Clinical Investigations
Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes☆

First presented at the 8th Symposium of Pediatric Neurooncology in Rome, Italy, May 6–9, 1998.
https://doi.org/10.1016/S0360-3016(99)00177-7Get rights and content

Abstract

Purpose: To analyze the relationship between craniospinal irradiation (CSI) and intellectual outcome in children with posterior fossa (PF) tumors.

Methods and Materials: A neuropsychological evaluation was performed retrospectively in 31 children, aged 5–15 years, who had received radiotherapy for PF tumors, and who had been off therapy for at least 1 year. Factors evaluated for impact on intellectual outcome were: socioeconomic status, disease presentation, histology, complications, chemotherapy, age at radiotherapy, interval between radiotherapy and testing, and radiation doses and volumes. Patients were divided into 3 subgroups according to the CSI doses (0 Gy [ i.e., PF irradiation only], 25 Gy, and 35 Gy), with 11, 11, and 9 patients, respectively.

Results: Long-term cognitive impairment occurred in most of the patients, even after PF irradiation only. Moreover, there was a significant correlation between the full-scale IQ score (FSIQ) and the CSI dose, with mean FSIQ scores at 84.5 (SD = 14.0), 76.9 (SD = 16.6), and 63.7 (SD = 15.4) for 0 Gy, 25 Gy, and 35 Gy of CSI, respectively. A marked drop in verbal comprehension scores was noted in children who had received the higher dose.

Conclusion: This preliminary study further supports the rationale for de-escalation of CSI doses and volumes in standard-risk PF tumors.

Introduction

The oncologist’s prime objective of curing disease when treating children with malignant brain tumors is in conflict with another important goal, namely the preservation of the patient’s quality of life. With encouraging long-term remission rates attaining at least 50% at 5 years in multiple studies in children with posterior fossa medulloblastoma (MB) and ependymoma (EP) 1, 2, 3, 4, attention has recently been directed to the long-term effects of these tumors and their treatment. The reasons for sequelae in these patients are complex and not fully understood.

Cranial irradiation required for disease control has been incriminated as one of the major causes of long-term cognitive impairment. For the moment, it is difficult not to deliver irradiation, at least to the posterior fossa in these patients; however, most of the groups have decided to dispense with craniospinal irradiation (CSI) in children with localized ependymoma, because most relapses are exclusively local 4, 5. With the progress achieved in surgery and chemotherapy, many attempts have been made to lower the radiation dose for prophylaxis against metastasis in children with standard-risk medulloblastoma 1, 6, 7 or to replace it with high-dose chemotherapy (8). However, limited data have been provided by these studies on intellectual outcome. Hyperfractionation of radiotherapy is also under study (9); however, the benefits in terms of neuropsychological outcome have not yet been assessed. Updated reports on trials, in which decreased CSI doses were delivered to standard-risk patients, have shown that treatment failures are not necessarily increased when 25 Gy is used instead of 35 Gy 1, 6. However, studies on late effects do not confirm that the higher risk of disease failure and death is counterbalanced by a significantly improved intellectual outcome. Recently, a pilot study of reduced CSI (18 Gy) combined with 9 months of multiagent conventional chemotherapy suggested that intellectual function could be noticeably preserved in standard-risk MB patients (10). In a previous study, we confirmed the influence of the radiation volume on the intellectual outcome of children with posterior fossa tumors (11). As there is no valuable comparison to date concerning neuropsychological outcome in children with PF tumors according to the dose of CSI, we decided to evaluate the benefits gained with reduced doses of craniospinal prophylactic radiotherapy in survivors of PF tumors in terms of attenuated neuropsychological sequelae, by comparing three subgroups of patients who had undergone either PF radiotherapy alone, 25 Gy CSI with a boost to the PF (CSI low + PF) or 35 Gy CSI with a boost to the PF(CSI high + PF).

Section snippets

Patients

All children treated with radiotherapy at the Institut Gustave Roussy (IGR), Villejuif, France, for PF tumors were eligible for the study. Age at evaluation was between 5 and 15.5 years, to permit valid comparisons of the results, as similar items were used in the neuropsychological evaluation. Patients were all disease-free and off therapy for at least 1 year. Study patients included those with MB or EP.

Over a 1-year period, 31 children (24 boys and 7 girls) entered the study. Only 3 children

Results

The mean full scale intellectual quotient (FSIQ), the verbal IQ (VIQ), and the performance IQ (PIQ) were 76 (SD = 17), 83 (SD = 18), and 73 (SD = 16), respectively. The VIQ scores of most children were usually above their PIQ scores, with a mean difference of 10 points (SD = 11). The mean results of the WISC III performance subtests were constantly below 7 (mean value in normal children = 10), with a marked drop for coding and picture arrangement. Among the WISC III factors, the mean scores for

Discussion

Reducing CSI doses in children with standard-risk medulloblastoma (total or subtotal surgery and absence of metastasis) is a potential means of limiting toxicity during the subacute and late phases. Earlier studies in children with leukemia provided convincing arguments in favor of this attitude by showing a significant improvement of IQ scores when the prophylactic craniospinal radiation dose was lowered from 24 to 18 Gy, or even avoided 20, 21, 22. As a reduced CSI dose combined with

Conclusion

This study confirms that CSI, and more specifically, the dose, is mainly responsible for the poor neuropsychological outcome of children treated for posterior fossa tumors. After the analysis of neuropsychological sequelae, this preliminary report supports the use of reduced-dose CSI doses as prophylaxis against metastasis in children with standard-risk medulloblastoma. The gain in terms of intellectual outcome may be substantial in these settings. However, attention should be paid to the

Acknowledgements

The authors thank Ms. Lorna Saint-Ange for editing the manuscript.

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    ☆

    Supported by grants of the Comité de Recherche Clinique - IGR 1996 and 1997.

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