Prospective International Cohort Study Demonstrates Inability of Interim PET to Predict Treatment Failure in Diffuse Large B-Cell Lymphoma

Robert Carr*, Stefano Fanti, Diana Paez, Juliano Cerci, Tamas Gyoerke, Francisca Redondo, Tim P. Morris, Claudio Meneghetti, Chirayu Auewarakul, Reena Nair, Charity Gorospe, June-Key Chung, Isinsu Kuzu, Monica Celli, Sumeet Gujral, Rose Ann Padua, Maurizio Dondi, IAEA Lymphoma Study Grp

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    61 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 2014

    Keywords

    • diffuse large B-cell lymphoma
    • positron emission tomography
    • prospective observational study
    • risk stratification
    • risk-adapted therapy
    • POSITRON-EMISSION-TOMOGRAPHY
    • NON-HODGKINS-LYMPHOMA
    • CHEMOTHERAPY PLUS RITUXIMAB
    • PROGNOSTIC VALUE
    • CRITERIA
    • SCANS
    • SURVIVAL
    • CYCLES
    • SUVMAX
    • TRIALS

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