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Wilms' tumor is a disease in which cancer cells are found in the kidney, and may spread to the lungs, liver, or nearby lymph nodes. Wilms' tumor usually occurs in children younger than 5 years old. Learn about Wilms' tumor and find information on how we support and care for children with Wilms' tumor before, during, and after treatment.
The Solid Tumors Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center treats children and teens with a variety of solid malignancies, including bone and soft tissue tumors, liver and kidney tumors, neuroblastomas, retinoblastomas and rare tumors. Our doctors provide unparalleled expertise in the diagnosis, treatment and management of these diseases.
Your child's care team will include pediatric oncologists, radiation oncologists, surgeons, pathologists, radiologists, and nurses with expertise in treating your child's specific type of cancer.
Our physicians are focused on family-centered care: From your first visit, you'll work with a team of professionals who are committed to supporting your family's needs. We consider you and your child integral parts of the care team. Our specialists will collaborate with you to customize a treatment plan that takes the needs of your child and your family into account.
As well as providing access to a range of innovative clinical trials through Dana-Farber/Boston Children's, we are New England's Phase I referral center for the Children's Oncology Group, which means we're able to offer clinical trials unavailable at other regional centers.
Your child will have access to long-term treatment and childhood cancer survivor support through Dana-Farber's David B. Perini, Jr. Quality of Life Clinic.
From diagnosis through treatment and survivorship, our team will be able to answer all of your questions about your child's care.
Find out more about our Solid Tumors Center, including the diseases we treat and our specialized programs for bone and soft tissue tumors, liver tumors, neuroblastoma, rare tumors, and retinoblastoma.
Wilms' tumor is a cancerous tumor in the cells of the kidney. It most often starts in the kidneys but, in rare cases, it can occur in other parts of the body.
If Wilms' tumor spreads, it most often moves into the lungs. Fortunately, with the right treatment, Wilms' tumor is often highly treatable.
Your child will be seen through Dana-Farber/Boston Children's Cancer and Blood Disorders Center, an integrated pediatric oncology program through Dana-Farber Cancer Institute and Boston Children's Hospital that provides — in one specialized program — all the services of both a leading cancer center and a pediatric hospital. Major advancements have occurred in treatment of Wilms' tumor over the last two decades, primarily because of studies by the National Wilms' Tumor Study Group, of which Boston Children's Hospital was a member. These studies have rigorously compared treatment regimens to determine the most effective and safest treatments. For example, one study showed that briefer courses of therapy are as effective as longer courses, and less harmful. Boston Children's Hospital is now an active member of the Children's Oncology Group (COG) and many Children's Hospital experts serve on their Wilms' Tumor Committee.
We understand how overwhelming a diagnosis of Wilms' tumor can be. Right now, you probably have a lot of questions. How dangerous is this condition? What is the very best treatment? What do we do next?We've tried to provide some answers to those questions in the following pages, and our experts can explain your child's condition fully when you meet with us.
As a parent, you undoubtedly want to know what may have caused your child's tumor. Most cases of Wilms' occur by chance with no family history of the disease or other known cause. The tumors can be the result of genetic mutations that affect cell growth in the kidney. These mutations generally arise after birth, but, in some rare cases, children are born with a genetic predisposition to cancer.
A small percentage of patients with Wilms' tumor have certain rare genetic syndromes such as:
The most common symptom of Wilms' tumor is the sudden appearance of a non-tender mass in the abdomen.Though each child may experience symptoms differently, your child's symptoms may include the following:
Keep in mind that the symptoms of Wilms' tumor may resemble other, more common conditions or medical problems. Always consult your child's physician for a diagnosis.
The first step in treating your child is forming an accurate and complete diagnosis. Your child's physician may recommend a number of different tests to determine the cause of her symptoms. In addition to a complete medical history and physical examination, your child's doctor may order one or more of the following:
An important part of diagnosing Wilms' tumor involves staging and classifying the disease, which will help your child's doctor determine treatment options and prognosis. Staging is the process of determining whether the cancer has spread and, if so, how far. Kidney tumors are typically categorized into five stages. Wilms' tumor, the most common type of pediatric kidney tumor is staged as follows by the Children's Oncology Group (COG):
Your child's doctor can provide additional information on the classification of Wilms' tumors.After we complete all necessary tests, our experts meet to review and discuss what they have learned about your child's condition. Then we will meet with you and your family to discuss the results and outline the best treatment options.
We know how difficult a diagnosis of Wilms' tumor can be, both for your child and for your whole family. That's why our physicians are focused on family-centered care: From your first visit, you'll work with a team of professionals who are committed to supporting all of your family's physical and psychosocial needs. We'll work with you to create a care plan that's best for your child. If your child has been diagnosed with a Wilms' tumor, you'll naturally be eager to know how your child's physician will treat the tumor. Your child's physician will determine a specific course of treatment based on several factors, including:
There are a number of treatments we may recommend. Some of them help to treat the tumor while others are intended to address complications of the disease or side effects of the treatment.
Treatment will then depend on the extent of spread of your child's tumor and its stage. Treatment for Wilms' tumor is based on a comprehensive risk assessment that includes factors such as:
The first step in most treatments is surgery to remove the tumor. The most common operation is a radical nephrectomy, which removes the whole kidney, the tissue around the kidney, the ureter and the adrenal gland (which sits on top of the kidney). This operation is performed if the tumor has occurred in only one of the kidneys. In some cases, low-stage Wilms' tumors may be treated with surgery alone.If your child has tumors in both kidneys or has a known predisposition to kidney cancer, your child's physician make recommend a partial nephrectomy or kidney-sparing surgery which aim to remove the tumor while leaving healthy kidney tissue alone. In rare cases — when the tumor is too big or has spread too far — your child's doctor will recommend chemotherapy to try to shrink the tumor before surgery.During surgery, a biopsy may need to be done in your child's other kidney if a suspicious area is found on examination.Surgery is followed by chemotherapy and sometimes radiation. The type of chemotherapy and the need for radiation are determined by tumor stage and type. The type of chemotherapy will be determined based on the tumor size, tumor type and the extent of spread of the tumor. Radiation therapy may be indicated for some tumors.In very rare cases, a stem cell transplant, involving a transplant of your child's own stem cells (autologous transplant) may be used. This allows your child's physician to give high-intensity chemotherapy in difficult to treat cases of Wilms' tumor. Stem cell transplantation and the treatment needed to manage its effects are complex and involve some risk. Your physician will give you more detailed information on what to expect.
Side effects in the treatment of Wilms' tumor can arise from surgery, radiation and chemotherapy.
Our cancer treatment center has specialists who deliver complementary or alternative medicines. These treatments, which may help control pain and side effects of therapy include the following:
Talk to your child's physician about whether complementary medicine or integrative therapies might be a good option for your child.
You and your child's care team will establish a schedule of regular follow-up care to monitor ongoing response to treatment and possible late effects of treatment, and to evaluate the health of the remaining kidney.
As with any cancer, prognosis and long-term survival can vary greatly from child to child. Prompt medical attention, aggressive therapy and continued follow-up are important for the best possible prognosis. Factors that influence the outlook for a child with Wilms' tumor include:
With the appropriate therapy, which may include surgery, chemotherapy and/or radiation, the overall prognosis for children with Wilms' tumor is excellent. More aggressive tumors or tumors that have spread significantly may be harder to treat.The goal of treatment of Wilms' tumor is both to cure the cancer and to minimize the long-term effects of therapy. Therefore, patients are carefully assessed so that they receive the appropriate amount of therapy with minimal side effects.
Researchers at Dana-Farber/Boston Children's Kidney Tumor Program conduct laboratory and clinical research designed to improve understanding and treatment of pediatric kidney tumors. We offer clinical trials through the Children's Oncology Group. Here are some of the things we've been working on:
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of Wilms tumor and other childhood kidney tumors. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board.
Information about the following is included in this summary:
This summary is intended as a resource to inform and assist clinicians and other health professionals who care for pediatric cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal evidence ranking system in developing their level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for reimbursement determinations.
This summary is also available in a patient version, which is written in less technical language, and in Spanish.
