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Necrosis after craniospinal irradiation: results from a prospective series of children with central nervous system embryonal tumors.

ABSTRACT: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series.Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis.With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% ± 1.3% (n = 236) for the entire cohort and 4.4% ± 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: ? 50 Gy (92.12% ± 4.58% vs 72.89% ± 1.96%; P=.0337), ? 52 Gy (88.95% ± 5.50% vs 69.16% ± 1.97%; P=.0275), and ? 54 Gy (82.28% ± 7.06% vs 63.37% ± 1.96%; P=.0488), respectively.Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.

SUBMITTER: Murphy ES

PROVIDER: S-EPMC3529413 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Necrosis after craniospinal irradiation: results from a prospective series of children with central nervous system embryonal tumors.

Murphy Erin S ES Merchant Thomas E TE Wu Shengjie S Xiong Xiaoping X Lukose Renin R Wright Karen D KD Qaddoumi Ibrahim I Armstrong Gregory T GT Broniscer Alberto A Gajjar Amar A

International journal of radiation oncology, biology, physics 20120801 5

<h4>Purpose</h4>Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series.<h4>Patients and methods</h4>Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n ...[more]

PMID: 22768993

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Project description:BackgroundSurvivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.MethodsIntelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups.ResultsParticipants were mostly males (65%) diagnosed with embryonal tumors (98%) at a median age of 8.3 years. Overall, 1150 neurocognitive evaluations were obtained (median = 5, range: 2-10 per participant). One of the five loci previously associated with cognitive outcomes in pediatric CNS tumors survivors demonstrated significant time-dependent IQ declines (PPARA rs6008197, P = .004). Two variants associated with IQ in the general population were associated with declines in IQ after Bonferroni correction (rs9348721, P = 1.7 × 10-5; rs31771, P = 7.8 × 10-4). In genome-wide analyses, we identified novel loci associated with accelerated declines in IQ (rs116595313, meta-P = 9.4 × 10-9), WM (rs17774009, meta-P = 4.2 × 10-9), and PS (rs77467524, meta-P = 1.5 × 10-8; rs17630683, meta-P = 2.0 × 10-8; rs73249323, meta-P = 3.1 × 10-8).ConclusionsInherited genetic variants involved in baseline cognitive functioning and novel susceptibility loci jointly influence the degree of treatment-associated cognitive decline in pediatric CNS tumor survivors.

Dataset Information

Necrosis after craniospinal irradiation: results from a prospective series of children with central nervous system embryonal tumors.

Publications

Necrosis after craniospinal irradiation: results from a prospective series of children with central nervous system embryonal tumors.

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