eMedicine Specialties > Pediatrics: General Medicine > Oncology

Neuroblastoma: Follow-up

Author: Norman J Lacayo, MD, Assistant Professor, Department of Pediatrics, Division of Hematology-Oncology, Stanford University and Lucile Salter Packard Children's Hospital
Coauthor(s): Neyssa Marina, MD, Professor, Department of Pediatrics, Division of Pediatric Hematology-Oncology, Lucile Packard Children's Hospital and Stanford University; Kara L Davis, DO, Fellow, Department of Pediatric Hematology/Oncology, Stanford University School of Medicine
Contributor Information and Disclosures

Updated: Jul 31, 2009

Follow-up

Further Inpatient Care

  • Children with neuroblastoma are admitted to the hospital to expedite the diagnostic workup when unstable or significantly symptomatic.
  • In an asymptomatic child, workup can be performed in the outpatient setting.
  • A central line is commonly placed when biopsy or resection is scheduled in intermediate- or high-risk patients.
  • A pediatric oncologist and surgeons with expertise in managing childhood malignancies perform the initial evaluation.
  • Other subspecialists, such as neurosurgeons or radiation oncologists, may participate in patient care, especially in cases of cord compression.
  • Once the diagnosis is established and the staging workup is completed, the patient and family are instructed on the diagnosis and therapeutic options.
  • Once the treatment plan is developed, chemotherapy is administered, usually in the inpatient setting.
  • Following completion of the treatment cycle, patients are discharged home with detailed instructions for home care and with outpatient follow-up.

Further Outpatient Care

  • Patients are periodically monitored in the clinic after each course of therapy to monitor for complications and to assess response to therapy with diagnostic imaging.
    • Myelosuppression and pancytopenia are common complications, and a CBC count with platelet count is obtained as often as twice per week.
    • Some drugs (eg, cisplatin, carboplatin, ifosfamide) affect renal function; thus, close monitoring of electrolytes is required, with oral electrolyte supplementation when necessary.
    • Blood product support is provided when the hemoglobin drops to less than 8 g/dL, the platelet count drops to less than 10,000, or any signs of bleeding are present.
  • Long-term follow-up care and surveillance
    • After completion of therapy, successfully treated patients require follow-up care and close surveillance for any signs or symptoms of recurrent disease.
    • Follow-up care includes monitoring of urinary catecholamines, physical examination, and diagnostic imaging.
    • Because most recurrences occur during the first 2 years following treatment, most protocols recommend close follow-up care during this interval.
  • Long-term issues 
    • Patients who remain free of recurrent disease for 5 years are considered cured, although rare late relapses have been reported.
    • Long-term follow-up care to assess impact of therapy on growth, development, and organ toxicity is essential.

Inpatient & Outpatient Medications

  • Infection prophylaxis
    • Chemotherapy agents cause myelosuppression and immunosuppression.
    • All patients should receive prophylaxis against Pneumocystis jiroveci with trimethoprim/sulfamethoxazole (trimethoprim 2.5 mg/kg/dose twice daily), administered on 3 consecutive days per week.
    • Prophylaxis is started before chemotherapy and continued for at least 3 months after completing therapy.
  • Colony-stimulating factors
    • Granulocyte colony stimulating factor (G-CSF) support has become common in pediatric oncology as intensity of chemotherapy has increased.
    • Treat with 5-10 mcg/kg/d subcutaneously to start 24-36 hours after the last dose of chemotherapy. G-CSF is continued until the absolute neutrophil count is 2,000-10,000.

Transfer

  • Management by primary care provider
    • With oncology team supervision, routine care can be carried out by the primary care provider for patient convenience.
    • Monitoring of blood counts or chemistries and administration of blood products are common.
    • Some primary care providers with experience in the treatment of febrile neutropenia may be able to manage this complication of chemotherapy. Patients may quickly destabilize upon initiation of antibiotic therapy; thus, access to critical care services is required.
    • Maintain close contact with subspecialists and transfer the patient to the pediatric oncology center for any complications that may require specialized care.

Deterrence/Prevention

  • The cause of neuroblastoma is unknown.
  • No specific environmental exposure or risk factors have been identified.
  • Currently, no specific recommendations on how to prevent this disease are known.
  • Screening for neuroblastoma in an attempt to diagnose high-risk patients earlier in the course of their disease has uncovered many patients with low-risk disease but has not had an impact on outcome in high-risk disease.