The National Cancer Institute (NCI) provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.
Cancer in children and adolescents is rare. Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologists, pediatric medical oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others in order to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. (Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[1] At these pediatric cancer centers, clinical trials are available for most of the types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up since cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Wilms tumor is a curable disease in the majority of affected children. Approximately 500 cases are diagnosed in the United States annually. More than 90% of patients survive 4 years after diagnosis, which is an improvement over the 80% survival observed from 1975 to 1984 (COG-Q9401). The prognosis is related not only to the stage of disease at diagnosis, the histopathologic features of the tumor, patient age, and tumor size, but also to the team approach to each patient by the pediatric surgeon, radiation oncologist, and pediatric oncologist (COG-Q9401).[2][3][4] Previous clinical trials have, in part, evaluated with some success whether reduced therapy is sufficient to control disease in patients with early-stage, favorable-histology Wilms tumor.[5][6][7]
Wilms tumor normally develops in otherwise healthy children; however, 10% of cases occur in individuals with recognized malformations. Children with Wilms tumor may have associated anomalies, including hemihypertrophy, cryptorchidism, and hypospadias. Approximately 10% of patients with Wilms tumor have a recognizable phenotypic syndrome (including overgrowth disease, aniridia, genetic malformations, and others). These syndromes have provided clues to the genetic basis of the disease. The phenotypic syndromes have been divided into overgrowth and nonovergrowth categories. Overgrowth syndromes are the result of excessive prenatal and postnatal somatic growth, and result in macroglossia, nephromegaly, and hemihypertrophy. Examples of overgrowth syndromes are Beckwith-Wiedemann syndrome (10%–20% of Wilms tumor incidence), isolated hemihypertrophy (3%–5% of Wilms tumor incidence), Perlman syndrome (characterized by fetal gigantism, renal dysplasia, Wilms tumor, islet cell hypertrophy, multiple congenital anomalies, and mental retardation),[8] Sotos syndrome (characterized by cerebral gigantism), and Simpson-Golabi-Behemel syndrome (characterized by macroglossia, macrosomia, renal and skeletal abnormalities, and increased risk of embryonal cancers).[9][10][11][12][13] Klippel-Trénaunay syndrome, a unilateral limb overgrowth syndrome, is not associated with Wilms tumor.[14] Examples of nonovergrowth syndromes associated with Wilms tumor are isolated aniridia; trisomy 18; Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome; Blooms syndrome, Alagille syndrome,[15][Level of evidence: 3iii] and Denys-Drash syndrome (characterized by intersexual disorders, nephropathy, and Wilms tumor).[16] The constellation of WAGR syndrome occurs in association with an interstitial deletion on chromosome 11 (del[11p13]).[17][18] Children with pseudo-hermaphroditism and/or renal disease (glomerulonephritis or nephrotic syndrome) who develop Wilms tumor may have the Denys-Drash or Frasier syndrome (characterized by male hermaphroditism, primary amenorrhea, chronic renal failure, and other abnormalities),[19] both of which are associated with mutations in the Wilms tumor 1 (WT1) gene at chromosome 11p13.[20] Specifically, germline missense mutations in the WT1 gene are responsible for most Wilms tumors that occur as part of the Denys-Drash syndrome.[21] Children with a predisposition to develop Wilms tumor (e.g., Beckwith-Wiedemann syndrome, WAGR, hemihypertrophy, or aniridia) should be screened with ultrasound every 3 months until they reach age 8 years.[9][10][11][12][13][22][23][24]
Wilms tumor (hereditary or sporadic) appears to result from changes in one or more of at least ten genes. The WT1 gene is located on the short arm of chromosome 11 (11p13). The normal function of WT1 is required for normal genitourinary development and is important for differentiation of the renal blastema. Germline mutations in WT1 have been found in about 2% of phenotypically normal children with Wilms tumor.[25]
Germline WT1 mutations in children with Wilms tumor does not confer a poor prognosis per se, but is more common in those with:
A somatic mutation in CTNNB1 is found in most, if not all, Wilms tumors that develop in children with germline WT1 mutations.[26][Level of evidence: 3iiiDiii]
The offspring of such patients may also be at increased risk of developing Wilms tumor. A gene that causes aniridia (PAX-6) is located near the WT1 gene on chromosome 11p13, and deletions encompassing the WT1 and aniridia genes explain the association between aniridia and Wilms tumor. PAX-6 also affects brain development, and children with WAGR syndrome have a variety of central nervous system development disorders.[18]
Patients with aniridia or hemihypertrophy should be screened with ultrasound every 3 months until they reach age 8 years.[9] For patients with WAGR syndrome, the risk of developing Wilms tumor is as high as 45%.[27] Children with WAGR syndrome are found to have small, favorable-histology tumors with low stage at diagnosis and a high incidence of intralobar nephrogenic rests. (Refer to the Cellular Classification section of this summary for more information.) The incidence of bilateral Wilms tumor in children with WAGR syndrome is high (about 15%).[28] Treatment outcome at 4 years is similar to that of non-WAGR patients.[28] Children with WAGR syndrome are at increased risk of eventually developing renal failure and should be monitored.[29] Patients with Wilms tumor and aniridia without genitourinary abnormalities are at lesser risk but should be monitored for nephropathy or renal failure.[30] Children with Wilms tumor and any genitourinary anomalies are also at increased risk for late renal failure and should be monitored.[29] The incidence of Wilms tumor in children with sporadic aniridia is estimated to be about 5%.[28]
A second Wilms tumor locus, Wilms tumor 2 (WT2) gene, maps to an imprinted region of chromosome 11p15.5 in association with Beckwith-Wiedemann syndrome. There are several candidate genes at the WT2 locus, comprising the two independent imprinted domains IGF2/H19 and KIP2/LIT1.[31] Loss of heterozygosity (LOH), which exclusively affects the maternal chromosome, has the effect of upregulating paternally active genes and silencing maternally inactive ones. A loss or switch of the imprint for genes in this region has also been frequently observed and results in the same functional aberrations. A study of 35 sporadic primary Wilms tumors suggests that more than 80% have either LOH or loss of imprinting at 11p15.5.[32] Loss of imprinting or gene methylation are rarely found at other loci supporting the specificity of loss of imprinting at IGF2.[33] Wilms tumors in Asian children are not associated with either nephrogenic rests or IGF2 loss of imprinting.[34]
Observations suggest genetic heterogeneity in the etiology of Beckwith-Wiedemann syndrome with differing levels of association with risk of tumor formation.[35] Approximately one-fifth of patients with Beckwith-Wiedemann syndrome who develop Wilms tumor present with bilateral disease, though metachronous bilateral disease is also observed.[9][10][11] A third gene, WTX, has been identified on the X chromosome and plays a role in normal kidney development. This gene is inactivated in approximately one-third of Wilms tumors.[36]
Additional tumor-suppressor or tumor-progressive genes may lie on chromosomes 16q and 1p as evidenced by LOH for these regions in 17% and 11% of Wilms tumors, respectively. Patients classified by tumor-specific loss of these loci had significantly worse relapse-free and overall survival rates. Combined loss of 1p and 16q are used to select favorable-histology Wilms tumor patients for more aggressive therapy in the current Children's Oncology Group study.[37] Overexpression and amplification of the gene CACNA1E located at 1q25.3, which encodes the ion-conducting alpha-1 subunit of R-type voltage-dependent calcium channels, is associated with relapse in favorable-histology Wilms tumor.[38]
Despite the number of genes that appear to be involved in the development of Wilms tumor, hereditary Wilms tumor is uncommon, with approximately 2% of patients having a positive family history for Wilms tumor. Siblings of children with Wilms tumor have a low likelihood of developing Wilms tumor.[39] Two familial Wilms tumor genes have been localized to FWT1 (17q12-q21) and FWT2 (19q13.4).[40] The risk of Wilms tumor among offspring of persons who have had unilateral (sporadic) tumors is quite low (<2%).[41] About 4% to 5% of patients have bilateral Wilms tumors, but these are not usually hereditary.[42] Many bilateral tumors are present at the time Wilms tumor is first diagnosed (i.e., synchronous), but a second Wilms tumor may also develop later in the remaining kidney of 1% to 3% of children treated successfully for Wilms tumor. The incidence of such metachronous bilateral Wilms tumors is much higher in children whose original Wilms tumor was diagnosed before age 12 months and/or whose resected kidney contains nephrogenic rests. Periodic abdominal ultrasound is recommended for early detection of metachronous bilateral Wilms tumor as follows: children with nephrogenic rests in the resected kidney (if younger than 48 months at initial diagnosis)—every 3 months for 6 years; children with nephrogenic rests in the resected kidney (if older than 48 months at initial diagnosis)—every 3 months for 4 years; other patients—every 6 months for 2 years, then yearly for an additional 1 to 3 years.[43][44]
Clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, neuroepithelial tumor of the kidney, and cystic partially-differentiated nephroblastoma are childhood renal tumors unrelated to Wilms tumor.[45][46] (Refer to the Cellular Classification section of this summary for more information.)
