TY - JOUR
T1 - Prospective international cohort study demonstrates inability of interim PET to predict treatment failure in diffuse large B-cell lymphoma
AU - IAEA Lymphoma Study Group
AU - Carr, Robert
AU - Fanti, Stefano
AU - Paez, Diana
AU - Cerci, Juliano
AU - Györke, Tamás
AU - Redondo, Francisca
AU - Morris, Tim P.
AU - Meneghetti, Claudio
AU - Auewarakul, Chirayu
AU - Nair, Reena
AU - Gorospe, Charity
AU - Chung, June Key
AU - Kuzu, Isinsu
AU - Celli, Monica
AU - Gujral, Sumeet
AU - Padua, Rose Ann
AU - Dondi, Maurizio
AU - El-Haj, Noura
AU - Coutinho, Artur
AU - Soares, Jose
AU - Levy, Debora
AU - Bydtowsky, Segio
AU - Pereria, Juliana
AU - Costa, Renata
AU - Coelho, Sheila
AU - Redondo, Francisco
AU - Conget, Paulette
AU - Bustamante, Eva
AU - Bruna, Flavia
AU - Masszi, Tamás
AU - Timár, Botond
AU - Szepesi, Ágota
AU - Sipos, Andrea
AU - Demeter, Judith
AU - Gergely, Lajos
AU - Garai, Ildikó
AU - Rangarajan, Venkatesh
AU - Basak, Ranjan
AU - Zinzani, Pier Luigi
AU - Kang, Keon Wook
AU - Eo, Jae Seon
AU - Campo, Maejoy Vena
AU - Natividad, Filipinas
AU - Dinamay, Mark Piere
AU - Sritana, Narongrit
AU - Ozdag, Hilal
AU - Tekin, Nilgun
AU - Kucuk, Ozem
AU - Aras, Gulseren
AU - Ozbilgin, Melike
N1 - Publisher Copyright:
Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). Methods: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually. Results: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. Conclusion: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.
AB - The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). Methods: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually. Results: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. Conclusion: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.
KW - Diffuse large B-cell lymphoma
KW - Positron emission tomography
KW - Prospective observational study
KW - Risk stratification
KW - Risk-adapted therapy
UR - http://www.scopus.com/inward/record.url?scp=84915770565&partnerID=8YFLogxK
U2 - 10.2967/jnumed.114.145326
DO - 10.2967/jnumed.114.145326
M3 - Article
C2 - 25429159
AN - SCOPUS:84915770565
SN - 0161-5505
VL - 55
SP - 1936
EP - 1944
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 12
ER -