Introduction:

Malignant rhabdoid tumor (MRT) is one of the most aggressive and lethal malignancies in pediatric oncology. MRT was initially described in 1978 as a rhabdomyosarcomatoid variant of a Wilms tumor because of its occurrence in the kidney and because of the resemblance of its cells to rhabdomyoblasts. The absence of muscular differentiation led Haas and colleagues to coin the term rhabdoid tumor of the kidney in 1981.

Although renal MRT was historically included in treatment protocols of the National Wilms Tumor Study (NWTS) Group, this tumor is now recognized as an entity separate from a Wilms tumor. In contrast to a Wilms tumor, an MRT of the kidney is characterized by the early onset of local and distant metastases and resistance to chemotherapy. Whereas the overall survival rate for Wilms tumors exceeds 85%, the survival rate for renal MRTs is only 20-25%.

Since rhabdoid tumor of the kidney was originally described, malignant rhabdoid tumors have been reported in practically every location in the body, including the brain, liver, soft tissues, lung, skin, and heart. This article focuses on renal and extrarenal rhabdoid tumors that arise outside the CNS.

Frequency: United States
MRT is a rare tumor. According to registration data from NWTS 1-5, MRT accounts for only 158 (1.6%) of 10,031 registrants with childhood renal tumors. Likewise, only 26 (0.9%) of 3000 participants in the Intergroup Rhabdomyosarcoma Studies I-III had tumors consistent with MRT. About 15 cases of extrarenal or non-CNS MRTs are diagnosed each year in the North America.

Mortality/Morbidity:

The overall survival rate for patients with MRT enrolled in NWTS 1-5 was 23.2%.

*MRT is a rapidly progressive tumor, with most deaths occurring within 12 months of presentation. The most common sites of metastasis at presentation are the lungs, abdominal lymph nodes, liver, and brain.

*A young age at diagnosis is strongly associated with an adverse outcome. Four-year event-free survival rates according to age at diagnosis were 8.8% for patients 0-5 months, 17.2% for patients 6-11 months, 28.6% for patients 12-23 months, and 41.1% for patients >24 months.

*High-stage disease is correlated with an adverse outcome, and most patients present with stage III or IV disease (see Table 1 below). Table 1. Survival of Patients with MRT in NWTS 1-5


Race:

MRT has no apparent racial predilection.

Sex:

MRT occurs slightly more frequently in male individuals than in female individuals, with male-to-female ratio of 1.4:1.

Age:

The median age at presentation is 10.6 months, with a mean age of 15 months. Most patients are younger than 2 years. MRT has been reported in children older than this and in adults, but whether these patients have true rhabdoid tumors or other poorly differentiated tumors with rhabdoid features is unclear.

TREATEMENT:

Medical Care:

After the primary tumor is surgically removed, chemotherapy is indicated as adjuvant treatment for MRT. Chemotherapy for MRT was historically based on therapy for a Wilms tumor, which included vincristine, actinomycin, and doxorubicin with or without cyclophosphamide. With these agents, the estimated survival rate for patients with MRT was only 23%.

To try to improve these results, investigators in NWTS 5 used a regimen consisting of carboplatin-etoposide alternating with cyclophosphamide. However, this strategy, did not improve outcomes. Recent case reports have documented successful outcomes in patients with metastatic MRT treated with ifosfamide-carboplatin-etoposide (ICE) or ifosfamide-etoposide (IE) alternating with vincristine-doxorubicin-cyclophosphamide (VDC). On the basis of these reports, cyclophosphamide-carboplatin-etoposide (CCE) alternating with VDC is the main treatment in the current COG study.

Insights into the treatment of MRT may be derived from the experience with AT/RT of the CNS. Like its extra-CNS counterparts, AT/RT results in an unfavorable prognosis and is characterized by resistance to chemotherapy. A review of the AT/RT registry by Hilden and colleagues revealed that 14 (33%) of 42 patients with AT/RT survived disease-free over 9.5- to 96-month follow-up.

Survivors were treated with surgery, radiation therapy, and various chemotherapy regimens that typically included cisplatin, etoposide, vincristine, ifosfamide, doxorubicin, actinomycin, cyclophosphamide, and intrathecal agents. Some survivors received high-dose therapy with autologous stem-cell rescue. In general, the experience with AT/RT indicated that these tumors initially respond to chemotherapy but then quickly become refractory to treatment.

The lack of treatment uniformity among reported patients makes it difficult to determine if radiotherapy is effective for MRT. In NWTS 1-5, radiation therapy was given to the flank or abdomen at total doses of 1080-3500 cGy. However, the optimal dose remains to be determined. Radiation therapy is a cornerstone of treatment for CNS AT/RT, and some suggest that the high doses delivered to the posterior fossa improve patients' outcomes.
Surgical Care