Early Interim PET/CT beim Hodgkin-Lymphom des Erwachsenen – Von der Risikostratifizierung zur Therapiestratifizierung

Zusammenfassung

Die PET/CT beim Hodgkin-Lymphom, durchgeführt bereits nach wenigen Zyklen Chemotherapie als Early Interim PET/CT, unterscheidet zwischen Patienten mit günstiger und ungünstiger Prognose. Basierend auf dieser Erkenntnis untersuchen zahlreiche laufende Studien, ob bei Patienten mit günstiger Prognose weniger Chemotherapie zu gleichwertigen Überlebensraten führt bzw. ob bei Patienten mit ungünstiger Prognose die Überlebensraten verbessert werden können. Bei den hohen Heilungsraten des Hodgkin-Lymphoms ist die Anzahl der zu beobachtenden Ereignisse klein. Das macht hohe Rekrutierungszahlen erforderlich, um eine statistische Signifikanz zu erreichen. Outcome-Daten mit hohem Evidenzgrad liegen daher noch nicht vor. Die Verwendung einheitlicher Scores bei der Referenzbeurteilung zur Beschreibung der FDG-Speicherintensität im Restgewebe ist eine Vor­aussetzung, um später die Ergebnisse der verschiedenen internationalen Studien vergleichen zu können. Neben dieser Studienfrage einer PET-basierten Deeskalation bzw. Therapie-Eskalation wird die Early Interim PET/CT eingesetzt, um Pa­tienten mit Progress oder fehlendem Therapieansprechen frühzeitig von einer unwirksamen Therapie auszuschließen und individualisiert einer anderen Therapie zuzuführen.

Abstract

PET/CT in Hodgkin lymphoma, performed after few cycles of chemotherapy as early interim PET/CT, has shown a high predictive value for progression free survival (PFS). Many ongoing clinical trials evaluate whether a reduction of chemotherapy in PET-negative patients will offer an equivalent PFS, or whether an intensification of chemotherapy in PET-positive patients will improve PFS, respectively. The number of events is low as the cure rate in Hodgkin lymphoma is high. Therefore, high numbers of recruited patients are necessary to reach statistical significance. Data on outcome are not yet available. The use of comparable scores in the central review process to describe the intensity of FDG-accumulation in residual tissue is necessary to compare the results of the different international trials in the future. Additionally, early interim PET/CT is used to exclude patients with therapeutic failure or progress from an ineffective therapy as early as possible and to change management individually.

Schlüsselwörter

Hodgkin-Lymphom - PET/CT - Early Interim PET - Therapiemonitoring - Therapiekontrolle

Key words

Hodgkin lymphoma - PET/CT - early interim PET - therapy monitoring - response assessment

