Outcome of Patients Progressing or Relapsing after Primary Treatment with Two Cycles of Chemotherapy and Radiotherapy for Early Stage (Favorable) Hodgkin’s Disease.
Authors: Josting Andreas , Franklin Jeremy , Sieniawski Michal , Pfistner Beate , Schober Thomas , Nisters-Backes Hildtrud , Engert Andreas , Diehl Volker 
Published: April 2020

Abstract
Purpose: To evaluate treatment outcome of patients (pts) with early stage (favorable) Hodgkin’s disease (HD) with disease progression or relapse after primary treatment with two cycles of polychemotherapy followed by radiotherapy.
Patients & Methods: From 1994 to 2002 pts with early stage HD were enrolled in two trial generations (HD7/HD10) of the German Hodgkin Study Group (GHSG). HD7 randomized CS IA-IIB patients with no risk factors (RF) to extended field radiotherapy (EFRT) alone or to 2 cycles of ABVD and EFRT. The HD10 trial randomized CS IA-IIB pts (ø RF) to 2 or 4 cycles of ABVD and 20 or 30 Gy involved field RT (IFRT). Treatment outcome and prognostic factors (PF) in pts with progressive or relapsed disease after 2 x ABVD + EF RT (HD7 Arm B) or 2 x ABVD + IF RT (HD10 Arm C + D) were retrospectively analysed and compared to pts registered in our database with treatment failure after RT alone or after 4 or 8 cycles polychemotherapy as front-line therapy.
Results: A total of 1831 pts with early stage HD were enclosed in HD 7 and HD 10. 915 pts were treated with two cycles of ABVD followed by EFRT in 316 patiens (HD7 Arm B) or IFRT in 599 pts (HD 10 Arm C+D). 35 patients had progressive (17%) or relapsed HD (83%). Pts characteristics at relapse: median age: 40 yrs (range 19–72 yrs); histology: MC 39%, NS 37%, LCRHD 9%, LPHD 9%, LD 3%, not classified 3%; stage: CS I 26%, CS II 43 %, III 20 %, CS IV 11 %; B symptoms 8%; anemia (m &lt; 12.0 g/dl; f &lt; 10.5 g/dl) 23%; outfield relapse 40%. At progress/relapse 29% were treated with BEACOPP escalated, 29 % with HDCT/ASCT, 20% with COPP-ABVD-like regimens, 14% with BEACOPP baseline, and 8% with salvage RT. At 58 months median follow-up FF2F and OS were 49% and 62%, respectively. According to our recently developed prognostic score for relapsed HD (PF: duration of first remission, stage at relapse and anemia at relapse) patients with 2 or more RF had a FF2F and OS of 15 and 18% compared to 67% and 82% for pts with 0 or 1 RF. FF2F and OS at 58 months were comparable for pts treated with HDCT/ASCT (FF2F: 70%, OS 81%) or BEACOPP escalated (FF2F 64%, OS 78%). In contrast, pts tretaed with COPP-ABVD like regimens (FF2F 30%, OS 43%) or BEACOPP baseline (FF2F 19%, OS 22%) did worse. Compared to pts receiving RT as front line therapy alone pts treated with 2 x ABVD had a poorer outcome (RT alone: FF2F 79%, OS 82%). The outcome of pts pretreated with 4 (intermediate stages) or 8 cycles (advanced stages) of polychemotherapy at first diagnosis did not differ significantly and was inferior to pts pretreated with 2 x ABVD + RT.
Conclusion: Disease progression or relapse after primary tretament with 2 x ABVD followed by radiotherapy is a rare event. The prognosis of pts treated with 2 x ABVD is impaired compared to patients treated with front-line radiotherapy alone. Modern treatment regimens like BEACOPP escalated or HDCT/ASCT should be used to salvage patients relapsing after a brief chemotherapy course and RT for early stage (favorable) HD.