Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients

P L Zinzani, S Fanti, G Battista, M Tani, P Castellucci, V Stefoni, L Alinari, M Farsad, G Musuraca, A Gabriele, E Marchi, C Nanni, R Canini, N Monetti, M Baccarani, P L Zinzani, S Fanti, G Battista, M Tani, P Castellucci, V Stefoni, L Alinari, M Farsad, G Musuraca, A Gabriele, E Marchi, C Nanni, R Canini, N Monetti, M Baccarani

Abstract

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41 CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0 out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET(-)/CT(+) (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

Figures

Figure 1
Figure 1
RFS curves of patients with PET negativity (n=59) or PET positivity (n=16) after induction treatment.
Figure 2
Figure 2
FDG PET (maximum intensity projection – MIP-image) showing no area of increased uptake. PET transaxial image shows no left lung increased uptake; corresponding transaxial CT image shows an equivocal subpleural area of consolidation in the left lower lobe. After lobectomy, this finding turned out to be benign (fibrosis and necrosis).
Figure 3
Figure 3
FDG PET (maximum intensity projection – MIP-image) showing an area of increased uptake in a left latero-crevical lymph node and a second area of increased uptake in abdomen, likely consistent with juxtaintestinal lymph node. Corresponding transaxial PET and CT images show the enlarged left laterocervical lymph node. Biopsy was positive for lymphoma relapse.

