# Radiation Oncology/Peds/ATRT
## Epidemiology

* Estimated 2-3% of primary CNS tumors in <18 population.
* Majority of patients present at age <3 yrs.
* A workshop on ATRT (PMID 12142780) reported that pathologic review of a recent CCG study suggests ATRT may represent a significant proportion of brain tumors in children <3 yrs old.

## Diagnosis

* Major diagnostic dilemma is distinguishing from medulloblastoma.
* IHC necessary for diagnosis (vimentin, EPA, and SMA found in rhabdoid tumors but not medulloblastoma)
* INI1 gene mutated in ~85% of ATRT.

## Treatment

* Treatment strategy includes maximum surgical debulking, chemotherapy and radiation therapy.

### Radiation Therapy

* Neurological Institute, Taipei, 2006 (1990-2003) - PMID 16406394 -- "Impact of radiotherapy for pediatric CNS atypical teratoid/rhabdoid tumor (single institute experience)." Chen YW et al. Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1038-43.
** 17 pts w/ ATRT who received radiotherapy as part of their treatment regimen.
** Time interval b/w surgery and RT initiation was important prognostic factor on multi-variate analysis for overall survival.
** No difference in OS was seen for patients receiving > or < 50Gy
* St. Jude's, 2005 (1984-2003) - PMID 15735125 -- "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.
** 37 pts w/ ATRT (22 pts 3 yrs or younger)
** Majority of pts >3 yrs received CSI.
** 2yr OS was significantly better for pts >3 yrs old.
** The only survivors who were <3 y/o received RT as part of their tx.
* Boston Regimen - PMID 15803379 -- "Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor."
** Early pilot data, reported in detail in:
* "'The DFCI study (02-294)"' - PMID: 19064966 -- "Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor." (2008) had the following design:
* Following diagnosis, patients underwent maximal surgical resection. Patients were reported as GTR, Subtotal or biopsy according to surgical opinion and MRI after surgery. • All patients underwent brain and spine MRI, CSF examination, CT chest and abdomen, bone marrow aspiration and trephine. Staging was according to that of Chang (REF) • Chemotherapy was begun within 50 days of surgery. Blocks of chemotherapy were given as follow: 1/ Pre-irradiation induction (weeks 1-6) 2/ Chemo-radiation induction (weeks 7-12) 3/ Post-irradiation induction (weeks 13-18 4/ Maintenance (weeks 19-44) 5/ Continuation ± Doxorubicin (weeks 45-51) Outcome from this study
** Two year PFS was 53±13% and OS 70 ±10%.
** 20 evaluable patients: 14 M0, 1 M2 and 5 M3.
** 1 treatment-related death, 4 PD in the first 13 weeks, 1 radiation recall, 1 transverse myelitis.
** Metastatic stage was prognostic. Eight of fourteen patients with localized disease were alive, NED. One patient with M2 disease remained alive with disease. Four of five with M3 disease died of disease, but one achieved CR with induction chemotherapy, received CSRT and remained alive, NED.
** The degree of surgical resection was of prognostic value.
Three patients underwent biopsy alone, and all died rapidly. Five of seven who had subtotal resection and 9/10 who had gross total resection were alive at the time of publication.
** Response to chemotherapy was prognostic. Seven of seven in continued CR, and a further 2 of 2 who achieved CR after induction chemotherapy were alive with NED at publication. One of 6 with a mixed or PR remained alive (with disease). This patient had stable disease after radiotherapy. Three patients had stable disease after induction. One achieved CR after RT and remained alive, NED. One had continued SD after RT, and remained alive with disease. One progressed after RT and died.
Fifteen patients received RT on study, 11 focal and 4 craniospinal. Status after radiotherapy was prognostic. All ten patients in CCR (n=9) or CR (n=1) after RT were alive, although one had ongoing disease. Two patients with persistent stable disease remained alive with disease. All others (n=8) had died.

## Reviews

* Brown; 2007 - PMID 16855864 — "Atypical teratoid/rhabdoid tumor: the controversy behind radiation therapy." (Squire SE, J Neurooncol. 2007 Jan;81(1):97-111.)