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      A multidisciplinary team care approach improves outcomes in high-risk pediatric neuroblastoma patients

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          Abstract

          We assessed the impact of a multidisciplinary team care program on treatment outcomes in neuroblastoma patients. Newly diagnosed neuroblastoma patients received treatment under the Taiwan Pediatric Oncology Group (TPOG) N2002 protocol at the National Taiwan University Hospital beginning in 2002. A multidisciplinary team care approach that included nurse-led case management for patients treated under this protocol began in January 2010. Fifty-eight neuroblastoma patients, including 29 treated between 2002 and 2009 (Group 1) and 29 treated between 2010 and 2014 (Group 2), were enrolled in the study. The 5-year overall survival (OS) and event-free survival (EFS) rates for all 58 patients were 59% and 54.7%, respectively. Group 2 patients, who were treated after implementation of the multidisciplinary team care program, had better 3-year EFS ( P = 0.046), but not OS ( P = 0.16), rates than Group 1 patients. In a multivariate analysis, implementation of the multidisciplinary team approach was the only significant independent prognostic factor for neuroblastoma patients. In further subgroup analyses, the multidisciplinary team approach improved EFS, but not OS, in patients with stage 4 disease, those in the high-risk group, and those with non-MYCN amplified tumors. These data indicate a multidisciplinary team care approach improved survival outcomes in high-risk neuroblastoma patients. However, further investigation will be required to evaluate the long-term effects of this approach over longer follow-up periods.

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          Most cited references20

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          The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report.

          The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% +/- 4% v 90% +/- 3%; P = .0010). Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.
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            Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study.

            PURPOSE We assessed the long-term outcome of patients enrolled on CCG-3891, a high-risk neuroblastoma study in which patients were randomly assigned to undergo autologous purged bone marrow transplantation (ABMT) or to receive chemotherapy, and subsequent treatment with 13-cis-retinoic acid (cis-RA). PATIENTS AND METHODS Patients received the same induction chemotherapy, with random assignment (N = 379) to consolidation with myeloablative chemotherapy, total-body irradiation, and ABMT versus three cycles of intensive chemotherapy. Patients who completed consolidation without disease progression were randomly assigned to receive no further therapy or cis-RA for 6 months. Results The event-free survival (EFS) for patients randomly assigned to ABMT was significantly higher than those randomly assigned to chemotherapy; the 5-year EFS (mean +/- SE) was 30% +/- 4% versus 19% +/- 3%, respectively (P = .04). The 5-year EFS (42% +/- 5% v 31% +/- 5%) from the time of second random assignment was higher for cis-RA than for no further therapy, though it was not significant. Overall survival (OS) was significantly higher for each random assignment by a test of the log(-log(.)) transformation of the survival estimates at 5 years (P < .01). The 5-year OS from the second random assignment of patients who underwent both random assignments and who were assigned to ABMT/cis-RA was 59% +/- 8%; for ABMT/no cis-RA, it was 41% +/- 8% [corrected]; for continuing chemotherapy/cis-RA, it was 38% +/- 7%; and for chemotherapy/no cis-RA, it was 36% +/- 7%. Myeloablative therapy and autologous hematopoietic cell rescue result in significantly better 5-year EFS than nonmyeloablative chemo therapy; neither myeloablative therapy with [corrected] autologous hematopoietic cell rescue nor cis-RA given after consolidation therapy significantly improved OS.
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              Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment.

              Based on preliminary experience, there was a need for modifications and clarifications in the International Neuroblastoma Staging System (INSS) and International Neuroblastoma Response Criteria (INRC). In 1988, a proposal was made to establish an internationally accepted staging system for neuroblastoma, as well as consistent criteria for confirming the diagnosis and determining response to therapy (Brodeur GM, et al: J Clin Oncol 6:1874-1881, 1988). A meeting was held to review experience with the INSS and INRC and to revise or clarify the language and intent of the originally proposed criteria. Substantial changes included a redefinition of the midline, restrictions on age and bone marrow involvement for stage 4S, and the recommendation that meta-iodobenzylguanidine (MIBG) scanning be implemented for evaluating the extent of disease. Other modifications and clarifications of the INSS and INRC are presented. In addition, the criteria for the diagnosis of neuroblastoma were modified. Finally, proposals were made for the development of risk groups that incorporate both clinical and biologic features in the prediction of prognosis. The biologic features that were deemed important to evaluate prospectively included serum ferritin, neuron-specific enolase (NSE), and lactic dehydrogenase (LDH); tumor histology; tumor-cell DNA content; assessment of N-myc copy number; assessment of 1p deletion by cytogenetic or molecular methods; and TRK-A expression. Modifications of the INSS and INRC made at this conference are presented. In addition, proposals are made for future modifications in these criteria and for the development of International Neuroblastoma Risk Groups.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                17 January 2017
                10 December 2016
                : 8
                : 3
                : 4360-4372
                Affiliations
                1 Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                2 Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan
                3 Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                4 Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                5 Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                6 Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                7 Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan
                8 Department of Life Science, National Taiwan University, Taipei, Taiwan
                9 Institutes of Zoology, National Taiwan University, Taipei, Taiwan
                10 Institutes of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan
                11 Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan
                12 Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
                13 Department of Nursing, National Taiwan University College of Medicine, Taipei, Taiwan
                14 Department of Nursing, Central Taiwan University of Science and Technology, Taichung, Taiwan
                15 Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
                Author notes
                Correspondence to: Ya-Ling Lee, yallee@ 123456ntu.edu.tw
                Article
                13874
                10.18632/oncotarget.13874
                5354838
                27966455
                08b357a7-8c5a-4c79-818b-903dc37f247f
                Copyright: © 2017 Chang et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 June 2016
                : 1 December 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                chemotherapy,high-risk,multidisciplinary team care,neuroblastoma,outcomes
                Oncology & Radiotherapy
                chemotherapy, high-risk, multidisciplinary team care, neuroblastoma, outcomes

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