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Hoyme HE, Seaver LH, Jones KL, et al.: Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review. Am J Med Genet 79 (4): 274-8, 1998.
Greene AK, Kieran M, Burrows PE, et al.: Wilms tumor screening is unnecessary in Klippel-Trenaunay syndrome. Pediatrics 113 (4): e326-9, 2004.
Bourdeaut F, Guiochon-Mantel A, Fabre M, et al.: Alagille syndrome and nephroblastoma: Unusual coincidence of two rare disorders. Pediatr Blood Cancer 50 (4): 908-11, 2008.
Pelletier J, Bruening W, Kashtan CE, et al.: Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67 (2): 437-47, 1991.
Clericuzio CL: Clinical phenotypes and Wilms tumor. Med Pediatr Oncol 21 (3): 182-7, 1993.
Fischbach BV, Trout KL, Lewis J, et al.: WAGR syndrome: a clinical review of 54 cases. Pediatrics 116 (4): 984-8, 2005.
Barbosa AS, Hadjiathanasiou CG, Theodoridis C, et al.: The same mutation affecting the splicing of WT1 gene is present on Frasier syndrome patients with or without Wilms' tumor. Hum Mutat 13 (2): 146-53, 1999.
Koziell AB, Grundy R, Barratt TM, et al.: Evidence for the genetic heterogeneity of nephropathic phenotypes associated with Denys-Drash and Frasier syndromes. Am J Hum Genet 64 (6): 1778-81, 1999.
Royer-Pokora B, Beier M, Henzler M, et al.: Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development. Am J Med Genet A 127 (3): 249-57, 2004.
Gracia Bouthelier R, Lapunzina P: Follow-up and risk of tumors in overgrowth syndromes. J Pediatr Endocrinol Metab 18 (Suppl 1): 1227-35, 2005.
Lapunzina P: Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet C Semin Med Genet 137 (1): 53-71, 2005.
Scott RH, Walker L, Olsen ØE, et al.: Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice. Arch Dis Child 91 (12): 995-9, 2006.
Little SE, Hanks SP, King-Underwood L, et al.: Frequency and heritability of WT1 mutations in nonsyndromic Wilms' tumor patients: a UK Children's Cancer Study Group Study. J Clin Oncol 22 (20): 4140-6, 2004.
Royer-Pokora B, Weirich A, Schumacher V, et al.: Clinical relevance of mutations in the Wilms tumor suppressor 1 gene WT1 and the cadherin-associated protein beta1 gene CTNNB1 for patients with Wilms tumors: results of long-term surveillance of 71 patients from International Society of Pediatric Oncology Study 9/Society for Pediatric Oncology. Cancer 113 (5): 1080-9, 2008.
Muto R, Yamamori S, Ohashi H, et al.: Prediction by FISH analysis of the occurrence of Wilms tumor in aniridia patients. Am J Med Genet 108 (4): 285-9, 2002.
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Satoh Y, Nakadate H, Nakagawachi T, et al.: Genetic and epigenetic alterations on the short arm of chromosome 11 are involved in a majority of sporadic Wilms' tumours. Br J Cancer 95 (4): 541-7, 2006.
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Natrajan R, Little SE, Reis-Filho JS, et al.: Amplification and overexpression of CACNA1E correlates with relapse in favorable histology Wilms' tumors. Clin Cancer Res 12 (24): 7284-93, 2006.
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Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
Although most patients with a histologic diagnosis of Wilms tumor fare well with current treatment, approximately 10% of patients have histopathologic features that are associated with a poorer prognosis, and, in some types, with a high incidence of relapse and death. Wilms tumor can be separated into three prognostic groups on the basis of histopathology:
Clear cell sarcoma of the kidney (CCSK) is not a Wilms tumor variant, but it is an important primary renal tumor associated with a significantly higher rate of relapse and death than favorable–histology Wilms tumor. In addition to pulmonary metastases, clear cell sarcoma also spreads to bone, brain, and soft tissue. The classic pattern of CCSK is defined by nests or cords of cells separated by regularly spaced fibrovascular septa.[6] Previously, relapses have occurred in long intervals after the completion of chemotherapy (up to 10 years), however with current therapy relapses after 3 years are uncommon.[7] The brain is a frequent site of recurrent disease.[8][9]
Rhabdoid tumors (RTs) are extremely aggressive malignancies that generally occur in infants and young children. The most common locations are the kidney and central nervous system (CNS) (atypical teratoid/rhabdoid tumor), although RTs can also arise in most soft-tissue sites. Initially they were thought to be a rhabdomyosarcomatoid variant of Wilms tumor when they occurred in the kidney.
Histologically, the most distinctive features of rhabdoid tumors of the kidney (RTK) are rather large cells with large vesicular nuclei, a prominent single nucleolus, and in some cells, the presence of globular eosinophilic cytoplasmic inclusions. A distinct clinical presentation with fever, hematuria, young age (mean 11 months), and high tumor stage at presentation suggests a diagnosis of RTK.[10] RTK tends to metastasize to the lungs and the brain. As many as 10% to 15% of patients with RTK also have CNS lesions.[11]
RTs in all anatomical locations have a similar molecular origin. Mutation or deletion of both copies of the hSNF5/INI1 gene that maps to chromosome band 22q11.2 is observed in approximately 70% of primary tumors. An additional 20% to 25% of tumors have reduced expression at the RNA or protein level, indicative of a loss-of-function event. The INI1 protein is a component of the SWI/SNF chromatin remodeling complex (a group of genes involved in cell signaling, growth, and differentiation). Identical mutations may give rise to a brain or kidney tumor. Germline mutations of INI1 have been documented for patients with one or more primary tumors of the brain and/or kidney, consistent with a genetic predisposition to the development of rhabdoid tumors.[12][13] In most cases, the mutations are de novo, and not inherited from a parent. Germline mosaicism has been suggested for several families with multiple affected siblings. It does appear that those patients with germline mutations have the worst prognosis.[14]
Mesoblastic nephroma (MN) comprises about 5% of childhood kidney tumors. The median age of diagnosis is 2 months and more than 90% of cases appear within the first year of life. Twice as many males are diagnosed as females. The diagnosis should be questioned when applied to individuals older than 2 years. When diagnosed in the first 7 months of life, the 5 year event-free survival (EFS) and overall survival (OS) rates are 94% and 96%, respectively.[15]
Grossly, MNs appear as solitary, unilateral masses indistinguishable from nephroblastoma. Microscopically, they consist of spindled mesenchymal cells. They can be divided into two major types: classic and cellular. Classic MN is often diagnosed by prenatal ultrasound or within 3 months after birth and closely resembles infantile fibromatosis.[16] Infantile fibrosarcoma and cellular MN contain the same t(12;15)(p13;q25) chromosomal translocation suggestive of a potential linkage.[17] The risk for recurrence within MN is closely associated with the presence of a cellular component and with stage.[16]
Malignant epithelial tumors arising in the kidneys of children account for more than 5% of new pediatric renal tumors; therefore, they are more common than CCSK or RTK. Renal cell carcinoma (RCC), the most common primary malignancy of the kidney in adults, occurs rarely in children younger than 15 years. In the older age group of adolescents (aged 15–19 years), approximately two-thirds of renal malignancies are RCC.[18] The annual incidence rate is approximately 4 per 1 million children compared with an incidence of Wilms tumor of the kidney that is at least 29-fold higher. RCC in young patients has a different genetic and morphologic spectrum than that seen in older adults.[19][20][21][22] RCC may be associated with von Hippel-Lindau (VHL) disease, a hereditary condition in which blood vessels within the retina and cerebellum grow excessively.[19] The gene for VHL is located on chromosome 3p25-26 and is a tumor-suppressor gene whose function is lost in patients with the syndrome. Screening for the VHL gene is available.[23] RCC has also been associated with tuberous sclerosis, a hereditary disease characterized by benign fatty cysts in the kidney.[24][25] In tuberous sclerosis, the renal lesions may actually be epithelioid angiomyolipoma (also called perivascular epithelioid cell tumor or PEComa), which is associated with aggressive or malignant behavior and expresses melanocyte and smooth muscle markers.[26][27] Familial RCC has been associated with an inherited chromosome translocation involving chromosome 3.[25] A high incidence of chromosome 3 abnormalities has also been demonstrated in nonfamilial renal tumors. RCCs have been described in patients several years after diagnosis and therapy for neuroblastoma.[28] A rare subtype of RCC, renal medullary carcinoma, may be associated with sickle cell hemoglobinopathy.[29] Renal medullary carcinomas are highly aggressive malignancies characterized clinically by a high stage at the time of detection, with widespread metastases and lack of response to chemotherapy and radiation therapy.[30][ Level of evidence: 3iiA] Survival is poor and ranges from 2 weeks to 15 months, with a mean survival of 4 months.[29][30][31][Level of evidence: 3iiA]
Pediatric RCC differs histologically from the adult counterparts. Although the two main morphological subgroups of papillary and clear cell can be identified, about 25% of RCCs show heterogeneous features that do not fit into either one of these categories. Childhood RCCs are more frequently of the papillary subtype (20%–50% of pediatric RCCs) and can sometimes occur in the setting of Wilms tumor, metanephric adenoma, and metanephric adenofibroma.
