il-2. a meta analysis has found evidence that in children with high-risk neuroblastoma, treatment with myeloablative therapy improves event-free survival but may increase the risk of side effects such as kidney problems when compared to conventional chemotherapy. people with low and intermediate risk disease have an excellent prognosis with cure rates above 90% for low risk and 70–90% for intermediate risk. in contrast, therapy for high-risk neuroblastoma the past two decades resulted in cures only about 30% of the time. the addition of antibody therapy has raised survival rates for high-risk disease significantly. in march 2009, an early analysis of a children's oncology group (cog) study with 226 people that are high-risk showed that two years after stem cell transplant 66% of the group randomized to receive ch14.18 antibody with gm-csf and il-2 were alive and disease-free compared to only 46% in the group that did not receive the antibody. the randomization was stopped so all people enrolling on the trial would receive the antibody therapy. chemotherapy agents used in combination have been found to be effective against neuroblastoma. agents commonly used in induction and for stem cell transplant conditioning are platinum compounds (cisplatin, carboplatin), alkylating agents (cyclophosphamide, ifosfamide, melphalan), topoisomerase ii inhibitor (etoposide), anthracycline antibiotics (doxorubicin) and vinca alkaloids (vincristine). some newer regimens include topoisomerase i inhibitors (topotecan and irinotecan) in induction which have been found to be effective against recurrent disease. in november 2020, naxitamab was approved for medical use in the united states in combination with granulocyte-macrophage colony-stimulating factor (gm-csf) to treat people one year of age and older with high-risk neuroblastoma in bone or bone marrow whose tumor did not respond to or has come back after previous treatments and has shown a partial response, minor response, or stable disease to prior therapy. prognosis by data from england, the overall 5-year survival rate of neuroblastoma is 67%. between 20% and 50% of high-risk cases do not respond adequately to induction high-dose chemotherapy and are progressive or refractory. relapse after completion of frontline therapy is also common. further treatment is available in phase i and phase ii clinical trials that test new agents and combinations of agents against neuroblastoma, but the outcome remains very poor for relapsed high-risk disease. most long-term survivors alive today had low or intermediate risk disease and milder courses of treatment compared to high-risk disease. the majority of survivors have long-term effects from the treatment. survivors of intermediate and high-risk treatment often experience hearing loss, growth reduction, thyroid function disorders, learning difficulties, and greater risk of secondary cancers affect survivors of high-risk disease. an estimated two of three survivors of childhood cancer will ultimately develop at least one chronic and sometimes life-threatening health problem within 20 to 30 years after the cancer diagnosis. cytogenetic profiles based on a series of 493 neuroblastoma samples, it has been reported that overall genomic pattern, as tested by array-based karyotyping, is a predictor of outcome in neuroblastoma: tumors presenting exclusively with whole chromosome copy number changes were associated with excellent survival. tumors presenting with any kind of segmental chromosome copy number changes were associated with a high risk of relapse. within tumors showing segmental alterations, additional independent predictors of decreased overall survival were n-myc amplification, 1p and 11q deletions, and 1q gain. earlier publications categorized neuroblastomas into three major subtypes based on cytogenetic profiles: subtype 1: favorable neuroblastoma with near triploidy and a predominance of numerical gains and losses, mostly representing non-metastatic nb stages 1, 2 and 4s. subtypes 2a and 2b: found in unfavorable widespread neuroblastoma, stages 3 and 4, with 11q loss and 17q gain without n-myc amplification (subtype 2a) or with n-myc amplification often together with 1p deletions and 17q gain (subtype 2b). virtual karyotyping can be performed on fresh or paraffin-embedded tumors to assess copy number at these loci. snp array virtual karyotyping is preferred for tumor samples, including neuroblastomas, because they can detect copy neutral loss of heterozygosity (acquired uniparental disomy). copy neutral loh can be biologically equivalent to a deletion and has been detected at key loci in neuroblastoma. arraycgh, fish, or conventional cytogenetics cannot detect copy neutral loh. epidemiology incidences and prognoses of adrenal tumors, with "neuronal tumor" at right neuroblastoma comprises 6–10% of all