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      Treatment and outcomes of 1041 pediatric patients with neuroblastoma who received multidisciplinary care in China

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          Abstract

          Importance

          Neuroblastoma is the most common extracranial malignant solid tumor in children. Multidisciplinary care is critical to improving the survival of pediatric patients with neuroblastoma.

          Objective

          To systematically summarize the clinical characteristics of children with neuroblastoma and evaluate their prognosis with multidisciplinary care provided in a single center.

          Methods

          This retrospective study analyzed the clinical data of 1041 patients with neuroblastoma who were diagnosed, treated, and followed‐up in the Hematology‐Oncology Center of Beijing Children’s Hospital from 2007 to 2019.

          Results

          The median age at diagnosis was 34 months; 80.8% of the patients were younger than 5 years of age. Notably, 243 patients (23.3%) were classified as low‐risk, 249 patients (23.9%) were classified as intermediate‐risk, and 549 (52.7%) were classified as high‐risk. Furthermore, 956 patients underwent surgical resections; 986 (94.7%) patients received chemotherapy; and 176 patients with high‐risk neuroblastoma received hematopoietic stem cell transplantation. The 5‐year event‐free survival (EFS) rate was 91.3% and 5‐year overall survival (OS) rate was 97.5% in low‐risk group; in the intermediate‐risk group, these rates were 85.1% and 96.7%, respectively, while they were 37.7% and 48.9% in the high‐risk group ( P < 0.001 for both). The 5‐year EFS and OS rates were significantly higher in patients diagnosed between 2015 and 2019 than in patients diagnosed between 2007 and 2014 ( P < 0.001). In total, 278 patients (26.7%) exhibited tumor relapse or progression; the median interval until relapse or progression was 14 months. Of the 233 patients who died, 83% died of relapse or progression of neuroblastoma and 4.3% died of therapy‐related complications.

          Interpretation

          The 5‐year OS rate was low in high‐risk patients, compared with low‐and intermediate‐risk patients. Multidisciplinary care is critical for improvement of survival in pediatric patients with neuroblastoma. Additional treatment strategies should be sought to improve the prognosis of patients with high‐risk neuroblastoma.

          Abstract

          A multidisciplinary modality for the diagnosis and treatment of neuroblastoma is the key to improve the survival of children with neuroblastoma.

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          Most cited references22

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          New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

          E A Eisenhauer, P Therasse, J. Bogaerts … (2009)
          Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.
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            Recent advances in neuroblastoma.

            John Maris (2010)
            Article 0 comments Cited 739 times – based on 0 reviews     Review now
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              The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report.

              Susan L. Cohn, Andrew D.J. Pearson, Wendy B. London … (2009)
              Because current approaches to risk classification and treatment stratification for children with neuroblastoma (NB) vary greatly throughout the world, it is difficult to directly compare risk-based clinical trials. The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors. Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to or = 50% to < or = 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively. By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.
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                Author and article information

                Contributors
                Qi Zeng: zengqi-1@163.com
                Huanmin Wang: wanghuanmin@bch.com.cn
                Xiaoli Ma: mxl1123@vip.sina.com
                Xin Ni: nixin@bch.com.cn
                Journal
                Journal ID (nlm-ta): Pediatr Investig
                Journal ID (iso-abbrev): Pediatr Investig
                Journal ID (doi): 10.1002/(ISSN)2574-2272
                Journal ID (publisher-id): PED4
                Title: Pediatric Investigation
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 2096-3726
                ISSN (Electronic): 2574-2272
                Publication date (Electronic): 27 September 2020
                Publication date Collection: September 2020
                Volume: 4
                Issue: 3 , Solid Tumor ( doiID: 10.1002/ped4.v4.3 )
                Pages: 157-167
                Affiliations
                [ 1 ] Beijing Key Laboratory of Pediatric Hematology Oncology National Key Discipline of Pediatrics Ministry of Education Key Laboratory of Major Diseases in Children Hematology Oncology Center Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 2 ] Department of Surgical Oncology Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 3 ] Department of Thoracic Surgery Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 4 ] Department of Otorhinolaryngology Head and Neck Surgery Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 5 ] Imaging Center Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 6 ] Department of Pathology Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 7 ] Department of Ultrasound Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 8 ] Pediatric Intensive Care Unit Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 9 ] Department of Neurosurgery Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China
                [ 10 ] Department of Radiation Oncology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing China
                Author notes
                [*] [* ] Correspondence

                Xin Ni, Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China.

                Email: nixin@ 123456bch.com.cn

                Xiaoli Ma, Hematology Oncology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China.

                Email: mxl1123@ 123456vip.sina.com

                Huanmin Wang, Department of Surgical Oncology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China.

                Email: wanghuanmin@ 123456bch.com.cn

                Qi Zeng, Department of Thoracic Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China.

                Email: zengqi-1@ 123456163.com

                [*]

                These authors contributed equally to this study

                Article
                Publisher ID: PED412214
                DOI: 10.1002/ped4.12214
                PMC ID: 7520112
                PubMed ID: 33150309
                SO-VID: 778b017f-2200-4e21-ab78-bc1ee8271eb1
                Copyright © © 2020 The Authors. Pediatric Investigation published by John Wiley & Sons Australia, Ltd on behalf of Futang Research Center of Pediatric Development
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Date received : 29 May 2020
                Date accepted : 20 August 2020
                Page count
                Figures: 5, Tables: 3, Pages: 11, Words: 7093
                Categories
                Subject: Original Article
                Subject: Original Article
                Custom metadata
                source-schema-version-number 2.0
                cover-date September 2020
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:27.09.2020

                Keywords: neuroblastoma,pediatric,multidisciplinary care,prognosis
                Data availability:
                Keywords: neuroblastoma, pediatric, multidisciplinary care, prognosis

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