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Radiology review

Overview

Radiotherapy is a well proven treatment modality in malignant lymphomas. However, its planning and execution require a high technical standard and vast experience in this field. In order to assure the quality of radiotherapy in patients with Hodgkin lymphoma, the GHSG has established a radiotherapy review center that develops an individual radiotherapy plan for each trial patient and supervises the course of irradiation.

Since the beginning of the GHSG’s fourth trial generation, HD10-12, the radiotherapy review center in Cologne has been headed by Prof. Dr. R.-P. Müller and PD Dr. H.T. Eich. They draw up prospective radiotherapy plans for patients with early and intermediate stage Hodgkin lymphoma, and for advanced stage patients (HD12) an interdisciplinary expert panel was founded. Besides, an expert panel directed by the Department of Radiation Oncology of the University of Cologne evaluates the quality of completed radiotherapies.

The fifth GHSG trial generation, HD13-15, was conducted from January 2002 to November 2009. In the trials for early stages of Hodgkin lymphoma, HD13 and HD14, the concept of combined chemotherapy and subsequent involved-field radiotherapy, which was already applied in the preceding trials, HD10 and HD11, was further optimized. HD13 and HD14 primarily aimed to investigate the right kind of systemic chemotherapy. While in HD10 and HD11, patients were randomized between involved-field radiotherapy with either 20 Gy or 30 Gy, the HD13 and HD14 trials used involved-field radiotherapy with 30 Gy as standard in all treatment arms.

The final analysis of the HD10 showed that involved-field radiotherapy with a dose of 20 Gy is sufficient in early favorable stages. The combination of 2 cycles of ABVD plus 20 Gy IF-RT is now accepted as the new international standard for patients of this risk group (Engert et al. NEJM 2010). In the currently ongoing HD16 trial (for early favorable stages), treatment stratification by means of FDG-PET is applied. All patients receive 2 cycles of ABVD and a subsequent FDG-PET scan. In the standard arm, patients are treated with 20 Gy involved-field radiotherapy. In the experimental arm, only patients with PET-positive residual tumor tissue after chemotherapy are irradiated, and patients with a negative PET result are followed up from then on.

Also in the HD17 trial (for early unfavorable stages), FDG-PET is used for treatment stratification. All patients receive 2 cycles of escalated BEACOPP, followed by 2 cycles of ABVD. After that, an FDG-PET examination is performed. In the standard arm, patients receive involved-field radiotherapy with 30 Gy. In the experimental arm, only patients with a positive PET result are irradiated. Similar to the HD16 protocol, in the experimental arm PET-negative patients are not given radiotherapy and are followed up from then on. PET-positive patients receive involved-node radiotherapy. This kind of radiotherapy is used in Hodgkin lymphoma patients in Germany for the first time ever.

Prior to radiotherapy in Hodgkin lymphoma patients, the respective disease stage must be determined very accurately, based on imaging techniques, in order to ensure an optimal planning of irradiation. Like in the fourth and fifth trial generation, the trial centers have to send the complete cross-sectional diagnostic images to the radiotherapy review center (Referenzstrahlentherapie) in Cologne. The center will then evaluate the images, verify the trial to which the respective patient should be assigned and draw up an individual recommendation for radiotherapy. After completion of radiotherapy, the radiotherapy plans as well as the simulation and verification images have to be sent to the review center in Cologne for quality control by an expert panel.

Planning the target volume is a very complex task, particularly in terms of the new involved-node radiotherapy. For an ideal radiotherapy plan, a planning CT in which the patient is positioned as for irradiation should be performed. After completion of chemotherapy the CT scans taken before and after chemotherapy are compared and correlated with each other to outline the target volume according to the involved node definition of the GHSG (Eich et al. Strahlenther. 2008).

An expert panel analyzes the quality of the completed involved-field radiotherapy retrospectively with regard to whether the recommended radiation volume was fully covered and with regard to the applied radiation dose, total treatment duration and technical radiation parameters (Eich et al. IJROBP 2008).

