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Evaluation of response to fractionated radioimmunotherapy with ⁹⁰Y-epratuzumab in non-Hodgkin’s lymphoma by ¹⁸F-fluorodeoxyglucose positron emission tomography

¹ Nuclear Medicine Department, University Hospital, Nantes
² Nuclear Medicine Department, René Gauducheau Cancer Center, Nantes, France
³ INSERM Unit 892, Cancerology Center, Nantes
⁴ Radiology Department, University Hospital, Nantes
⁵ Hematology Department, University Hospital, Lille
⁶ Hematology Department, University Hospital, Nantes
⁷ Statistical Department, René Gauducheau Cancer Center, Nantes, France
⁸ Immunomedics Inc., Morris Plains, NJ, USA
⁹ Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ, USA
¹⁰ Nuclear Medicine Department, University Hospital, Lille, France

Correspondence: Françoise Kraeber-Bodéré, Nuclear Medicine Department, University Hospital, Place Alexis Ricordeau, 44093 Nantes cedex 1, France. Phone: +33.2.40084747. Fax: +33.2.40356697. E-mail: francoise.bodere{at}chu-nantes.fr

Background: The study aimed to evaluate FDG-PET imaging for early prediction of response to radioimmunotherapy in patients with non-Hodgkin’s lymphoma.

Design and Methods: Twenty-seven patients from a large ongoing, multicenter, phase I/II trial of fractionated radioimmunotherapy using anti-CD22 ⁹⁰Y-epratuzumab underwent FDG-PET imaging. They also underwent assessment by conventional diagnostic methods that included chemotherapy at baseline and six weeks post-radioimmunotherapy, and every three months until progression. Responses evaluated from conventional methods were classified using International Workshop Response Criteria as complete response, unconfirmed CR, partial response, stable disease, or progression of disease. FDG-PET images were evaluated visually and were classified as complete response, partial response or progression of disease. The gold standard was histology and follow-up.

Results: A total of 81 paired imaging studies were obtained post-radioimmunotherapy (including 3 patients after retreatment) and evaluated as complete response (n=34), partial response (n=24) or progression of disease (n=23) by FDG-PET, and complete response (n=12), unconfirmed complete response (n=31), partial response (n=15), stable disease (n=8) or progression of disease (n=15) by conventional methods. Of the 31 responses evaluated as unconfirmed complete response by conventional methods, 20 (65%) were classified as negative for disease (complete response) by PET while the other 11 (35%) were positive for disease (7 partial response and 4 progression of disease). Among 22 assessable PET images acquired at six weeks post-radioimmunotherapy, the mean time-to-progression was 15.6 months when PET was negative for disease (complete response), compared with 5.4 months when PET was positive (partial response or progression of disease) (p=0.008). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET six weeks after radioimmunotherapy were 86%, 63%, 80%, 71% and 77% respectively, compared with 36%, 87%, 83%, 44% and 55% respectively using conventional methods.

Conclusions: A positive assessment of disease by PET acquired six weeks after radioimmunotherapy corresponded with a shorter time to progression.

Key words: CD22, FDG-PET, non-Hodgkin’s lymphoma, radioimmunotherapy, tumor response.