Malignant Rhabdoid Tumor Treatment & Management
- Author: James I Geller, MD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
After the primary tumor is surgically removed, chemotherapy is indicated as adjuvant treatment for malignant rhabdoid tumor (MRT). Chemotherapy for malignant rhabdoid tumor 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 malignant rhabdoid tumor 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 malignant rhabdoid tumor 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 malignant rhabdoid tumor may be derived from the experience with atypical teratoid/rhabdoid tumors (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-month 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 a separate review by Tekautz et al, AT/RT presenting in older patients demonstrated a 2 year event-free survival of 78% when treated with a combination of radiation and high-dose alkylating therapy. More recently, a multisite study of a multimodal therapy plan incorporating surgery, radiation, and a systemic and intrathecal conventional chemotherapeutic regimen based on a modified IRS-III regimen demonstrated a 2 year progression-free survival of 58%. This later study includes infants younger than 3 years. Considering all data, the COG AT/RT protocol is currently testing a regimen incorporating surgery, conventional chemotherapy, radiation, and tandem high dose chemotherapy with stem cell rescue.
Two reports describe the successful use of high dose chemotherapy with stem cell rescue to treat non-CNS malignant rhabdoid tumor. However, in combination, none of the 4 children described had metastatic disease at presentation. Based on the limited data available at this time, whether high-dose chemotherapy with stem cell rescue is of any added benefit for non-CNS malignant rhabdoid tumor is unclear.
Similarly, anecdotal reports suggest a benefit from the use of radiotherapy as part of multimodal therapy for malignant rhabdoid tumor. However, the lack of treatment uniformity among reported patients makes it difficult to determine if radiotherapy is effective for malignant rhabdoid tumor. 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.
Furtwängler et al conducted a review of 3 prospective studies comparing the change of tumor volume as a result of treatment with either actinomycin D and vincristine combination therapy (AV) or doxorubicin-intensified antinomycin D and vincristine combination therapy (AVD) in all patients with malignant rhabdoid tumor of the kidney who had been treated from 1991 to 2013 in Austria, Switzerland, and Germany. The investigators concluded that a significantly better treatment response is achieved with neoadjuvant AVD than with AV alone.
Children with a renal tumor or soft tissue mass should be referred to a pediatric surgeon with experience in oncologic surgery.
For renal tumors, a large transabdominal, transperitoneal incision is recommended for adequate exposure. If the mass is unilateral, a radical nephrectomy with subtotal ureterectomy should be performed. The tumor should be removed en bloc to avoid tumoral spillage into the peritoneal cavity because this spillage increases the stage of the tumor. If the mass involves the upper pole of the kidney, the adrenal gland should be removed.
Lymph nodes from the iliac, para-aortic, and celiac areas should be sampled, even if they do not appear abnormal. Lymph node dissection is not indicated. If the tumor is bilateral or unresectable, biopsy should be performed. If a bilateral or unresectable Wilms tumor is diagnosed, preoperative chemotherapy is recommended to shrink the tumor and facilitate subsequent resection. If malignant rhabdoid tumor is diagnosed, complete removal of the tumor is advised.
For extrarenal tumors, the surgical approach depends on the site of disease. Complete resection should be attempted if feasible. If not initially feasible, a preoperative course of chemotherapy is advised.
Therapy for malignant rhabdoid tumor is intensive and requires a multidisciplinary effort.
Practitioners who should be consulted include the following:
Pediatric surgeon or urologist
Pediatric clinical geneticist or genetics counselor
No dietary restrictions are necessary. The patient's nutritional status should be closely monitored to ensure adequate caloric intake during the intensive chemotherapy. Parenteral nutrition may be required at some point during treatment.
No restrictions on activity are necessary except during periods of thrombocytopenia. Standard neutropenic precautions should be employed when appropriate.
Haas JE, Palmer NF, Weinberg AG, Beckwith JB. Ultrastructure of malignant rhabdoid tumor of the kidney. A distinctive renal tumor of children. Hum Pathol. 1981 Jul. 12(7):646-57. [Medline].
Jackson EM, Sievert AJ, Gai X, et al. Genomic analysis using high-density single nucleotide polymorphism-based oligonucleotide arrays and multiplex ligation-dependent probe amplification provides a comprehensive analysis of INI1/SMARCB1 in malignant rhabdoid tumors. Clin Cancer Res. Mar 2009. 15:1923-30. [Medline]. [Full Text].