• Literatur

• 1 Aleman BM, van den Belt-Dusebout AW, Klokman WJ et al. Long-term cause-specific mortality of patients treated for Hodgkin’s disease. J Clin Oncol 2003; 21: 3431-3439
• 2 André MPE, Reman O, Federico M et al. Interim analysis of the randomized EORTC/Lysa/Fil Intergroup H10 trial on early PET-scan driven treatment adaptation in stage I/II Hodgkin lymphoma. Blood (ASH Annual Meeting Abstracts) 2012; 120: 549
• 3 Canellos GP. Residual mass in lymphoma may not be residual disease. J Clin Oncol 1988; 6: 931-933
• 4 Cheson BD, Pfistner B, Juweid ME et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007; 25: 579-586
• 5 Clinicaltrials.gov [Internet]. Fluorodeoxyglucose F 18 PET scan-guided therapy or standard therapy in treating patients with previously un­treated stage I or II Hodgkin’s lymphoma (EORTC/GELA/FIL). Available from http://clinicaltrials.gov/ct2/show/NCT00433433
• 6 Clinicaltrials.gov [Internet]. Response-based therapy assessed by PET-scan in treating patients with bulky stage I and stage II classical ­Hodgkin lymphoma. Available from http://clinicaltrials.gov/ct2/show/NCT01118026
• 7 Clinicaltrials.gov [Internet]. Chemotherapy based on PET scan in treating patients with stage I or stage II Hodgkin lymphoma (ECOG). Available from http://clinicaltrials.gov/ct2/show/NCT01390584
• 8 Clinicaltrials.gov [Internet]. Chemotherapy based on positron emission tomography scan in treating patients with stage I or stage II Hodgkin lymphoma (CALGB 50604). Available from http://clinicaltrials.gov/ct2/show/NCT01132807
• 9 Clinicaltrials.gov [Internet]. PET scan in planning treatment in pa­tients undergoing combination chemotherapy for stage IA or stage IIA Hodgkin lymphoma. Available from http://clinicaltrials.gov/ct2/show/NCT00943423
• 10 Clinicaltrials.gov [Internet]. Positron emission tomography (PET)-adapted chemotherapy in advanced Hodgkin lymphoma (HD0607). Available from http://clinicaltrials.gov/ct2/show/NCT00795613
• 11 Clinicaltrials.gov [Internet]. Fluorodeoxyglucose F-18-PET/CT imaging and combination chemotherapy with or without additional chemotherapy and G-CSF in treating patients with stage III or stage IV Hodg­kin lymphoma (SWOG-CALG-B). Available from http://clinicaltrials.gov/ct2/show/NCT00822120
• 12 Clinicaltrials.gov [Internet]. Study of a treatment driven by early PET response to a treatment not monitored by early PET in patients with a stage 3-4 or 2B HL (AHL 2011). Available from http://clinicaltrials.gov/ct2/show/NCT01358747
• 13 Clinicaltrials.gov [Internet]. Fluorodeoxyglucose F-18-PET/CT imaging in assessing response to chemotherapy in patients with newly diagnosed stage II, stage III, or stage IV Hodgkin lymphoma (RATHL). Available from http://clinicaltrials.gov/ct2/show/NCT00678327
• 14 Clinicaltrials.gov [Internet]. HD18 for advanced stages in Hodgkin’s lymphoma.  Available from http://clinicaltrials.gov/ct2/show/NCT00515554
• 15 Clinicaltrials.gov [Internet]. High-dose chemotherapy and stem cell transplantation in patients PET-2 positive after 2 courses of ABVD (HD0801) and comparison of RT versus no RT in PET-2 negative patients (HD0802). Available from http://clinicaltrials.gov/ct2/show/NCT00784537
• 16 Clinicaltrials.gov [Internet]. Tailored therapy for Hodgkin lymphoma using early interim therapy PET for therapy decision. Available from http://clinicaltrials.gov/ct2/show/NCT00392314
• 17 Dann EJ, Bar-Shalom R, Tamir A et al. Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high-risk Hodgkin lymphoma with no impairment of outcome. Blood 2007; 109: 905-909
• 18 Dann EJ, Bar-Shalom R, Tamir A et al. A functional dynamic scoring model to elucidate the significance of post-induction interim fluorine-18-fluorodeoxyglucose positron emission tomography findings in pa­tients with Hodgkin’s lymphoma. Haematologica 2010; 95: 1198-1206
• 19 Diehl V, Franklin J, Pfreundschuh M et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 2003; 348: 2386-2395
• 20 Dietlein M, Eich HT, Fuchs M et al. PET beim Hodgkin-Lymphom – Verbessert die Positronenemissionstomographie die Behandlung?. Der Onkologe 2010; 16: 18-27