Complications

  • At disease presentation
    • The most worrisome complication at disease presentation is cord compression from a paraspinal tumor. Evaluation of the patient by a neurosurgeon and consultation with a radiation oncologist are important.
    • In some individuals with neuroblastomas, early institution of chemotherapy is accepted if the tumor can be biopsied within 72 hours to make a diagnosis and to obtain necessary biologic studies. In the acute setting, chemotherapy may be as efficient as radiotherapy or laminectomy, and it may cause less morbidity. Treatment of cord compression with chemotherapy and steroids usually results in less complications; however, radiation therapy or surgery is often used as front-line treatment to prevent impending or progressive neurologic damage. In children who present with significant neurologic symptoms, none of these interventions assure a return of normal neurologic (motor) function.
    • Tumor lysis syndrome is unusual in neuroblastoma
    • Patients may present with severe hypertension or renal insufficiency, making initiation of chemotherapy, especially with platinum drugs, more difficult.
  • During therapy
    • Myelosuppression and immunosuppression place the patient at risk of bleeding and infection. Febrile neutropenia is a medical emergency and requires immediate admission to the hospital and initiation of broad-spectrum antibiotic treatment.
    • After several cycles of therapy, depending on drugs administered, patients may develop impaired renal function, hearing loss, or delayed count recovery.

Prognosis

  • Determinants of response and outcome
    • Stage, age, and several biologic characteristics of the tumor determine outcome.
    • Similarly, the patient may also have genetic polymorphism characteristics that influence drug absorption, distribution, metabolism, and excretion.
  • Several treatment strategies are available to treat patients with recurrent neuroblastoma.
    • A local recurrence in a patient with low-stage disease generally has a good prognosis, and patients usually receive standard chemotherapy, surgery, and/or radiation as necessary.
    • Patients with disseminated disease at presentation have a high recurrence rate and a poor outcome.
    • For patients with recurrent disease in this setting, various phase I/II agents are generally available.
  • Response criteria are used to evaluate the efficacy of therapy.
    • Complete clinical response - More than 90% decrease (sum of the products of the greatest perpendicular diameters) of the primary tumor and metastatic disease (if any), no new lesions, healing of bone lesions
    • Partial clinical response -  A decrease of 50% or less (sum of the products of the greatest perpendicular diameters) of the primary tumor and metastatic disease (if any), no new lesions, healing of bone lesions
    • Minor response - More than 25% and less than 50% decrease (sum of the products of the greatest perpendicular diameters) of primary tumor and metastatic disease (if any), no new lesions, healing of bone lesions
    • No response - Less than 25% decrease (sum of the products of the greatest perpendicular diameters) of primary tumor or metastatic disease (if any), no new lesions
    • Progressive disease - More than 25% increase (sum of the products of the greatest perpendicular diameters) of the primary tumor or all metastatic lesions (if any), appearance of new lesions

Patient Education

  • For compliance and good medical care, patients and families must understand the importance of treatment and adverse effects of medications used.
  • In addition, they should learn to recognize and identify signs and symptoms of complications that require urgent medical care.

Miscellaneous

Medicolegal Pitfalls

  • Diagnostic workup: Cancer is rare in children; therefore, if neuroblastoma is suspected, prompt referral to a pediatric oncology center for multidisciplinary evaluation and appropriate care is essential. Most patients initially present for evaluation to either the primary care providers or a general surgeon. A surgeon without expertise in the management of pediatric tumors may attempt to biopsy or resect a mass without the availability of the necessary resources to obtain and process tumor samples for biologic studies. This intervention can lead to difficulty in risk-assignment and in administration of appropriate therapy.
  • Informed consent: Pediatric oncology has benefited from the high level of participation of children in clinical trials. The pediatric oncologist must be an effective communicator in providing informed consent to patients and families; a thorough discussion of the potential benefits and risks is warranted. Without compromising the enthusiasm and desire by the subspecialist to achieve a cure for the patient, families must be made aware that complications during cancer treatment can result in death or long-term morbidities.