Translocation-positive carcinomas of the kidney are recognized as a distinct form of RCC and may be the most common form of RCC in children. They are characterized by translocations involving the transcription factor E3 (TFE3) located on Xp11.2. The TFE3 gene may partner with one of the following three genes: (ASPL)-TFE3, renal cell carcinoma papillary 1 gene (PRCC)-Xp11.2, or the transcription factor EB (TFEB) gene on chromosome 6p21. The translocations involving TFE3 and TFEB induce overexpression of these proteins which can be identified by immunohistochemistry. These RCCs are characterized by advanced stage at presentation (N+, M0) but have a favorable short-term prognosis with surgery alone.[19][22][32][33][34]
RCC may present with an abdominal mass, abdominal pain, or hematuria. In a series of 41 children with RCC, the median age was 124 months with 46% presenting with localized stage I and stage II disease, 29% with stage III disease, and 22% with stage IV disease using the Robson classification system. The sites of metastases were the lungs, liver, and lymph nodes. EFS and OS were each about 55% at 20 years post treatment. Patients with stage I and stage II disease had an 89% OS rate, while those with stage III and stage IV disease had a 23% OS rate at 20 years posttreatment.[24] An important difference between the outcomes in children and adults with RCC is the prognostic significance of local lymph node involvement. Adults presenting with RCC and involved lymph nodes have a 5-year OS of approximately 20%, but the literature suggests that 72% of children with RCC and local lymph node involvement at diagnosis (without distant metastases) survive their disease.[35] In another series of 49 patients from a population-based cancer registry, the findings were essentially confirmed. In this series, 33% of the patients had papillary subtype, 22% had translocation type, 16% were unclassified, and 6% had clear-cell subtype. Survival at 5 years was 96% for patients with localized disease, 75% for patients with positive regional lymph nodes, and 33% for patients with distant metastatic RCC.[36]
Some nephrogenic rests may become hyperplastic which may produce a thick rind of blastemal or tubular cells that enlarge the kidney. The diagnosis may be made radiographically, most readily by magnetic resonance imaging, in which the homogeneity of the hypointense rind-like lesion on contrast-enhanced imaging differentiates it from Wilms tumor. Biopsy often cannot discriminate Wilms tumor from these hyperplastic nephrogenic rests. If left untreated, they may regress. Differentiation may occur following the administration of chemotherapy. Current recommendations are for treatment with vincristine and dactinomycin until nearly complete resolution as determined by imaging. Even with treatment with vincristine and dactinomycin, about half of children will develop Wilms tumor, within an average of 36 months after diagnosis. In a series of 52 patients, three patients died of recurrent Wilms tumor.[37] In treated children, as many as one-third of Wilms tumors are anaplastic, probably as a result of selection of chemotherapy-resistant tumors, so early detection is critical. Patients are followed by imaging at a maximum interval of 3 months for a minimum of 7 years. Given the high incidence of bilaterality and the subsequent Wilms tumors, renal-sparing surgery is indicated.[37] These patients will be eligible for treatment on the COG-AREN0534 trial with vincristine and dactinomycin.
Neuroepithelial tumors of the kidney (NETK) are extremely rare and demonstrate a unique proclivity for young adults. It is a highly aggressive neoplasm, more often presenting with penetration of the renal capsule, extension into the renal vein, and metastases.[38][39] Primary NETK consist of primitive neuroectodermal tumors characterized by CD99 (MIC-2) positivity and the detection of EWS/FLI-1 fusion transcripts. Within NETK, focal, atypical histologic features have been seen including clear cell sarcoma, RT, malignant peripheral nerve sheath tumors, and paraganglioma.[38][40] (Refer to the PDQ summary on Ewing Sarcoma Family of Tumors for more information about neuroepithelial tumors.)
Desmoplastic small round cell tumor of the kidney (DSRCT) is a rare, small, round blue tumor of the kidney. It is diagnosed by its characteristic EWS-WT1 translocation.[41] (Refer to the PDQ summary on Childhood Soft Tissue Sarcoma Treatment for more information about DSRCT.)
Cystic partially differentiated nephroblastoma is a rare cystic variant of Wilms tumor (1%) with unique pathologic and clinical characteristics. It is composed entirely of cysts and their thin septa are the only solid portion of the tumor. The septa contain blastemal cells in any amount with or without embryonal stromal or epithelial cell type. Several pathologic features distinguish this neoplasm from standard Wilms tumor. Patients with stage I disease have a 100% survival rate with surgery alone. Patients with stage II disease have an excellent outcome with tumor resection followed by postoperative vincristine and dactinomycin.[5]
Multilocular cystic nephromas (MCNs) are benign lesions consisting of cysts lined by renal epithelium. These lesions can occur bilaterally and a familial pattern has been reported. MCN has been associated with pleuropulmonary blastomas, so radiographic imaging studies of the chest should be followed in patients with MCN.[42] Recurrence has been reported following tumor spillage at surgery.[43][Level of evidence: 3iiiA]
Primary renal synovial sarcoma (PRSS) is a subset of embryonal sarcoma of the kidney and is characterized by the t(x;18)(p11;q11) SYT-SSX translocation. It is similar in histology to the monophasic spindle cell synovial sarcoma. PRSS contains cystic structures derived from dilated, trapped renal tubules. PRSS occurs more often in young adults and this type of renal tumor should be treated with different chemotherapy regimens than traditional Wilms tumor.[44]
Anaplastic sarcoma of the kidney is a rare renal tumor that has been identified mainly in patients younger than 15 years. Patients present with a renal mass with the most common sites of metastases being the lung, liver, and bones. These tumors show pathologic features similar to pleuropulmonary blastoma of childhood (see the PDQ summary on Unusual Cancers of Childhood for more information) and undifferentiated embryonal sarcoma of the liver (see the PDQ summary on Childhood Liver Cancer for more information). Optimal therapy for this diagnosis is not clear. In the past, these tumors have been identified as anaplastic Wilms tumor and treated accordingly.[45]
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The stage is determined by the results of the imaging studies and both the surgical and pathologic findings at nephrectomy and is the same for tumors with favorable or anaplastic histology. Thus, patients should be characterized by a statement of both criteria (for example, stage II, favorable histology or stage II, anaplastic histology).[1][2]
The staging system (originally developed by the National Wilms Tumor Study Group and still used by the Children's Oncology group) and incidence by stage are outlined below.[2]
In stage I Wilms tumor, all of the following criteria must be met:
For a tumor to qualify for certain therapeutic protocols as stage I, regional lymph nodes must be examined microscopically.
