eMedicine Specialties > Pediatrics: General Medicine > Oncology

Hepatoblastoma: Follow-up

Author: Jennifer R Willert, MD, Assistant Clinical Professor of Pediatrics, University of California at San Diego; Consulting Staff, Department of Pediatrics, Division of Hematology, Oncology and Bone Marrow Transplant, San Diego Children's Hospital; Member, Rebecca Moore's Cancer Center, Translational Oncology, University of California San Diego Medical Center
Coauthor(s): Gary Dahl, MD, Professor, Department of Pediatrics, Division of Hematology/Oncology, Stanford University School of Medicine
Contributor Information and Disclosures

Updated: Jan 14, 2008

Follow-up

Further Inpatient Care

• Follow-up care: Children may be admitted to the hospital to expedite the diagnostic workup or when severe signs or symptoms are present. For medically stable patients, the workup can be performed in the outpatient setting. A central line is typically placed when the patient is scheduled for biopsy or resection. Double-lumen central lines are preferred if vessel access is adequate because this allows concurrent administration of multiple parenteral medications. 
• Multidisciplinary evaluation: The child is initially evaluated by a pediatric oncologist and surgeons with expertise in childhood malignancies. Evaluation should be performed at a pediatric cancer center. Once the diagnosis is established and the staging workup is completed, the patient and family are instructed on the diagnosis and therapeutic options. Most children and families are offered participation in cooperative group trials. Once the treatment plan is developed, chemotherapy is most frequently administered in the inpatient setting. However, with improvements in supportive care, some chemotherapy may be administered in the outpatient setting. Following completion of the treatment cycle, patients are discharged home with detailed instructions for home care and outpatient follow-up visits. 
• Patients who undergo liver transplantation require a multidisciplinary team with experienced hepatologist and liver transplant surgeons as well as the team outlined above.

Further Outpatient Care

• Patients are periodically monitored in the clinic after each course of therapy to assess for complications and response to therapy. 
• Myelosuppression and pancytopenia are common complications, and a CBC count with a platelet count is obtained once or twice weekly.
• Some drugs, such as cisplatin and carboplatin, affect renal function and require close monitoring of electrolytes and oral or parenteral electrolyte supplementation.
• Blood product support is provided when the hemoglobin drops below 8 g/dL, symptoms of anemia are present, the platelet count drops below 10,000 X 10⁹/L, or any signs of bleeding are evident.
• Fever must be treated as a medical emergency during therapy because the risk of a bacterial or fungal infection is high in patients with myelosuppression.
• Children with central lines are susceptible to bacteremia and life-threatening sepsis. In addition, all children with central lines must receive appropriate antimicrobial prophylaxis against subacute bacterial endocarditis (SBE) for all procedures, including dental procedures.
• Close contact with the liver transplant team is required for patients who require this treatment. All medical decisions for patients with this complex condition should be communicated to all members of the team including oncologists, primary surgeon, hepatologists, and transplant surgeons.
• Late effects clinics are available at most major oncology centers, and children with hepatoblastoma should be referred to these clinics if they remain disease free for more than 2 years. Even if the risk of recurrence decreases with time, these children are still at risk for late effects, which include secondary cancers (etoposide and anthracycline), cardiotoxicity (anthracycline), renal toxicity (platinum agents), ototoxicity (platinum agents), and potential speech and developmental delays due to therapy administered.
• Psychosocial team members, child life experts, medical social workers, nutritionists, and all care providers can help families adjust to life after cancer and can also help encourage a cancer preventive lifestyle for these at-risk patients.

Inpatient & Outpatient Medications

• Infection prophylaxis: Chemotherapy agents cause myelosuppression and immunosuppression. Prophylaxis against Pneumocystis jiroveci, which causes Pneumocystis carinii pneumonia, is recommended for all patients. The drug of choice is trimethoprim-sulfamethoxazole (2.5 mg/kg/dose of trimethoprim administered orally twice daily) administered on 3 consecutive days per week. Prophylaxis is initiated before chemotherapy and is 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 the intensity of chemotherapy has increased. The doses recommended are 5-10 mcg/kg/d, starting 24-36 hours after the last dose of chemotherapy. G-CSF administration is continued for 10-14 days or until the absolute neutrophil count (ANC) is greater than 2,000-10,000/mcL.
• Erythropoietin: The use of erythropoietin is discouraged because of reports that hepatoblastoma has receptors for this agent and may therefore be stimulated to grow from exogenous sources.

Transfer

• With supervision by the oncology team, routine care can be performed by the primary care provider for patient convenience. CBC counts and blood chemistries may be obtained and blood products may be administered by primary care providers. 
• Some patients may even be evaluated and treated for febrile neutropenia by the primary care provider. However, the primary care provider must maintain close contact with the subspecialist physicians and transfer the patient to the pediatric oncology center for any complications that require specialized care.