Kohashi K, Oda Y, Yamamoto H, et al. SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma. Am J Surg Pathol. Aug 2008. 32:1168-74. [Medline].
Cheng JX, Tretiakova M, Gong C, Mandal S, Krausz T, Taxy JB. Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression as markers of aggressive behavior. Mod Pathol. Jun 2008. 21:647-52. [Medline].
Kreiger PA, Judkins AR, Russo PA, et al. Loss of INI1 expression defines a unique subset of pediatric undifferentiated soft tissue sarcomas. Mod Pathol. Jan 2009. 22:142-50. [Medline].
Trobaugh-Lotrario AD, Tomlinson GE, Finegold MJ, Gore L, Feusner JH. Small cell undifferentiated variant of hepatoblastoma: adverse clinical and molecular features similar to rhabdoid tumors. Pediatr Blood Cancer. Mar 2009. 52:328-34. [Medline].
Russo P, Biegel JA. SMARCB1/INI1 alterations and hepatoblastoma: another extrarenal rhabdoid tumor revealed?. Pediatr Blood Cancer. Mar 2009. 52:312-3. [Medline].
Reinhard H, Reinert J, Beier R, et al. Rhabdoid tumors in children: prognostic factors in 70 patients diagnosed in Germany. Oncol Rep. Mar 2008. 19:819-23. [Medline].
Mestre-Fusco A, Trampal C, Intriago B, Wessling H, Fuertes J, Suárez-Piñera M, et al. Assessment of rhabdoid brain tumor by F-18 FDG PET, C-11 methionine PET and MRI. Clin Nucl Med. 2012 Feb. 37(2):e33-5. [Medline].
Hilden JM, Meerbaum S, Burger P, et al. Central nervous system atypical teratoid/rhabdoid tumor: results of therapy in children enrolled in a registry. J Clin Oncol. 2004 Jul 15. 22(14):2877-84. [Medline].
Tekautz TM, Fuller CE, Blaney S, et al. Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. J Clin Oncol. 2005 Mar 1. 23(7):1491-9. [Medline].
Koga Y, Matsuzaki A, Suminoe A, et al. Long-term survival after autologous peripheral blood stem cell transplantation in two patients with malignant rhabdoid tumor of the kidney. Pediatr Blood Cancer. Jul 2009. 52:888-90. [Medline].
Furtwängler R, Nourkami-Tutdibi N, Leuschner I, Vokuhl C, Niggli F, Kager L, et al. Malignant rhabdoid tumor of the kidney: significantly improved response to pre-operative treatment intensified with doxorubicin. Cancer Genet. 2014 Jul 18. [Medline].
Agarwala S. Primary Malignant Liver Tumors in Children. Indian J Pediatr. 2012 Mar 1. [Medline].
Agrons GA, Kingsman KD, Wagner BJ, Sotelo-Avila C. Rhabdoid tumor of the kidney in children: a comparative study of 21 cases. AJR Am J Roentgenol. 1997 Feb. 168(2):447-51. [Medline].
Amar AM, Tomlinson G, Green DM, et al. Clinical presentation of rhabdoid tumors of the kidney. J Pediatr Hematol Oncol. 2001 Feb. 23(2):105-8. [Medline].
Biegel JA, Fogelgren B, Wainwright LM, et al. Germline INI1 mutation in a patient with a central nervous system atypical teratoid tumor and renal rhabdoid tumor. Genes Chromosomes Cancer. 2000 May. 28(1):31-7. [Medline].
Biegel JA, Zhou JY, Rorke LB, et al. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999 Jan 1. 59(1):74-9. [Medline].
Bruch LA, Hill DA, Cai DX, et al. A role for fluorescence in situ hybridization detection of chromosome 22q dosage in distinguishing atypical teratoid/rhabdoid tumors from medulloblastoma/central primitive neuroectodermal tumors. Hum Pathol. 2001 Feb. 32(2):156-62. [Medline].
Burger PC, Yu IT, Tihan T, et al. Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric Oncology Group study. Am J Surg Pathol. 1998 Sep. 22(9):1083-92. [Medline].