References

    1. A predictive model for aggressive non-Hodgkin's lymphoma (1993) The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 32: 987–994
    1. Armitage JO, Weisenburger DD, Hutchins M, Moravec DF, Dowling M, Sorensen S, Mailliard J, Okerbloom J, Johnson PS, Howe D (1986) Chemotherapy for diffuse large-cell lymphoma-rapidly responding patients have more durable remissions. J Clin Oncol 4: 160–164
    1. Becherer A, Mitterbauer M, Jaeger U, Kalhs P, Greinix HT, Karanikas G, Potzi C, Raderer M, Dudczak R, Kletter K (2002) Positron emission tomography with [18F]2-flouro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation. Leukemia 16: 260–267
    1. Bonadonna G, Zucali R, De Lena M, Valagussa P (1977) Combined chemotherapy (MOPP or ABVD)–radiotherapy approach in advanced Hodgkin's disease. Cancer Treat Rep 61: 769–777
    1. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (2000) Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. (J Clin Oncol 1999; 17: 1244; Erratum in J Clin Oncol18: 2351)
    1. Cremerius U, Fabry U, Neuerburg J, Zimny M, Osieka R, Bull U (1998) Positron emission tomography with 18F-FDG to detect residual disease after therapy for malignant lymphoma. Nucl Med Commun 19: 1055–1063
    1. Cremerius U, Fabry U, Neuerburg J, Zimmy M, Bares R, Osieka R, Bull U (2001) Prognostic significance of positron emission tomography using fluorine-18-fluorodeoxyglucose in patients treated for malignant lymphoma. Nuklearmedizin 40: 23–30
    1. Cremerius U, Fabry U, Wildberger JE, Zimny M, Reinartz P Nowak B, Schaefer W, Buell U, Osieka R (2002) Pretransplant positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose (FDG) predicts outcome in patients treated with high-dose chemotherapy and autologous stem cell transplantation for non Hodgkin's lymphoma. Bone Marrow Transplant 30: 103–111
    1. DeVita Jr VT, Mauch PM, Harris NL (1997) Hodgkin's disease. In Cancer, DeVita Jr VT, Hellman S, Rosenberg SA (eds). 5th edn, Vol 224 Philadelphia: Lippincott
    1. de Wit M, Bohuslavizki KH, Buchert R, Bumann D, Clausen M, Hossfeld DK (2001) 18 FDG-PET following treatment as valid predictor for disease-free survival in Hodgkin's lymphoma. Ann Oncol 12: 29–37
    1. Dittmann H, Sokler M, Kollmannsberger C, Dohmen BM, Baumann C, Kopp A, Bares R, Claussen CD, Kanz L, Bokemeyer C (2001) Comparison of 18FDG-PET with CT scans in the evaluation of patients with residual and recurrent Hodgkin's lymphoma. Oncol Rep 8: 1393–1399
    1. Fihnont JE, Czenin J, Yap C (2003) Value of f-18 fluorodeoxyglucose positron emission tomography for predicting the clinical outcome of patients with aggressive lymphoma prior to and after autologous stem-cell transplantation. Chest 124: 608–613
    1. Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G (1997) High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med 336: 1290–1297
    1. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC (1994) A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84: 1361–1392
    1. Hasenclever D, Diehl V (1998) A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's disease. N Engl J Med 339: 1506–1514
    1. Hill M, Cunningham D, MacVicar D, Roldan A, Husband J, McCready R, Mansi J, Milan S, Hickish T (1993) Role of magnetic resonance imaging in predicting relapse in residual masses after treatment of lymphoma. J Clin Oncol 11: 2273–2278
    1. Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, Fillet G (2001) Whole-body positron emission tomography using 18 F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin's diseas. Haematologica 86: 266–273
    1. Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, Fillet G (1999) Whole-body positron emission tomography using 18 F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 94: 429–433
    1. Kaplan ES, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481
    1. Klimo P, Connors JM (1985) MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med 102: 596–602
    1. Kostakoglu L, Yeh SD, Portlock C, Heelan R, Yao TJ, Niedzwiecki D, Larson SM (1992) Validation of gallium-67-citrate single-photon emission computed tomography in biopsy-confirmed residual Hodgkin's disease in the mediastinum. J Nucl Med 33: 345–350
    1. Kostakoglu L, Goldsmith SJ (2000) Fluorine-18 fluorodeoxyglucose positron emission tomography in the staging and follow-up of lymphoma: is it time to shift gears? Eur J Nucl Med 27: 1564–1578
    1. Mantel H, Haenzel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719–748
    1. Naumann R, Vaic A, Beuthien-Baumann B, Bredow J, Kropp J, Kittner T, Franke WG, Ehninger G (2001) Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Br J Haematol 115: 793–800
    1. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5: 649–655
    1. Setoain FJ, Pons F, Herranz R, Vidal-Sicart S, Lomena F, Ayuso C, Montserrat E, Setoain J (1997) 67 Ga scintigraphy for the evaluation of recurrences and residual masses in patients with lymphoma. Nucl Med Commun 18: 405–411
    1. Spaepen K, Stroobants S, Dupont P, Van Steenweghen S, Thomas J, Vandenberghe P, Vanuytsel L, Bormans G, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G (2001a) Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18 F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: is [18 F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol 19: 414–419
    1. Spaepen K, Stroobants S, Dupont P, Thomas J, Vandenberghe P, Balzarini J, De Wolf-Peeters C, Motelmans L, Verhoef G (2001b) Can positron emission tomography with [(18) F]-fluorodeoxyglucose after first-line treatment distinguish Hodgkin's disease patients who need additional therapy from others in whom additional therapy would mean avoidable toxicity? Br J Haematol 115: 272–278
    1. Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Thomas J, de Groot T, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G (2002) Early restaging positron emission tomography with 18F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann Oncol 13: 1356–1363
    1. Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Maertens J, Bormans G, Thomas J, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G (2003) Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood 102: 53–59
    1. Visvikis D, Ell PJ (2003) Impact of technology on the utilisation of positron emission tomography in lymphoma: current and future perspectives. Eur J Nucl Med Mol Imaging 30: 106–116
    1. Weihrauch MR, Re D, Scheidhauer K, Ansen S, Dietlein M, Bischoff S, Bohlen H, Wolf J, Schicha H, Diehl V, Tesch H (2001) Thoracic positron emission tomography using 18 F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease. Blood 98: 2930–2934
    1. Weihrauch MR, Dietlein M, Schicha H, Diehl V, Tesch H (2003) Prognostic significance of 18F-fluorodeoxyglucose positron emission tomography in lymphoma. Leuk Lymphoma 44: 15–22
    1. Zinzani PL, Zompatori M, Bendandi M, Battista G, Fanti S, Barbieri E, Gherlinzoni F, Rimondi MR, Frezza G, Pisi P, Merla E, Gozzetti A, Canini R, Monetti N, Babini L, Tura S (1996) Monitoring bulky mediastinal disease with gallium-67, CT-scan and magnetic resonance imaging in Hodgkin's disease and high-grade non-Hodgkin's lymphoma. Leuk Lymphoma 22: 131–135
    1. Zinzani PL, Martelli M, Magagnoli M, Pescarmona E, Scaramucci L, Palombi F, Bendandi M, Martelli MP, Ascani S, Orcioni GF, Pileri SA, Mandelli F, Tura S (1999a) Treatment and clinical management of primary mediastinal large B-cell lymphoma with sclerosis: MACOP-B regimen and mediastinal radiotherapy monitored by 67-Gallium scan in 50 patients. Blood 94: 3289–3293
    1. Zinzani PL, Magagnoli M, Chierichetti F, Zompatori M, Garraffa G, Bendandi M, Gherlinzoni F, Cellini C, Stefoni V, Ferlin G, Tura S (1999b) The role of positron emission tomography (PET) in the management of lymphoma patients. Ann Oncol 10: 1181–1184
    1. Zinzani PL, Chierichetti F, Zompatori M, Tani M, Stefoni V, Garraffa G, Albertini P, Alinari L, Ferlin G, Baccarani M, Tura S (2002) Advantages of positron emission tomography (PET) with respect to computed tomography in the follow-up of lymphoma patients with abdominal presentation. Leuk Lymphoma 43: 1239–1243

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren