Prospective international cohort study demonstrates inability of interim PET to predict treatment failure in diffuse large B-cell lymphoma

IAEA Lymphoma Study Group

Research output: Article

30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1936-1944
Number of pages9
JournalJournal of Nuclear Medicine
Volume55
Issue number12
DOIs
Publication statusPublished - dec. 1 2014

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Lymphoma, Large B-Cell, Diffuse
Treatment Failure
Cohort Studies
Confidence Intervals
Disease-Free Survival
Drug Therapy
Survival
Nuclear Energy
Delivery of Health Care
Republic of Korea
Philippines
Hungary
Chile
Biodiversity
Vincristine
Thailand
Therapeutics
Prednisolone
Positron-Emission Tomography
Cyclophosphamide

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

@article{e5c8a6b0606a4dc1ab5bd38c3078cafe,
title = "Prospective international cohort study demonstrates inability of interim PET to predict treatment failure in diffuse large B-cell lymphoma",
abstract = "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.",
keywords = "Diffuse large B-cell lymphoma, Positron emission tomography, Prospective observational study, Risk stratification, Risk-adapted therapy",
author = "{IAEA Lymphoma Study Group} and Robert Carr and Stefano Fanti and Diana Paez and Juliano Cerci and Tam{\'a}s Gy{\"o}rke and Francisca Redondo and Morris, {Tim P.} and Claudio Meneghetti and Chirayu Auewarakul and Reena Nair and Charity Gorospe and Chung, {June Key} and Isinsu Kuzu and Monica Celli and Sumeet Gujral and Padua, {Rose Ann} and Maurizio Dondi and Noura El-Haj and Artur Coutinho and Jose Soares and Debora Levy and Segio Bydtowsky and Juliana Pereria and Renata Costa and Sheila Coelho and Francisco Redondo and Paulette Conget and Eva Bustamante and Flavia Bruna and T. Masszi and Botond Tim{\'a}r and {\'A}gota Szepesi and Andrea Sipos and J. Demeter and L. Gergely and Ildik{\'o} Garai and Venkatesh Rangarajan and Ranjan Basak and Zinzani, {Pier Luigi} and Kang, {Keon Wook} and Eo, {Jae Seon} and Campo, {Maejoy Vena} and Filipinas Natividad and Dinamay, {Mark Piere} and Narongrit Sritana and Hilal Ozdag and Nilgun Tekin and Ozem Kucuk and Gulseren Aras and Melike Ozbilgin",
year = "2014",
month = "12",
day = "1",
doi = "10.2967/jnumed.114.145326",
language = "English",
volume = "55",
pages = "1936--1944",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "12",

}

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, T.

AU - Timár, Botond

AU - Szepesi, Ágota

AU - Sipos, Andrea

AU - Demeter, J.

AU - Gergely, L.

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

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

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U2 - 10.2967/jnumed.114.145326

DO - 10.2967/jnumed.114.145326

M3 - Article

C2 - 25429159

AN - SCOPUS:84915770565

VL - 55

SP - 1936

EP - 1944

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

IS - 12

ER -