In stage II Wilms tumor, the tumor is completely resected, and there is no evidence of tumor at or beyond the margins of resection. The tumor extends beyond the kidney as evidenced by any one of the following criteria:
Rupture or spillage confined to the flank, including biopsy of the tumor, is no longer included in stage II and is now included in stage III.
In stage III Wilms tumor, there is residual nonhematogenous tumor present following surgery that is confined to the abdomen. Any one of the following may occur:
In stage IV Wilms tumor, hematogenous metastases (lung, liver, bone, brain), or lymph node metastases outside the abdominopelvic region are present. (The presence of tumor within the adrenal gland is not interpreted as metastasis and staging depends on all other staging parameters present.)
In stage V Wilms tumor, bilateral involvement by tumor is present at diagnosis. An attempt should be made to stage each side according to the above criteria on the basis of the extent of disease. The 4-year survival is 94% for those patients whose most advanced lesion is stage I or stage II, and 76% for those whose most advanced lesion is stage III.[3]
Anaplastic histology accounts for about 10% of Wilms tumors. Children with anaplastic tumors have a worse prognosis than children with favorable histology when compared stage to stage. These tumors are more resistant to the chemotherapy traditionally used in children with Wilms tumor (favorable histology).[4]
Wilms' tumor: status report, 1990. By the National Wilms' Tumor Study Committee. J Clin Oncol 9 (5): 877-87, 1991.
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Because of the relative rarity of this tumor, all patients with Wilms tumor should be considered for entry into a clinical trial. Treatment planning by a multidisciplinary team of cancer specialists (pediatric surgeon or pediatric urologist, pediatric radiation oncologist, and pediatric oncologist) with experience treating Wilms tumor is required to determine and implement optimum treatment.
The National Wilms Tumor Study (NWTS) Group, which is now part of the Children's Oncology Group, has established standard treatment for Wilms tumor in North America which consists of surgery followed by chemotherapy and, in some patients, radiation therapy.[1][2][3] The major treatment conclusions of the National Wilms Tumor Studies (NWTS 1—5) are as follows:
Operative principles have evolved from NWTS trials. The most important role for the surgeon is to ensure complete tumor removal without rupture and perform an assessment of the extent of disease. Radical nephrectomy and lymph node sampling via a transabdominal incision is the procedure of choice.[9] For patients with resectable tumors, preoperative biopsy should not be performed.[9] Routine exploration of the contralateral kidney is not necessary if technically adequate imaging studies do not suggest a bilateral process. If the initial imaging studies are suggestive of regional and contralateral kidney involvement, the contralateral kidney should be formally explored to rule out bilateral involvement. This should be done prior to nephrectomy since the diagnosis of bilateral disease would dramatically alter the approach.[10] Partial nephrectomy remains controversial and is not recommended except for bilateral tumors. Also, some rare, very small tumors may be discovered by ultrasound screening, and these cases may be considered for partial nephrectomy.[11] In North America, renal-sparing partial nephrectomy of unilateral Wilms tumor following administration of chemotherapy to shrink the tumor mass is considered investigational.[12][13] Hilar, periaortic, iliac, and celiac lymph node sampling is mandatory.[9] Furthermore, any suspicious node basin should be sampled. Margins of resection, residual tumor, and any suspicious node basins should be marked with titanium clips. Liver wedge resection or partial duodenal or colonic resections are acceptable for complete en bloc excision. Wilms tumor arising in a horseshoe kidney is rare and accurate preoperative diagnosis is important in planning the operative approach. Primary resection is possible in most cases. Inoperable cases can usually be resected after chemotherapy.[14]
Patients with massive, nonresectable unilateral tumors, bilateral tumors, or venacaval tumor thrombus above the hepatic veins are candidates for preoperative chemotherapy because of the risk of initial surgical resection.[9][15][16][17] Preoperative chemotherapy should follow a biopsy, which may be performed percutaneously through a flank approach.[18][19][20][21][22][23] Preoperative chemotherapy makes tumor removal easier and may reduce the frequency of surgical complications.[15][16][23][24][25] Although progressive tumor growth on chemotherapy is rare, such growth is associated with a poorer prognosis.[26] Current therapy in North America for patients diagnosed by needle biopsy alone is for a stage III tumor (in the absence of metastases) of favorable or anaplastic histology.
Newborns and all infants younger than 12 months require a reduction in chemotherapy doses to 50% of those given to older children.[27] This reduction diminishes toxic effects reported in children in this age group enrolled in NWTS studies while maintaining an excellent overall outcome.[28] Liver function tests in children with Wilms tumor should be monitored closely during the early course of therapy based on hepatic toxic effects (veno-occlusive disease) reported in those patients.[29][30] Dactinomycin should not be administered during radiation therapy. Patients who develop renal failure while on therapy can continue receiving chemotherapy with vincristine, dactinomycin, and doxorubicin. Vincristine and doxorubicin can be given at full doses, however, dactinomycin was associated with severe neutropenia. Reductions in dosing these agents may not be necessary, but accurate pharmacologic and pharmacokinetic studies are needed while the patient is receiving the therapy.[31][32]
Children treated for Wilms tumor are at increased risk for developing second malignant neoplasms. This risk depends on the intensity of their therapy, including the use of radiation and doxorubicin, and on possible genetic factors.[33] Congestive heart failure has been shown to be a risk in children treated with doxorubicin with the degree of risk influenced by cumulative doxorubicin dose, radiation to the heart, and gender (females are at increased risk).[34] Efforts, therefore, have been aimed toward reducing the intensity of therapy when possible. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for a full discussion of the late effects of cancer treatment in children and adolescents.)
As mentioned previously, clear cell sarcoma of the kidney, rhabdoid tumor of the kidney, neuroepithelial tumor of the kidney, and cystic partially-differentiated nephroblastoma are childhood renal tumors unrelated to Wilms tumor. Because of their renal location, they have been treated on clinical trials developed by the NWTS Group. The approach to their treatment, however, is distinctive from that of Wilms tumor, and requires timely and accurate diagnosis by a pathologist and pediatric oncologist with experience with these types of renal tumors.[35]
Jereb B, Burgers JM, Tournade MF, et al.: Radiotherapy in the SIOP (International Society of Pediatric Oncology) nephroblastoma studies: a review. Med Pediatr Oncol 22 (4): 221-7, 1994.
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Morgan E, Baum E, Breslow N, et al.: Chemotherapy-related toxicity in infants treated according to the Second National Wilms' Tumor Study. J Clin Oncol 6 (1): 51-5, 1988.
Green DM, Norkool P, Breslow NE, et al.: Severe hepatic toxicity after treatment with vincristine and dactinomycin using single-dose or divided-dose schedules: a report from the National Wilms' Tumor Study. J Clin Oncol 8 (9): 1525-30, 1990.
Raine J, Bowman A, Wallendszus K, et al.: Hepatopathy-thrombocytopenia syndrome--a complication of dactinomycin therapy for Wilms' tumor: a report from the United Kingdom Childrens Cancer Study Group. J Clin Oncol 9 (2): 268-73, 1991.
Feusner JH, Ritchey ML, Norkool PA, et al.: Renal failure does not preclude cure in children receiving chemotherapy for Wilms tumor: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer 50 (2): 242-5, 2008.
Veal GJ, English MW, Grundy RG, et al.: Pharmacokinetically guided dosing of carboplatin in paediatric cancer patients with bilateral nephrectomy. Cancer Chemother Pharmacol 54 (4): 295-300, 2004.
Breslow NE, Takashima JR, Whitton JA, et al.: Second malignant neoplasms following treatment for Wilm's tumor: a report from the National Wilms' Tumor Study Group. J Clin Oncol 13 (8): 1851-9, 1995.
