Prospective Study on Pediatric Patients with Atypical
Teratoid Rhabdoid Tumors (ATRT) of the Central
Nervous System (CNS)
1
Chang ,
John Han-Chih
Michael
Andrew
3
1
1
Stewart Goldman , Megan Dunn , William Hartsell .
1CDH
2
Confer ,
2
Chang ,
2Procure
Proton Center,
Proton Therapy Center – Oklahoma City,
3Anne and Robert H. Lurie Children’s Hospital of Chicago.
Background/Purpose
ATRT is a rare and aggressive CNS tumor usually
presenting in very young children (age less than 5
years). Aggressive treatments have improved
outcomes. Such strategies have included radiation
therapy as studies have demonstrated the benefit of
instituting radiation early in the treatment course.
However, at such a young age, short and long term
radiation toxicities can be devastating. We
prospectively enrolled pediatric CNS ATRT patients
onto the Proton Collaborative Group registry protocol
to evaluate the efficacy and toxicities of proton
radiation therapy in this population.
Materials and Methods
Twelve consecutive pediatric ATRT patients were
treated with at the Central DuPage Hospital Proton
Center (n = 7) and the Procure Proton Therapy Center
– Oklahoma City (n = 5) between March 2010 –
December 2013 utilizing 3D Conformal Proton
Therapy. Eight patients were treated per the DanaFarber Cancer Institute protocol approach, while 4
were treated either on or per Children’s Oncology
Group Protocol ACNS 0333. Survival data was
calculated from the date of diagnosis, while follow up
interval was analyzed from last day of radiation
therapy.
Results
All twelve patients were evaluable. They were all 3
years of age or younger (range 4.4 – 37.7 months).
Seven patients had gross total resections, while 4
had subtotal resections along with another 1 not
documented. All patients received multiagent
intensive chemotherapy. Radiation was to local
fields for 9 patients, while 3 had craniospinal
irradiation. The median follow up was 14.2 months
at our last update (range of 1 – 43 months). At last
follow up 10 patients were alive without evidence
of disease. The other 2 children died of progressive
disease at 9.3 and 24.7 months from diagnosis.
Median overall survival was 21 months (range of
4.9 – 49.2 months). All patients received the
intended course of therapy to 50 – 54 Cobalt Gray
Equivalent (CGE). Proton therapy was able to
reduce the dose to the cochlea, optic chiasm,
hippocampus, and integral whole brain dose
relative to historic controls. Only 4 children had
grade 3 toxicities during radiation therapy (all were
acute nausea, vomiting and anorexia that responded
to steroids).
Average (CGE) Median (CGE) Range (CGE)
Planned Target Volume Dose
52.34
54.12
50.5 – 54.34
Mean Cochlear Dose
9.15
1.97
0 – 36.3
Maximum Chiasm Dose
25.67
36.62
0 – 50.02
Mean Hippocampus Dose
22.14
24.5
0 – 54.94
Table 1: Doses to Target Volume and Critical OAR
Conclusion
A
B
C
D
Figures A & B: Proton Treatment Plan for a 2 year old with Left Frontal ATRT
Figures C & D: Proton Treatment Plan for a 2 year old with 4th Ventricular ATRT
The initial results on the largest prospective series of
CNS ATRT patients treated with proton therapy seem
to be favorable. The aggressive treatment regimens
utilizing proton beam therapy yield proven efficacy
and improved acute toxicity profiles, which is
critically important in this young patient population
with such an aggressive disease. We look forward to
continuing patient treatments and follow up on long
term quality of life measures.