2010, Number 1
Gallium Scan after the Second and Fourth Chemotherapy Cycle is Predictive in Aggressive Non-Hodgkin’s Lymphomas
PDF size: 154.91 Kb.
ABSTRACTPurpose: To evaluate utility of gallium scans as a predictor of survival and response duration in patients with aggressive NHL.
Patients and Methods: From 1992 to 1996, 190 patients with aggressive non-Hodgkin’s lymphoma (NHL) were enrolled in two different anthracyclin-containing treatment protocols. One hundred-sixteen of these patients (61%) had an International Prognostic Score (IPI), of low, and low-intermediate risk; 74 (39%) had high-intermediate and high-risk. All patients had positive gallium scans (Ga67) prior to initiation of chemotherapy, and additional scans were performed after cycles two (n=139), four (n=113), and six (n=24) of chemotherapy. Patients also received radiation to known sites of bulky disease.
Results: Patients whose gallium scan remained positive after two courses of chemotherapy had a median overall survival (OS) of only 23 months compared to a median OS of 107 months for those whose gallium scans turned negative (p=.00434). Similarly, Ga67 positivity after two cycles of chemotherapy was associated with a disease-free survival (DFS) of 6.6 months compared to 106 months for those who had Ga-67 negativity (p=.00279). After four courses of chemotherapy, persistent Ga67- positivity also correlated with a shorter median OS (14.6 months vs. 102.5 months respectively, p=.00092) and a shorter median DFS (6.2 months vs. 90 months respectively, p=.00006). By Cox regression analysis, the result of the gallium scan was independent of the International Prognostic Index (IPI) as a predictor of poor outcomes in aggressive NHL.
Conclusions: Persistent gallium scan positivity after two, four, or six cycles of chemotherapy identifies a group of patients with great tendency for early disease progression and poor overall survival. The effect appears to be independent of IPI. This test targets patients with disease which has intrinsic resistance to their treatment and who may benefit from more aggressive and innovative therapies such as early intensification.
Shipp MA, Harington DP, Anderson JR, et al. A predictive model for aggressive NHL: The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med 1993;329:987-994.
Swan F, Velasquez WS, Tucker S, et al. A new serologic system for the large-cell lymphomas based on initial b2- microglobulin and lactate dehydrogenase levels. J Clin Oncol 1989;7:1518-1527.
Seymour JF, Talpaz M, Cabanillas F, et al. Serum Interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma. J Clin Oncol 1995;13:575-582.
Miller TP, Grogan TM, Dahlberg S, et al. Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin’s lymphomas: A prospective Southwest Oncology Group Trial. Blood 1994;83:1460-1466.
Rodriguez J, Cabanillas F, McLaughlin F, et al. A proposal for a simple staging system for intermediate grade lymphoma and immunoblastic lymphoma based on the “tumor score”. Annals Oncol 1992;3:711-717.
Coiffier B, Bryon PA, Berger F, et al. Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (Protocol LNH-80). J Clin Oncol 1986;4:147-153.
Armitage JO, Weisenburger DD, Hutchins M, et al. Chemotherapy for diffuse large-cell lymphoma -Rapidly responding patients have more durable remission. J Clin Oncol 1986;4:160-164.
Amadori S, Guglielmi C, Anselmo AP, et al. Treatment of diffuse aggressive NHL with intensive multidrug regimen included high dose cytosine arabinoside (F-MACHOP). Semin Oncol 1985;12:218-222.
Vitolo U, Bertini M, Tarella C, Bertoncelli MC, et al. MACOP -B treatment for advanced stage diffuse large cell lymphomas: A multicentre Italian study. Eur J Cancer Clin Oncol 1989;25:1441-1449.
Guglielmi C, Amadori S, Ruco LP, et al. Combination chemotherapy for the treatment of diffuse aggressive lymphomas: F-MACHOP update. Semin Oncol 1987;14:104-109.
Anderson JR, Ginsberg S, Gottlieb AJ. Chemotherapy of diffuse large cell lymphoma -Rapidly responding patients have more durable remissions. J Clin Oncol 1986;4:1420-1421. (Letter)
Gordon LI, Harrington D, Andersen J, et al. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with standard regimen (CHOP) for advanced diffuse non-Hodgkin’s lymphoma. N Engl J Med 1992;327:1342-1349.
Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med 1993;328:1002-1006.
Radford JA, Cowan RA, Flanagan M, et al. The significance of residual mediastinal abnormality on the chest radiograph following treatment for Hodgkin’s disease. J Clin Oncol 1988;6:940-946.
Surbone A, Longo D, DeVita V, et al. Residual abdominal masses in aggressive non-Hodgkin’s lymphoma after combination chemotherapy: significance and management. J Clin Oncol 1988;6:1832-1837.
Canellos GP. Residual mass in lymphoma may not be residual disease (Editorial). J Clin Oncol 1988;6:931-932.
Pappa VI, Hussain HK, Reznek RH, et al. Role of imageguided core-needle biopsy in the management of patients with lymphoma. J Clin Oncol 1996;14:2427-2430.
Anderson KC, Leonard RCF, Canellos GP, et al. High-dose Gallium imaging in lymphoma. Am J Med 1983;75:327-331.
Israel O, Front D, Lam M, et al. Gallium 67 imaging in monitoring lymphoma response to treatment. Cancer 1988;61:2439-2443.
Kaplan WD, Jochelson MS, Herman TS, et al. Gallium-67 imaging: A predictor of residual tumor viability and clinical outcome in patients with diffuse large cell lymphoma. J Clin Oncol 1990:8:1966-1970.
