Neuroblastoma
Neuroblastoma | |
---|---|
five-year survival ~95% (< 1 year old), 68% (1–14 years old)[2] | |
Frequency | 1 in 7,000 children[2] |
Deaths | 15% of deaths due to cancer in children[3] |
Neuroblastoma (NB) is a type of
Typically, neuroblastoma occurs due to a
Treatment and outcomes depends on the risk group a person is in.
Neuroblastoma is the most common cancer in babies and the third-most common cancer in children after
Signs and symptoms
The first
- In the abdomen, a tumor may cause abdominal distension and constipation.
- A tumor in the breathing problems.
- A tumor pressing on the spinal cord may cause weakness, thus an inability to stand, crawl, or walk.
- Bone lesions in the legs and hips may cause pain and limping.
- A tumor in the bones around the eyes or orbits may cause distinct bruising and swelling.
- Infiltration of the bone marrow may cause pallor from anemia.
Neuroblastoma often spreads to other parts of the body before any symptoms are apparent, and 50 to 60% of all neuroblastoma cases present with metastases.[8]
The most common location for neuroblastoma to originate (i.e., the primary tumor) is in the adrenal glands. This occurs in 40% of localized tumors and in 60% of cases of widespread disease. Neuroblastoma can also develop anywhere along the sympathetic nervous system chain from the neck to the pelvis. Frequencies in different locations include: neck (1%), chest (19%), abdomen (30% nonadrenal), or pelvis (1%). In rare cases, no primary tumor can be discerned.[9]
Rare but characteristic presentations include transverse
Cause
The cause of neuroblastoma is not well understood. The great majority of cases are sporadic and nonfamilial. About 1–2% of cases run in families and have been linked to specific gene mutations. Familial neuroblastoma in some cases is caused by rare
Duplicated segments of the LMO1 gene within neuroblastoma tumor cells have been shown to increase the risk of developing an aggressive form of the cancer.[14]
Other genes might have a prognostic role in neuroblastoma. A
Neuroblastoma has been linked to
One study strongly indicates that miRNAs that are excessively expressed in 1p-deleted neuroblastoma cells, as opposed to other genetic subgroups of neuroblastoma, could potentially disrupt the regulation of genes associated with neuronal differentiation, thereby contribute to the pathogenesis of neuroblastoma. Furthermore, it was noted that miR-495 primarily targeted the majority of mRNAs that are involved in neuronal differentiation.[17]
Several risk factors have been proposed and are the subject of ongoing research. Due to characteristic early onset, many studies have focused on parental factors around conception and during gestation. Factors investigated have included occupation (i.e. exposure to chemicals in specific industries), smoking, alcohol consumption, use of medicinal drugs during pregnancy, and birth factors; however, results have been inconclusive.[18]
Other studies have examined possible links with atopy and exposure to infection early in life,[19] use of hormones and fertility drugs,[20] and maternal use of hair dye.[21][22]
Diagnosis
The diagnosis is usually confirmed by a surgical pathologist, taking into account the clinical presentation, microscopic findings, and other laboratory tests. It may arise from any neural crest element of the sympathetic nervous system (SNS).
Esthesioneuroblastoma, also known as olfactory neuroblastoma, is believed to arise from the olfactory epithelium and its classification remains controversial. However, since it is not a sympathetic nervous system malignancy, esthesioneuroblastoma is a distinct clinical entity and is not to be confused with neuroblastoma.[23][24]
Biochemistry
In about 90% of cases of neuroblastoma, elevated levels of
Imaging
Another way to detect neuroblastoma is the
Histology
On microscopy, the tumor cells are typically described as small, round and blue, and
Neuroblastoma is one of the peripheral neuroblastic
Staging
The "International Neuroblastoma Staging System" (INSS) established in 1986 and revised in 1988 stratifies neuroblastoma according to its anatomical presence at diagnosis:[33][34][35]
- Stage 1: Localized tumor confined to the area of origin.
- Stage 2A: Unilateral tumor with incomplete gross resection; identifiable ipsilateral and contralateral lymph node negative for tumor.
- Stage 2B: Unilateral tumor with complete or incomplete gross resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor.
- Stage 3: Tumor infiltrating across midline with or without regional lymph node involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement.
- Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S.
- Stage 4S: Age <1 year old with localized primary tumor as defined in Stage 1 or 2, with dissemination limited to liver, skin, or bone marrow (less than 10 percent of nucleated bone marrow cells are tumors).
