Neuroblastoma medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Zahir Ali Shaikh, MD[2]Haytham Allaham, M.D. [3]
Overview
Children oncology group (COG) risk stratification system determines the protocol of management used for neuroblastoma patients. COG risk stratification system divides the patients into 03 groups: low risk, intermediate risk and high risk patients. Low risk neuroblastoma patients are usually managed by either observation or surgical resection of the tumor. Intermediate risk patients are managed by neoadjuvant therapy in advance of a definitive surgical resection. High risk neuroblastoma patients are usually managed by a combination of surgery, chemotherapy, radiation therapy, hematopoietic stem cell transplantation, immunotherapy and isotretrinoin.
Medical Therapy
Risk Stratification[1][2][3][4]
- Children Oncology Group (COG) risk stratification system determines the protocol of management used for neuroblastoma patients.
- Low risk neuroblastoma patients are usually managed by either observation or surgical resection of the tumor.
- Intermediate risk neuroblastoma patients are usually managed by neoadjuvant chemotherapy in advance of a definitive surgical resection.
- High risk neuroblastoma patients are usually managed by a combination of surgery, chemotherapy, radiation therapy, hematopoietic stem cell transplantation, differentiation therapy, immunotherapy, and isotretinoin.[5]
- The algorithm below summarizes the management approach for neuroblastoma patients:
Children's Oncology Group risk stratification | |||||||||||||||||||||||||||||
Low risk patients | Intermediate risk patients | High risk patients | |||||||||||||||||||||||||||
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Management of Low Risk Neuroblastoma Patients[5][6][7]
Observation
- Low risk neuroblastoma patients younger than 6 months of age may be safely observed without obtaining a definitive histologic diagnosis or performing any surgical intervention.
- Observation among such patients avoids potential surgical complications, as the majority of neuroblastomas occurring among this age group demonstrate spontaneous regression.
Radiotherapy
- Radiotherapy is generally not recommended for the management of low risk neuroblastoma patients.
Chemotherapy
- Indications for chemotherapy for the management of low risk neuroblastoma patients include:
- Stage 1 or stage 2 tumors associated with MYCN amplification
- Patients older than 18 months of age presenting with a stage 2B tumor and an unfavorable histology
- Symptomatic patients due to spinal cord compression, respiratory compromise, or hepatic infiltration
- Chemotherapeutic regimens recommended for the management of low risk neuroblastoma patients may include agents such as:
Management of Intermediate Risk Neuroblastoma Patients[5][8]
Observation
- Observation is generally not recommended for the management of intermediate risk neuroblastoma patients.
Radiotherapy
- Indications for radiotherapy for the management of intermediate risk neuroblastoma patients include:
- Symptomatic life-threatening neuroblastoma refractory to chemotherapy and/or surgery
- Rapidly growing neuroblastoma associated with progressive disease symptoms
Chemotherapy
- Chemotherapeutic agents are generally effective for the management of intermediate risk neuroblastoma patients.
- Intermediate risk neuroblastoma patients with favorable histology are successfully managed by 4 cycles of chemotherapy following surgery.
- Intermediate risk neuroblastoma patients with unfavorable histology are successfully managed by 8 cycles of chemotherapy following surgery.
- Neoadjuvant chemotherapy may be used to facilitate the partial resection of previously unresectable neuroblastomas among intermediate risk patients.
- Chemotherapeutic regimens recommended for the management of intermediate risk neuroblastoma patients may include agents such as:
Management of High Risk Neuroblastoma Patients[5][9][10]
Observation
- Observation is generally not recommended for the management of high risk neuroblastoma patients.
Radiotherapy
- Radiation therapy to consolidate local control after surgical resection is recommended for the management of high risk neuroblastoma patients.
Chemotherapy
- Chemotherapy for high risk neuroblastoma patients is divided into the following three phases:
- Induction therapy:
- Chemotherapeutic regimens used in the induction therapy may include:
- Consolidation therapy:
- Consolidation therapy of high risk neuroblastoma patients consists of high dose chemotherapeutic agents administered in tandem with hematopoietic stem cell transplantation.
- Chemotherapeutic regimens used in the consolidation therapy may include:
- Maintenance therapy:
- A combination of differentiation therapy (GM-CSF and IL-2), isotretinoin, and immunotherapy (chimeric anti-GD2 antibody-ch14.18) are adminstered following hematopoietic stem cell transplantation to improve the survival of high risk neuroblastoma patients.
