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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Haematology, Guy's and St. Thomas' Hospital, King's College, London, United Kingdom robtcarr@gmail.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Carr
authors.affiliation: Policlinico S. Orsola Malpighi, Universita de Bologna, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fanti
authors.affiliation: Division of Human Health, Department of Nuclear Sciences and Application, International Atomic Energy Agency, Vienna, Austria.
authors.forename: Diana
authors.initials: D
authors.lastname: Paez
authors.affiliation: Quanta Diagnóstico e Terapia, Curitiba, Sâo Paulo, Brazil.
authors.forename: Juliano
authors.initials: J
authors.lastname: Cerci
authors.affiliation: ScanoMed Medical Diagnostic Ltd., Budapest, Hungary Department of Nuclear Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Györke
authors.affiliation: Oncologic Clinic, Fundación Arturo Lopez Perez, Santiago, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Redondo
authors.affiliation: Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom.
authors.forename: Tim P
authors.initials: TP
authors.lastname: Morris
authors.affiliation: Hospital de Clinicas, Universidade de Sâo Paulo, Sâo Paulo, Brazil.
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneghetti
authors.affiliation: Chulabhorn Cancer Centre and Faculty of Medicine Siriraj Hospital, Bangkok, Thailand.
authors.forename: Chirayu
authors.initials: C
authors.lastname: Auewarakul
authors.affiliation: Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.
authors.forename: Reena
authors.initials: R
authors.lastname: Nair
authors.affiliation: St Luke's Medical Centre, Manila, Philippines.
authors.forename: Charity
authors.initials: C
authors.lastname: Gorospe
authors.affiliation: Seoul National University Hospital, Seoul, South Korea.
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Department of Pathology, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Isinsu
authors.initials: I
authors.lastname: Kuzu
authors.affiliation: Policlinico S. Orsola Malpighi, Universita de Bologna, Bologna, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Celli
authors.affiliation: Department of Pathology, Tata Memorial Hospital, Mumbai, India; and.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Gujral
authors.affiliation: Université Paris-Diderot, UMRS-940, Institut d'Hématologie, Hôpital Saint-Louis, Paris, France.
authors.forename: Rose Ann
authors.initials: RA
authors.lastname: Padua
authors.affiliation: Division of Human Health, Department of Nuclear Sciences and Application, International Atomic Energy Agency, Vienna, Austria.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Dondi
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D012307:Risk Factors; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
keywords: diffuse large B-cell lymphoma; positron emission tomography; prospective observational study; risk stratification; risk-adapted therapy