Increased Relapse Rates in Early Stage Hodgkin Lymphoma (HL) Patients without Radiotherapy: The German Society of Radiooncology (DEGRO) Advises to Treat all Early Stage HL Patients with Radiotherapy

In the EORTC/LYSA/FIL H10 trial stage I/II HL patients with favorable and unfavorable risk profile and a negative 18-fluoro-desoxy-D-glucose positron emission tomography (FDG-PET) after 2 cycles of ABVD were randomized for radiotherapy (RT) vs. no radiotherapy after the end of chemotherapy. After an interim futility analysis the data monitoring and safety committee considered it unlikely to demonstrate non-inferiority of the experimental arm (with omission of RT) compared to the standard RT arm. Therefore the study was suspended. The decrease in the 1-year PFS with omission of RT was 3–5%, but absolute PFS was still in the range of 95%. The authors conclude their article “The final analysis will reveal whether this finding is maintained over time…. [5]”.

Recently, the German Society of Radiooncology (DEGRO) circulated a statement advising that all patients with early stage HL should receive RT based on the results of the H10 trial. Although the current evidence-based S3 guideline “Hodgkinʼs Lymphoma” of the German Cancer Society does advise involved-field radiotherapy with 20 Gy following chemotherapy for all patients over 18 years of age – if treated outside of clinical trials [11] – the general recommendation of radiotherapy for all HL patients cannot be extended to pediatric patients.

The strategy of the upcoming EuroNet-PHL-C2 trial stands in striking contrast to the DEGROʼs advice. In this upcoming trial the EuroNet-PHL group aims at a 5-year EFS rate of more than 90% and at omitting radiotherapy in early favourable HL patients with a negative FDG-PET result (Deauville score<4) after 2 cycles of OEPA. In addition, early favourable HL patients treated without RT will receive one additional cycle of COPDAC, a regimen with a low toxicity profile [3], to minimize the decrease of event-free survival (EFS; including second cancers as events) in patients without RT. It is expected that more than 90% of the early favourable HL patients will be PET negative. The patients with early unfavourable HL will be treated in group of intermediate stage patients. These patients will be randomized between standard COPDAC consolidation and an intensified DECOPDAC regimen. Again, patients who are PET-negative after 2 cycles of OEPA will not receive RT. In the light of the results of the H10 trial and the advice of the DEGRO the EuroNet-PHL group has to ask:

^* For the GPOH-HD committee within the EuroNet-PHL group.

• References

• 1 Bhatia S, Yasui Y, Robison LL et al. Late Effects Study Group . High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin’s lymphoma: report from the Late Effects Study Group. J Clin Oncol 2003; 21: 4386-4394
• 2 Engert A, Haverkamp H, Kobe C et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin’s lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet 2012; 379: 1791-1799
• 3 Mauz-Körholz C, Hasenclever D, Dörffel W et al. Procarbazine-free OEPA-COPDAC-28 chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin’s lymphoma: the GPOH-HD-2002 study. J Clin Oncol 2010; 28: 3680-3686
• 4 O’Brien MM, Donaldson SS, Balise RR et al. Second malignant neoplasms in survivors of pediatric Hodgkin’s lymphoma treated with low-dose radiation and chemotherapy. J Clin Oncol 2010; 28: 1232-1239
• 5 Raemaekers JM, André MP, Federico M et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 2014; 32: 1188-1194
• 6 Schellong G, Dörffel W, Claviez A et al. Salvage therapy of progressive and recurrent Hodgkin’s disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group. J Clin Oncol 2005; 23: 6181-6189
• 7 Schellong G, Riepenhausen M, Ehlert K et al. Breast cancer in young women after treatment for Hodgkin’s disease during childhood or adolescence – an observational study with up to 33-year follow-up. Dtsch Arztebl Int 2014; 111: 3-9
• 8 Schellong G, Riepenhausen M, Bruch C et al Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents: report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies. Pediatr Blood Cancer 2010; 55: 1145-1152
• 9 Schmitz N, Pfistner B, Sextro M et al Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet 2002; 359: 2065-2071
• 10 Wolden SL, Chen L, Kelly KM et al. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin’s lymphoma – a report from the Children’s Oncology Group. J Clin Oncol 2012; 30: 3174-3180
• 11 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF) Hodgkin Lymphom – S3-Leitlinie Diagnostik, Therapie und Nachsorge des Hodgkin Lymphoms bei erwachsenen Patienten, Version 1.0, Februar 2013, Registrierungsnummer: 018/029OL; http://www.krebsgesellschaft.de/download/s3_hodgkin-ol-langversion.pdf