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Prognostic Value of International Neuroblastoma Pathology Classification in Localized Resectable Peripheral Neuroblastic Tumors: A Histopathologic Study of Localized Neuroblastoma European Study Group 94.01 Trial and Protocol

From the Departamento de Patologia, Universidad de Valencia, Spain; Klinisches Institut für Pathologie der Medizinischen Universität Wien, Austria; Avdeling for Patologi, Rikshospitalet, Oslo, Norway; Histopathology Department, Leeds Teaching Hospitals National Health Service Trust, United Kingdom; Unita Ospedaliera di Anatomia Patologica, Ospedale San Bortolo, Vicenza; Unita Ospedaliera di Anatomia Patologica, Istituto G. Gaslini; Unita Ospedaliera di Oncoematologia Pediatrica, Istituto G. Gaslini, Genova, Italia; Service de Biostatistiques and Département d'Oncologie Pédiatrique, Institut Curie; and Service de Pathologie, Hôpital R. Debré AP-HP and EA3102 Université Paris 7, Paris, France

Address reprint requests to Samuel Navarro, MD, Department of Pathology, University of Valencia, Medical School, Valencia, Avda Blasco Ibañez 17, 46010 Valencia, Spain; e-mail: samuel.navarro{at}uv.es

PURPOSE: To assess the prognostic value of clinical, biologic, and morphologic data in peripheral neuroblastic tumors, International Neuroblastoma Staging System (INSS) stages 2A and 2B MYCN nonamplified, a multinational protocol entitled Localized Neuroblastoma European Study Group trial 94.01, with a trial of surgery as the only treatment, was initiated in 1995. We present the prognostic value of the revised International Neuroblastoma Pathology Classification (INPC) applied to the patients included in this protocol until its closure in 1999.

MATERIALS AND METHODS: A total of 120 neuroblastic tumors from trial patients were reviewed by the European International Society of Pediatric Oncology neuroblastoma pathology panel and assigned to a favorable or unfavorable prognostic category according to the INPC guidelines. Overall survival and relapse-free survival (RFS) were estimated by the Kaplan-Meier method and compared by the log-rank test.

RESULTS: A total of 115 of 120 patients were assessable and were assigned to the favorable (90 patients; 78.3%) or unfavorable (25 patients; 21.7%) category. The 60-month survival rate was 97.7% in favorable patients compared with 73.8% in unfavorable patients (P = .0002). RFS analysis showed a 60-month relapse rate of 13.4% and 32% in favorable and unfavorable patients (P < .025), respectively. Statistical analysis demonstrated a significant association of unfavorable INPC category and high lactate dehydrogenase level (P < .045).

CONCLUSION: This European study shows for the first time that the INPC prognostic categorization has a significant impact on outcome prediction in INSS stage 2 localized peripheral neuroblastic tumors.

Supported by the Association pour la Recherche sur le Cancer, France; United Kingdom Children Cancer Study Group, UK Grant No. G03/89 from Instituto Carlos III, Madrid, Spain; Italian Neuroblastoma Foundation, Italy; and European Society of Pediatric Oncology Neuroblastoma Research Network, European Community.

All of the authors contributed equally to this study.

Presented in part at the Advances in Neuroblastoma Research Meeting, 11th Conference, June 16-19, 2004, Genova, Italy.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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