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Williams KM, Shah NR, Chukkapalli S, King S, Grant CN, Brown EG, Avanzini S, Lal DR, Sarnacki S, Newman EA. Modern surgical strategies in pediatric neuroblastoma: Evolving approaches and treatment principles. Pediatr Blood Cancer 2025; 72 Suppl 2:e31317. [PMID: 39313754 DOI: 10.1002/pbc.31317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 08/23/2024] [Accepted: 08/27/2024] [Indexed: 09/25/2024]
Abstract
Neuroblastoma, the most common extracranial solid tumor in children under the age of 5, has been described as early as the 19th century, and its complexity has continued to intrigue researchers, as well as medical and surgical specialists. At one end of the phenotypic spectrum, neuroblastoma is self-limiting with minimal to no intervention required, while on the opposite end exists the challenge of refractory disease despite aggressive management and toxic systemic treatments. The goal of this review is to describe a comprehensive surgical perspective and contemporary approach to neuroblastoma.
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Affiliation(s)
- Keyonna M Williams
- Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Nikhil R Shah
- Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Sahiti Chukkapalli
- Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Sarah King
- Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Christa N Grant
- Department of Pediatric Surgery, Maria Fareri Children's Hospital, Valhalla, New York, USA
| | - Erin G Brown
- Division of Pediatric Surgery, University of California Davis Medical Center, Sacramento, California, USA
| | - Stefano Avanzini
- Department of Pediatric Surgery, IRCCS Istituto G. Gaslini, Genoa, Italy
| | - Dave R Lal
- Department of Pediatric Surgery, Children's Wisconsin, Milwaukee, Wisconsin, USA
| | - Sabine Sarnacki
- Department of Pediatric Surgery, Hôpital Universitaire Necker, Paris, France
| | - Erika A Newman
- Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, USA
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2
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Simons DC, Buser MAD, Fitski M, van de Ven CP, Ten Haken B, Wijnen MHWA, Tan CO, van der Steeg AFW. Multi-modal 3-Dimensional Visualization of Pediatric Neuroblastoma: Aiding Surgical Planning Beyond Anatomical Information. J Pediatr Surg 2024; 59:1575-1581. [PMID: 38461108 DOI: 10.1016/j.jpedsurg.2024.02.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 02/16/2024] [Indexed: 03/11/2024]
Abstract
BACKGROUND Patient-specific 3D models of neuroblastoma and relevant anatomy are useful tools for surgical planning. However, these models do not represent the heterogenous biology of neuroblastoma. This heterogeneity is visualized with the ADC and 123I-MIGB-SPECT-CT imaging. Combining these multi-modal data into preoperative 3D heatmaps, may allow differentiation of the areas of vital and non-vital tumor tissue. We developed a workflow to create multi-modal preoperative 3D models for neuroblastoma surgery. METHODS We included 7 patients who underwent neuroblastoma surgery between 2022 and 2023. We developed 3D models based on the contrast enhanced T1-weighted MRI scans. Subsequently, we aligned the corresponding ADC and 123I-MIBG-SPECT-CT images using rigid transformation. We estimated registration precision using the Dice score and the target registration error (TRE). 3D heatmaps were computed based on ADC and 123I-MIBG uptake. RESULTS The registration algorithm had a median Dice score of 0.81 (0.75-0.90) for ADC and 0.77 (0.65-0.91) for 123I-MIBG-SPECT. For the ADC registration, the median TRE of renal vessels was 4.90 mm (0.86-10.18) and of the aorta 4.67 mm (1.59-12.20). For the 123I -MIBG-SPECT imaging the TRE of the renal vessels was 5.52 mm (1.71-10.97) and 5.28 mm (3.33-16.77) for the aorta. CONCLUSIONS We successfully developed a registration workflow to create multi-modal 3D models which allows the surgeon to visualize the tumor and its biological behavior in relation to the surrounding tissue. Future research will include linking of pathological results to imaging data, to validate these multi-modal 3D models. LEVEL OF EVIDENCE Level IV. TYPE OF STUDY Clinical Research.
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Affiliation(s)
- Dominique C Simons
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, the Netherlands; University of Twente, Technical Medicine, Hallenweg 5, 7522, NH, Enschede, the Netherlands
| | - Myrthe A D Buser
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, the Netherlands
| | - Matthijs Fitski
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, the Netherlands
| | - Cornelis P van de Ven
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, the Netherlands
| | - Bernhard Ten Haken
- University of Twente, Magnetic Detection and Imaging, Enschede, the Netherlands
| | - Marc H W A Wijnen
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, the Netherlands
| | - Can Ozan Tan
- University of Twente, Electrical Engineering, Mathematics, and Computer Science, Hallenweg 5, 7522, NH, Enschede, the Netherlands
| | - Alida F W van der Steeg
- Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584, CS, Utrecht, the Netherlands.
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Lee WG, Kim ES. Precision Oncology in Pediatric Cancer Surgery. Surg Oncol Clin N Am 2024; 33:409-446. [PMID: 38401917 DOI: 10.1016/j.soc.2023.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2024]
Abstract
Pediatric precision oncology has provided a greater understanding of the wide range of molecular alterations in difficult-to-treat or rare tumors with the aims of increasing survival as well as decreasing toxicity and morbidity from current cytotoxic therapies. In this article, the authors discuss the current state of pediatric precision oncology which has increased access to novel targeted therapies while also providing a framework for clinical implementation in this unique population. The authors evaluate the targetable mutations currently under investigation-with a focus on pediatric solid tumors-and discuss the key surgical implications associated with novel targeted therapies.
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Affiliation(s)
- William G Lee
- Department of Surgery, Cedars-Sinai Medical Center, 116 North Robertson Boulevard, Suite PACT 700, Los Angeles, CA 90048, USA. https://twitter.com/william_ghh_lee
| | - Eugene S Kim
- Division of Pediatric Surgery, Department of Surgery, Cedars-Sinai Medical Center, 116 North Robertson Boulevard, Suite PACT 700, Los Angeles, CA 90048, USA.