Chai J, Charboneau AL, Betz BL, Weissman BE. Loss of the hSNF5 gene concomitantly inactivates p21CIP/WAF1 and p16INK4a activity associated with replicative senescence in A204 rhabdoid tumor cells. Cancer Res. 2005 Nov 15. 65(22):10192-8. [Medline].
Chai J, Lu X, Godfrey V, et al. Tumor-specific cooperation of retinoblastoma protein family and Snf5 inactivation. Cancer Res. Apr 2007. 67:3002-9. [Medline].
Chung CJ, Lorenzo R, Rayder S, et al. Rhabdoid tumors of the kidney in children: CT findings. AJR Am J Roentgenol. 1995 Mar. 164(3):697-700. [Medline].
D'Angio GJ, Breslow N, Beckwith JB, et al. Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study. Cancer. 1989 Jul 15. 64(2):349-60. [Medline].
Fruhwald MC, Hasselblatt M, Wirth S, et al. Non-linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome. Pediatr Blood Cancer. 2006 Sep. 47(3):273-8. [Medline].
Fujisawa H, Misaki K, Takabatake Y, et al. Cyclin D1 is overexpressed in atypical teratoid/rhabdoid tumor with hSNF5/INI1 gene inactivation. J Neurooncol. 2005 Jun. 73(2):117-24. [Medline].
Gururangan S, Bowman LC, Parham DM, et al. Primary extracranial rhabdoid tumors. Clinicopathologic features and response to ifosfamide. Cancer. 1993 Apr 15. 71(8):2653-9. [Medline].
Han TI, Kim MJ, Yoon HK, et al. Rhabdoid tumour of the kidney: imaging findings. Pediatr Radiol. 2001 Apr. 31(4):233-7. [Medline].
Hoot AC, Russo P, Judkins AR, et al. Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors. Am J Surg Pathol. 2004 Nov. 28(11):1485-91. [Medline].
Isakoff MS, Sansam CG, Tamayo P, et al. Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Proc Natl Acad Sci U S A. 2005 Dec 6. 102(49):17745-50. [Medline].
Jafri SZ, Freeman JL, Rosenberg BF, et al. Clinical and imaging features of rhabdoid tumor of the kidney. Urol Radiol. 1991. 13(2):94-7. [Medline].
Janson K, Nedzi LA, David O, et al. Predisposition to atypical teratoid/rhabdoid tumor due to an inherited INI1 mutation. Pediatr Blood Cancer. 2006 Sep. 47(3):279-84. [Medline].
Kordes U, Gesk S, Fruhwald MC, et al. Clinical and molecular features in patients with atypical teratoid rhabdoid tumor or malignant rhabdoid tumor. Genes Chromosomes Cancer. 2010 Feb. 49(2):176-81. [Medline].
Madigan CE, Armenian SH, Malogolowkin MH, Mascarenhas L. Extracranial malignant rhabdoid tumors in childhood: the Childrens Hospital Los Angeles experience. Cancer. Nov 2007. 110:2061-6. [Medline].
Parham DM, Weeks DA, Beckwith JB. The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy. [published erratum appears in Am J Surg Pathol. 1995;19(4):488-9.]. Am J Surg Pathol. 1994 Oct. 18(10):1010-29. [Medline].
Puri DR, Meyers PA, Kraus DH, Laquaglia MP, Wexler LH, Wolden SL. Radiotherapy in the multimodal treatment of extrarenal extracranial malignant rhabdoid tumors. Pediatr Blood Cancer. Jan 2008. 50:167-9. [Medline].
Reddy AT. Atypical teratoid/rhabdoid tumors of the central nervous system. J Neurooncol. 2005 Dec. 75(3):309-13. [Medline].
Roberts CW, Galusha SA, McMenamin ME, et al. Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice. Proc Natl Acad Sci U S A. 2000 Dec 5. 97(25):13796-800. [Medline].
Roberts CW, Leroux MM, Fleming MD, Orkin SH. Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5. Cancer Cell. 2002 Nov. 2(5):415-25. [Medline].
Rorke LB, Packer RJ, Biegel JA. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg. 1996 Jul. 85(1):56-65. [Medline].
Rousseau-Merck MF, Fiette L, Klochendler-Yeivin A, et al. Chromosome mechanisms and INI1 inactivation in human and mouse rhabdoid tumors. Cancer Genet Cytogenet. 2005 Mar. 157(2):127-33. [Medline].