Holman BL, Tumeh SS. Single-photon emission computed tomography (SPECT). Applications and potential. JAMA 1990;263:561-564.
Weeks JC, Yeap BY, Canellos GP, et al. Value of follow-up procedures in patients with large-cell lymphoma who achieved complete remission. J Clin Oncol 1991;9:1193-1203.
Front D, Ben-Haim S, Israel O, Epelbaum R, et al. Predictive value of Ga-67 scintigraphy after treatment. Radiology 1992;182:359-363.
Front D, Bar-Shalom R, Epelbaum R, et al. Early detection of lymphoma recurrence with Gallium-67 scintigraphy. J Nucl Med 1993;34:2101-2104.
Front D, Israel O. The role of Gallium-67 in evaluating the results of therapy of lymphoma patients. Semin Nucl Med 1995;25:60-71.
Even-Sapir E, Bar Shalom R, Israel O, et al. Single-photon emission computed tomography quantification of gallium citrate uptake for the differentiation of lymphoma from benign hilar uptake. J Clin Oncol 1995;13:942-946.
Vose JM, Bierman PJ, Anderson JR, et al. Single-photon emission computed tomography gallium imaging versus computed tomography: Predictive values in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation for non-Hodgkin’s lymphoma. J Clin Oncol 1996;14:2473-2479.
Janicek M, Kaplan W, Neuberg D, et al. Early restaging gallium predicts outcome in poor-prognosis patients with aggressive non-Hodgkin’s Lymphoma treated with high-dose CHOP chemotherapy. J Clin Oncol 1997;15:1631-1637.
Zinzani PL, Magagnoli M, Franchi R, et al. Diagnostic role of gallium scanning in the management of lymphoma with mediastinal involvement. Hematological 1999;84(7): 604-607.
Front D, Bar-Shalom R, Mor M, et al. Aggressive non-Hodgkin lymphoma: early prediction of outcome with 67Ga scintigraphy. Radiology 2000;214(1):253-257.
Israel O, Mor M, Epelbaum R, et al. Clinical pretreatment risk factors and Ga-67 scintigraphy early during treatment for prediction of outcome of patients with aggressive non-Hodgkin lymphoma. Cancer 2002;94(4):873-878.
Gasparini M, Bombardieri E, Castellani M, et al. Gallium-67 scintigraphy evaluation of therapy in non-Hodgkin’s lymphoma. J Nucl Med 1998;39(9):1586-1590.
Tuli MN, Al-Shemmari SH, Ameen RM, et al. The use of gallium-67 scintigraphy to monitor tumor response rates and predict long-term clinical outcome in patients with lymphoma. Clin Lymphoma 2004;5(1):56-61.
Rodriguez J, Cabanillas F, McLaughlin P, et al. A proposal for a simple staging system for intermediate grade lymphoma and immunoblastic lymphoma based on the ‘tumor score’. Ann Oncol 1992;3(9):711-717.
Cabanillas F, Rodriguez-Diaz Pavon J, Hagemeister FB, McLaughlin P, et al. Alternating triple therapy for the treatment of intermediate grade and immunoblastic lymphoma. Ann Oncol 1998;9(5):511-518.
Kaplan E, Meier P. Non-parametric estimation for incomplete observations. J Am Stat Assoc 1958;53:457-481.
Brice P, Rain JD, Frija J. Value of imaging for the diagnosis of residual mediastinal mass in malignant lymphomas. Nouv Rev Fr Hematol 1991;33:531-532.
Hill M, Cunningham D, MacVicar D, et al. Role of magnetic resonance imaging in predicting relapse in residual masses after treatment of lymphoma. J Clin Oncol 1993;11:2273-2278.
Devizzi L, Maffioli L, Bonfante V, et al. Comparison of gallium scan. Computed tomography, and magnetic resonance in patients with mediastinal Hodgkin’s disease. Ann Oncol 1997;8(Suppl 1):S53-S56.
Rˆmer W, Hanauske A-R, Ziegler S, et al. Positron emission tomography in non-Hodgkin’s lymphoma: Assessment of chemotherapy with fluorodeoxyglucose. Blood 1998;91:4464-4471.
Kostakoglu L, Leonard JP, Kuji I, et al. Comparison of fluorine-18 fluorodeoxyglucose position emission tomography and Ga-67 scintigraphy in evaluation of lymphoma. Cancer 2002;94:879-888.
Wirth A, Seymour JF, Hicks RJ, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography, gallium-67 scintigraphy, and conventional staging for Hodgkin’s disease and non-Hodgkin’s lymphoma. Am J Med 2002;112:262-268.
Zijlstra JM, Hoekstra OS, Raijmakers PG, et al. 18FDG positron emisino tomography versus 67Ga scintigraphy as prognostic test during chemotherapy for non-Hodgkin’s lymphoma. Br J Haematol 2003;123:454-462.
Filmont JE, Vranjesevic D, Quon A, et al. Conventional imaging and 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography for predicting the clinical outcome of previously treated non-Hodgkin’s lymphoma patients. Mol Imaging Biol 2003;5:232-239.
Haioun C, Itti E, Rahmouni A, et al. [18F]fluor-2-deoxy-Dglucose positron emission tomografie (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood 2005;106:1376-1381.
Torizuka T, Nakamura F, Kanno T, et al. Early therapy monitoring with FDG-PET in aggressive non-Hodgkin’s lymphoma and Hodgkin’s lymphoma. Eur J Nucl Med Imaging 2003;31(1): 22-28.
Mikhaeel NG, Hutchings M, Fields PA, et al. FDG-PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma. Ann Oncol 2005;16:1514-1523.