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Ren Q, Yang S, Chang S, Yang W, Cheng H, Chang X, Zhu Z, Yu T, Feng J, Han J, Mou J, Qin H, Wang H. Renal preservation in high-risk retroperitoneal neuroblastoma: Impact on survival and local progression. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107303. [PMID: 38056023 DOI: 10.1016/j.ejso.2023.107303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 11/04/2023] [Accepted: 11/24/2023] [Indexed: 12/08/2023]
Abstract
BACKGROUND Retroperitoneal neuroblastomas predominantly encroach upon critical structures, complicating surgical intervention and yielding elevated rates of surgery-associated complications. The kidney and renal vasculature represent the organs most susceptible to retroperitoneal neuroblastoma infiltration. Prior investigations have revealed high nephrectomy incidence and a paucity of renal-preserving surgical approaches. METHODS A retrospective analysis was undertaken, examining patients with retroperitoneal neuroblastoma who underwent surgical procedures from January 2018 to December 2019 at Beijing Children's Hospital. RESULTS The study encompassed 225 patients, presenting a median age of 37 months. Concomitant nephrectomy and tumor excision were performed in 11 (4.9%) patients, while 214 (95.1%) patients successfully preserved their kidneys during surgery. Among the patients who retained their kidneys, 8 (3.5%) experienced renal atrophy postoperatively. Predominant rationales for simultaneous nephrectomy included tumor invasion into the renal hilum (n = 9), markedly diminished function of the affected kidney (n = 2), and ureteral infiltration (n = 1). Subsequent to a median follow-up duration of 43 months, the outcomes demonstrated no considerable divergence in overall survival (OS) and event-free survival (EFS) between the nephrectomy and renal-preserving cohorts among high-risk (HR) neuroblastoma patients. Among the eight HR children who underwent nephrectomy, four experienced local recurrence. The nephrectomy cohort exhibited a significantly elevated cumulative incidence of local progression (CILP) relative to the renal-preserving group. CONCLUSION In high-risk retroperitoneal neuroblastoma patients, nephrectomy does not enhance CILP, EFS, or OS. The guiding surgical tenet involves preserving the kidney while striving for gross total resection of the primary neoplasm, barring instances of severe deterioration of the affected renal function.
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Affiliation(s)
- Qinghua Ren
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Shen Yang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Saishuo Chang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Wei Yang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Haiyan Cheng
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Xiaofeng Chang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Zhiyun Zhu
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Tong Yu
- Department of Radiology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Jun Feng
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Jianyu Han
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Jianing Mou
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Hong Qin
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
| | - Huanmin Wang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China; MOE Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
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Pio L, Guérin F, Martucci C, Martelli H, Gauthier F, Branchereau S. The Use of Cavitron Ultrasonic Surgical Aspirator for High-Risk Neuroblastoma with Image-Defined Risk Factors in Children. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10010089. [PMID: 36670640 PMCID: PMC9857095 DOI: 10.3390/children10010089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 12/26/2022] [Accepted: 12/31/2022] [Indexed: 01/03/2023]
Abstract
Aim of the study: The cavitron ultrasonic surgical aspirator (CUSA) has gained popularity in adult surgical oncology, but its application in children is limited to liver surgery and neurosurgical procedures. The complete resection of neuroblastoma with image-defined risk factors (IDRFs) is still considered one of the most difficult procedures to achieve in pediatric surgical oncology, with a high morbidity rate and potential risk of intraoperative mortality. The aim of our study is to describe the application of ultrasonic dissection in neuroblastoma with IDRFs. Methods: A retrospective study was performed, analyzing patients operated on from 2000 to 2018. Patient characteristics, resection completeness, and postoperative surgical and oncology outcomes were analyzed. Main results: Twenty-six patients with high-risk neuroblastoma and IDRFs were operated on in the study period with a CUSA. A complete macroscopic resection was performed in 50% of patients, while the other half was operated on with minimal residual (<5 mL). Six post-operative complications occurred without the need for surgery (Clavien−Dindo < 3). The overall survival was 50%, with a median follow-up of 69.6 months (5.6−140.4). Conclusions: The application of the CUSA in neuroblastoma with IDRFs can be considered an effective and safe alternative technique to achieve a radical resection.
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Affiliation(s)
- Luca Pio
- Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
- Paediatric Surgery Department, Hôpital Bicêtre APHP, Paris Saclay University, 91190 Paris, France
- Correspondence:
| | - Florent Guérin
- Paediatric Surgery Department, Hôpital Bicêtre APHP, Paris Saclay University, 91190 Paris, France
| | - Cristina Martucci
- Paediatric Surgery Department, Hôpital Bicêtre APHP, Paris Saclay University, 91190 Paris, France
| | - Helene Martelli
- Paediatric Surgery Department, Hôpital Bicêtre APHP, Paris Saclay University, 91190 Paris, France
| | - Frédéric Gauthier
- Paediatric Surgery Department, Hôpital Bicêtre APHP, Paris Saclay University, 91190 Paris, France
| | - Sophie Branchereau
- Paediatric Surgery Department, Hôpital Bicêtre APHP, Paris Saclay University, 91190 Paris, France
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van Heerden J, Kruger M, Esterhuizen TM, van Zyl A, Hendricks M, Cox S, Mangray H, Poole J, Naidu G, Büchner A, de Villiers M, du Plessis J, van Emmenes B, Matthews E, Manickchund Y, Harrison DS. The pre-surgical factors that determine the decision to proceed to resection in children diagnosed with high-risk neuroblastoma in a resource limited setting. Pediatr Hematol Oncol 2022; 40:242-257. [PMID: 36271813 DOI: 10.1080/08880018.2022.2137610] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Surgical control has prognostic value in neuroblastoma (NB). Advanced NB is common at diagnosis in South Africa. We investigated the pre-surgery factors that influenced decisions to perform surgical resections. We included 204 patients with high-risk NB from a national retrospective study, who completed induction chemotherapy between 2000 and 2016.The median age was 32.4 months (IQR 15.1 - 53.5 months). Primary tumor resection was achieved in 76.9% of patients between 0-18 months of age, 51.8% between 18-60 months and 51.7% older than 60 months (p < 0.001). Only 43.2% of patients with distant metastatic disease had surgery done (p < 0.001). LDH was >750 U/L in 46.8% and ferritin >120 g/dL in 53.1% of those who had surgery (p = 0.005). The majority (80.4%), who had achieved post-induction metastatic complete remission (mCR), were operated, while 28.7% without mCR had surgery (p < 0.001). The long-term overall survival in patients with mCR and primary tumor resection was 36.5% compared to those with mCR without primary tumor resection (25.4%) and without mCR (≤3.0%)(p < 0.001). Age (p < 0.001), stage (p < 0.001), mCR (p < 0.001) and treatment setting (p < 0.001) were of prognostic significance. The tumor site and MYCN-amplification did not significantly predict resection rates. Post-induction mCR and stage were associated with surgical resection and five-year OS (p < 0.001) on multivariate analysis.Patients with high-risk NB who achieved mCR and had primary tumor resections are curable in limited resourced settings. Stage and post-induction mCR were significant variables that led to surgery. These variables should be included as indications in the management of metastatic NB in resource limited settings.
