Atypical teratoid rhabdoid tumor: improved long-term survival with an intensive multimodal therapy and delayed radiotherapy. The Medical University of Vienna Experience 1992-2012

Abstract

Atypical teratoid rhabdoid tumors (ATRTs) are recently defined highly aggressive embryonal central nervous system tumors with a poor prognosis and no definitive guidelines for treatment. We report on the importance of an initial correct diagnosis and disease-specific therapy on outcome in 22 consecutive patients and propose a new treatment strategy. From 1992 to 2012, nine patients initially diagnosed correctly as ATRT (cohort A, median age 24 months) were treated according to an intensive multimodal regimen (MUV-ATRT) consisting of three 9-week courses of a dose-dense regimen including doxorubicin, cyclophosphamide, vincristine, ifosfamide, cisplatin, etoposide, and methotrexate augmented with intrathecal therapy, followed by high-dose chemotherapy (HDCT) and completed with local radiotherapy. Thirteen patients were treated differently (cohort B, median age 30 months) most of whom according to protocols in use for their respective diagnoses. As of July 2013, 5-year overall survival (OS) and event-free survival (EFS) for all 22 consecutive patients was 56.3 ± 11.3% and 52.9 ± 11.0%, respectively. For MUV-ATRT regimen-treated patients (cohort A) 5-year OS was 100% and EFS was 88.9 ± 10.5%. For patients treated differently (cohort B) 5-year OS and EFS were 28.8 ± 13.1%. All nine MUV-ATRT regimen-treated patients are alive for a median of 76 months (range: 16-197), eight in first complete remission. Our results compare favorably to previously published data. The drug combination and sequence used in the proposed MUV-ATRT regimen appear to be efficacious in preventing early relapses also in young children with M1-M3 stage disease allowing postponement of radiotherapy until after HDCT.

Keywords: ATRT; delayed local radiotherapy; high-dose chemotherapy; improved survival; multimodal therapy.

Figure 1

MUV-ATRT regimen for newly diagnosed ATRT patients. (A) Week 0–27. (B) Week 28–43 and cumulative doses. MUV-ATRT, Medical University of Vienna ATRT-protocol; ATRT, atypical teratoid rhabdoid tumor.

Figure 2

(A) Overall survival (OS) and (B) event-free survival (EFS) of ATRT patients treated according to the MUV-ATRT regimen versus other therapy protocols. OS after 1 year was 100% (MUV) versus 46.2 ± 13.8% (other), after 3 years 100% (MUV) versus 38.5 ± 13.5% (other), and after 5 years 100% (MUV) versus 28.8 ± 13.1% (other). EFS after 1 year was 100% (MUV) versus 46.2 ± 13.8% (other), after 3 years 88.9 ± 10.5% (MUV) versus 38.5 ± 13.5% (other), and after 5 years 88.9 ± 10.5% (MUV) versus 28.8 ± 13.1% (other). MUV-ATRT, Medical University of Vienna ATRT-protocol; ATRT, atypical teratoid rhabdoid tumor.