Zusammenfassung
Hintergrund
Durch Kombination einer Polychemotherapie mit einer konsolidierenden IF-Strahlentherapie können in den frühen und intermediären Stadien des Hodgkin-Lymphoms (HL) Langzeitremissionsraten von ca. 85 % erzielt werden. International werden die Rolle der konsolidierenden Strahlentherapie und die in den intermediären Stadien des HL anzuwendende Chemotherapie kontrovers diskutiert. Aktuelle Therapieansätze widmen sich der weiteren Reduktion der Strahlentherapiefelder bzw. der Frage eines PET-basierten Strahlentherapieansatzes sowie der Optimierung der Chemotherapie-Regime, um die therapieassoziierte Toxizität bei gleicher Effektivität zu reduzieren.
Ziele
Herleitung des Standards der Deutschen Hodgkin-Studiengruppe (GHSG) und Diskussion aktueller Studien in frühen und intermediären Stadien des HL.
Ergebnisse
In den frühen Stadien des HL sind 2 Zyklen ABVD, gefolgt von 20 Gy IF-RT, in den intermediären Stadien 4 Zyklen Chemotherapie, gefolgt von 30 Gy IF-RT, nach wie vor als Standardtherapie anzusehen. Die bisherigen Daten zur Anwendung eines PET-basierten Strahlentherapieansatzes erlauben es bisher nicht, auf die Strahlentherapie zu verzichten. In den intermediären Stadien ist das „2 + 2“-Schema der Gabe von 4 Zyklen ABVD hinsichtlich der Tumorkontrolle signifikant überlegen und gilt daher als GHSG-Standard.
Schlussfolgerungen
Die Frage, ob bei PET-Negativität nach der Chemotherapie auf die Strahlentherapie verzichtet werden kann, wird voraussichtlich durch die HD16- bzw. HD17-Studie beantwortet. Durch Implementierung von Brentuximab Vedotin in die Erstlinientherapie der frühen und intermediären Stadien könnte künftig eine weitere Reduktion der therapieassoziierten Toxizität erreicht werden.
Abstract
Background
With combined modality treatment which includes a polychemotherapy regimen and a consolidating IF-radiotherapy strategy long-term remission rates of about 85% can be achieved in early favorable and unfavorable HL patients. International points of discussion are the role of the consolidating radiotherapy and the optimal chemotherapy regimen for patients with early unfavorable HL. Current treatment approaches aim at further reduction of radiotherapy field size and at optimizing of the chemotherapy regimens and additionally evaluate PET-response based radiotherapy approaches in order to reduce treatment-associated toxicity, while maintaining treatment efficacy.
Aims
Deduction of the GHSG-standard and discussion of current trials in early favorable and unfavourable HL patients.
Results
Two courses of ABVD followed by 20 Gy IF-RT have to be regarded as standard of care in early favorable HL, and four courses of chemotherapy followed by 30 Gy IF-RT are standard in early unfavorable HL. So far, the available data to a PET-response guided radiotherapy approach do not permit to omit the consolidating radiotherapy.
In early unfavorable HL, “2+2” results in a significantly improved tumor control compared to four courses of ABVD and is therefore recommended by the GHSG as standard chemotherapy regimen in patients with early unfavorable HL.
Conclusions/perspectives
The ongoing HD16 and HD17 trials are designed to answer the question whether radiotherapy can be omitted in those patients with a negative PET response after completion of chemotherapy. By implementing brentuximab vedotin in the first line treatment of early favorable and unfavorable HL we might achieve a further reduction of treatment-associated toxicity.