Deterrence/Prevention

• The cause of hepatoblastoma is unknown. Because onset of hepatoblastoma is in patients at a young age, investigators have focused on events before conception and during gestation. Factors for which evidence is limited or inconsistent include medications, hormones, birth characteristics, congenital anomalies, previous spontaneous abortion or fetal death, alcohol consumption, tobacco use, and paternal occupational exposures. 
• Children with hemihypertrophy or BWS and children born to individuals affected by familial adenomatous polyposis (FAP) should be screened regularly using blood AFP levels as dictated in current protocols. Children found to harbor a FAP mutation should be monitored periodically for the development of polyps by a gastroenterologist as they reach the teenage years.

Complications

• At diagnosis: Tumor rupture may occur, resulting in acute abdomen or severe hemorrhage, both of which constitute medical emergencies. Intraoperative and postoperative complications may occur as a result of resection or biopsy procedures.
• During therapy: Complications can develop with the administration of chemotherapy. Myelosuppression and immunosuppression place the patient at risk for bleeding and infection. After several cycles of therapy, organ toxicity may occur; for example, renal function or hearing may be impaired.
• Posttransplantation: Complications due to liver transplantation can develop and require close long-term follow-up by the liver transplant team.
• Long term: Particular attention must be paid to cardiac, renal, and hearing status to assess for the toxic effects of anthracyclines, cisplatin, or carboplatin. Psychosocial effects of frequent painful procedures, hospitalizations, and interference with normal childhood growth and development must be addressed, and children and families must be referred to appropriate specialists when needed. The family's psychosocial needs are affected greatly by having a child with cancer.

Prognosis

• See Mortality/Morbidity.

Patient Education

• Medications: To ensure compliance and good medical care, patient and family understanding regarding the importance of treatment and the toxic effects of the medications is critical. In addition, patients and their families should learn to recognize and identify signs and symptoms of complications that require urgent medical care.
• Long-term follow-up surveillance: After completion of therapy, patients in whom treatment was successful require close surveillance for any signs or symptoms of recurrent disease. Follow-up care includes monitoring AFP levels, physical examination, and diagnostic imaging. Because most recurrences occur during the first 2 years following treatment, most protocols recommend close follow-up monitoring during this interval. Hepatoblastoma does not usually recur more than 3 years after completion of therapy.
• Long-term issues: Growth and development and long-term toxic effects on organs are long-term issues. Patients who remain free of recurrent disease for 5 years are considered cured; long-term follow-up monitoring to assess the impact of therapy on growth, development, and organ toxicity is essential. Patients are usually monitored by pediatric oncologists, but some sequelae may require the involvement of other subspecialist health care providers.
• Other issues: Most centers have late effects clinics, and all children treated for cancer should continue to see their oncology providers regularly to monitor for potential long-term complications of therapy. When appropriate, most centers help transition to an adult provider, with guidelines on what to watch for and which tests should be performed to monitor for potential late effects. A cancer-preventive lifestyle is encouraged and includes avoiding passive or primary tobacco exposure, wearing sunscreen, healthy eating habits, maintaining a healthy weight, and an exercise regimen.

Miscellaneous

Medicolegal Pitfalls

• Prompt referral to a pediatric oncology center for multidisciplinary evaluation and appropriate care is essential because childhood cancer is a rare disease. The vast majority of patients initially present for evaluation to either the primary care provider or a general surgeon. A surgeon without expertise in the management of pediatric tumors may attempt to perform a biopsy or resection of a mass without the necessary resources to obtain and process tumor samples for histologic and molecular genetics studies. Without these studies, assigning risk and administering appropriate therapy become difficult.
• The field of pediatric oncology has benefited from the high level of patient participation in clinical trials. Pediatric oncologists must be effective in communicating the goals of clinical trial protocols and obtaining informed consent from patients and families. A thorough discussion of the potential benefits and risk of clinical trial participation is warranted. Without compromising the family's enthusiasm and desire to achieve a cure for the patient, the oncologist must make them aware that complications during both the standard of care and clinical trial therapies can result in death.