Although international agreement on staging (INSS) has been used, the need for an international consensus on risk assignment has also been recognized in order to compare similar cohorts in results of studies. Beginning in 2005, representatives of the major pediatric oncology cooperative groups have met to review data for 8,800 people with neuroblastoma treated in Europe, Japan, USA, Canada, and Australia between 1990 and 2002. This task force has proposed the International Neuroblastoma Risk Group (INRG) classification system. Retrospective studies revealed the high survival rate of 12–18 month-old age group, previously categorized as high-risk, and prompted the decision to reclassify 12–18 month-old children without N-myc (also commonly referred to as
The new INRG risk assignment will classify neuroblastoma at diagnosis based on a new International Neuroblastoma Risk Group Staging System (INRGSS):
- Stage L1: Localized disease without image-defined risk factors.
- Stage L2: Localized disease with image-defined risk factors.
- Stage M: Metastatic disease.
- Stage MS: Metastatic disease "special" where MS is equivalent to stage 4S.
The new risk stratification will be based on the new INRGSS staging system, age (dichotomized at 18 months), tumor grade,
Screening
Urine
Treatment
When the
Biologic and genetic characteristics have been identified, which, when added to classic clinical staging, has allowed assignment to risk groups for planning treatment intensity.
The therapies for these different risk categories are very different.
- Low-risk disease can frequently be observed without any treatment at all or cured with surgery alone.[48]
- Intermediate-risk disease is treated with surgery and chemotherapy.[49]
- High-risk neuroblastoma is treated with intensive 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[
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 (
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.[57][58]
Prognosis
By data from
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.[63][64] 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.[65][66][67]
Cytogenetic profiles
Based on a series of 493 neuroblastoma samples, it has been reported that overall genomic pattern, as tested by
- 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-mycamplification, 1p and 11q deletions, and 1q gain.
Earlier publications categorized neuroblastomas into three major subtypes based on cytogenetic profiles:[69][70]
- 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).
Epidemiology
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.[73]
The highest number of cases is in the first year of life, and some cases are
History
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.[76][77] 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.[78]
Scientific research
Preclinical models
Neuroblastoma
Treatments
Recent focus has been to reduce therapy for low and intermediate risk neuroblastoma while maintaining survival rates at 90%.[82] 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.[83][84]
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
Refractory and relapsed neuroblastoma
Chemotherapy with topotecan and cyclophosphamide is frequently used in refractory setting and after relapse.[85]
A haploidentical
It has been shown that neuroblastoma display a high expression of somatostatin receptors [87][88][89] 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.[90][91][92]
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,[93] while University of Chicago launched the Pediatric Cancer Data Commons.[94] 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.[95]
Organisations
The Advances in Neuroblastoma Research Association (ANRA) is the
References
- ^ a b c d e f g h i j k l m n o "Neuroblastoma Treatment". National Cancer Institute. 20 January 2016. Archived from the original on 10 November 2016. Retrieved 9 November 2016.
- ^ a b c d e "Neuroblastoma Treatment". National Cancer Institute. 25 August 2016. Archived from the original on 10 November 2016. Retrieved 10 November 2016.
- ^ ISBN 978-92-832-0429-9. Archived from the originalon 2016-09-19. Retrieved 2016-11-10.
- PMID 36973454.
- ^ S2CID 208790138.
- ISBN 978-0-313-25889-3. Archivedfrom the original on 2017-09-10.
- ^ Wheeler K (January 1, 2013). "Neuroblastoma in children". Macmillan. Archived from the original on October 5, 2015.
- ^ "Neuroblastoma: Pediatric Cancers: Merck Manual Professional". Archived from the original on 2007-12-18. Retrieved 2008-01-01.
- S2CID 37657305.
- S2CID 24523263.
- ISBN 978-3-540-40841-3.
- PMID 18724359.
- PMID 6719137.
- PMID 21124317.
- PMID 19536264.
- PMID 36800078– via Springer.
- ISBN 978-0-444-50222-3.
- PMID 15105177.
- PMID 10547138.
- S2CID 24323871.
- PMID 19159399.
- ^ Esthesioneuroblastoma at eMedicine
- ISBN 978-3-540-40841-3.
- S2CID 34838939.
- ^ PMID 17544628.
- PMID 15653652.
- ^ PMID 26417712.
