Phase II study of pre-irradiation chemotherapy for childhood intracranial ependymoma. Children's Cancer Group protocol 9942: A report from the Children's Oncology Group

Division of Pediatric Oncology, Columbia University Medical Center, New York, New York.
Pediatric Blood & Cancer (Impact Factor: 2.35). 09/2012; 59(7):1183-1189. DOI: 10.1002/pbc.24274
Source: PubMed

ABSTRACT PURPOSE: Standard therapy for childhood intracranial ependymoma is maximal tumor resection followed by involved-field irradiation. Although not used routinely, chemotherapy has produced objective responses in ependymoma, both at recurrence and in infants. Because the presence of residual tumor following surgery is consistently associated with inferior outcome, the potential impact of pre-irradiation chemotherapy was investigated. METHODS: Between 1995 and 1999, the Children's Cancer Group undertook a Phase II trial of pre-irradiation chemotherapy in children 3-21 years of age with intracranial ependymoma and radiological evidence of post-operative residual tumor. RESULTS: Of 84 patients, 41 had residual tumor, and were given four cycles of cisplatin-based chemotherapy prior to irradiation. Of 35 patients fully evaluable for response to chemotherapy, 14 (40%) demonstrated complete response, 6 (17%) partial response, 10 (29%) minor response or stable disease, and 5 (14%) demonstrated progressive tumor growth. For the entire group, 5-year overall survival (OS) and event-free survival (EFS) was 71 ± 6%, and 57 ± 6%, respectively. The pre-irradiation chemotherapy group demonstrated EFS comparable to that of patients with no residual tumor who received irradiation alone (55 ± 8% vs. 58 ± 9%, P = 0.45). Any benefit of chemotherapy was restricted to patients with greater than 90% tumor resection. CONCLUSIONS: Children with near total resection of ependymoma may benefit from pre-irradiation chemotherapy. Patients with subtotal resection have inferior outcome despite responses to chemotherapy, and should be considered for second-look surgery prior to irradiation. Pediatr Blood Cancer 2012; 59: 1183-1189. © 2012 Wiley Periodicals, Inc.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neoadjuvant chemotherapy (NC) may be utilized for treatment of various tumors, and a proportion of patients on active NC may require resection of a primary or secondary brain tumor. The objective of this study is to examine the impact of NC on postoperative neurosurgical outcomes. Elective cranial neurosurgical patient data was obtained from the American College of Surgeons National Surgical Quality Improvement Program database between 2006 and 2012. The impact of NC on 30day stroke, all-cause postoperative morbidity, and mortality were assessed. Adjusted odds ratios (OR) were estimated for stroke, overall morbidity, and mortality using a multivariable logistic regression model, accomplished in stepwise fashion, for patients receiving NC versus those not receiving NC. This study analyzed 3812 patients undergoing elective cranial surgery, with 152 on concurrent NC. NC patients had a complication rate of 23.68%, while patients not receiving NC had a lower complication rate at 17.65% (p=0.057). Multivariable regression analysis revealed that patients who received NC had significantly increased odds of developing a stroke with neurological deficit (OR 3.39; 95% confidence interval [CI] 1.37-8.40) and all-cause postoperative morbidity (OR 1.57; 95% CI 1.04-2.37) over the control group. Finally, the NC cohort demonstrated higher odds of mortality following surgery than their non-NC counterparts (OR 3.81; 95% CI 1.81-8.02). Ninety-two patients (2.41%) died within 30days, of whom 10 (6.58%) were receiving NC versus 82 non-NC (2.24%) patients (p=0.001). Concurrent NC is associated with an increased risk of short-term stroke with neurological deficit, all-cause morbidity, and mortality in patients undergoing brain tumor resection.
    Journal of Clinical Neuroscience 07/2014; DOI:10.1016/j.jocn.2014.05.010 · 1.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report a population-based study examining long-term outcomes for common pediatric CNS tumors comparing results from the UK with the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data set and with the literature. No such international study has previously been reported. Data between 1996 and 2005 from the UK National Registry of Childhood Tumours (NRCT) and the SEER registry were analyzed. We calculated actuarial survival at each time point from histological diagnosis, with death from any cause as the endpoint. Kaplan-Meier estimation and log-rank testing (Cox proportional hazards regression analysis) were used to calculate survival differences among tumor subtypes, adjusting for age at diagnosis. Population-based outcomes for each tumor type are presented. Overall age-adjusted survival, stratifying for histology (combining pilocytic astrocytoma, anaplastic astrocytoma, glioblastoma, primitive neuroectodermal tumor, medulloblastoma, and ependymoma), is significantly lower for NRCT than SEER (hazard ratio 0.71, P < .001) and at 1, 5, and 10 years. Both NRCT and SEER outcomes are worse than those reported from trials. Analyzing data from comprehensive registries minimizes bias associated with trials and institutional studies. The reasons for the poorer outcomes in children treated in the UK are unclear. Likewise, the differences in outcomes between patients in trials and those not in trials need further investigation. We recommend that all children with CNS tumors be recruited into studies-even if these are observational studies. We also suggest that registries be suitably funded to publish independent outcome data (including morbidity) at both a national and an institutional level.
    Neuro-Oncology 05/2014; 16(8). DOI:10.1093/neuonc/nou056 · 5.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This article reviews current approaches to management of central nervous system tumours of childhood, highlighting aspects particularly pertinent to the paediatric population.
    Clinical Oncology 05/2014; DOI:10.1016/j.clon.2014.04.029 · 2.83 Impact Factor


Available from
May 28, 2014