Rochelle Bagatell1, Kieran McHugh2, Arlene Naranjo2, Collin Van Ryn2, Chaim Kirby2, Penelope Brock2, Karen A Lyons2, Lisa J States2, Yesenia Rojas2, Alexandra Miller2, Sam L Volchenboum2, Thorsten Simon2, Barbara Krug2, Sabine Sarnacki2, Dominique Valteau-Couanet2, Dietrich von Schweinitz2, Birgit Kammer2, Claudio Granata2, Luca Pio2, Julie R Park2, Jed Nuchtern2. 1. Rochelle Bagatell, Lisa J. States, and Alexandra Miller, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA; Arlene Naranjo and Collin Van Ryn, University of Florida, Gainesville, FL; Chaim Kirby and Sam L. Volchenboum, University of Chicago, Chicago, IL; Karen A. Lyons, Yesenia Rojas, and Jed Nuchtern, Texas Children's Hospital and Baylor College of Medicine, Houston, TX; Julie R. Park, Seattle Children's Hospital and University of Washington, Seattle, WA; Kieran McHugh and Penelope Brock, Great Ormond Street Hospital for Children, London, United Kingdom; Thorsten Simon and Barbara Krug, University of Cologne Medical School, Cologne; Dietrich von Schweinitz and Birgit Kammer, Dr von Hauner Children's Hospital and University of Munich, Munich, Germany; Sabine Sarnacki, Hopital Necker-Enfants Malades and Paris Descartes University; Dominique Valteau-Couanet, Institut Gustave Roussy, Universite Paris Sud, Paris, France; and Claudio Granata and Luca Pio, Istituto Giannina Gaslini, Genoa, Italy. bagatellr@email.chop.edu. 2. Rochelle Bagatell, Lisa J. States, and Alexandra Miller, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA; Arlene Naranjo and Collin Van Ryn, University of Florida, Gainesville, FL; Chaim Kirby and Sam L. Volchenboum, University of Chicago, Chicago, IL; Karen A. Lyons, Yesenia Rojas, and Jed Nuchtern, Texas Children's Hospital and Baylor College of Medicine, Houston, TX; Julie R. Park, Seattle Children's Hospital and University of Washington, Seattle, WA; Kieran McHugh and Penelope Brock, Great Ormond Street Hospital for Children, London, United Kingdom; Thorsten Simon and Barbara Krug, University of Cologne Medical School, Cologne; Dietrich von Schweinitz and Birgit Kammer, Dr von Hauner Children's Hospital and University of Munich, Munich, Germany; Sabine Sarnacki, Hopital Necker-Enfants Malades and Paris Descartes University; Dominique Valteau-Couanet, Institut Gustave Roussy, Universite Paris Sud, Paris, France; and Claudio Granata and Luca Pio, Istituto Giannina Gaslini, Genoa, Italy.
Abstract
PURPOSE: The International Neuroblastoma Response Criteria (INRC) require serial measurements of primary tumors in three dimensions, whereas the Response Evaluation Criteria in Solid Tumors (RECIST) require measurement in one dimension. This study was conducted to identify the preferred method of primary tumor response assessment for use in revised INRC. PATIENTS AND METHODS: Patients younger than 20 years with high-risk neuroblastoma were eligible if they were diagnosed between 2000 and 2012 and if three primary tumor measurements (antero-posterior, width, cranio-caudal) were recorded at least twice before resection. Responses were defined as ≥ 30% reduction in longest dimension as per RECIST, ≥ 50% reduction in volume as per INRC, or ≥ 65% reduction in volume. RESULTS: Three-year event-free survival for all patients (N = 229) was 44% and overall survival was 58%. The sensitivity of both volume response measures (ability to detect responses in patients who survived) exceeded the sensitivity of the single dimension measure, but the specificity of all response measures (ability to identify lack of response in patients who later died) was low. In multivariable analyses, none of the response measures studied was predictive of outcome, and none was predictive of the extent of resection. CONCLUSION: None of the methods of primary tumor response assessment was predictive of outcome. Measurement of three dimensions followed by calculation of resultant volume is more complex than measurement of a single dimension. Primary tumor response in children with high-risk neuroblastoma should therefore be evaluated in accordance with RECIST criteria, using the single longest dimension.
PURPOSE: The International Neuroblastoma Response Criteria (INRC) require serial measurements of primary tumors in three dimensions, whereas the Response Evaluation Criteria in Solid Tumors (RECIST) require measurement in one dimension. This study was conducted to identify the preferred method of primary tumor response assessment for use in revised INRC. PATIENTS AND METHODS: Patients younger than 20 years with high-risk neuroblastoma were eligible if they were diagnosed between 2000 and 2012 and if three primary tumor measurements (antero-posterior, width, cranio-caudal) were recorded at least twice before resection. Responses were defined as ≥ 30% reduction in longest dimension as per RECIST, ≥ 50% reduction in volume as per INRC, or ≥ 65% reduction in volume. RESULTS: Three-year event-free survival for all patients (N = 229) was 44% and overall survival was 58%. The sensitivity of both volume response measures (ability to detect responses in patients who survived) exceeded the sensitivity of the single dimension measure, but the specificity of all response measures (ability to identify lack of response in patients who later died) was low. In multivariable analyses, none of the response measures studied was predictive of outcome, and none was predictive of the extent of resection. CONCLUSION: None of the methods of primary tumor response assessment was predictive of outcome. Measurement of three dimensions followed by calculation of resultant volume is more complex than measurement of a single dimension. Primary tumor response in children with high-risk neuroblastoma should therefore be evaluated in accordance with RECIST criteria, using the single longest dimension.
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