childhood cancers, and 15% of cancer deaths in children. the annual mortality rate is 10 per million children in the 0- to 4-year-old age group, and 4 per million in the 4- to 9-year old age group. the highest number of cases is in the first year of life, and some cases are congenital. the age range is broad, including older children and adults, but only 10% of cases occur in people older than 5 years of age. a large european study reported less than 2% of over 4000 neuroblastoma cases were over 18 years old. history rudolf virchow: the first to describe an abdominal tumor in a child as a "glioma" in 1864 german physician rudolf virchow was the first to describe an abdominal tumor in a child as a "glioma". the characteristics of tumors from the sympathetic nervous system and the adrenal medulla were then noted in 1891 by german pathologist felix marchand. in 1901 the distinctive presentation of stage 4s in infants (liver but no bone metastases) was described by william pepper. in 1910 james homer wright understood the tumor to originate from primitive neural cells, and named it neuroblastoma. he also noted the circular clumps of cells in bone marrow samples which are now termed "homer wright rosettes". of note, "homer-wright" with a hyphen is grammatically incorrect, as the eponym refers to just dr. wright. scientific research microscopic view of a nb cell line (sh-sy5y) used in preclinical research for testing new agents preclinical models neuroblastoma patient derived tumor xenografts (pdxs) have been created by orthotopic implantation of tumor samples into immunodeficient mice. pdx models have several advantages over conventional cancer cell lines (ccl)s. neuroblastoma pdxs retain the genetic hallmarks of their corresponding tumors and pdxs display infiltrative growth and metastasis to distant organs. pdx models are more predictive of clinical outcome as compared to conventional cancer cell line xenografts. neuroblastoma pdxs might thus serve as clinically relevant models to identify effective compounds against neuroblastoma. treatments recent focus has been to reduce therapy for low and intermediate risk neuroblastoma while maintaining survival rates at 90%. a study of 467 people that are at intermediate risk enrolled in a3961 from 1997 to 2005 confirmed the hypothesis that therapy could be successfully reduced for this risk group. those with favorable characteristics (tumor grade and response) received four cycles of chemotherapy, and those with unfavorable characteristics received eight cycles, with three-year event free survival and overall survival stable at 90% for the entire cohort. future plans are to intensify treatment for those people with aberration of 1p36 or 11q23 chromosomes as well as for those who lack early response to treatment. by contrast, focus the past 20 years or more has been to intensify treatment for high-risk neuroblastoma. chemotherapy induction variations, timing of surgery, stem cell transplant regimens, various delivery schemes for radiation, and use of monoclonal antibodies and retinoids to treat minimal residual disease continue to be examined. recent phase iii clinical trials with randomization have been carried out to answer these questions to improve survival of high-risk disease: refractory and relapsed neuroblastoma chemotherapy with topotecan and cyclophosphamide is frequently used in refractory setting and after relapse. a haploidentical stem cell transplant, that is, donor cells derived from parents, is being studied in those with refractory or relapsing neuroblastoma as stem cells from the person themselves is not useful. it has been shown that neuroblastoma display a high expression of somatostatin receptors and this enables potential therapy using 177lu-dota-tate, a type of radionuclide therapy that specifically targets the somatostatin receptors. several early phase clinical trials using 177lu-dota-tate for treatment of high-risk refractory/relapsed neuroblastoma have been conducted with promising results. electronic health records' data several international initiatives have been recently launched for the sharing of data of electronic health records of patients with neuroblastoma: these data in fact can be analyzed with machine learning and statistics models to infer new knowledge about this disease. to this end, the international neuroblastoma risk group (inrg) recently released the inrg data commons, while university of chicago launched the pediatric cancer data commons. these two repositories contain data of electronic health records of thousands of patients that are available for scientific research, with prior authorization. in 2022, researchers released a new data repository of electronic health records called neuroblastoma electronic health records open data repository where data can be downloaded freely without any restriction.