Special Concerns

• The cornerstone of pediatrics is the prevention and treatment of disease to foster the normal growth and development of children. Use of chemotherapy in infants, children, and adolescents with cancer presents many challenges to the pediatric oncologist, who must strive to maintain a balance between the appropriate administration of curative therapy and the minimization of the long-term toxic effects of that therapy. 
• Understanding the effects that chemotherapy may have on the growth and development of children is important. For example, when administered to infants, cisplatin and carboplatin may have ototoxic effects that affect language development, vincristine may have neurotoxic effects that interfere with motor development, and any chemotherapy agent may cause refractory nausea and emesis that lead to food aversion. Recognizing these sequelae is vital to allowing appropriate intervention. 
• 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 lower during the first year of life, thereby increasing the amount of unbound drug. These variables affect the distributed volume of drugs; therefore, drug doses are calculated differently in infants. 
• Drug doses in pediatric oncology are calculated most commonly 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 use chemotherapy doses based on weight in kilograms rather than BSA in infants. 
• The practice of altering dosing in infants may be unwise because any rational approach should be based on the pharmacokinetic behavior of each agent. As more is learned about the pharmacokinetics of drugs and their relationship to efficacy and toxicity, the use of pharmacokinetically guided dosing may become more common. 
• Data are lacking concerning the disposition of most antineoplastic agents in young children and infants. However, guidelines are available for doxorubicin, etoposide, teniposide, and VCR. The caveat is that only a small number of infants were included in the studies used to formulate most of these recommendations. In addition, not all studies included analysis of plasma-binding proteins, unbound drug systemic clearance, and other relevant factors.
• Because evidence of increased toxicity with VCR and doxorubicin is lacking, adjustment of dosing by weight rather than BSA is recommended in infants or children younger than 2 years and in those with a BSA 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% in infants, whereas it is 25% in an older child or adult.
• Ifosfamide and, less frequently, cyclophosphamide can cause renal tubular injury manifested as Fanconi syndrome, metabolic acidosis, hypokalemia, hypophosphatemia, proteinuria, or rickets. The chronic nature of these injuries may interfere with normal growth and requires close follow-up monitoring. Cisplatin and, less frequently, carboplatin can cause glomerular injury manifested as acute or chronic decrease in the GFR.
• The heart is another organ at risk for early and late toxic effects. 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 development of 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.
• Several agents (ie, carboplatin, cisplatin, CPM, ifosfamide) require prehydration to achieve adequate renal perfusion, urine filtration, and bladder flow and to avoid delayed excretion or bladder toxicity. The use of high-dose therapy in children frequently results in myelosuppression requiring blood product support. 
• Treatment of infectious diseases is also very important in the pediatric population. Advances in the care and support of the patients with neutropenia who are febrile have improved the survival rate in children. Prophylactic antibiotics commonly are used in patients on immunosuppressive therapy to prevent P carinii pneumonia.
• Drugs that modify the toxicity of antineoplastic agents (mesna, amifostine, leucovorin) and the availability of hematopoietic growth factors (G-CSF, granulocyte-macrophage colony-stimulating factor [GM-CSF]) have allowed the use of the maximally tolerated doses of many chemotherapy agents and the development of more dose-intensive protocols.
• Future directions include the following: 
  • The need for better chemotherapeutic options, with better efficacy and less toxicity, is clear. Bioinformatics and genetic profiling may identify new patterns correlating with prognosis and, thus, potential therapeutic targets. The significance of molecular genetic abnormalities seen in human malignancy is just beginning to be understood, and these molecular abnormalities need to be correlated with a patient's clinical prognosis.
  • Most pediatric chemotherapeutic protocols (eg, COG, SIOP) have incorporated molecular genetic testing of tumor specimens and, in some cases, normal tissues as control. This information is being collected to determine the prognostic significance of oncogene mutations, translocations, gene rearrangements, and tumor suppressor genes, and, in some cases, to determine treatment options. Current research efforts may ultimately identify specific molecular targets that can be used to develop more specific chemotherapeutic agents.
  • Microarray technology currently is being used to determine the molecular profiles of malignancies to better define therapies targeted to specific molecular profiles. Microarray technology was used to analyze patterns of TP53- mediated gene expression, which will undoubtedly contribute to the understanding of how inactivation of this tumor suppressor gene contributes to neoplasia. This information may be used to guide treatment options. Pediatric solid tumors may ultimately be candidates for this type of genetic profiling as well.
  • As physicians gain a better understanding of the molecular abnormalities inherent in cancer cells and critically analyze the prognostic significance and therapeutic implications of the abnormalities, the ability to modify treatment based on this information increases. Sometimes, this means administering more aggressive therapy to patients, thus potentially increasing the chance for long-term survival. At other times, this involves sparing the patient unnecessary toxic effects of therapy. More specifically targeted therapies are likely to have less general systemic toxicity.
  • Identification of the aberrant expression of genes involved in regulation of cellular growth and differentiation and clinical correlation of these abnormalities will likely lead to improvements in therapeutic options for patients with cancer.

The authors would like to thank all of our patients and families, as well as all of our mentors along this path towards a better outcome for children with hepatoblastoma!

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