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Affiliation(s)
- Jaques van Heerden
- Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa.,Paediatric Haematology and Oncology, Department of Paediatrics, Antwerp University Hospital, Antwerp, Belgium.,Department of Medicine, Molecular imaging, Pathology, Radiotherapy and Oncology (MIPRO), University of Antwerp, Antwerp, Belgium
| | - Mariana Kruger
- Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa
| | - Tonya Marianne Esterhuizen
- Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
| | - Anel van Zyl
- Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa
| | - Marc Hendricks
- Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town.,Paediatric Haematology and Oncology Service, Red Cross War Memorial Children's Hospital, South Africa
| | - Sharon Cox
- Division of Paediatric Surgery, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa
| | - Hansraj Mangray
- Department of Paediatric Surgery, University of Kwa-Zulu Natal, Greys Hospital, Pietermaritzburg, South Africa
| | - Janet Poole
- Faculty of Health Sciences, Division of Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa
| | - Gita Naidu
- Faculty of Health Sciences, Division of Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
| | - Ané Büchner
- Paediatric Haematology and Oncology, Department of Paediatrics, University of Pretoria, Steve Biko Academic Hospital, Pretoria, South Africa
| | - Mariza de Villiers
- Department of Paediatric Surgery, University of Pretoria, Steve Biko Academic Hospital, Pretoria, South Africa
| | - Jan du Plessis
- Department of Paediatrics Faculty of Health Sciences, University of the Free State, Division of Paediatric Haematology and Oncology, Universitas Hospital, South Africa
| | - Barry van Emmenes
- Division of Paediatric Haematology and Oncology Hospital, Department of Paediatrics, Walter Sisulu University, South Africa
| | - Elmarie Matthews
- Paediatric Haematology Oncology, Department of Paediatrics and Child Health, Port Elizabeth Provincial Hospital, Walter Sisulu University, Port Elizabeth, South Africa
| | - Yashoda Manickchund
- Department of Paediatric Surgery, Walter Sisulu University, East London, South Africa
| | - Derek Stanley Harrison
- Department of Paediatric Surgery, Faculty of Health Sciences, University of the Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
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Abbas AA, Samkari AMN. High-Risk Neuroblastoma: Poor Outcomes Despite Aggressive Multimodal
Therapy. CURRENT CANCER THERAPY REVIEWS 2022. [DOI: 10.2174/1573394717666210805114226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
:
Neuroblastoma (NBL) is a highly malignant embryonal tumor that originates from the
primordial neural crest cells. NBL is the most common tumor in infants and the most common extracranial
solid tumor in children. The tumor is more commonly diagnosed in children of 1-4 years
of age. NBL is characterized by enigmatic clinical behavior that ranges from spontaneous regression
to an aggressive clinical course leading to frequent relapses and death. Based on the likelihood
of progression and relapse, the International Neuroblastoma Risk Group classification system categorized
NBL into very low risk, low risk, intermediate risk, and high risk (HR) groups. HR NBL is
defined based on the patient's age (> 18 months), disease metastasis, tumor histology, and MYCN
gene amplification. HR NBL is diagnosed in nearly 40% of patients, mainly those > 18 months of
age, and is associated with aggressive clinical behavior. Treatment strategies involve the use of intensive
chemotherapy (CTR), surgical resection, high dose CTR with hematopoietic stem cell support,
radiotherapy, biotherapy, and immunotherapy with Anti-ganglioside 2 monoclonal antibodies.
Although HR NBL is now better characterized and aggressive multimodal therapy is applied, the
outcomes of treatment are still poor, with overall survival and event-free survival of approximately
40% and 30% at 3-years, respectively. The short and long-term side effects of therapy are tremendous.
HR NBL carries a high mortality rate accounting for nearly 15% of pediatric cancer deaths.
However, most mortalities are attributed to the high frequency of disease relapse (50%) and disease
reactiveness to therapy (20%). Newer treatment strategies are therefore urgently needed. Recent
discoveries in the field of biology and molecular genetics of NBL have led to the identification
of several targets that can improve the treatment results. In this review, we discuss the different
aspects of the epidemiology, biology, clinical presentations, diagnosis, and treatment of HR
NBL, in addition to the recent developments in the management of the disease.
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Affiliation(s)
- Adil Abdelhamed Abbas
- College of Medicine King Saud bin Abdulaziz, University for Health Sciences Consultant Pediatric Hematology / Oncology
& BMT The Pediatric Hematology/Oncology Section Princess Nourah Oncology Centre King Abdulaziz Medical
City, Jeddah, Saudi Arabia
| | - Alaa Mohammed Noor Samkari
- College of Medicine King Saud bin Abdulaziz, University for Health Sciences Consultant
Anatomical Pathologist Department of Laboratory Medicine King Abdulaziz Medical City, Jeddah, Saudi Arabia
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Qi Y, Zhan J. Roles of Surgery in the Treatment of Patients With High-Risk Neuroblastoma in the Children Oncology Group Study: A Systematic Review and Meta-Analysis. Front Pediatr 2021; 9:706800. [PMID: 34722415 PMCID: PMC8548868 DOI: 10.3389/fped.2021.706800] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 09/03/2021] [Indexed: 01/10/2023] Open
Abstract
Purpose: Neuroblastoma is the most common extracranial solid tumor in children, and most patients are at high risk when they are initially diagnosed. The roles of surgery and induction chemotherapy in patients with high-risk neuroblastoma have been a subject of much controversy and debate. The objective of the current study was to assess the roles of surgery in high-risk neuroblastoma. Method: The review protocol was prospectively registered (PROSPEROID: CRD42021253961). The PubMed, Embase, Cochrane, and CNKI databases were searched from inception to January 2020 with no restrictions on language or publication date. Clinical studies comparing the outcomes of different surgical ranges for the treatment of high-risk neuroblastoma were analyzed. The Mantel-Haenszel method and a random effects model was utilized to calculate the hazard ratio (95% CI). Results: Fourteen studies that assessed 1,915 subjects met the full inclusion criteria. Compared with the gross tumor resection (GTR) group, complete tumor resection (CTR) did not significantly improve the 5-year EFS [p = 1.0; HR = 0.95 (95% CI, 0.87-1.05); I 2 = 0%], and the 5-year OS [p = 0.76; HR = 1.08 (95% CI, 0.80-1.46); I 2 = 0%] of patients. GTR or CTR resection had significantly better 5-year OS [p = 0.45; HR = 0.56 (95% CI, 0.43-0.72); I 2 = 0%] and 5-year EFS [p = 0.15; HR = 0.80 (95% CI, 0.71-0.90); I 2 = 31%] than subtotal tumor resection (STR) or biopsy only; however, both CTR or GTR showed a trend for more intra and post-operative complications compared with the STR or biopsy only [p = 0.37; OR = 1.54 (95% CI, 1.08-2.20); I 2 = 0%]. The EFS of the patients who underwent GTR or CTR at the time of diagnosis and after induction chemotherapy were similar [p = 0.24; HR = 1.53 (95% CI, 0.84-2.77); I 2 = 29%]. Conclusion: For patients with high-risk neuroblastoma, complete tumor resection and gross tumor resection of the primary tumor were related to improved survival, with very limited effects on reducing intraoperative and postoperative complications. It is necessary to design strong chemotherapy regimens to improve the survival rate of advanced patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPEROID [CRD42021253961].