Literatur
Andre MP, Reman O, Federico M et al (2009) First Report On the H10 EORTC/GELA/IIL Randomized Intergroup Trial On Early FDG-PET Scan Guided Treatment Adaptation Versus Standard Combined Modality Treatment in Patients with Supra-Diaphragmatic Stage I/II Hodgkin’s Lymphoma, for the Groupe d’Etude Des Lymphomes De l’Adulte (GELA), European Organisation for the Research and Treatment of Cancer (EORTC) Lymphoma Group and the Intergruppo Italiano Linfomi (IIL). ASH Annual Meeting Abstracts 114:97
Andre MP, Reman O, Federico M et al (2012) Interim analysis of the randomized Eortc/Lysa/Fil Intergroup H10 Trial On Early PET-Scan Driven Treatment Adaptation in Stage I/II Hodgkin lymphoma. ASH Annual Meeting Abstracts 120:549
Behringer K, Thielen I, Mueller H et al (2012) Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial. Ann Oncol 23:1818–1825
Campbell BA, Hornby C, Cunninghame J et al (2012) Minimising critical organ irradiation in limited stage Hodgkin lymphoma: a dosimetric study of the benefit of involved node radiotherapy. Ann Oncol 23:1259–1266
Eich HT, Diehl V, Gorgen H et al (2010) Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol 28:4199–4206
Engert A, Franklin J, Eich HT et al (2007) Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin’s lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 25:3495–3502
Engert A, Plutschow A, Eich HT et al (2010) Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med 363:640–652
Ferme C, Eghbali H, Meerwaldt JH et al (2007) Chemotherapy plus involved-field radiation in early-stage Hodgkin’s disease. N Engl J Med 357:1916–1927
Hay AE, Klimm B, Chen BE et al (2012) Treatment of Stage I-II A Non-Bulky Hodgkin’s Lymphoma (HL): an Individual Patient-Data Comparison of German Hodgkin Study Group (GHSG) HD10 and HD11 Combined-Modality Therapy (CMT) and NCIC Clinical Trials Group (NCIC CTG) HD.6 ABVD Alone. ASH Annual Meeting Abstracts 120:548-
Klimm B, Goergen H, Fuchs M et al (2012) Discrimination of an early unfavorable risk group has significant impact on treatment outcome in early-stage Hodgkin lymphoma: an analysis of International staging definitions and risk factors. ASH Annual Meeting Abstracts 120:54
Lister TA, Crowther D, Sutcliffe SB et al (1989) Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol 7:1630–1636
Maraldo MV, Brodin NP, Vogelius IR et al (2012) Risk of developing cardiovascular disease after involved node radiotherapy versus mantle field for Hodgkin lymphoma. Int J Radiat Biol 83:1232–1237
Meyer RM, Gospodarowicz MK, Connors JM et al (2012) ABVD alone versus radiation-based therapy in limited-stage Hodgkin’s lymphoma. N Engl J Med 366:399–408
Noordijk EM, Carde P, Dupouy N et al (2006) Combined-modality therapy for clinical stage I or II Hodgkin’s lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials. J Clin Oncol 24:3128–3135
Press OW, LeBlanc M, Lichter AS et al (2001) Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin’s disease. J Clin Oncol 19:4238–4244
Radford J (2012) Treatment for early-stage hodgkin lymphoma: has radiotherapy had its day? J Clin Oncol 30:3783–3785
Sasse S, Klimm B, Gorgen H et al (2012) Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin’s lymphoma. Ann Oncol 23:2953–2959
Sasse S, Von Tresckow B, Pluetschow A et al (2013) Impact of dose intensification on the outcome in early-stage unfavorable HL: 7-year follow-up analysis of the GHSG HD14 trial. Haematologica 98:13
Einhaltung der ethischen Richtlinien
Interessenkonflikt. A. Engert, S. Sasse, K. Behringer und R. Semrau geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
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Sasse, S., Behringer, K., Semrau, R. et al. Kontroversen in der Behandlung früher und mittlerer Stadien des klassischen Hodgkin-Lymphoms. Onkologe 20, 448–456 (2014). https://doi.org/10.1007/s00761-013-2636-4
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DOI: https://doi.org/10.1007/s00761-013-2636-4
Schlüsselwörter
- Hodgkin-Lymphom
- Frühe und intermediäre Stadien
- Kombinierte Therapie
- 18Fluorodeoxyglucose-Positronenemissionstomographie
- Progressionsfreies Überleben