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Wilms Tumor Treatment & Management

  • Author: Arnold C Paulino, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
 
Updated: Apr 27, 2016
 

Approach Considerations

The usual approach in most patients is nephrectomy followed by chemotherapy, with or without postoperative radiotherapy. Table 1 summarizes the current approach to patients with favorable histology Wilms tumor according to Children’s Oncology Group (COG) studies. Children found to have loss of heterozygosity at 1p and 16q receive more aggressive chemotherapy because they have a worse prognosis than do children without this heterozygosity loss.[5]

Table 1. Current Approach to Favorable Histology Wilms Tumor by Stage (Open Table in a new window)

Stage and Histology Surgery Chemotherapy Radiation Therapy*
Stage I or II favorable histology without loss of heterozygosity (LOH) 1p and 16q† Nephrectomy Vincristine, dactinomycin No
Stage I or II favorable histology with LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin No
Stage III and IV favorable histology without LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin Yes
Stage III and IV favorable histology with LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide Yes
* The current dose for radiation therapy for favorable histology Wilms tumor is approximately 1080 cGy for the abdomen and 1200 cGy for the lung.[28] Postoperative radiotherapy is started within 14 days of nephrectomy.[29] Patients with stage IV favorable histology Wilms tumor and lung metastases whose pulmonary lesions do not disappear after 6 weeks of chemotherapy receive whole-lung radiation therapy.



† Some evidence suggests that certain children with stage I disease and favorable histology do well with nephrectomy alone.[30] Children younger than 24 months with small (< 550 g) Wilms tumors with favorable histology are noted in the current COG protocol.



Currently, patients enrolled in the COG AREN0321 protocol for high risk Wilms tumor are treated as follows:

  • Focal anaplastic stage I-III Wilms tumors and diffuse anaplastic stage I Wilms tumors - Nephrectomy followed by vincristine, actinomycin-D, and doxorubicin in addition to local radiotherapy
  • Focal anaplastic stage IV Wilms tumors and diffuse anaplastic stage II-III tumors –Patients undergo the same treatment, with the addition of cyclophosphamide, etoposide, and carboplatin
  • Stage IV diffuse anaplastic Wilms tumors - More aggressive treatment is delivered; nephrectomy is followed by initial irinotecan and vincristine administration, which in turn is followed by actinomycin-D, doxorubicin, cyclophosphamide, carboplatin, etoposide, and radiotherapy.

Management of lung metastasis

Patients with negative findings on chest radiography and positive findings on CT scanning of the lungs require tissue diagnosis of the lung nodules because several conditions (eg, histoplasmosis, atelectasis, pseudotumor, intrapulmonary lymph node, pneumonia) can mimic pulmonary metastases.

NWTS studies have not shown any survival benefit from treating nodules that have negative chest radiograph findings but positive CT scan findings with whole lung radiotherapy. In one study, patients treated with whole lung radiotherapy had fewer lung relapses but suffered higher treatment-related deaths.[31] A study from the NWTS-4 and NWTS-5 showed that CT-only lung nodules may have improved event-free survival but not overall survival from the addition of doxorubicin.[32]

In the current COG study, patients with favorable histology Wilms tumor with lung metastasis and no other sites of distant spread or presence of 1p and 16q deletion undergo 6 weeks of actinomycin-D, doxorubicin, and vincristine. If a complete response in the pulmonary nodules occurs, then patients are not given whole lung irradiation. This is supported by a European study which showed that whole lung irradiation may not be needed in many patients with pulmonary metastasis.[33]

Management of bilateral Wilms tumor

One report of patients with bilateral Wilms tumor treated according to the National Wilms Tumor Study-4 demonstrated that preservation of renal parenchyma is possible following initial preoperative chemotherapy. Patients with bilateral Wilms tumor had an increased incidence of end-stage renal failure, including patients who did not have bilateral nephrectomies. Further investigation is required to determine the need for earlier biopsy in nonresponsive tumors and earlier definitive surgery in patients with unfavorable histology.[34]

Additional treatment considerations

Whether patients younger than age 6 months who have stage III disease should receive radiation therapy is controversial. In the NWTS-5 protocol, physicians were required to call an NWTS-5 radiation oncologist to discuss guidelines. The late toxicity of irradiating young children has been a concern for many, even with relatively low doses of radiation.

Female patients have an increased risk of giving birth prematurely. Possible explanations include loss of elasticity of the uterine wall, surgical adhesions, and a high incidence of uterine anomalies.

As many as one third of patients with Wilms tumor present with hypertension. Their blood pressure usually normalizes after nephrectomy, but they occasionally require prolonged therapeutic intervention.

Activity

No precautions regarding activity are advised, although the patient and his or her parents should be aware that the patient will have only 1 kidney after therapy. Activities that carry an inherent risk of kidney injury, such as boxing and hockey, should be avoided.

Consultations

The patient should be referred to a pediatric surgeon, a pediatric oncologist, and, in some cases, a radiation oncologist.

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Considerations in von Willebrand Disease

About 5-10% of patients present with acquired von Willebrand disease at the time of diagnosis. Several hypothesis have been postulated to explain acquired von Willebrand disease, including absorption of the von Willebrand factor (vWF) by tumor cells, hyperviscosity caused by elevated serum levels of hyaluronic acid, and an immunoglobulin G (IgG)–type antibody that prevents aggregation of normal platelet cells (immunologic inactivation).