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Affiliation(s)
- Yingyi Qi
- Graduate College, Tianjin Medical University, Tianjin, China.,Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Jianghua Zhan
- Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
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9
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Abstract
Although intensive multimodal treatment has improved outcomes for patients with high-risk neuroblastoma, the specific role of primary tumor resection remains controversial. Many studies have been designed to determine whether the extent of surgical resection impacts survival; however, these reports have demonstrated conflicting results. There is also ongoing debate regarding the timing of primary tumor resection, with subtle differences in the approach between the large pediatric oncology cooperative consortia. Most of the published literature to date has been approached from a surgical viewpoint. Although most evidence supports surgery as part of the local control approach for high-risk neuroblastoma, recommendations for timing and extent of surgical resection are not consistent. This review summarizes our current understanding from the perspectives of both the pediatric oncologist and pediatric surgeons and discusses how the objectives of neuroblastoma primary surgical resection are different from that of other malignancies. Furthermore, this commentary will address how retrospective surgical outcome data may be interpreted in the setting of modern era high-risk neuroblastoma treatment.
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10
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Fahy AS, Roberts A, Nasr A, Irwin MS, Gerstle JT. Long term outcomes after concurrent ipsilateral nephrectomy versus kidney-sparing surgery for high-risk, intraabdominal neuroblastoma. J Pediatr Surg 2019; 54:1632-1637. [PMID: 30029845 DOI: 10.1016/j.jpedsurg.2018.06.031] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 06/28/2018] [Accepted: 06/29/2018] [Indexed: 12/29/2022]
Abstract
PURPOSE The impact of the extent of surgical resection including nephrectomy for high-risk neuroblastoma patients is controversial. In this study, we compared the renal late effects and long-term survival for patients who underwent kidney-sparing surgery (KSS) versus concurrent ipsilateral nephrectomy (CIN) for high-risk, intraabdominal neuroblastoma (HRIN). METHODS A retrospective analysis of patients diagnosed with HRIN between Jan 1998 and Dec 2008 in a tertiary referral center was performed. Demographics, preoperative features, surgical resection extent and outcomes were analyzed. RESULTS Of 58 patients who underwent surgical management of HRIN, 6 underwent CIN and 52 underwent KSS. Renal image-defined risk factors (IDRFs) were more common in patients who underwent CIN. Operating time was longer and EBL higher in CIN patients. There was no difference in recurrence or overall survival between the groups. Estimated GFR (eGFR) was comparable between the groups preoperatively, but was reduced postoperatively and at long-term follow-up in patients who underwent CIN. CONCLUSION Compared to KSS, CIN is not associated with an increase in local recurrence or inferior survival but does lead to reduced kidney function (eGFR of 90 ml/min/1.73 m2 for CIN versus 127 ml/min/1.73 m2 for KSS, p = 0.03) but without significant impact on clinical outcome. LEVELS OF EVIDENCE III (Retrospective comparative study).
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Affiliation(s)
- Aodhnait S Fahy
- Division of General and Thoracic Surgery, Hospital for Sick Children, University of Toronto, Toronto, Canada.
| | - Amanda Roberts
- Division of General and Thoracic Surgery, Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Ahmed Nasr
- Department of General Surgery, Children's Hospital of Eastern Ontario, University of Ottawa, Canada
| | - Meredith S Irwin
- Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Canada
| | - Justin T Gerstle
- Division of General and Thoracic Surgery, Hospital for Sick Children, University of Toronto, Toronto, Canada
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11
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Chen DX, Hou YH, Jiang YN, Shao LW, Wang SJ, Wang XQ. Removal of pediatric stage IV neuroblastoma by robot-assisted laparoscopy: A case report and literature review. World J Clin Cases 2019; 7:1499-1507. [PMID: 31363479 PMCID: PMC6656671 DOI: 10.12998/wjcc.v7.i12.1499] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/29/2019] [Accepted: 05/11/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Neuroblastoma (NB) is the most common extracranial solid tumor in children, with an incidence of approximately 1/10000. Surgical resection is an effective treatment for children with NB. Robot-assisted laparoscopic surgery is a new method and is superior to conventional laparoscopic surgery, since it has been preliminarily applied in clinical practice with a significant curative effect. This paper discusses significance and feasibility of complete resection of stage IV NB using robot-assisted laparoscopic surgery, while comparing its safety and effectiveness with conventional laparoscopic surgery.
CASE SUMMARY In June 2018, a girl with stage IV retroperitoneal NB, aged 3 years and 5 mo, was admitted. Her weight was 15 kg, and her height was 100 cm. Robot-assisted, five-port laparoscopic resection of NB was performed. Starting from the middle point between the navel and the anterior superior iliac spine to the left lower abdomen, the pneumoperitoneum and observation hole (10 mm) were established using the Hasson technique. Operation arm #1 was located between the left anterior axillary line, the navel, and the costal margin (8 mm); operation arm #2 was located at the intersection of the right anterior axillary line and Pfannenstiel line (8 mm); one auxiliary hole was located between arm #2 (on the Pfannenstiel line) and the observation hole (12 mm); and another auxiliary hole (5 mm) was located slightly below the left side of the xiphoid. Along the right line of Toldt and the hepatic flexure of the transverse colon, the colon was turned to the left and below with a hook electrode. Through Kocher's incision, the duodenum and the pancreatic head were turned to the left to expose the inferior vena cava and the abdominal aorta. The vein was separated along the right external iliac, and the inferior vena cava was then lifted to expose the right renal vein from the bottom to the top. The tumor was transected horizontally below the renal vein, and it was first cut into pieces and then resected. The right renal artery and the left renal vein were also exposed, and the retrohepatic inferior vena cava was isolated. The tumor was resected along the surface of the psoas muscle, the back of the inferior vena cava, and the right side of the abdominal aorta. Finally, the lymph node metas-tases in front of the abdominal aorta and left renal vein were completely removed. The specimens were loaded into a disposable specimen retrieval bag and removed from the enlarged auxiliary hole. T-tube drainage was placed and brought out through a hole in the right lower quadrant of the abdomen. The operative time was 389 min, the time of pneumoperitoneum was 360 min, the intraoperative blood loss was approximately 200 mL, and the postoperative recovery was smooth. There were no complications, such as lymphatic fistula, diarrhea, bleeding, and paralytic ileus. Two months after discharge, there were no other complications. The literature on the application of robot-assisted laparoscopic surgery in the treatment of NB in children was reviewed
CONCLUSION The robot has the advantages of a three-dimensional view and flexible operation, and it can operate finely along blood vessels. The successful experience of this case confirmed that robot-assisted laparoscopic surgery can skeletonize the abdominal blood vessels in the tumor and cut the tumor into pieces, indicating that robot-assisted laparoscopic surgery is feasible.