In the HD12 trial, advanced stage Hodgkin lymphoma patients received polychemotherapy according to the BEACOPP regimen with different grades of intensity. In order to determine whether additional radiotherapy is still necessary after this kind of intensive pre-treatment, an additional radiotherapy with 30 Gy (on the initial bulk region and/or the site of the residual tumor) was applied on a randomized basis. With the aim to identify patients with an inadequate treatment response, the complete diagnostic images available after end of chemotherapy were sent to the radiotherapy review center in Cologne for assessment by an interdisciplinary panel, consisting of a radio-oncologist, a diagnostic radiologist and an oncologist. In patients with a large residual tumor and massive bone involvement (endangering stability), radiotherapy was applied independent of the treatment arm they were randomized into. The final analysis of this trial proved that patients with a residual tumor after chemotherapy benefit from additional radiotherapy.

The succeeding trial, HD15, was the first to use treatment stratification by means of FDG-PET after completion of BEACOPP chemotherapy. Patients with a PET-positive residual tumor ?2.5 cm received a local RT with 30 Gy. PET-negative patients were only followed up from then on. The negative predictive value of FDG-PET was defined to be 95%. PET-negative patients show a significantly more favorable progression-free survival (PFS) than PET-positive. However, the prognosis for PET-positive patients who received additional radiotherapy is still rather good (PFS after 5 years in almost 90%), so for patients with a PET-positive residual tumor, local radiotherapy of the residual tumor region is still recommended.

Like in its preceding trials, in the currently ongoing HD18 trial (for advanced stages) the complete cross-sectional images are assessed by an interdisciplinary expert panel. After 2 cycles of chemotherapy patients receive an FDG-PET examination, according to which treatment is stratified. PET-positive patients receive further 6 cycles of chemotherapy and another FDG-PET is performed afterwards. PET-positive patients with a residual tumor ?2.5 cm, receive a local RT with 30 Gy. PET-negative patients either receive further 2 or further 6 cycles of BEACOPP, depending on the treatment arm they have been randomized into, and are followed up afterwards.

Tasks of the radiotherapy review center

  1. To give a second opinion on the initial diagnostics for early and intermediate stage patients and provide an according recommendation for radiotherapy.
  2. To consult radiotherapy clinics and practices in the planning and execution of radiotherapy.
  3. To assess the radiotherapeutic treatment performed on the individual patient retrospectively on the basis of the respective radiation plans, simulation images and verification images.
  4. To participate in the PET panel meeting for advanced stages (HD18). Patients with residual tumors and a positive PET result receive additional radiotherapy. In these cases, the radiotherapy review center draws up a corresponding recommendation for radiotherapy.
  5. To develop national and international standards concerning the definition of radiation volumes on the basis of anatomical structures or lymph node regions.
  6. To organize and manage the annual workshops for radiotherapists of centers participating in the GHSG’s trials to continuously optimize the quality of radiotherapy in Hodgkin lymphoma treatment.
  7. To manage the radiotherapy sub-project of the Competence Network for Malignant Lymphomas, which is supported by the BMBF (Federal Ministry of Education and Research)

Head of radiotherapy review

Prof. Dr. med. R.-P. Müller

Director of the Department of Radiation Oncology of the University of Cologne

PD Dr. med. H.T. Eich

Senior consultant of the Department of Radiation Oncology of the University of Cologne

Privatdozent (PD) Dr. med. Hans Theodor Eich

Deputy head of radiotherapy review of the GHSG

Contact

Klinik und Poliklinik für Strahlentherapie
Uniklinik Köln
Kerpener Str. 62
50937 Köln

Office: Frau S. Keiner
Phone: +49 221 478-5449 / 5084
Fax: +49 221 478-6158
E-mail: hans.eich@uk-koeln.de