Special Concerns

  • Drug toxicity
    • The cornerstone of pediatrics is prevention and treatment of disease to foster the normal growth and development of children. The use of chemotherapy in infants, children, and adolescents with cancer presents many challenges.
    • The pediatric oncologist must strive to maintain a balance between administering curative therapy and minimizing long-term morbidity.
    • Chemotherapy may have effects on the growth and development of children (eg, when administered to infants, ototoxicity of cisplatin and carboplatin may affect language development; neurotoxicity of vincristine may interfere with motor development; refractory nausea and emesis may lead to food aversion). Recognizing these sequelae is important, so that patients can receive appropriate therapy.
  • Physiologic processes
    • Equally important is the understanding that several physiologic processes during infancy and childhood can affect the pharmacokinetics and pharmacodynamics of drugs. Body composition varies during infancy, childhood, and adolescence. Total body water and extracellular fluid volumes are larger in the first year of life, and blood volume and fat composition do not approach adult levels until adolescence. Protein binding is also lower during the first year of life, therefore increasing the amount of unbound drug. These variables affect the volume of distribution of drugs; therefore, drug dosages are calculated differently in infants.
    • Drug doses in pediatric oncology most commonly are calculated using body surface area (BSA). However, because the BSA is larger in relation to an infant's weight, the use of BSA for dose calculation results in a larger dose per weight in infants than in older children and adults. As a result, many physicians and clinical protocols dose chemotherapy in infants on a per kilogram basis rather than by BSA.
    • Data are lacking concerning the disposition of most antineoplastic agents in young children and infants. However, guidelines are available for doxorubicin, etoposide, teniposide, and vincristine. The caveat for most of these recommendations is that only a small number of infants were included in the studies used to formulate these recommendations. In addition, not all studies included analysis of plasma-binding proteins, unbound drug systemic clearance, and other relevant factors.
    • The widespread practice of altering dosing in infants may be unwise because any rational approach should be based on the pharmacokinetic behavior of each agent. As we learn more about the pharmacokinetics of drugs and their relationship to efficacy and toxicity, the use of pharmacokinetically guided dosing may become more common.
    • Because evidence of increased toxicity with vincristine and doxorubicin is lacking, adjustment of dosing based on weight rather than on BSA is recommended in infants or children younger than 2 years and those with a BSA of less than 0.5 m2. Drugs that are excreted via the kidney can have limited clearance in young infants because the percentage of the cardiac output that reaches the kidneys is only 5%, whereas it is 25% in an older child or adult.
  • Nephrotoxicity
    • Drugs excreted via the kidney can have limited clearance in young infants because the amount of cardiac output that reaches the kidneys is only 5%, compared with 25% in an older child or adult.
    • Ifosfamide can cause renal tubular injury manifested as Fanconi syndrome, metabolic acidosis, hypokalemia, hypophosphatemia proteinuria, and rickets. The chronic nature of these injuries may interfere with normal growth, and close follow-up monitoring is required. Age younger than 3 years, presence of a single kidney, and the use of a cumulative dose of ifosfamide more than 45-72 g/m2 are important risk factors for nephrotoxicity.
    • The use of ifosfamide in patients with preexisting renal abnormalities is indicated only if potential benefit outweighs risk of further nephrotoxicity. Although this type of injury appears reversible, its long-term outcome remains unknown.
    • Cisplatin and, less frequently, carboplatin can cause glomerular injury manifested as acute or chronic decreased glomerular filtration rate.
  • Cardiotoxicity
    • The heart is another organ at risk for early and late toxicity
    • Anthracyclines have been useful in the treatment of a large number of pediatric cancers. However, the use of anthracyclines, especially in high cumulative doses, can lead to the development of a cardiomyopathy.
    • Several studies have suggested that age is an important risk factor for this complication because these drugs appear to damage cardiac myocytes and limit the heart's ability to grow.
  • Chemoprotectants and growth factors: Drugs that modify toxicity of antineoplastic agents (ie, mesna, amifostine, leucovorin) and availability of hematopoietic growth factors (eg, GCSF, granulocyte microphage colony stimulating factor [GMCSF]) have allowed use of maximally tolerated doses of many chemotherapy agents. These drugs have allowed development of more dose-intensive protocols.
  • Future directions in diagnosis and therapy
    • Discoveries related to the application of gene expression profiling, single nucleotide polymorphisms (SNPs), and protein arrays leads to a new taxonomy of neuroblastoma.
    • Understanding the molecular pathophysiology of neuroblastoma and the identification of new markers for the disease will revolutionize diagnosis, therapy, and, perhaps, prevention.
    • Discovery of abnormal signal transduction pathways in cancers are identifying new targets for therapy.
    • Numerous biologic agents are presently in phase 1 or phase 2 trials. These include tubulin binding molecules, immune stimulators, Trk inhibitors, anti-GD2 antibodies, BCL2 inhibitors, and tyrosine kinase inhibitors. Antiangiogenesis treatment strategies are also being used to treat recurrent disease.
    • The design of clinical trials should be based on understanding the biology of the disease (ie, the identification of a target and use of a target inhibitor that can be assayed in real-time with concomitant evaluation of the efficacy of targeted therapy on patient outcome).
 


More on Neuroblastoma

Overview: Neuroblastoma
Differential Diagnoses & Workup: Neuroblastoma
Treatment & Medication: Neuroblastoma
Follow-up: Neuroblastoma
Multimedia: Neuroblastoma
References
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Further Reading

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Keywords

neuroblastoma, sympathetic nervous system tumors of childhood, cancer, tumor, malignancy, neuroblasts, paraspinal dumbbell tumors, ganglioneuroblastoma, ganglioneuroma, hypertension, periorbital ecchymosis, thoracic neuroblastoma, cervical neuroblastoma, Horner syndrome, rubella, opsoclonus, myoclonus, Ewing sarcoma, stem cell transplantation, blueberry muffin baby, treatment, diagnosis

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Contributor Information and Disclosures

Author

Norman J Lacayo, MD, Assistant Professor, Department of Pediatrics, Division of Hematology-Oncology, Stanford University and Lucile Salter Packard Children's Hospital
Norman J Lacayo, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Hematology, and Children's Oncology Group
Disclosure: Nothing to disclose.

Coauthor(s)

Neyssa Marina, MD, Professor, Department of Pediatrics, Division of Pediatric Hematology-Oncology, Lucile Packard Children's Hospital and Stanford University
Neyssa Marina, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Kara L Davis, DO, Fellow, Department of Pediatric Hematology/Oncology, Stanford University School of Medicine
Kara L Davis, DO is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania
Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland
Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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