Green DM, Grigoriev YA, Nan B, et al.: Congestive heart failure after treatment for Wilms' tumor: a report from the National Wilms' Tumor Study group. J Clin Oncol 19 (7): 1926-34, 2001.
Table 1 describes the standard chemotherapy regimens used to treat Wilms tumor.
Regimen Name
Regimen Description
Regimen EE-4A [1]
Vincristine, dactinomycin x 18 weeks postnephrectomy
Regimen DD-4A [1]
Vincristine, dactinomycin, doxorubicin x 24 weeks postnephrectomy
Regimen I [2]
Vincristine, doxorubicin, cyclophosphamide, etoposide x 24 weeks
Table 2 provides an overview of the standard treatment based on published results for all stages of Wilms tumor and survival information.
RFS or EFS
Treatment (see Table 1 for chemotherapy regimen definitions)
Stage I [1][2][3]
Nephrectomy + lymph node sampling followed by regimen EE-4A
FA or DA
Nephrectomy + lymph node sampling followed by regimen EE-4A and XRT
Stage II [1][2][4]
FA (very small numbers)
Nephrectomy + lymph node sampling followed by abdominal XRT and regimen DD-4A
Nephrectomy + lymph node sampling followed by abdominal XRT and regimen I
Stage III [1][2]
Preoperative treatment with regimen DD-4A followed by nephrectomy + lymph node sampling and abdominal XRT
Preoperative treatment with regimen I followed by nephrectomy + lymph node sampling and abdominal XRT
Immediate nephrectomy + lymph node sampling followed by abdominal XRT and regimen I
Stage IV [1][2][4]
Nephrectomy + lymph node sampling, followed by abdominal XRT,a bilateral pulmonary XRT,b and regimen DD-4A
Immediate nephrectomy + lymph node sampling followed by abdominal XRT,a whole-lung XRT,b and regimen I
Preoperative treatment with regimen I followed by nephrectomy + lymph node sampling, followed by abdominal XRT,a and whole-lung XRTb
Stage V [1][5][6][7][8][9][10][11][12][13]
78% (10-year OS)
Bilateral renal biopsies and staging of each kidney followed by preoperative treatment with regimen EE-4A (if disease in both kidneys ≤ stage II) or regimen DD-4A (if disease in both kidneys > stage II), followed by second-look surgery and possibly more chemotherapy and/or XRT
Bilateral renal biopsies and staging of each kidney followed by preoperative treatment with regimen I, followed by second-look surgery and possibly more chemotherapy and/or XRT
AH = anaplastic histology; DA = diffuse anaplastic; EFS = event-free survival; FA = focal anaplastic; FH = favorable histology; OS = overall survival; RFS = relapse-free survival; XRT = radiation therapy
aAbdominal XRT is planned according to local stage of renal tumor.
bPulmonary XRT is reserved for patients with chest x-ray evidence of pulmonary metastases.
It may be possible to treat a subset of stage I Wilms tumor patients with surgery alone without chemotherapy. The Children's Oncology Group is addressing this question in a large study. In the National Wilms Tumor Study-5 (COG-Q9401) trial, for children older than 2 years at diagnosis with stage I favorable histology (FH) Wilms tumors that weigh more than 550 g, results suggested the costs of the therapy may outweigh the benefits.[14] In NWTS-5 these patients did not receive any postoperative chemotherapy or radiation. The study was designed conservatively based on the assumption that only 50% of the patients with recurrence could be successfully salvaged. The 3-year interim analysis showed a 2-year event–free survival (EFS) of 86.5% which indicated, according to the statistical design, that there was 95% probability that "no treatment" had failed. This part of the study was closed to further accrual and children with recent nephrectomy were advised to receive treatment as per regimen EE-4A (see Table 1). Of the 75 children treated with nephrectomy only prior to closure of the protocol, 11 patients relapsed or developed metachronous disease in the contralateral kidney 0.3 to 2.3 years after diagnosis (median: 4 months, mean: 0.64 years). The sites of relapse were lung (five patients) and operative bed (three patients). Three patients developed disease in the contralateral kidney. The overall survival (OS) of these 11 relapsed patients was 91%. The salvage rate in this cohort of patients from NWTS-5 was much higher (91%) than the postulated rate of 50%, a finding that supports a less conservative approach.[14]
For patients with stage IV FH Wilms tumor, the role of pulmonary irradiation has been examined retrospectively (based on chest x-ray results) and is being examined prospectively (based on computerized tomography scan results) to identify clinical and radiological features in patients that suggest that radiation can be omitted in certain subsets. Investigators in the United Kingdom reviewed outcomes in children with stage IV Wilms tumor with pulmonary metastases at diagnosis and the factors that contributed to the decision to withhold pulmonary radiation. Patients who underwent pulmonary irradiation had a 9-year EFS of 79% versus 53% in patients who did not, although there was no difference in OS. Pulmonary radiation decreased the chance of lung relapse (8% vs 23%). No consistent features could be identified to aid in the selection of patients who could safely avoid pulmonary irradiation.[15]
The treatment of children with bilateral Wilms tumor must be individualized. The goals of therapy are to eradicate all tumor and to preserve as much normal renal tissue as possible with the hope of decreasing the risk of chronic renal failure among these children.[5][6] Studies demonstrate no difference in survival for children who undergo initial bilateral biopsy followed by chemotherapy and then surgical resection compared with patients who have initial resection followed by chemotherapy. Initially, patients should undergo bilateral renal biopsies with staging of each kidney. Primary tumor excision should not be attempted, but patients should be given preoperative chemotherapy. Initial treatment is with regimen EE-4A (see Table 1) if the renal tumors are of FH and not more extensive than stage II. Those with higher stage and FH disease should receive regimen DD-4A (see Table 1), and those with anaplastic histology (AH) should receive regimen I (see Table 1). Following 6 weeks of chemotherapy, the patient should be reassessed. If serial imaging studies show no further reduction in tumor, a second-look surgical procedure should be performed (partial nephrectomy or wedge excision) if negative margins can be obtained; otherwise, sequential biopsies should be done to establish the reason for failure to respond. This approach will identify patients with anaplasia or differentiation, select them for early surgery, and define the intensity of chemotherapy to be administered.[7][8][16] Chemotherapy and/or radiation therapy following the second-look operation is dependent on the response to initial therapy, with more aggressive therapy required for patients with inadequate response to initial therapy observed at the second procedure.[7][9][10][11][12][13]
Renal transplantation for children with Wilms tumor is usually delayed until 1 to 2 years have passed without evidence of malignancy.[17] Similarly, renal transplantation for children with Denys-Drash syndrome and Wilms tumor, all of whom require bilateral nephrectomy, is generally delayed 1 to 2 years after completion of treatment for the tumor.[17]
Approximately 10% of patients with bilateral tumors have AH and may benefit from more aggressive chemotherapy and radiation therapy, and an aggressive surgical approach at the second-look operation.[2]
Patients who have tumors with caval extension above the hepatic veins or that are so massive that their surgeons consider the risk of initial surgical removal too great should be biopsied and treated with preoperative chemotherapy.[12][18] If surgery is performed on a patient with caval or atrial extension, care should be taken to ensure that appropriate resources are available for pediatric cardiopulmonary bypass.[19][20] On the NWTS-5, these patients were treated after biopsy by initial chemotherapy with vincristine and dactinomycin with or without doxorubicin. If no reduction in tumor size occurred after using three drugs, then radiation therapy was used.[21] Surgery was performed as soon as sufficient tumor shrinkage had occurred, generally at week 6 of therapy. If resection of the tumor could not occur at that time, the patient had a second-look procedure to confirm a persistent tumor. Failure of the tumor to shrink could be a result of a predominance of skeletal or benign elements. Patients were subsequently treated as for stage III tumors, which includes postoperative radiation therapy.[22] Because of the 5% to 10% error rate in preoperative diagnosis of renal masses after radiographic assessment, confirmation of the diagnosis by biopsy (which may be performed percutaneously) should be obtained prior to chemotherapy.[12]
Green DM, Beckwith JB, Breslow NE, et al.: Treatment of children with stages II to IV anaplastic Wilms' tumor: a report from the National Wilms' Tumor Study Group. J Clin Oncol 12 (10): 2126-31, 1994.