References
- ↑ Chizuko Okamatsu, Wendy B. London, Arlene Naranjo, Michael D. Hogarty, Julie M. Gastier-Foster, A. Thomas Look, Michael LaQuaglia, John M. Maris, Susan L. Cohn, Katherine K. Matthay, Robert C. Seeger, Tsutomu Saji & Hiroyuki Shimada (2009). "Clinicopathological characteristics of ganglioneuroma and ganglioneuroblastoma: a report from the CCG and COG". Pediatric blood & cancer. 53 (4): 563–569. doi:10.1002/pbc.22106. PMID 19530234. Unknown parameter
|month=ignored (help) - ↑ Susan L. Cohn, Andrew D. J. Pearson, Wendy B. London, Tom Monclair, Peter F. Ambros, Garrett M. Brodeur, Andreas Faldum, Barbara Hero, Tomoko Iehara, David Machin, Veronique Mosseri, Thorsten Simon, Alberto Garaventa, Victoria Castel & Katherine K. Matthay (2009). "The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report". Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 27 (2): 289–297. doi:10.1200/JCO.2008.16.6785. PMID 19047291. Unknown parameter
|month=ignored (help) - ↑ Chrystal U. Louis & Jason M. Shohet (2015). "Neuroblastoma: molecular pathogenesis and therapy". Annual review of medicine. 66: 49–63. doi:10.1146/annurev-med-011514-023121. PMID 25386934.
- ↑ Andrew M. Davidoff (2012). "Neuroblastoma". Seminars in pediatric surgery. 21 (1): 2–14. doi:10.1053/j.sempedsurg.2011.10.009. PMID 22248965. Unknown parameter
|month=ignored (help) - ↑ 5.0 5.1 5.2 5.3 Neuroblastoma treatment–for health professionals. National Cancer Institute (2015) http://www.cancer.gov/types/neuroblastoma/hp/neuroblastoma-treatment-pdq#section/_1 Accessed on October, 8 2015
- ↑ Jed G. Nuchtern, Wendy B. London, Carol E. Barnewolt, Arlene Naranjo, Patrick W. McGrady, James D. Geiger, Lisa Diller, Mary Lou Schmidt, John M. Maris, Susan L. Cohn & Robert C. Shamberger (2012). "A prospective study of expectant observation as primary therapy for neuroblastoma in young infants: a Children's Oncology Group study". Annals of surgery. 256 (4): 573–580. doi:10.1097/SLA.0b013e31826cbbbd. PMID 22964741. Unknown parameter
|month=ignored (help) - ↑ Douglas R. Strother, Wendy B. London, Mary Lou Schmidt, Garrett M. Brodeur, Hiroyuki Shimada, Paul Thorner, Margaret H. Collins, Edward Tagge, Stanton Adkins, C. Patrick Reynolds, Kevin Murray, Robert S. Lavey, Katherine K. Matthay, Robert Castleberry, John M. Maris & Susan L. Cohn (2012). "Outcome after surgery alone or with restricted use of chemotherapy for patients with low-risk neuroblastoma: results of Children's Oncology Group study P9641". Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 30 (15): 1842–1848. doi:10.1200/JCO.2011.37.9990. PMID 22529259. Unknown parameter
|month=ignored (help) - ↑ David L. Baker, Mary L. Schmidt, Susan L. Cohn, John M. Maris, Wendy B. London, Allen Buxton, Daniel Stram, Robert P. Castleberry, Hiroyuki Shimada, Anthony Sandler, Robert C. Shamberger, A. Thomas Look, C. Patrick Reynolds, Robert C. Seeger & Katherine K. Matthay (2010). "Outcome after reduced chemotherapy for intermediate-risk neuroblastoma". The New England journal of medicine. 363 (14): 1313–1323. doi:10.1056/NEJMoa1001527. PMID 20879880. Unknown parameter
|month=ignored (help) - ↑ Valeria Smith & Jennifer Foster (2018). "High-Risk Neuroblastoma Treatment Review". Children (Basel, Switzerland). 5 (9). doi:10.3390/children5090114. PMID 30154341. Unknown parameter
|month=ignored (help) - ↑ K. Beiske, S. A. Burchill, I. Y. Cheung, E. Hiyama, R. C. Seeger, S. L. Cohn, A. D. J. Pearson & K. K. Matthay (2009). "Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force". British journal of cancer. 100 (10): 1627–1637. doi:10.1038/sj.bjc.6605029. PMID 19401690. Unknown parameter
|month=ignored (help)