20 Gy comparing to 30 Gy in early stage HL was also shown noninferior is some randomised clinical trials . Nevertheless, there are still many patients surveilled in clinical practice, who were irradiated by these older radiotherapy techniques and with increasing prevalence, there is a need of updated reasonable follow‐up schemas as provided in our study.…”

“…6,14,15,22,23 Reduced dose to 20 Gy comparing to 30 Gy in early stage HL was also shown noninferior is some randomised clinical trials. 24 Nevertheless, there are still many patients surveilled in clinical practice, who were irradiated by these older radiotherapy techniques and with increasing prevalence, there is a need of updated reasonable follow-up schemas as provided in our study. We aimed to describe the whole consecutive cohort of patients treated in general clinical practice outside of clinical trials, what may also bias results considering wide range of stage, dosage of medication used or age of patients.…”

Therapeutic recommendations for early stage Hodgkin lymphomas

“…HD8 demonstrated long‐term noninferiority of IF‐RT compared with EF‐RT. With regard to treatment‐associated long‐term toxicity, a non‐significant trend toward less secondary neoplasia with IF‐RT was observed in the recent follow‐up analysis (15‐year cumulative, 14% vs. 17%; P = 0·3) (Sasse et al , ). This trend is more pronounced when examining only the incidence of acute myeloid leukaemia or myelodysplastic syndromes (2·4% vs. 0·8%; P = 0·1), but not in non‐Hodgkin lymphoma (2·6% vs. 2·9%; P = 1·0).…”