paediatrics Brussels 17

I. J. Radiation Oncology ● Biology ● Physics

292

Volume 46, Number 2, 2000

Tumor site The impact of the tumor site on outcome is controversial. For example, Foreman et al. (20) observed a survival ad- vantage in patients with supratentorial ependymomas, though the difference was not significant. Needle et al. (34), on the other hand, observed a significant survival advantage in patients with supratentorial ependymomas, but there were only 9 such patients with anaplastic tumors in their series. A worse prognosis for patients with supratentorial tumors was attributed to a higher rate of anaplastic histology (10, 16, 29) or less gross total resection (15). Differences in outcome according to tumor site have been attributed to perioperative mortality (16, 28, 31, 35). No association of outcome with tumor site was described by Salazar (36). Read (37) and Vanuytsel et al. (3) observed no association between tumor site and survival, but they did observe a higher rate of spinal seeding in infratentorial tumors. Our study results showed no impact of tumor site on treatment outcome. Dissemination Most studies have not analyzed the influence of tumor dissemination at presentation. A reason for this may be that insufficient staging techniques may very rarely identify spread. Pollack et al. (2), however, surprisingly found no correlation between the rate of tumor dissemination and prognosis. They thought that this finding might be due to the fact that they diagnosed spread on the basis of cytologic, rather than gross, evidence of spread or to the fact that they used more aggressive therapy. We also had cytologic evi- dence of dissemination in 3 of 5 children, and all 5 children were treated with irradiation of the neuraxis with an addi- tional boost to the primary tumor site. However, all children died in less than 2 years after surgery and had a significantly worse outcome in our analysis. But it must be considered that many children in our study did not undergo a cytologic analysis of the CSF; it therefore is possible that some children with disseminated disease may still be alive, which would mean that the outcome in such patients in our series was actually better than our data showed. In addition, neg- ative cytology findings are no absolute proof for an absence of tumor cells in the CSF, a possibility that could also mean that the outcome was actually better than we observed. Extent of resection In the Italian Pediatric Neurooncology Group series of 93 children (38), the completeness of resection emerged as the most significant predictor of outcome. Many studies have shown such an influence of total resection (7, 8, 13, 15, 18, 30, 32, 39). However, some studies failed to show an advantage for complete resection (34, 36). In the present series, total macroscopic removal was associated with con- siderably improved progression-free and overall survival rates. In addition, the rate of total or gross total resections has improved over time with total resection in half the patients in our study versus lower rates in previous studies. Vanuytsel et al. (3) described 72 incomplete resections in 93 (77.2%) children treated between 1952 and 1988. The pre-

Fig. 6. Relationship between treatment volume and estimated progression-free survival rate for all 24 supratentorial ependymo- mas. CSI, craniospinal irradiation; local, tumor region only.

studies (2, 6, 15, 18–21). We also observed that the fre- quency of leptomeningeal seeding after therapy (9.1%) is similar to those reported previously, ranging from to 0% to 50% in clinical and autopsy studies (4, 22–28). Kun et al. (29) and Shaw et al. (14) reported failures occurring shortly after treatment, with a median time to failure of 18 months. In our study, despite the short fol- low-up period, the majority of failures occurred after 3 years, with an estimated median time of 45 months to disease progression. This finding might be an effect of the long duration of combined treatment, ranging from about half a year in the preirradiation arm to 1 year in the main- tenance arm. Merchant et al. (15) reported a median time of 37 months to disease progression with 61% of the patients receiving preirradiation or maintenance chemotherapy. Our study results indicate that, age, sex, and tumor site do not influence outcome, in contrast to findings in other series. Age In previous studies, younger children had a lower survival rate than older patients (2, 13, 19, 24, 30, 31). However, Salazar et al. (21) found a reverse trend; in their study, patients older than 12 years fared worse than the younger children. We, on the other hand, found no impact of age on the survival rate, but this may be related to the fact that only children older than 3 years of age were enrolled in our trials. Foreman et al. (20) also observed no age-related effect on survival. Sex Only a few studies have analyzed the prognostic influ- ence of sex on outcome in patients with ependymomas. Some authors have reported a worse prognosis in male patients (3, 32). In contrast, Shaw et al. (14), Foreman et al. (20), and Zorlu et al. (33) did not find any significant difference, as confirmed by our analysis. The ratio of infratentorial to supratentorial anaplastic ependymomas is 1:1 (15).