Montgomery BT, Kelalis PP, Blute ML, et al.: Extended followup of bilateral Wilms tumor: results of the National Wilms Tumor Study. J Urol 146 (2 ( Pt 2)): 514-8, 1991.
Fuchs J, Wünsch L, Flemming P, et al.: Nephron-sparing surgery in synchronous bilateral Wilms' tumors. J Pediatr Surg 34 (10): 1505-9, 1999.
Shamberger RC, Haase GM, Argani P, et al.: Bilateral Wilms' tumors with progressive or nonresponsive disease. J Pediatr Surg 41 (4): 652-7; discussion 652-7, 2006.
Ritchey ML, Green DM, Thomas PR, et al.: Renal failure in Wilms' tumor patients: a report from the National Wilms' Tumor Study Group. Med Pediatr Oncol 26 (2): 75-80, 1996.
Horwitz JR, Ritchey ML, Moksness J, et al.: Renal salvage procedures in patients with synchronous bilateral Wilms' tumors: a report from the National Wilms' Tumor Study Group. J Pediatr Surg 31 (8): 1020-5, 1996.
Ritchey ML: The role of preoperative chemotherapy for Wilms' tumor: the NWTSG perspective. National Wilms' Tumor Study Group. Semin Urol Oncol 17 (1): 21-7, 1999.
Zuppan CW, Beckwith JB, Weeks DA, et al.: The effect of preoperative therapy on the histologic features of Wilms' tumor. An analysis of cases from the Third National Wilms' Tumor Study. Cancer 68 (2): 385-94, 1991.
Nicolin G, Taylor R, Baughan C, et al.: Outcome after pulmonary radiotherapy in Wilms' tumor patients with pulmonary metastases at diagnosis: a UK Children's Cancer Study Group, Wilms' Tumour Working Group Study. Int J Radiat Oncol Biol Phys 70 (1): 175-80, 2008.
Davidoff AM, Giel DW, Jones DP, et al.: The feasibility and outcome of nephron-sparing surgery for children with bilateral Wilms tumor. The St Jude Children's Research Hospital experience: 1999-2006. Cancer 112 (9): 2060-70, 2008.
Kist-van Holthe JE, Ho PL, Stablein D, et al.: Outcome of renal transplantation for Wilms' tumor and Denys-Drash syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant 9 (3): 305-10, 2005.
Ritchey ML, Kelalis PP, Haase GM, et al.: Preoperative therapy for intracaval and atrial extension of Wilms tumor. Cancer 71 (12): 4104-10, 1993.
Green DM, Breslow NE, Evans I, et al.: The effect of chemotherapy dose intensity on the hematological toxicity of the treatment for Wilms' tumor. A report from the National Wilms' Tumor Study. Am J Pediatr Hematol Oncol 16 (3): 207-12, 1994.
The following treatment options are currently under investigation in Children's Oncology Group (COG) clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
The following treatment options are currently under investigation in COG clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
Patients with an LOH at chromosomes 1p and 16q will be treated with regimen M with radiation therapy to all sites of disease. Patients with metastases outside or in addition to lung metastases will be treated with regimen M and radiation therapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I Wilms tumor, stage II Wilms tumor, stage III Wilms tumor, stage IV Wilms tumor and recurrent Wilms tumor and other childhood kidney tumors. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Because of the relative rarity of this tumor, all patients with clear cell sarcoma of the kidney (CCSK) should be considered for entry into a clinical trial. Treatment planning by a multidisciplinary team of cancer specialists (pediatric surgeon or pediatric urologist, pediatric radiation oncologist, and pediatric oncologist) with experience treating renal tumors is required to determine and implement optimum treatment.
For CCSK, 5-year event-free survival (EFS) and overall survival (OS) for stage I is 100%; stage II is 87% and 97%, respectively; stage III is 74% and 87%, respectively; and stage IV is 36% and 45%, respectively (regimen I [ see description below]).[1]
The approach for treating CCSK is different from Wilms tumor since the OS of children with CCSK remains considerably lower than for patients with favorable histology Wilms tumor. In the National Wilms Tumor Study-3 (NWTS-3), the addition of doxorubicin to the combination of vincristine, dactinomycin, and radiation therapy resulted in an improvement in disease-free survival for patients with CCSK.[2]NWTS-4 showed that patients treated with vincristine, doxorubicin, and dactinomycin for 15 months had an improved relapse-free survival compared with patients treated for 6 months (88% vs. 61% at 8 years).[3] In the COG-Q9401 study, children with stages I to IV CCSK were treated with a new chemotherapeutic regimen combining vincristine, doxorubicin, cyclophosphamide, and etoposide in an attempt to further improve the survival of these high-risk groups. All patients received radiation therapy to the tumor bed. With this treatment, the 5-year EFS was approximately 89%, and OS was approximately 79%. Stage I patients had 100% 5-year EFS and OS. Stage II patients had a 5-year EFS of approximately 87% and OS of approximately 97%. Stage III patients had an approximately 74% 5-year EFS and an approximately 87% 5-year OS. Stage IV patients had a 5-year EFS of approximately 36% and 5-year OS of 45%. CCSK has been characterized by late relapses; however, in NWTS-5, most relapses occurred within 3 years. In NWTS-5, the most common site of recurrence was the brain,[1] which has been successfully treated with combination chemotherapy, surgery, and radiation therapy.[4][Level of evidence: 2A]
The following treatment option is currently under investigation in a Children's Oncology Group (COG) clinical trial. Information about ongoing clinical trials is available from the NCI Web site.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with clear cell sarcoma of the kidney. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Because of the relative rarity of this tumor, all patients with rhabdoid tumor of the kidney (RTK) should be considered for entry into a clinical trial. Treatment planning by a multidisciplinary team of cancer specialists (pediatric surgeon or pediatric urologist, pediatric radiation oncologist, and pediatric oncologist) with experience treating renal tumors is required to determine and implement optimum treatment.
Patients with RTK continue to have a poor prognosis with 4-year overall survival (OS) for stage I patients of 33%, stage II of 47%, stage III of 22%, and stage IV of 8%.[1]
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with rhabdoid tumor of the kidney. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Waldron PE, Rodgers BM, Kelly MD, et al.: Successful treatment of a patient with stage IV rhabdoid tumor of the kidney: case report and review. J Pediatr Hematol Oncol 21 (1): 53-7, 1999 Jan-Feb.
Wagner L, Hill DA, Fuller C, et al.: Treatment of metastatic rhabdoid tumor of the kidney. J Pediatr Hematol Oncol 24 (5): 385-8, 2002 Jun-Jul.
Optimal treatment has not been established for these tumors. Treatment according to Ewings/primitive neuroectodermal tumor protocols should be considered.[1]
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with peripheral primitive neuroectodermal tumor of the kidney. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
When diagnosed in the first 7 months of life, the 5 year event-free survival and overall survival rates are 94% and 96%, respectively.[1]
A prospective clinical trial that enrolled 50 patients confirmed that complete surgical resection, which includes the entire capsule, is adequate therapy for most patients with mesoblastic nephroma.[2] In this study, only two of 50 patients died. Patients were at increased risk for local and eventually metastatic recurrence if there was stage III (incomplete resection and/or histologically positive resection margin), cellular subtype, and aged 3 months or older at diagnosis. Because of the small numbers of patients and the overlapping incidence of these characteristics (five of 50 patients), the significance of the individual characteristics could not be discriminated. Adjuvant chemotherapy has been recommended for patients who share these three characteristics, though the benefit of adjuvant therapy will remain unproven with such a low incidence of disease.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with congenital mesoblastic nephroma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Survival of patients with renal cell carcinoma (RCC) is affected by stage of disease at presentation and the completeness of resection at radical nephrectomy. Overall survival rates range from 64% to 87%. The 5-year survival for stage I is 90% or higher, for stages II and III it is 50% to 80%, and for stage IV it is 9%, which is similar to the stage-for-stage survival in RCC in adults. Retrospective analyses and the small number of patients involved place limitations on the level of evidence in the area of treatment. The primary treatment for RCC includes total surgical removal of the kidney and associated lymph nodes.[1] In two small series, patients who had partial nephrectomies seem to have outcomes equivalent to those who have radical nephrectomies. Partial nephrectomy may be considered in carefully selected patients with low–volume localized disease.[2][3] There is no evidence that adjuvant therapy is beneficial in children with lymph-node positive, nonmetastatic disease.[1] Treatment of unresectable metastatic disease is presently unsatisfactory, similar to adult RCC; it is poorly responsive to radiation and there is no effective chemotherapy regimen. Immunotherapy, such as interferon-alpha and interleukin-2, may have some effect on cancer control.[4] Rare spontaneous regression of pulmonary metastasis may occur with resection of the primary tumor. (Refer to the PDQ summary on adult Renal Cell Cancer Treatment for more information.)