Rousseau-Merck MF, Versteege I, Legrand I, et al. hSNF5/INI1 inactivation is mainly associated with homozygous deletions and mitotic recombinations in rhabdoid tumors. Cancer Res. 1999 Jul 1. 59(13):3152-6. [Medline].
Sigauke E, Rakheja D, Maddox DL, et al. Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis. Mod Pathol. 2006 May. 19(5):717-25. [Medline].
Sisler CL, Siegel MJ. Malignant rhabdoid tumor of the kidney: radiologic features. Radiology. 1989 Jul. 172(1):211-2. [Medline].
Tomlinson GE, Breslow NE, Dome J, et al. Rhabdoid tumor of the kidney in the National Wilms' Tumor Study: age at diagnosis as a prognostic factor. J Clin Oncol. 2005 Oct 20. 23(30):7641-5. [Medline].
Tsikitis M, Zhang Z, Edelman W, et al. Genetic ablation of Cyclin D1 abrogates genesis of rhabdoid tumors resulting from Ini1 loss. Proc Natl Acad Sci U S A. 2005 Aug 23. 102(34):12129-34. [Medline].
Versteege I, Sevenet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998 Jul 9. 394(6689):203-6. [Medline].
Wagner L, Hill DA, Fuller C, et al. Treatment of metastatic rhabdoid tumor of the kidney. J Pediatr Hematol Oncol. 2002 Jun-Jul. 24(5):385-8. [Medline].
Waldron PE, Rodgers BM, Kelly MD, Womer RB. Successful treatment of a patient with stage IV rhabdoid tumor of the kidney: case report and review. J Pediatr Hematol Oncol. 1999 Jan-Feb. 21(1):53-7. [Medline].
Weeks DA, Beckwith JB, Mierau GW, Luckey DW. Rhabdoid tumor of kidney. A report of 111 cases from the National Wilms' Tumor Study Pathology Center. Am J Surg Pathol. 1989 Jun. 13(6):439-58. [Medline].
Weeks DA, Beckwith JB, Mierau GW, Zuppan CW. Renal neoplasms mimicking rhabdoid tumor of kidney. A report from the National Wilms' Tumor Study Pathology Center. Am J Surg Pathol. 1991 Nov. 15(11):1042-54. [Medline].
Winger DI, Buyuk A, Bohrer S, et al. Radiology-Pathology Conference: rhabdoid tumor of the kidney. Clin Imaging. 2006 Mar-Apr. 30(2):132-6. [Medline].
Yamamoto M, Suzuki N, Hatakeyama N, et al. Treatment of stage IV malignant rhabdoid tumor of the kidney (MRTK) with ICE and VDCy: a case report. J Pediatr Hematol Oncol. May 2006. 28:286-9. [Medline].
Zhang ZK, Davies KP, Allen J, et al. Cell cycle arrest and repression of cyclin D1 transcription by INI1/hSNF5. Mol Cell Biol. 2002 Aug. 22(16):5975-88. [Medline].
|Carboplatin||Target dose to the AUC of 6 mg/mL/min by using the Calvert equation||IV||Day 1|
|Etoposide||3.3 mg/kg/dose or 100 mg/m2/dose||IV||Days 1, 2, and 3|
|Ifosfamide||65 mg/kg/dose or 2 g/m2/dose||IV||Days 1, 2, and 3|
|Mesna||16 mg/kg/dose or 500 mg/m2/dose||IV||Start immediately after and at 3 h, 6 h, and 9 h after ifosfamide|
|Filgrastim G-CSF||5 mcg/kg/dose||SC||Start 24 h after chemotherapy and continue until ANC recovers|
|Vincristine||0.05 mg/kg/dose or 1.5 mg/m2/dose; not to exceed 2 mg/dose||IV||Days 1, 8, and 15|
|Doxorubicin||1.2 mg/kg/dose or 37.5 mg/m2/dose||IV||Days 1 and 2|
|Cyclophosphamide||60 mg/kg/dose or 1.8 g/m2/dose||IV||Day 1|
|Mesna||15 mg/kg/dose or 450 mg/m2/dose||IV||Start immediately after and at 3, 6, and 9 h after cyclophosphamide|
|Filgrastim G-CSF||5 mcg/kg/dose||SC||Start 24 h after chemotherapy and continue until ANC recovers|