September 16, 2015
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Gross total resection improves outcomes for pediatric high-grade gliomas, especially among females

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Gross total resection improved OS for pediatric patients with glioblastoma multiforme and anaplastic astrocytoma, according to results of a retrospective analysis.

This association appeared strongest among female patients, results also showed.

It was previously assumed that pediatric high-grade gliomas were comparable to adult high-grade gliomas. However, genomic studies have demonstrated differences in the two patient populations, and researchers have been seeking data to better define treatment algorithms for pediatric patients.

Jeffrey P. Greenfield, MD, PhD, a pediatric neurosurgeon at NewYork-Presbyterian and Weill Cornell Medical Center, and colleagues sought to identify factors contributing to OS and PFS in a pediatric population.

The investigators retrospectively identified 97 patients (median age, 11 years) with high-grade gliomas aged 21 or younger at the time of their diagnosis at Memorial Sloan Kettering Cancer Center between 1988 and 2010.

The median OS for the cohort was 1.7 years (95% CI, 1.3-2.4) and the median PFS was 0.7 years (95% CI, 0.52-1.09). Forty-five percent (95% CI, 34-56) of the patients achieved 2-year OS, and 25% (95% CI, 16-34) remained progression-free at 2 years.

In a univariate analysis, improved PFS appeared associated with age 3 years and younger or 13 years or older (P = .003) and female sex (P = .001). Results of a multivariate analysis indicated tumor type (P = .03), age at diagnosis (P = .002) and sex (P = .001) significantly affected PFS.

OS appeared significantly associated with tumor location, extent of resection and sex. Median OS was longer among children with supratentorial tumors (2.4 years; 95% CI, 1.5-3.4) and cerebellar tumors (1.9 years; 95% CI, 1-6.1) than children with brain stem tumors (1 year; 95% CI, 0.4-1.5) and thalamic tumors (1.3 years; 95% CI, 0.9-1.8; P ˂ .001).

Thirty-three percent of patients achieved a gross total resection.

Results of a post-hoc analysis showed gross tumor resection improved median PFS for females (2.9 years vs. 0.9 years) but not males (0.5 years vs. 0.6 years; P = .002).

Patients who had a gross total resection achieved significantly longer median OS (3.4 years: 95% CI, 1.4-8.1) than patients with a subtotal resection (1.6 years; 95% CI, 1.1-2.3) and biopsy patients (1.3 years; 95% CI, 1-1.7).

Median OS was 2.4 years (95% CI, 1.3-4.7) among female patients and 1.4 years (95% CI, 1-1.9) among male patients (P = .01).

Although both males and females derived benefit from more aggressive surgery, females who received a gross total resection had a superior benefit compared with males. Median OS was 8.1 years (95% CI, 2.9-no upper limit) among females who received gross total resection, compared with 1.4 years (95% CI, 1.1-2.6) among all other females, 2.4 years (95% CI, 1-4) among males who had a gross total resection, and 1.4 years (95% CI, 0.9-1.9) among all other males (P = .001).

“Our study provides strong evidence in support of an attempt at gross total resection over subtotal resection or biopsy, and demonstrates that age, tumor location and sex are important prognostic factors in pediatric high-grade glioma,” Greenfield and colleagues wrote. “Additionally, our article provides compelling evidence that gross total resection is even more critical in female patients.”

The inclusion of high-grade gliomas with unspecific tumor grade or tumors with oligodendroglial components in the outcomes may confound interpretation of these results, Tomas Garzon-Muvdi, MD, neurosurgeon resident at Johns Hopkins Medicine, and George Jallo, MD, clinical director of pediatric neurosurgery and professor of neurosurgery at The Johns Hopkins Children’s Center, wrote in an accompanying comment.

“Furthermore, there was no analysis of the survival according to the type of adjuvant therapy, leaving a void in the examination,” they wrote. “Overall, this study redemonstrates the findings of analysis of cohorts of adult patients. It also emphasizes the need of thorough molecular analysis of pediatric anaplastic astrocytomas and glioblastomas to obtain more meaningful information and guide therapy for pediatric patients with primary malignant brain tumors.” – by Anthony SanFilippo

Disclosure: The researchers, Garzon-Muvdi and Jallo report no relevant financial disclosures.

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