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Affiliation(s)
- Di-Xiang Chen
- Department of Pediatrics, PLA General Hospital, Beijing 100853, China
| | - Yi-Han Hou
- Beijing University of Chinese Medicine, Beijing 100029, China
| | - Ya-Nan Jiang
- Beijing University of Chinese Medicine, Beijing 100029, China
| | - Li-Wei Shao
- Department of Pathology, PLA General Hospital, Beijing 100853, China
| | - Shan-Jie Wang
- Department of Hepatobiliary Disease, Sixth People’s Hospital of Jinan Affiliated to Jining Medical School, Jinan 250200, Shandong Province, China
| | - Xian-Qiang Wang
- Department of Pediatrics, PLA General Hospital, Beijing 100853, China
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Newman EA, Abdessalam S, Aldrink JH, Austin M, Heaton TE, Bruny J, Ehrlich P, Dasgupta R, Baertschiger RM, Lautz TB, Rhee DS, Langham MR, Malek MM, Meyers RL, Nathan JD, Weil BR, Polites S, Madonna MB. Update on neuroblastoma. J Pediatr Surg 2019; 54:383-389. [PMID: 30305231 DOI: 10.1016/j.jpedsurg.2018.09.004] [Citation(s) in RCA: 114] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Revised: 09/09/2018] [Accepted: 09/14/2018] [Indexed: 12/15/2022]
Abstract
Neuroblastoma is an embryonic cancer arising from neural crest stem cells. This cancer is the most common malignancy in infants and the most common extracranial solid tumor in children. The clinical course may be highly variable with the possibility of spontaneous regression in the youngest patients and increased risk of aggressive disease in older children. Clinical heterogeneity is a consequence of the diverse biologic characteristics that determine patient risk and survival. This review will focus on current progress in neuroblastoma staging, risk stratification, and treatment strategies based on advancing knowledge in tumor biology and genetic characterization. TYPE OF STUDY: Review article. LEVEL OF EVIDENCE: Level II.
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Affiliation(s)
- Erika A Newman
- C.S Mott Children's Hospital, The University of Michigan Medicine, Ann Arbor, MI.
| | | | | | - Mary Austin
- Memorial Hermann Texas Medical Center, Houston, TX
| | - Todd E Heaton
- Memorial Sloan Kettering Cancer Center, NY, New York
| | | | - Peter Ehrlich
- C.S Mott Children's Hospital, The University of Michigan Medicine, Ann Arbor, MI
| | | | | | - Timothy B Lautz
- Ann & Robert H Lurie Children's Hospital of Chicago, Northwestern University, Chicago, IL
| | | | - Max R Langham
- University of Tennessee Health Science Center and St. Jude Children's Research Hospital, Memphis, TN
| | - Marcus M Malek
- Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
| | - Rebecka L Meyers
- Primary Children's Hospital, University of Utah, Salt Lake City, UT
| | | | - Brent R Weil
- Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA
| | | | - Mary Beth Madonna
- Ann & Robert H Lurie Children's Hospital of Chicago, Northwestern University, Chicago, IL
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Nakagawara A, Li Y, Izumi H, Muramori K, Inada H, Nishi M. Neuroblastoma. Jpn J Clin Oncol 2018; 48:214-241. [PMID: 29378002 DOI: 10.1093/jjco/hyx176] [Citation(s) in RCA: 132] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Indexed: 02/07/2023] Open
Abstract
Neuroblastoma is one of the most common solid tumors in children and has a diverse clinical behavior that largely depends on the tumor biology. Neuroblastoma exhibits unique features, such as early age of onset, high frequency of metastatic disease at diagnosis in patients over 1 year of age and the tendency for spontaneous regression of tumors in infants. The high-risk tumors frequently have amplification of the MYCN oncogene as well as segmental chromosome alterations with poor survival. Recent advanced genomic sequencing technology has revealed that mutation of ALK, which is present in ~10% of primary tumors, often causes familial neuroblastoma with germline mutation. However, the frequency of gene mutations is relatively small and other aberrations, such as epigenetic abnormalities, have also been proposed. The risk-stratified therapy was introduced by the Japan Neuroblastoma Study Group (JNBSG), which is now moving to the Neuroblastoma Committee of Japan Children's Cancer Group (JCCG). Several clinical studies have facilitated the reduction of therapy for children with low-risk neuroblastoma disease and the significant improvement of cure rates for patients with intermediate-risk as well as high-risk disease. Therapy for patients with high-risk disease includes intensive induction chemotherapy and myeloablative chemotherapy, followed by the treatment of minimal residual disease using differentiation therapy and immunotherapy. The JCCG aims for better cures and long-term quality of life for children with cancer by facilitating new approaches targeting novel driver proteins, genetic pathways and the tumor microenvironment.