- ISBN 978-1-4557-2613-4.
- ^ Ependymoma at eMedicine
- S2CID 6461880.
- S2CID 27081822.
- ^ "Neuroblastoma Treatment—National Cancer Institute". 1980-01-01. Archived from the original on 2008-10-02. Retrieved 2008-07-30.
- PMID 3199170.
- PMID 8336186.
- PMID 16116154.
- doi:10.1200/jco.2007.25.18_suppl.9503. Archived from the originalon 2016-01-10.
- PMID 11932470.
- PMID 12880955.
- PMID 15128908.
- ^ "Neuroblastoma Screening". National Cancer Institute. 1980-01-01. Archived from the original on 2008-10-01. Retrieved 2008-07-30.
- ^ Darshak Sanghavi, "Screen Alert: How an Ounce of RX Prevention can Cause a Pound of Hurt" Archived 2006-12-01 at the Wayback Machine, Slate magazine, November 28, 2006
- S2CID 32358612.
- S2CID 6447457.
- PMID 17943719.
- ^ "Translating Neuroblastoma Genomics to the Clinic—J. Maris presentation ASCO 2007". Archived from the original on 2009-01-02. Retrieved 2008-01-13.
- PMID 17897457.
- ^ "Neuroblastoma Treatment". National Cancer Institute. 1980-01-01. Archived from the original on 2008-05-03. Retrieved 2008-02-02.
- PMID 9988866.
- PMID 18037943.
- PMID 10519894.
- PMID 20879881.
- PMID 26436598.
- ^ "Neuroblastoma Treatment". National Cancer Institute. 1980-01-01. Archived from the original on 2008-10-02. Retrieved 2008-07-30.
- ^ Yu AL, Gilman MF, Ozkaynak WB, London S, Kreissman HX, Chen KK, Matthay SL, Cohn JM, Maris JM, Sondel PM (2009). "A phase III randomized trial of the chimeric anti-GD2 antibody ch14.18 with GM-CSF and IL2 as immunotherapy following dose intensive chemotherapy for high-risk neuroblastoma: Childrens Oncology Group (COG) study ANBL0032". Journal of Clinical Oncology. 27 (15 Suppl): 10067z. Archived from the original on 2016-01-10. Retrieved 2015-09-10.
- PMID 37993417.
- ^ "Drugs Trials Snapshot: Danyelza". U.S. Food and Drug Administration (FDA). 25 November 2020. Retrieved 25 December 2020. This article incorporates text from this source, which is in the public domain.
- ^ "Drug Approval Package: Danyelza". U.S. Food and Drug Administration (FDA). 22 December 2020. Retrieved 25 December 2020.
- ^ "Neuroblastoma overview". Children with Cancer UK. Retrieved 2020-07-01.
- PMID 15611504.
- doi:10.1200/jco.2007.25.18_suppl.9505. Archived from the originalon 2016-01-10.
- S2CID 31490896.
- S2CID 10606999.
- PMID 17724446.
- ^ Mozes A (February 21, 2007). "Childhood Cancer Survivors Face Increased Sarcoma Risk". HealthDay. Archived from the original on September 8, 2015.
- PMID 17035650.
- PMID 19648511.
- PMID 19171713.
- PMID 15800319. Archived from the original(PDF) on 2020-10-30. Retrieved 2019-11-18.
- S2CID 14012430.
- PMID 18664255.
- ^ Data and references for pie chart are located at file description page in Wikimedia Commons.
- ISBN 978-1-60547-682-7.
- PMID 9149032.
- PMID 18545256.
- ISBN 978-3-540-26616-7.
- PMID 14099453.
- S2CID 19611725.
- ^ PMID 25220031.
- PMID 24157811.
- PMID 22508028.
- ^ "Neuroblastoma Committee—Current Focus of Research". Archived from the original on September 25, 2006. Retrieved 2008-01-13.
- PMID 20879880. Archived from the originalon 2013-01-13.
- PMID 20879880.
- S2CID 5529288.
- PMID 29307718.
- S2CID 33330859.
- S2CID 30833979.
- S2CID 11168638.
- S2CID 38660848.
- S2CID 25518501.
- PMID 20847174.
- ^ INRG Data Commons
- ^ Pediatric Cancer Data Commons
- ^ "Home". Advances in Neuroblastoma Research Association. 26 April 2014. Retrieved 11 April 2024.
External links