title: The effect of biological heterogeneity on R-CHOP treatment outcome in diffuse large B-cell lymphoma across five international regions.
abstract: Addressing the global burden of cancer, understanding its diverse biology, and promoting appropriate prevention and treatment strategies around the world has become a priority for the United Nations and International Atomic Energy Agency (IAEA), the WHO, and International Agency for Research on Cancer (IARC). The IAEA sponsored an international prospective cohort study to better understand biology, treatment response, and outcomes of diffuse large B-cell lymphoma (DLBCL) in low and middle-income countries across five UN-defined geographical regions. We report an analysis of biological variation in DLBCL across seven ethnic and environmentally diverse populations. In this cohort of 136 patients treated to a common protocol, we demonstrate significant biological differences between countries, characterized by a validated prognostic gene expression score (p < .0001), but International Prognostic Index (IPI)-adjusted survivals in all participating countries were similar. We conclude that DLBCL treatment outcomes in these populations can be benchmarked to international standards, despite biological heterogeneity.
authors.affiliation: a Department of Haematology , Guy's & St. Thomas' Hospital, King's College , London , UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Carr
authors.affiliation: b Biotechnology Institute, Ankara University , Ankara , Turkey.
authors.forename: Hilal
authors.initials: H
authors.lastname: Ozdag
authors.affiliation: b Biotechnology Institute, Ankara University , Ankara , Turkey.
authors.forename: Nilgun
authors.initials: N
authors.lastname: Tekin
authors.affiliation: c Medical Research Council Clinical Trials Unit , University College London , London , UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Morris
authors.affiliation: d Facultad de Medicina Clínica Alemana, Universidad del Desarrollo , Santiago , Chile.
authors.forename: Paulette
authors.initials: P
authors.lastname: Conget
authors.affiliation: d Facultad de Medicina Clínica Alemana, Universidad del Desarrollo , Santiago , Chile.
authors.forename: Flavia
authors.initials: F
authors.lastname: Bruna
authors.affiliation: e 1st Department of Pathology and Experimental Cancer Research , Semmelweis University , Budapest , Hungary.
authors.forename: Botond
authors.initials: B
authors.lastname: Timar
authors.affiliation: e 1st Department of Pathology and Experimental Cancer Research , Semmelweis University , Budapest , Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Gagyi
authors.affiliation: f Department of Medical Oncology and Pathology , Tata Memorial Hospital , Mumbai , India.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Basak
authors.affiliation: f Department of Medical Oncology and Pathology , Tata Memorial Hospital , Mumbai , India.
authors.forename: Omkar
authors.initials: O
authors.lastname: Naik
authors.affiliation: g Chulabhorn Cancer Centre, Siriraj Hospital , Bangkok , Thailand.
authors.forename: Chirayu
authors.initials: C
authors.lastname: Auewarakul
authors.affiliation: g Chulabhorn Cancer Centre, Siriraj Hospital , Bangkok , Thailand.
authors.forename: Narongrit
authors.initials: N
authors.lastname: Srithana
authors.affiliation: h Research and Biology Division , St. Luke's Medical Centre , Manila , Philippines.
authors.forename: Mark Pierre
authors.initials: MP
authors.lastname: Dimamay
authors.affiliation: h Research and Biology Division , St. Luke's Medical Centre , Manila , Philippines.
authors.forename: Filipinas
authors.initials: F
authors.lastname: Natividad
authors.affiliation: i Oncology Clinic , Seoul National University Hospital , Seoul , Republic of Korea.
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.affiliation: b Biotechnology Institute, Ankara University , Ankara , Turkey.
authors.forename: Nevin
authors.initials: N
authors.lastname: Belder
authors.affiliation: j Department of Pathology , Ankara University , Ankara , Turkey.
authors.forename: Isinsu
authors.initials: I
authors.lastname: Kuzu
authors.affiliation: k Department of Haematology , University of Cardiff , Cardiff , UK.
authors.forename: Nader
authors.initials: N
authors.lastname: Omidvar
authors.affiliation: l Nuclear Medicine Section, International Atomic Energy Agency , Vienna , Austria.
authors.forename: Diana
authors.initials: D
authors.lastname: Paez
authors.affiliation: m INSERM 1131 , University Paris-Diderot, Hôpital Saint-Louis , Paris , France.
authors.forename: Rose Ann
authors.initials: RA
authors.lastname: Padua
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D014943:Global Health; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: DLBCL; gene expression; prognosis; risk stratification