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Affiliation(s)
| | - Yuanyuan Li
- Laboratory of Molecular Biology, Life Science Research Institute, Saga Medical Center Koseikan
| | - Hideki Izumi
- Laboratory of Molecular Biology, Life Science Research Institute, Saga Medical Center Koseikan
| | | | - Hiroko Inada
- Department of Pediatrics, Saga Medical Center Koseikan
| | - Masanori Nishi
- Department of Pediatrics, Saga University, Saga 849-8501, Japan
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14
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A single center clinical analysis of children with high-risk neuroblastoma. Oncotarget 2018; 8:30357-30368. [PMID: 28423674 PMCID: PMC5444748 DOI: 10.18632/oncotarget.15996] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 02/13/2017] [Indexed: 11/25/2022] Open
Abstract
The current multidisciplinary treatment for patients with high-risk neuroblastoma (NB) is the common census. However, protocols and opinions are different in different regions and institutions. We aimed to assess the protocol formulated by Chinese Children's Cancer Group study in 2009, and the impact of surgery extent was highlightly evaluated. METHODS This study enrolled patients with high-risk neuroblastoma between 2009 and 2014 in Department of Pediatric Oncology of Tianjin Medical University Cancer Institute and Hospital. The clinical characteristics of patients were illustrated and surgery extent was evaluated by the impact on survival rate. RESULTS The 3-year overall survival (OS) and progression-free survival (PFS) were 56.2% and 50.5%, respectively. LDH (P<0.001), bone marrow metastasis at time of diagnosis (P=0.001), bone marrow negative after neoadjuvant chemotherapy (P<0.001), radiotherapy (P<0.001) were significant predictors of OS and PFS. And surgery extent had no impact on the enhancement of high-risk neuroblastoma patients in short time. CONCLUSIONS This study showed no substantial survival benefit in patients with high-risk NB undergoing gross total tumor resection. Multidisciplinary intensive treatment was essential, especially for patients received subtotal tumor resection. Longer term follow-up is needed to survey complications in surviving patients who received intensive chemotherapy and radiotherapy.
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Dübbers M, Simon T, Berthold F, Fischer J, Volland R, Hero B, Cernaianu G. Retrospective analysis of relapsed abdominal high-risk neuroblastoma. J Pediatr Surg 2018; 53:558-566. [PMID: 29021103 DOI: 10.1016/j.jpedsurg.2017.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 09/01/2017] [Accepted: 09/02/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND/PURPOSE The impact of abdominal topography and surgical technique on resectability and local relapse pattern of relapsed abdominal high-risk neuroblastoma (R-HR-NB) is not clearly defined. METHODS A sample of thirty-nine patients with R-HR-NB enrolled in the German neuroblastoma trials between 2001 and 2010 was analyzed retrospectively using surgical and imaging reports. We evaluated resectability and local relapse pattern within 6 standardized abdominal regions, impact of extent of the first resective surgery on overall survival (OS), and of number of operations and a higher cumulative surgical assessment score (C-SAS) on OS after the first event. RESULTS In the left upper abdomen, rates for tumor persistence and relapse were 45.9% and 13.5% and in the left lower abdomen 27.7% and 8.3%, respectively. OS in months did not differ between complete and incomplete first resections (median (interquartile range): 35 (45.6) vs. 40 (65.4), P=.649). Better OS after the first event was associated with repeated as compared to single surgery (47.7 (64.7) vs. 4.3 (12.5), P=.000), and with higher as compared to lower C-SAS (47.7 (64.3) vs. 7.6 (14.7), P=.002). CONCLUSIONS OS after relapse/progression was not dependent on the extent of first resection. The number of operations was associated with better outcome after event. TYPE OF STUDY Treatment study. LEVEL OF EVIDENCE LEVEL III Retrospective comparative study.
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Affiliation(s)
- Martin Dübbers
- Division of Pediatric Surgery, University Hospital Cologne, Kerpenerstr. 62, 50937, Köln, Germany.
| | - Thorsten Simon
- Department of Pediatric Oncology and Hematology, University Hospital Cologne, Kerpenerstr. 62, 50937, Köln, Germany.
| | - Frank Berthold
- Department of Pediatric Oncology and Hematology, University Hospital Cologne, Kerpenerstr. 62, 50937, Köln, Germany.
| | - Janina Fischer
- Department of Pediatric Oncology and Hematology, University Hospital Cologne, Kerpenerstr. 62, 50937, Köln, Germany.
| | - Ruth Volland
- Department of Pediatric Oncology and Hematology, University Hospital Cologne, Kerpenerstr. 62, 50937, Köln, Germany.
| | - Barbara Hero
- Department of Pediatric Oncology and Hematology, University Hospital Cologne, Kerpenerstr. 62, 50937, Köln, Germany.
| | - Grigore Cernaianu
- Division of Pediatric Surgery, University Hospital Cologne, Kerpenerstr. 62, 50937, Köln, Germany.
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Uehara S, Yoneda A, Oue T, Nakahata K, Zenitani M, Miyamura T, Hashii Y, Fukuzawa M, Okuyama H. Role of surgery in delayed local treatment for INSS 4 neuroblastoma. Pediatr Int 2017. [PMID: 28643949 DOI: 10.1111/ped.13349] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND The aim of the present study was to compare the efficacy, complications and outcomes of the following two surgical strategies for delayed local treatment for International Neuroblastoma Staging System (INSS) 4 neuroblastoma (NB): complete resection (CR; period A); and gross total resection/subtotal resection (GTR/STR) with local irradiation (period B). METHODS We retrospectively analyzed 17 patients with INSS 4 NB who received delayed local treatment (period A, n = 11; period B, n = 6). RESULTS Eleven patients in period A received CR. Two patients underwent GTR and four patients underwent STR in period B. The amount of blood loss in period A was significantly greater than that in period B. Postoperative complications were observed in eight patients in period A (73%), but in only one patient in period B (17%; P < 0.01). Recurrence was observed in five patients in period A and in one patient in period B (45.4% vs 16.6%; P = n.s.). Distant metastasis at recurrence was observed in four patients in period A and in one patient in period B. CONCLUSIONS Gross total resection/subtotal resection with local irradiation may be a safe and effective delayed local treatment for INSS 4 NB.
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Affiliation(s)
- Shuichiro Uehara
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Akihiro Yoneda
- Department of Pediatric Surgery, Osaka City General Hospital, Osaka City, Osaka, Japan
| | - Takaharu Oue
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kengo Nakahata
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Masahiro Zenitani
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takako Miyamura
- Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Yoshiko Hashii
- Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Masahiro Fukuzawa
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hiroomi Okuyama
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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18
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Yeung F, Chung PHY, Tam PKH, Wong KKY. Is complete resection of high-risk stage IV neuroblastoma associated with better survival? J Pediatr Surg 2015; 50:2107-11. [PMID: 26377869 DOI: 10.1016/j.jpedsurg.2015.08.038] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Accepted: 08/24/2015] [Indexed: 12/30/2022]
Abstract
BACKGROUND The role of surgery in the management of stage IV neuroblastoma is controversial. In this study, we attempted to study if complete tumor resection had any impact on event-free survival (EFS) and overall survival (OS). METHODS A retrospective analysis of patients with stage IV neuroblastoma between November 2000 and July 2014 in a tertiary referral center was performed. Demographics data, extent of surgical resection, and outcomes were analyzed. RESULTS A total of 34 patients with stage IV neuroblastoma according to International Neuroblastoma Staging System (INSS) were identified. The median age at diagnosis and operation was 3.5 (±1.9) years and 3.8 (±2.0) years, respectively. Complete gross tumor resection (CTR) was achieved in twenty-four patients (70.1%), in which one of the patients had nephrectomy and another had distal pancreatectomy. Gross total resection (GTR) with removal of >95% of tumor was performed in six patients (17.6%) and subtotal tumor resection (STR) with removal of >50%, but <95% of tumor was performed in four patients (11.8%). There was no statistical significance in terms of 5-year EFS and OS among the 3 groups. There was no surgery-related mortality or morbidity. CONCLUSIONS From our center's experience, as there was no substantial survival benefit in stage IV neuroblastoma patients undergoing complete tumor resection, organ preservation and minimalization of morbidity should also be taken into consideration.