• 21 Dietlein M, Kobe C, Kuhnert G et al. Interim PET/CT in HD18 der GHSG beim Hodgkin Lymphom – Lokale plus zentrale Interpretation und Patientensicherheit [Abstract]. Nuklearmedizin 2013; 52: A19
• 22 Engert A, Diehl V, Franklin J et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin’s lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol 2009; 27: 4548-4554
• 23 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
• 24 Furth C, Steffen IG, Amthauer H et al. Early and late response assessment with [18F]fluorodeoxyglucose positron emission tomography in pediatric Hodgkin’s lymphoma: analysis of a prospective multicenter trial. J Clin Oncol 2009; 27: 4385-4391
• 25 Furth C, Amthauer H, Hautzel H et al. Evaluation of interim PET response criteria in paediatric Hodgkin's lymphoma – results for dedicated assessment criteria in a blinded dual-centre read. Ann Oncol 2011; 22: 1198-1203
• 26 Gallamini A, Rigacci L, Merli F et al. The predictive value of posi­tron emission tomography scanning performed after two courses of standard therapy on treatment outcome in advanced stage Hodgkin’s lymphoma. Haematologica 2006; 91: 475-481
• 27 Gallamini A, Hutchings M, Rigacci L et al. Early interim 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin’s lymphoma: a report from a joint Italian-Danish study. J Clin Oncol 2007; 25: 3746-3752
• 28 Gallamini A, Kostakoglu L. Interim FDG-PET in Hodgkin lymphoma: a compass for a safe navigation in clinical trials?. Blood 2012; prepublished online August 28, 2012
• 29 Hutchings M, Loft A, Hansen M et al. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin Lymphoma. Blood 2006; 107: 52-59
• 30 Hutchings M, Mikhaeel NG, Fields PA et al. Prognostic value of interim PET after two or three cycles of chemotherapy in Hodgkin lymphoma. Ann Oncol 2005; 16: 1160-1168
• 31 Juweid ME, Stroobants S, Hoekstra OS et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the imaging subcommittee of international harmonization project in lymphoma. J Clin Oncol 2007; 25: 571-578
• 32 Kobe C, Dietlein M, Franklin J et al. Positron emission tomography has a high negative predictive value for progression or early relapse for pa­tients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma. Blood 2008; 112: 3389-3994
• 33 Kobe C, Dietlein M, Mauz-Körholz C et al. FDG-PET in Hodgkin lymphoma. Nuklearmedizin 2008; 47: 235-238
• 34 Kotzerke J, Dietlein M, Grünwald F et al. Vorbehalte der DGN zur Nutzenbewertung der PET durch das IQWiG. Nuklearmedizin 2010; 49: 6-12
• 35 Markova J, Kobe C, Skopalova M et al. FDG-PET for assessment of early treatment response after 4 cycles of chemotherapy in patients with advanced-stage Hodgkin lymphoma has a high negative predictive value. Ann Oncol 2009; 20: 1270-1274
• 36 Markova J, Kahraman D, Kobe C et al. Role of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography in early and late therapy assessment of patients with advanced Hodgkin lymphoma treated with bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine and prednisone. Leuk Lymphoma 2012; 53: 64-70
• 37 Meignan M, Gallamini A, Haioun C. Report on the first international workshop on interim-PET scan in lymphoma. Leuk Lymphoma 2009; 50: 1257-1260
• 38 Picardi M, De Renzo A, Pane F et al. Randomized comparison of consolidation radiation versus observation in bulky Hodgkin’s lymphoma with post-chemotherapy negative positron emission tomography scans. Leuk Lymphoma 2007; 48: 1721-1727
• 39 Radford J, Barrington S, Counsell N et al. Involved field radiotherapy versus no further treatment in patients with clinical stages IA and IIA Hodgkin lymphoma and a ‘negative’ PET scan after 3 cycles ABVD. Results of the UK NCRI RAPID Trial. Blood (ASH Annual Meeting Abstracts) 2012; 120: 547
• 40 Rancea M, Engert A, von Tresckow B et al. Interdisziplinäre S-3 Leitlinie zur Diagnostik, Therapie und Nachsorge des Hodgkin Lymphoms bei erwachsenen Patienten. Dtsch Ärztebl 2013; 110: C177-C183
• 41 Zinzani PL, Tani M, Fanti S et al. Early positron emission tomography (PET) restaging: a predictive final response in Hodgkin’s disease pa­tients. Ann Oncol 2006; 17: 1296-1300