Members

Dr. med. J. Kriz
Scientific assistant of the Department of Radiation Oncology of the University of Cologne

C. Baues
Scientific assistant of the Department of Radiation Oncology of the University of Cologne

C. von Pusch
Radiologic technologist

Radiotherapy expert panel

Prof. Dr. med. R.-P. Müller
Director of the Department of Radiation Oncology of the University of Cologne

PD Dr. med. H.T. Eich
Senior consultant of Department of Radiation Oncology of the University of Cologne

Prof. Dr. med. R. Engenhart-Cabillic
Director of the Department of Radiation Oncology of the University of Marburg-Giessen

Prof. Dr. med. P. Lukas
Director of the Department of Therapeutic Radiology and Oncology of the University of Innsbruck

Prof. Dr. med. H. Schmidberger
Director of the Department of Radiation Oncology of the University of Mainz

Ms. PD Dr. med. S. Staar
Director of the Department and Group Practice of Radiation Oncology of the University of Bremen-Mitte

Prof. Dr. med. N. Willich
Director of the Department of Radiation Oncology of the University of Münster

Radiotherapy references

  • Eich HT, Diehl V, Görgen H et al. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early favourable Hodgkin’s lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol 2010; 28(27):4199-206.
  • Engert A, Plütschow A, Eich HT et al. Reduced treatment intensity in patients with early stage Hodgkin’s Lymphoma. N Engl J Med 2010; 363(7): 640-52.
  • Eich HT, Engenhart-Cabillic R, Hansemann K et al. Quality control of involved field radiotherapy in patients with early-favorable (HD10) and early-unfavorable (HD11) Hodgkin's lymphoma: an analysis of the German Hodgkin Study Group. Int J Radiation Oncol Biol Phys 2008; 71(5): 1419-1429.
  • Macann A, Bredenfeld H, Müller R-P, Diehl V, Engert A, Eich HT. Radiotherapy does not influence the severe pulmonary toxicity observed with the administration of gemcitabine and bleomycin in patients with advanced-stage Hodgkin's lymphoma treated with the BAGCOPP regimen: A report by the German Hodgkin's Lymphoma Study Group. Int J Radiat Oncol Biol Phys. 2008; 70 (1): 161-5.
  • Eich HT, Engenhart-Cabillic R, Hansemann K, Lukas P, Schneeweiß A, Seegenschmiedt MH, Skripnitchenko R, Staar S, Willich N, Müller R-P. Quality control of involved field radiotherapy in patients with early-favorable (HD10) and early-unfavorable (HD11) Hodgkin's lymphoma – an analysis of the German Hodgkin Study Group (GHSG). Int J Radiat Oncol Biol Phys 2007
  • Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Witt M, Theophil B, Dörken B, Boissevain F, Hänel A, Paulus U, Hasenclever D, Löffler M, Müller R-P, Müller-Hermelink HK, Dühmke E, Diehl V. Two cycles of ABVD plus Extended Field Radiotherapy is Superior to Radiotherapy Alone in Early-Favourable Hodgkin’s Lymphoma: Final Results of the GHSG HD7 Trial. J Clin Oncol. 2007; 10; 25 (23): 3495-3502.
  • Eich HT, Gossmann A, Engert A, Kriz J, Bredenfeld H, Hansemann K, Skripnitchenko R, Brillant C, Pfistner B, Staar S, Diehl V, Müller R-P. A contribution to solve the problem of the need for consolidative radiotherapy after intensive chemotherapy in advanced stages of Hodgkin's lymphoma - analysis of a quality control program initiated by the radiotherapy reference center of the German Hodgkin Study Group (GHSG). Int J Radiat Oncol Biol Phys. 2007; 69 (4): 1187-92.