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Affiliation(s)
- Fanny Yeung
- Division of Paediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Patrick Ho Yu Chung
- Division of Paediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Paul Kwong Hang Tam
- Division of Paediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
| | - Kenneth Kak Yuen Wong
- Division of Paediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
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Irtan S, Brisse HJ, Minard-Colin V, Schleiermacher G, Galmiche-Rolland L, Le Cossec C, Elie C, Canale S, Michon J, Valteau-Couanet D, Sarnacki S. Image-defined risk factor assessment of neurogenic tumors after neoadjuvant chemotherapy is useful for predicting intra-operative risk factors and the completeness of resection. Pediatr Blood Cancer 2015; 62:1543-9. [PMID: 25820608 DOI: 10.1002/pbc.25511] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2014] [Accepted: 02/17/2015] [Indexed: 12/20/2022]
Abstract
BACKGROUND Patients with neuroblastoma are now stratified at diagnosis according to the presence and number of image-defined risk factors (IDRFs). We examined the added value of IDRF assessment after neoadjuvant chemotherapy for predicting surgical resection. MATERIAL AND METHODS From 2009-2012, 39 out of 91 patients operated on in our institution for neuroblastic tumors received neoadjuvant chemotherapy based on ongoing SIOPEN protocols or treatment guidelines. IDRFs were assessed both at diagnosis and preoperatively on CT and/or MRI. RESULTS Median age at diagnosis was 30 months [range 2-191]. The tumor locations were adrenal (n = 20), paravertebral (n = 13) and perivascular (n = 6). INRGSS stages were L2 (n = 13), M (n = 25) and Ms (n = 1). Eleven tumors (28%) were MYCN-amplified. Chemotherapy reduced the number of IDRFs in 54% of patients overall (21/39): 61.5% (16/26) of M and Ms patients, and 38.5% (5/13) of non metastatic patients (P < 0.001). The number of IDRFs lost after chemotherapy was proportional to the degree of tumor shrinkage (P = 0.002), independent of the primary tumor location (P = 0.73), although the number was higher in patients with left versus right adrenal locations (P = 0.004). Patients with neuroblastoma on post-surgical histology lost more IDRFs (median: 1[0-9]) than patients with ganglioneuroblastoma (median: 0[0-4]) (P < 0.001). The completeness of resection was related only to the number of preoperative IDRFs (P = 0.028). CONCLUSION IDRF assessment after neoadjuvant chemotherapy is useful for predicting completeness of resection of neurogenic tumors. A larger international study is needed to confirm these results and to explore a possible correlation between preoperative IDRF status and survival.
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Affiliation(s)
- Sabine Irtan
- Pediatric surgery department, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France
| | | | | | | | - Louise Galmiche-Rolland
- Pathology department, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France
| | - Chloé Le Cossec
- Biostatistics department, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France
| | - Caroline Elie
- Biostatistics department, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France
| | - Sandra Canale
- Radiology department, Gustave-Roussy Institute, Paris, France
| | - Jean Michon
- Pediatric Oncology department, Curie institute, Paris, France
| | | | - Sabine Sarnacki
- Pediatric surgery department, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France
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De Ioris MA, Crocoli A, Contoli B, Garganese MC, Natali G, Tomà P, Jenkner A, Boldrini R, De Pasquale MD, Milano GM, Madafferi S, Castellano A, Locatelli F, Inserra A. Local control in metastatic neuroblastoma in children over 1 year of age. BMC Cancer 2015; 15:79. [PMID: 25886486 PMCID: PMC4349468 DOI: 10.1186/s12885-015-1082-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Accepted: 02/11/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Local control is always considered in metastatic neuroblastoma (NBL). The aim of this study is to evaluate the impact of radical surgery on survival in children over 1 year of age. METHODS Fifty-eight patients older than 1 year of age with metastatic NBL were treated with conventional plus high-dose chemotherapy with or without addition of local radiotherapy (RT, 21Gy). Surgery was classified as radical surgery (complete resection and gross total resection) or non-radical surgery. The Kaplan-Meier method and the Cox proportional hazard model were used to calculate the probability of progression free and overall survival (PFS and OS) and for multivariate analysis. RESULTS The 5-year PFS and OS for patients with radical surgery were 26% (95% CI 14-40%) and 38% (95% CI 23-53%) respectively, while the PFS and OS for patients without radical surgery were 33% (95% CI 10-59%) and 31% (95% CI 10-55%) (respectively, P 0.85 and P 0.42). The 5-year PFS and OS for patients who received RT were 36% (95% CI 19-53%) and 46% (95% CI 26-64%) respectively, while the 5-year PFS and OS for patients who did not receive RT were 22% (95% CI 9-38%) and 27% (95% CI 13-42%) respectively (P 0.02 for PFS). Multivariate analysis confirmed the role of well-known prognostic factors, such as the presence of MYCN amplification, age and response before high-dose chemotherapy. CONCLUSIONS Our data suggest that the degree of resection does not influence survival in metastatic NBL patients treated with high-dose chemotherapy; local RT contributes to local disease control.
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Affiliation(s)
| | | | - Benedetta Contoli
- Hematology/Oncology Department, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy.
| | | | | | | | - Alessandro Jenkner
- Hematology/Oncology Department, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy.
| | - Renata Boldrini
- Pathology Department, Bambino Gesù Children's Hospital, Rome, Italy.
| | | | - Giuseppe Maria Milano
- Hematology/Oncology Department, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy.
| | | | - Aurora Castellano
- Hematology/Oncology Department, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy.
| | - Franco Locatelli
- Hematology/Oncology Department, Ospedale Pediatrico Bambino Gesù-IRCCS, Rome, Italy. .,University of Pavia, Pavia, Italy.
