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Children with ependymoma experience favorable outcomes with immediate postoperative radiation
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Immediate postoperative radiation appeared associated with favorable outcomes among children with ependymoma who were aged as young as 12 months, according to prospective study results presented at the ASTRO annual meeting.
These outcomes were consistent with single institution benchmarks and associated with known prognostics factors of extent of resection and tumor grade, according to researchers.
Thomas E. Merchant
Many children with ependymoma — a rare tumor of the brain and spinal cord that stems from tissue in the central nervous system — are diagnosed when aged younger than 3 years.
Thomas E. Merchant, DO, PhD, the Baddia J. Rashid endowed chair in radiation oncology at St. Jude Children’s Research Hospital, and colleagues of the Children’s Oncology Group conducted the largest prospective trial for pediatric ependymoma and the first to target the postoperative tumor bed using 3D conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT).
The study also was the first to use immediate postoperative radiation therapy in children aged younger than 3 years in this setting because prior studies did not include radiation therapy as a front-line treatment option for very young children.
Merchant and colleagues sought to reduce the volume of radiation therapy and decrease the risk for side effects without affecting the rate of tumor control.
The analysis included data from 378 newly diagnosed patients (median age, 5.3 years; range, 1.01-21.01 years) from 115 institutions who enrolled between 2003 and 2007. Patients had WHO grade II (n = 216) or grade III (n = 140) tumors and enrolled within 56 days following initial surgery.
The investigators treated the patients according to their assigned subgroup:
- Those who were grade II with supratentorial ependymoma following microscopically complete surgical resection were observed (stratum 1; n = 11);
- Those who were grade II with subtotal resection at time of enrollment received chemotherapy with an optional second surgery prior to 3D-CRT (stratum 2; n = 64);
- Those who were grade II with near-total (< 5 mm residual thickness) or macroscopic gross-total resection received immediate, postoperative 3D-CRT (stratum 3); and
- Those with grade III tumors following microscopically complete total resection received immediate, postoperative 3D-CRT (stratum 4).
Five patients in stratum 1 experienced progression. The 5-year EFS in this cohort was 61.4% + 14.4%.
Twenty-five patients in stratum 2 underwent a second surgery, 14 of whom achieved a gross total resection. However, researchers observed no difference in EFS between those who underwent the second surgery and those who did not. The EFS for the entire stratum 2 cohort was 39.2% + 7%.
EFS was 67.3% + 4.5% for stratum 3 and 69.5% + 3.8% for stratum 4. These cohorts included a total of 281 treated patients, for whom the EFS was 74.6% + 3.6% for those with grade 2 tumors and 60.7% + 4.7% for those with grade 3 tumors (P = .0047).
“These results indicate that radiation therapy may be safely administered to children of all ages with ependymoma and high-rates of tumor control may be achieved for the majority of children,” Merchant said in a press release. “All children with ependymoma should receive expert care and treatment teams should follow protocol guidelines similar to those used in this study with consideration given to the importance of gross-total tumor resection and advances in radiation therapy methods.
“Other treatments, in addition to surgery and radiation therapy, should be investigated to further increase the rate of tumor control.” – by Anthony SanFilippo
For more information: Merchant TE, et al. Abstract 1. Presented at: ASTRO Annual Meeting; Oct. 18-21, 2015; San Antonio, Texas.
Disclosure: HemOnc Today was unable to confirm the researchers’ relevant financial disclosures at the time of reporting.
Perspective
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Erin Murphy, MD
For ependymoma, the most common site of recurrence is local, which is why the treatment paradigm includes surgical resection and adjuvant radiotherapy. At ASTRO 2015, Tom Merchant, DO, PhD, from St. Jude Children’s Research Hospital, presented data from Children’s Oncology Group trial ACNS 0121.
This Phase 2 trial had several postoperative treatment strategies that were based on location of tumor and extent of tumor resection:
- Stratum 1: Patients with supratentorial WHO grade II ependymoma were observed after a microscopically complete resection.
- Stratum 2: Patients enrolled on trial after subtotal resection received chemotherapy — two 3-week cycles of vincristine, carboplatin, and cyclophosphamide (cycle 1) and etoposide (cycle 2) — and then underwent optional second look surgery.
- Stratum 3 and 4: Patients who underwent a near total resection or better received immediate postoperative conformal radiotherapy and were stratified based on degree of resection.
This trial accrued well with 216 children with WHO grade II and 140 children with WHO grade III tumors enrolled. The results compared well to the benchmark St. Jude Children’s Research Hospital data, of 87.3% 7-year year local control, 69% EFS and 81% OS for children with ependymoma treated with postoperative radiotherapy. Of note, participating institutions should be commended for very good adherence to trial radiotherapy guidelines.
In conclusion, ACNS 0121 supports that for children as young as 12 months of age with ependymoma, current standard of care is maximal safe resection followed by immediate postoperative radiotherapy. After subtotal resection, chemotherapy can be considered as a bridge to a second resection with the goal of improving rates of gross total resection. Extent of surgical resection and tumor grade are known prognostic factors confirmed by this trial. Observation for grade II supratentorial ependymoma following gross total resection is not considered standard at this time.
References:
Merchant TE, et al. Int J Radiat Oncol Biol Phys. 2002;doi:10.1016/S0360-3016(01)02801-2.
Merchant TE, et al. Int J Radiat Oncol Biol Phys. 2015;doi:10.1016/j.ijrobp.2015.07.009.
Merchant TE, et al. Lancet Oncol. 2009;doi:10.1016/S1470-2045(08)70342-5.
Pollack IF, et al. Neurosurg. 1995:37:655-666.
Rousseau P, et al. Int J Radiat Oncol Biol Phys. 1994:28:381-386.
van Veelen-Vincent ML, et al. J Neurosurg. 2002;97:827-835.
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