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood renal cell carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Cook A, Lorenzo AJ, Salle JL, et al.: Pediatric renal cell carcinoma: single institution 25-year case series and initial experience with partial nephrectomy. J Urol 175 (4): 1456-60; discussion 1460, 2006.
Fyfe G, Fisher RI, Rosenberg SA, et al.: Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 13 (3): 688-96, 1995.
Children with relapsed favorable-histology Wilms tumor have a variable prognosis, depending on the site of relapse, the time from initial diagnosis to relapse, and their previous therapy. Favorable prognostic factors include no prior treatment with doxorubicin, relapse more than 12 months after diagnosis, and intra-abdominal relapse in a patient not previously treated with abdominal radiation.[1][2][Level of Evidence: 2A][3]
Wilms tumor patients whose initial therapy consisted of immediate nephrectomy followed by chemotherapy with vincristine and dactinomycin who relapse can be successfully retreated. Fifty-eight patients were treated on the National Wilms Tumor Study-5 (COG-Q9401) relapse protocol with surgical excision when feasible, radiation therapy and alternating courses of vincristine, doxorubicin and cyclophosphamide, and etoposide and cyclophosphamide. Four-year event-free survival (EFS) after relapse was 71% and overall survival (OS) was 82%. For those patients who relapsed only to their lungs the 4-year EFS after relapse was 68% and OS was 81%.[4] Approximately 50% of unilateral Wilms tumor patients who relapse or progress after initial treatment with vincristine, dactinomycin, and doxorubicin and radiation can be successfully retreated. Sixty patients were treated on the NWTS-5 relapse protocol with alternating courses of cyclophosphamide/etoposide and carboplatin/etoposide, surgery and radiation therapy. EFS (4-year) and OS were 42% and 48%, respectively, and 49% and 53% for patients who relapsed in the lungs only.[2]
Patients with stages II, III, and IV anaplastic-histology tumors at diagnosis have a very poor prognosis upon recurrence.[5] The combination of ifosfamide, etoposide, and carboplatin has demonstrated activity in this group of patients, but significant hematologic toxic effects have been observed.[6][7] While high-dose chemotherapy followed by autologous hematopoietic stem cell transplant has been utilized,[8][9][10] an intergroup study of the former Pediatric Oncology Group and the former Children's Cancer Group used a salvage induction regimen of cyclophosphamide and etoposide (CE) alternating with carboplatin and etoposide (PE) followed by delayed surgery. Disease-free patients were assigned to maintenance chemotherapy with five cycles of alternating CE and PE, and the remainder of patients to ablative therapy and autologous marrow transplant. All patients received local radiation therapy. The 3-year survival was 52% for all eligible patients, while the 3-year survival was 64% and 42% for the chemotherapy consolidation and autologous marrow transplant subgroups, respectively.[2][3][Level of evidence: 2A] The outcome of hematopoietic stem cell rescue in selected patients may be superior,[10][11] however, patients with gross residual disease going into transplant do not do as well.[8] Patients in whom such salvage attempts fail should be offered treatment on available phase I or phase II studies.
Treatment of patients with recurrent clear cell sarcoma of the kidney (CCSK) depends on initial therapy. Cyclophosphamide and carboplatin should be considered if not used initially. Patients with recurrent CCSK involving the brain have responded to treatment with ifosfamide, carboplatin, and etoposide (ICE) coupled with local control consisting of either surgical resection and/or radiation.[12][Level of evidence: 2A] In NWTS-5,[13] patients with CCSK and brain metastases have been successfully treated with combination chemotherapy, surgery, and radiation therapy. Patients with recurrent rhabdoid tumor of the kidney, CCSK, neuroepithelial tumor of the kidney, and renal cell carcinoma should be considered for treatment on available phase I and phase II clinical trials.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent Wilms tumor and other childhood kidney tumors. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Grundy P, Breslow N, Green DM, et al.: Prognostic factors for children with recurrent Wilms' tumor: results from the Second and Third National Wilms' Tumor Study. J Clin Oncol 7 (5): 638-47, 1989.
Malogolowkin M, Cotton CA, Green DM, et al.: Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group. Pediatr Blood Cancer 50 (2): 236-41, 2008.
Tannous R, Giller R, Holmes E, et al.: Intensive therapy for high risk (HR) relapsed Wilms' tumor (WT): a CCG-4921/POG-9445 study report. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A2315, 2000.
Green DM, Cotton CA, Malogolowkin M, et al.: Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group. Pediatr Blood Cancer 48 (5): 493-9, 2007.
Abu-Ghosh AM, Krailo MD, Goldman SC, et al.: Ifosfamide, carboplatin and etoposide in children with poor-risk relapsed Wilms' tumor: a Children's Cancer Group report. Ann Oncol 13 (3): 460-9, 2002.
Kung FH, Bernstein ML, Camitta BM, et al.: Ifosfamide/carboplatin/etoposide (ICE) in the treatment of advanced, recurrent Wilms tumor. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A-2156, 559a, 1999.
Garaventa A, Hartmann O, Bernard JL, et al.: Autologous bone marrow transplantation for pediatric Wilms' tumor: the experience of the European Bone Marrow Transplantation Solid Tumor Registry. Med Pediatr Oncol 22 (1): 11-4, 1994.
Pein F, Michon J, Valteau-Couanet D, et al.: High-dose melphalan, etoposide, and carboplatin followed by autologous stem-cell rescue in pediatric high-risk recurrent Wilms' tumor: a French Society of Pediatric Oncology study. J Clin Oncol 16 (10): 3295-301, 1998.
Campbell AD, Cohn SL, Reynolds M, et al.: Treatment of relapsed Wilms' tumor with high-dose therapy and autologous hematopoietic stem-cell rescue: the experience at Children's Memorial Hospital. J Clin Oncol 22 (14): 2885-90, 2004.
Spreafico F, Bisogno G, Collini P, et al.: Treatment of high-risk relapsed Wilms tumor with dose-intensive chemotherapy, marrow-ablative chemotherapy, and autologous hematopoietic stem cell support: experience by the Italian Association of Pediatric Hematology and Oncology. Pediatr Blood Cancer 51 (1): 23-8, 2008.
About PDQ
Additional PDQ Summaries
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
This information is provided by the National Cancer Institute.
This information was last updated on December 16, 2009.
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text: As Season 3 of The Office gets underway, Pam (Jenna Fischer) remains unable to express her feelings for Jim (John Krasinski) after the pair recently shared a kiss and now Jim has taken a promotion that means transferring to Connecticut. Michael (Steve Carell) has discovered that Oscar (Oscar Nunez) is gay, and has enlisted the aid of Dwight (Rainn Wilson) in determining who else in the Scranton branch of Dunder Mifflin might be homosexual. Despite the fact that Pam called off her wedding to Roy (David Denman), her ex-fiancé is determined to win her back. Later, Michael holds a special meeting to encourage others who may be gay to openly express their sexuality. In a misguided effort to sincerely express that he believes there is nothing wrong with homosexuality, Michael attempts to kiss Oscar, who is clearly uncomfortable, on the lips. After that incident, Jan (Melora Hardin) attempts to get Oscar to sign a document saying he will not sue Dunder Mifflin. ~ Jason Buchanan, Rovi

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