Distinctive clinical course and pattern of relapse in adolescents with medulloblastoma.
ABSTRACT To report the clinical course of adolescents with medulloblastoma, with specific emphasis on prognosis and pattern of relapse.
We retrospectively studied the clinical course and outcomes of children aged 10-20 years with medulloblastoma, treated at centers throughout Canada between 1986 and 2003. To better assess time to relapse, a cohort of patients aged 3-20 years at diagnosis was generated.
A total of 72 adolescents were analyzed. Five-year overall survival and event-free survival rates were 78.3%+/-5.4% and 68.0%+/-6.2%, respectively. Late relapses occurred at a median of 3.0 years (range, 0.3-6.8 years). In univariate analysis, conventional risk stratification and the addition of chemotherapy to craniospinal radiation did not have prognostic significance. Female patients had improved overall survival (p=0.007). Time to relapse increased with age in a linear fashion. After relapse, patients faired poorly regardless of treatment modality. Patients who did not receive chemotherapy initially had improved progression-free survival at relapse (p=0.05).
Our study suggests that adolescents with medulloblastoma might have a unique prognosis and pattern of relapse, dissimilar to those in younger children. They might benefit from different risk stratifications and prolonged follow-up. These issues should be addressed in future prospective trials.
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ABSTRACT: Aggressive treatment of medulloblastoma, the most common pediatric brain tumor, has not improved survival. Identifying better prognostic indicators may warrant less morbid therapy. To investigate the role of sex on outcome of medulloblastoma. Retrospective study of significant factors for survival with a median follow-up of 82 months. University medical center. A total of 109 consecutive, pediatric patients treated for primary medulloblastoma from 1970 to 1995 with surgery and postoperative radiotherapy and, after 1979, chemotherapy. Factors independently associated with survival. The final multivariate model predicting improved survival included sex (hazard ratio, 0.52; 95% confidence interval [CI], 0.29-0.92; P=.03; favoring female), metastases at presentation (hazard ratio, 2.01; 95% CI, 1.14-3.52; P=.02), and extent of surgical resection (hazard ratio, 0.60; 95% CI, 0.34-1.04; P=.07; favoring greater resection). The overall, 5-year freedom from progression was 40% and survival was 49%. Radiotherapy dose (P=.72), and chemotherapy (P=.90) did not significantly affect a disease outcome. The sex of the child was an important predictor for survival of medulloblastoma; girls had a much better outcome. The difference in survival between sexes should be evaluated in prospective, clinical trials.JAMA The Journal of the American Medical Association 06/1998; 279(18):1474-6. · 29.98 Impact Factor
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ABSTRACT: Most reported data of chemoradiotherapy protocols for the treatment of medulloblastoma describe children who were treated in the first decade of life. To consider the feasibility of this approach in adolescents, the authors studied their clinical course with specific emphasis on toxicity, tolerability, and prognosis. In this retrospective study, the authors examined the toxicity profiles and outcomes of children age 10-20 years with medulloblastoma who were treated at centers throughout Canada between 1986 and 2003. Detailed toxicity data from 2 chemotherapy protocols were collected for teenagers and were compared with data from a group of control patients age 5-10 years. In total, 72 teenagers were analyzed. Grade >/= 2 ototoxicity and neurotoxicity occurred in 45% and 71% of chemotherapy-treated patients, respectively. Grade 3-4 hematotoxicty occurred in 95% of patients. Toxicity resulted in delay of treatment for 73% of patients and dose modification in 75% of patients, including protocol discontinuation in 25% of patients. Weight loss > 10% was encountered in 73% of patients and required intervention in 45% of patients. Teenagers had significantly more hematotoxicity and neurotoxicity compared with controls on both chemotherapeutic protocols. Ototoxicity was similar in both age groups. Toxicity resulted in significantly more treatment delays and dose modifications in teenager patients compared with controls. The 5-year overall and event-free survival rates (+/- standard deviation) were 78% +/- 6% and 70% +/- 6%, respectively. The mean time (+/- standard deviation) to disease recurrence was 3.2 +/- 2.2 years. The increased toxicity rate and high incidence of treatment modifications in this study suggested that current pediatric protocols may require modifications for teenagers with medulloblastoma. The results highlighted several issues that should be addressed in future prospective trials.Cancer 06/2005; 103(9):1874-80. · 5.20 Impact Factor
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ABSTRACT: To investigate toxicity, and progression-free survival (PFS) of children and adults with newly diagnosed medulloblastoma, pineoblastoma, and other primitive neuroectodermal tumors (PNET) with a combined modality regimen of radiation therapy and adjuvant nitrosourea-based chemotherapy. Between 1984 and 1992, 34 evaluable patients with newly diagnosed tumors were treated with chemotherapy and radiotherapy according to a single-arm phase II study. One cycle of chemotherapy was given prior to and for 6 cycles following craniospinal radiotherapy (CSA). Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) to enhance CCNU-induced tumor cell kill and to reduce alkyltransferase repair of ethylated DNA. Vincristine was given 1 and 3 weeks after CCNU to kill cells that began to cycle after the challenge of the first four drugs. Chemotherapy was given in the outpatient setting. CSA radiation was planned to deliver a dose of 54 Gy to the primary tumor site and 24 Gy to the rest of the neuroaxis. Additional radiation was given to bulky disease outside the primary site if present. Hydroxyurea was used during radiotherapy as a radiosensitizer. Patients treated included 27 with medulloblastoma, 5 with pineoblastoma, and 2 with supratentorial PNET. All but 3 medulloblastoma cases were considered high risk either because of bulky residual disease remaining after surgery and/or metastatic disease detected during staging. For the 34 patients, 24 have progressed, 20 have died. Overall estimated PFS was 55% at 3 years and 35% at 5 years. The 5-year survival estimate is 56%. One patient had inadequate staging to determine M stage. Of the remaining 33 patients, there were 19 patients who had metastatic disease at diagnosis (M1 or higher stage) who had a 3- and 5-year PFS of 42 and 21% respectively and 5-year survival of 42%. There were 14 patients who had negative staging (M0 stage) who had a 3- and 5-year PFS of 69 and 52% respectively and 5-year survival of 71%. Of the 27 patients with medulloblastoma, 15 had M1 or higher stage. These 15 patients had a 5-year PFS and overall survival of only 20 and 40% respectively. Medulloblastoma patients with M0 staging had a 5-year PFS and overall survival of 52 and 73% respectively. Overall toxicity was primarily due to mild hematological toxicity and related to the use of the chemotherapy. The results using this therapy in high-risk groups of patients does not offer any improvement over results reported in other recent studies. The reason for these results may be due to the lowered craniospinal radiation dose.Pediatric Neurosurgery 11/1996; 25(4):174-81. · 0.42 Impact Factor