  • 8)    Eich HT, Müller R-P. Current role and future developments of radiotherapy in early-stage favourable Hodgkin's lymphoma. Strahlenther Onkol 2007 (Sondernr 2): 16-18.
  •  Eich HT, Hansemann K, Müller R-P. Behandlung früher Stadien des Hodgkin-Lymphoms unter dem Aspekt der Qualitätssicherung. Onkologe 2005; 11: 924-932.
  • Eich HT, Müller R-P. Teleradiotherapeutisches Netzwerk für Lymphompatienten. Der Onkologe 2005; 11: 1183-1188.
  • Müller R-P, Eich HT. The developement of quality assurance of radiotherapy within the German Hodgkin Study Group (GHSG) - Introduction, continuing work and results of the radiotherapy reference panel. Strahlenther Onkol 2005; 181 (9): 557-566.
  • Müller R-P, Eich HT. Current role of radiotherapy in the treatment of Hodgkin’s disease. In: Perez CA, Brady LW, Halperin EC, Schmidt-Ullrich RK (eds.). Update Principles and Practice of Radiation Oncology. Lippincott Williams & Wilkins 2005; Vol 6 Number 2: 2-15.
  • Josting A, Nogova L, Franklin J, Glossmann JP, Eich HT, Sieber M, Schober T, Boettcher HD, Schulz U, Mueller R-P, Diehl V, Engert A. Salvage radiotherapy in patients with relapsed and refractory Hodgkin's Lymphoma: A retrospective analysis from the German Hodgkin Lymphoma Study Group. J Clin Oncol. 2005; 23 (7): 1522-1529.
  • Nogova L, Reineke T, Josting A, Müller-Hermelink HK, Eich HT, Behringer K, Müller R-P, Diehl V, Engert A. Lymphocyte-predominant and classical Hodgkin's Lymphoma – comparison of outcomes. Eur J Haematol 2005 ;75 Suppl 66: 106-110.
  • Eich HT, Müller R-P. The radiotherapy reference panel - experiences and results of the German Hodgkin Study Group (GHSG). Eur J Haematol 2005 ; 75 Suppl 66: 98-105 6. Gossmann A, Eich HT, Engert A, Josting A, Müller R-P, Diehl V, Lackner K-J. CT and MR imaging in Hodgkin’s disease – present and future. Eur J Haematol 2005; 75 Suppl 66: 83-89.
  • Eich HT, Haverkamp U, Engert A, Kocher M, Skripnitchenko R, Brillant C, Sehlen S, Dühmke E, Diehl V, Müller R-P. Biophysical analysis of the acute toxicity of radiotherapy in Hodgkin’s Lymphoma – a comparison between extended field and involved field radiotherapy based on the data of the German Hodgkin Study Group (GHSG). Int J Radiat Oncol Biol Phys 2005; 63 (3): 860-865.
  • Eich HT, Staar S, Gossmann A, Engert A, Franklin J, Krug B, Diehl V, Lackner K, Müller R-P. The HD 12 panel of the German Hodgkin Lymphoma Study Group (GHSG) – A quality assurance program based on a multidisciplinary panel reviewing all patients` imaging. Am J Clin Oncol 2004; 27 (3): 279-284.
  • Eich HT, Staar S, Gossmann A, Hansemann K, Skripnitchenko R, Kocher M, Semrau R, Engert A, Josting A, Franklin J, Krug B, Diehl V, Müller R-P. Centralized radiation oncological review of cross-sectional imaging of Hodgkin’s disease leads to significant changes of the required involved field – results of a quality assurance program of the German Hodgkin Study Group (GHSG). Int J Radiat Oncol Biol Phys 2004; 58 (4): 1121-1127.
  • Eich HT, Müller R-P, Schneeweiss A, Hansemann K, Semrau R, Willich N, Rübe C, Sehlen S, Hinkelbein M, Diehl V. Initiation of a teleradiotherapeutic network for patients in German lymphoma studies. Int J Radiat Oncol Biol Phys 2004; 58 (3): 805-808.