Atypical teratoid/rhabdoid tumor: the controversy behind radiation therapy

Abstract

To date, approximately 200 cases of atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system have been described in the literature. This CNS tumor tends to present at an age of less than 3 years, and most patients succumb to their disease within 1 year of diagnosis. Prior to the rise in utilization of immunohistochemical (IHC) testing in the late 1990s, this tumor was likely mistaken as medulloblastoma and treated as such. However, lessons learned from regimens based upon medulloblastoma have revealed that AT/RT requires more aggressive treatment. A significant portion of patients die of local recurrence in spite of aggressive surgery and chemotherapy. As most patients with AT/RT present as infants or young children, radiation therapy has been a less than standard treatment option. However, recent evidence suggests that long-term survival can occur with use of more aggressive treatment approaches including dose-intense chemotherapy as well as adjuvant radiation therapy. A standardized and effective approach to treating this usually fatal tumor remains elusive, and the role of radiation therapy presents a particular dilemma as young patients with this disease may experience devastating late effects of therapy if they achieve a long-term survival. Review of the literature reveals an association between initial radiation therapy and the ability to achieve a prolonged survival. Our review underscores the importance or enrolling patients in multi-institutional prospective studies to further investigate the value of radiation to treat this pediatric neoplasm.

Survival outcomes in atypical teratoid rhabdoid tumor for patients undergoing radiotherapy in a Surveillance, Epidemiology, and End Results analysis

“…5,11,14 Children aged <3 years constitute the majority of patients who are diagnosed with ATRT. RT in these patients historically has been delayed given the vulnerability to adverse neurocognitive effects on the developing brain.…”

“…[1][2][3][4][5] ATRT is extremely rare in adults, and only 31 patients have been reported in the literature. 6 Originally described in the 1980s, ATRT has been widely recognized as a rare but important clinical entity only over the past decade.…”

“…2,4 The diagnosis of ATRT has been greatly facilitated by the rise in accessibility of immunohistochemical testing in the late 1990s, which takes advantage of the frequent loss of switch/sucrose nonfermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1 (SMARCB1) (also known as SNF5 homolog [hSNF5] and INI1) tumor suppressor gene products in these tumors. 2,5,7 Although ATRT comprises <5% of CNS tumors in children aged <18 years, it reportedly represents up to 20% of CNS tumors in children aged <3 years. 1,4,8 However, it is believed that the true incidence may be higher because of misdiagnosis given similarities in imaging and histologic appearance to other high-grade embryonal CNS malignancies.…”

“…1,3,4,9,10 Therapeutic approaches for ATRT historically have relied on data from treatments of other childhood CNS tumors, particularly primitive neuroendocrine tumors and medulloblastoma, which have a considerably better prognoses. 5 However, preliminary results from the first prospective clinical trial in children with ATRT indicate that intensive multimodality treatment, including resection, CNS radiotherapy (RT), and chemotherapy based on the Intergroup Rhabdomyosarcoma Study Group (IRS) III protocol, may lead to longer survival, with an estimated 2-year OS survival rate of 70% AE 10%. 11 Although the use of RT has been controversial given the associated risk of adverse affects on neurocognitive development of young children, there is emerging nonrandomized evidence that RT may be important for the achievement of long-term survival in patients with ATRT.…”

“…11 Although the use of RT has been controversial given the associated risk of adverse affects on neurocognitive development of young children, there is emerging nonrandomized evidence that RT may be important for the achievement of long-term survival in patients with ATRT. 5,[10][11][12][13] Currently, there is no standard therapeutic regimen for ATRT outside of clinical trials. Given the rarity of ATRT, large retrospective analyses are important sources of information to guide the development of treatment strategies.…”