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Abstract
Neuroblastoma (NB) is the third most common pediatric cancer. Although NB accounts for 7% of pediatric malignancies, it is responsible for more than 10% of childhood cancer-related mortality. Prognosis and treatment are determined by clinical and biological risk factors. Estimated 5-year survival rates for patients with non-high-risk and high-risk NB are more than 90% and less than 50%, respectively. Recent clinical trials have continued to reduce therapy for patients with non-high-risk NB, including the most favorable subsets who are often followed with observation approaches. In contrast, high-risk patients are treated aggressively with chemotherapy, radiation, surgery, and myeloablative and immunotherapies.
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Du L, Liu L, Zhang C, Cai W, Wu Y, Wang J, Lv F. Role of surgery in the treatment of patients with high-risk neuroblastoma who have a poor response to induction chemotherapy. J Pediatr Surg 2014; 49:528-33. [PMID: 24726106 DOI: 10.1016/j.jpedsurg.2013.11.061] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 11/19/2013] [Accepted: 11/21/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND In instances of high-risk neuroblastoma that do not show a clinical response to induction therapy, whether it is worth performing surgical resection or not and whether gross total resection (GTR) is more important than subtotal resection (STR) remain controversial. METHODS We retrospectively analyzed the data of patients with stage 4 neuroblastoma aged 18 months or older at diagnosis. Primary tumor volumes were measured both at diagnosis and at the first tumor response evaluation (after 6 cycles of induction chemotherapy). If the tumor volume at the first response evaluation was > 50% of the initial tumor volume, the patient was categorized as a poor responder. Otherwise, the patient was categorized as a good responder. Only poor responders were included. Patients were evaluated for event-free survival (EFS), overall survival (OS), and complications of surgery based on extent of surgical intervention. RESULTS Sixty-five patients were included in this study. The 41 patients who underwent surgical intervention had a higher 3-year OS than the 24 patients who had a biopsy only (55.4% ± 8.1% vs. 31.3% ± 10.2%, P=0.02). However, there was limited improvement in 3-year EFS following surgical intervention. Three-year EFS rates of BX group (biopsy only) and OP group (surgical resection) were 24.2% ± 9.3% and 37.7% ± 7.9%, respectively (P=0.063). The extent of resection had no impact on 3-year OS (P=0.631) and 3-year EFS (P=0.796). Patients in the GTR group trended to have more severe surgical complications than patients in the STR group (P=0.105). CONCLUSIONS For high-risk neuroblastomas that do not show a clinical response to induction therapy, surgical resection is important in predicting outcome, but the extent of resection is not.
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Affiliation(s)
- Lei Du
- Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, No. 1665 Kongjiang Road, Shanghai 200092, China
| | - Ling Liu
- Huai'an First People's Hospital, Nanjing Medical University, No. 6 West Beijing Road, Huai'an 223300, China
| | - Chi Zhang
- Huai'an First People's Hospital, Nanjing Medical University, No. 6 West Beijing Road, Huai'an 223300, China.
| | - Wei Cai
- Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, No. 1665 Kongjiang Road, Shanghai 200092, China.
| | - Yeming Wu
- Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China
| | - Jun Wang
- Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China
| | - Fan Lv
- Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China
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Zhuo B, Wang R, Yin Y, Zhang H, Ma T, Liu F, Cao H, Shi Y. Adenovirus arming human IL-24 inhibits neuroblastoma cell proliferation in vitro and xenograft tumor growth in vivo. Tumour Biol 2013; 34:2419-26. [PMID: 23609032 DOI: 10.1007/s13277-013-0792-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Accepted: 04/03/2013] [Indexed: 11/25/2022] Open
Abstract
Data have increasingly shown that interlukin-24 (IL-24) has growth suppression activity and can induce apoptosis in a broad spectrum of tumor cells. However, the therapeutic effect of IL-24 on human neuroblastoma has rarely been explored. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to reveal the effect of adenovirus-mediated IL-24 (Ad-IL24) gene therapy for neuroblastoma. We showed that Ad-IL24 effectively inhibited the proliferation of SH-SY5Y cells in vitro by conspicuously inducing apoptosis. To further explore the molecular mechanism by which Ad-IL24 induced apoptosis in SH-SY5Y tumor cells, we found that Ad-IL24 increased the expression of Bax and promoted the activation of caspase-3, while decreasing Bcl-2 levels. We also demonstrated that Ad-IL24 significantly inhibited tumor growth in vivo in a xenograft neuroblastoma tumor in athymic nude mice. In summary, Ad-IL24 overexpression exerted potent antitumor activity via inducing apoptosis in neuroblastoma cells. Therefore, IL-24 has the potential to serve as an agent for gene therapy in the treatment of neuroblastoma.
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Affiliation(s)
- Baobiao Zhuo
- Department of Surgery, Xuzhou Children's Hospital, 18 Suti North Road, Xuzhou, Jiangsu, 221006, China.
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Simon T, Häberle B, Hero B, von Schweinitz D, Berthold F. Role of surgery in the treatment of patients with stage 4 neuroblastoma age 18 months or older at diagnosis. J Clin Oncol 2013; 31:752-8. [PMID: 23284039 DOI: 10.1200/jco.2012.45.9339] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
PURPOSE Although intensive multimodal treatment has improved the prognosis of patients with metastatic neuroblastoma, the impact of primary tumor resection on outcome is a matter of medical debate. PATIENTS AND METHODS Patients from the German prospective clinical trial NB97 with stage 4 neuroblastoma and age 18 months or older at diagnosis were included. Operation notes and imaging reports were reviewed by two independent experienced physicians. Finally, the extent of tumor resections was correlated with local control rate and outcome. RESULTS A total of 278 patients were included in this study. Image-defined risk factors present at diagnosis were found to be predictive for the extent of tumor resection at first (P < .001) and best (P < .001) operation. No patient died from surgery. Before chemotherapy, complete resection, incomplete resection, and biopsy or no surgery were performed in 6.1%, 5.0%, and 88.5% of patients, respectively. The extent of first operation had no impact on event-free survival (EFS; P = .207), local progression-free survival (LPFS; P = .195), and overall survival (OS; P = .351). After induction chemotherapy, 54.7% of patients underwent complete resection of the primary tumor, 30.6% underwent incomplete resection, and 13.3% had only biopsy or no surgery of the primary tumor. The extent of best operation also had no impact on EFS (P = .877), LPFS (P = .299), and OS (P = .778). Moreover, multivariate analyses showed that surgery did not affect EFS, LPFS, and OS. CONCLUSION In intensively treated patients with stage 4 neuroblastoma age 18 months or older at diagnosis, surgery of the primary tumor site has no impact on local control rate and outcome.
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Affiliation(s)
- Thorsten Simon
- Department of Pediatric Oncology and Hematology, Children's Hospital, University of Cologne, Cologne, Germany.
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