Atypical Teratoid/rhabdoid Tumors: Challenges and Search for Solutions

the ONA take:

Atypical teratoid/rhabdoid tumor (AT/RT) is a very rate, highly malignant cancer of the central nervous system, with about half of these tumors forming in the cerebellum or brain stem. Although it typically occurs in children aged 3 years and younger, it can occur in older children and adults.

Clinical features of AT/RT depend on the age of the patient and location of the tumor. Patients typically present with headache, vomiting, fatigue, irritability, failure to thrive, regression of developmental milestones, and in very young children, macrocephaly may be observed.

Chemotherapy is a vital component of multimodality treatment of patients with AT/RT. Two backbones of adjuvant chemotherapy, Children’s Cancer Group (CCG)-9921 and Intergroup Rhabdomyosarcoma III (IRS III), have demonstrated activity in this population. The CCG-9921 induction regimen is a 4-drug combination consisting of vincristine, cisplatin, cyclophosphamide, and etoposide, or vincristine, carboplatin, ifosfamide, and etoposide. The IRS III regimen consists of vincristine, cisplatin, doxorubicin, cyclophosphamide, dacarbazine, etoposide, actinomycin-D, and intrathecal administration of methotrexate, cytarabine, and hydrocortisone.

Adding radiotherapy has been shown to improve overall survival in patients with AT/RT; therefore, clinicians should include radiotherapy as part of multimodality management. Children older than 3 years should also receive craniospinal irradiation followed by boost to tumor bed using helical tomotherapy or proton beam therapy.

Cancer Management and Research
Cancer Management and Research

Abstract: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal central nervous system tumor commonly affecting children <3 years of age. It roughly constitutes 1%–2% of all pediatric central nervous system tumors. Recent data show that it is the most common malignant central nervous system tumor in children <6 months of age. Management of this aggressive tumor is associated with a myriad of diagnostic and therapeutic challenges. On the basis of radiology and histopathology alone, distinction of AT/RT from medulloblastoma or primitive neuroectodermal tumor is difficult, and hence this tumor has been commonly misdiagnosed as primitive neuroectodermal tumor for decades. Presence of a bulky heterogeneous solid-cystic mass with readily visible calcification and intratumor hemorrhage, occurring off-midline in children <3 years of age, should alert the radiologist toward the possibility of AT/RT. Presence of rhabdoid cells on histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal, and neuroectodermal markers along with loss of expression of SMARCB1/INI1 or SMARCA4/BRG1 help in establishing a diagnosis of AT/RT. The optimal management comprises maximal safe resection followed by radiation therapy and multiagent intensive systemic chemotherapy. Gross total excision is difficult to achieve in view of the large tumor size and location and young age at presentation. Leptomeningeal spread is noted in 15%–30% of patients, and hence craniospinal irradiation followed by boost to tumor bed is considered standard in children older than 3 years. However, in younger children, craniospinal irradiation may lead to long-term neurocognitive and neuroendocrine sequel, and hence focal radiation therapy may be a pragmatic approach. In this age group, high-dose chemotherapy with autologous stem cell rescue may also be considered to defer radiation therapy, but this approach is also associated with significant treatment-related morbidity and mortality. Novel small molecule inhibitors hold promise in preclinical studies and should be considered in patients with relapsed or refractory tumor.


Keywords: atypical teratoid/rhabdoid tumor, intracranial, medulloblastoma, primitive neuroectodermal tumor 
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