If present, excessive bleeding during surgery should be expected and prenephrectomy therapy should be started. Whenever possible, the use of blood derivatives should be avoided because of the potential to transmit viral infections. Instead, an initial trial of desmopressin (DDAVP), a drug that promotes the release of vWF from storage sites, is recommended. DDAVP has been effective in most patients with type I von Willebrand disease and in some with type II disease. If DDAVP is administered, fluid and electrolyte balance should be carefully monitored. If DDAVP is ineffective, cryoprecipitator (a specific vWF concentrate) should be administered.

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Long-Term Monitoring

The lungs are the most common site of relapse. This site is affected in more than two thirds of children who have a relapse. The tumor bed is the site of relapse only in about one fourth of patients. The brain and the bones are not usual sites of relapse for Wilms tumors with favorable histology.

The patient must be examined at the follow-up clinic after he or she completes all therapy. The purpose of follow-up care is to check for recurrence and for late effects of therapy.

Table 2 outlines the types and frequency of radiographic studies during follow-up according to the NWTSG.[35] For follow-up of late effects and recommended studies, please refer to the Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, from the COG.

Table 2. Recommended Follow-Up Imaging Studies in Children with Wilms Tumor Without Metastasis at Diagnosis* (Open Table in a new window)

Stage and Type of Wilms Tumor Imaging Studies Off-Treatment Schedule
Stages I, II, and III with favorable histology; stages I, II, and III with anaplastic histology Chest radiography 6 wk and 3 mo after surgery, then every 3 mo (5 times), then every 6 mo (3 times), then yearly (2 times)
All stages in patients aged < 48 mo at diagnosis with nephrogenic rests Abdominal ultrasonography Every 3 mo for 6 y
All stages in patients aged >48 mo at diagnosis with nephrogenic rests Abdominal ultrasonography Every 3 mo for 4 y
Stages I and II with favorable histology Abdominal ultrasonography Yearly (6 times)
Stage III with favorable histology Abdominal ultrasonography 6 wk and 3 mo after surgery, then every 3 mo (5 times), then every 6 mo (3 times), then yearly (2 times)
All stages with unfavorable histology Abdominal ultrasonography Every 3 mo (4 times), then every 6 mo (4 times)
* Subsequent imaging studies should be performed as clinically indicated.
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Contributor Information and Disclosures
Author

Arnold C Paulino, MD Professor of Radiation Oncology, Methodist Hospital and Weill-Cornell Medical College; Associate Professor of Pediatrics, Baylor College of Medicine

Arnold C Paulino, MD is a member of the following medical societies: Radiological Society of North America, Children's Oncology Group, American Society of Clinical Oncology, International Society of Paediatric Oncology, American Medical Association, American Radium Society, American Society for Radiation Oncology

Disclosure: Received royalty from Elsevier, Inc for author of book.

Coauthor(s)

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD 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, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Jennifer Reikes Willert, MD Associate Clinical Professor, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Section of Stem Cell Transplantation, Stanford University Medical Center, Lucile Packard Children's Hospital

Jennifer Reikes Willert, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society for Blood and Marrow Transplantation, Children's Oncology Group, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Kathleen M Sakamoto, MD, PhD Shelagh Galligan Professor, Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

References
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CT scan in a patient with a right-sided Wilms tumor with favorable histology.
CT scan of child with a stage IV Wilms tumor with favorable histology. Note the bilateral pulmonary metastases.
Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.
Table 3. Survival Rates in Patients with Favorable-Histology Wilms Tumor
Stage Relapse-Free Survival, % Overall Survival, %
I 92 98
II 85 96
III 90 95
IV 80 90
Table 1. Current Approach to Favorable Histology Wilms Tumor by Stage
Stage and Histology Surgery Chemotherapy Radiation Therapy*
Stage I or II favorable histology without loss of heterozygosity (LOH) 1p and 16q† Nephrectomy Vincristine, dactinomycin No
Stage I or II favorable histology with LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin No
Stage III and IV favorable histology without LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin Yes
Stage III and IV favorable histology with LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide Yes
* The current dose for radiation therapy for favorable histology Wilms tumor is approximately 1080 cGy for the abdomen and 1200 cGy for the lung.[28] Postoperative radiotherapy is started within 14 days of nephrectomy.[29] Patients with stage IV favorable histology Wilms tumor and lung metastases whose pulmonary lesions do not disappear after 6 weeks of chemotherapy receive whole-lung radiation therapy.



† Some evidence suggests that certain children with stage I disease and favorable histology do well with nephrectomy alone.[30] Children younger than 24 months with small (< 550 g) Wilms tumors with favorable histology are noted in the current COG protocol.



Table 2. Recommended Follow-Up Imaging Studies in Children with Wilms Tumor Without Metastasis at Diagnosis *
Stage and Type of Wilms Tumor Imaging Studies Off-Treatment Schedule
Stages I, II, and III with favorable histology; stages I, II, and III with anaplastic histology Chest radiography 6 wk and 3 mo after surgery, then every 3 mo (5 times), then every 6 mo (3 times), then yearly (2 times)
All stages in patients aged < 48 mo at diagnosis with nephrogenic rests Abdominal ultrasonography Every 3 mo for 6 y
All stages in patients aged >48 mo at diagnosis with nephrogenic rests Abdominal ultrasonography Every 3 mo for 4 y
Stages I and II with favorable histology Abdominal ultrasonography Yearly (6 times)
Stage III with favorable histology Abdominal ultrasonography 6 wk and 3 mo after surgery, then every 3 mo (5 times), then every 6 mo (3 times), then yearly (2 times)
All stages with unfavorable histology Abdominal ultrasonography Every 3 mo (4 times), then every 6 mo (4 times)
* Subsequent imaging studies should be performed as clinically indicated.
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