Survival of adults treated for medulloblastoma using paediatric protocols (original) (raw)
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Common Strategy for Adult and Pediatric Medulloblastoma: A Multicenter Series of 253 Adults
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To assess prognostic factors for adults with medulloblastoma in a multicenter, retrospective study. Methods and Materials: Data were collected by file review or mail inquiry for 253 adults treated between 1975 to 2004. Radiologists or surgeons assessed disease characteristics, such as volume and extension. Patients were classified as having either high-or standard-risk disease. Prognostic factors were analyzed. Results: Median patient age was 29 years. Median follow-up was 7 years. Radiotherapy was delivered in 246 patients and radiochemotherapy in 142. Seventy-four patients relapsed. Respective 5-and 10-year overall survival rates were 72% and 55%. Univariate analysis showed that survival significantly correlated with metastasis, postsurgical performance status, brainstem involvement, involvement of the floor of the fourth ventricle (V4), and radiation dose to the spine and to the posterior cerebral fossa (PCF). By multivariate analysis, brainstem, V4 involvement, and dose to the PCF were negative prognostic factors. In the standard-risk subgroup there was no overall survival difference between patients treated with axial doses of >34 Gy and patients treated with craniospinal doses <34 Gy plus chemotherapy. Conclusion: We report the largest series of medulloblastoma in adults. Prognostic factors were similar to those observed in children. Results suggest that patients with standard-risk disease could be treated with radiochemotherapy, reducing doses to the craniospinal area, maintaining at least 50 Gy to the PCF. The role of chemotherapy for this group is still unclear. A randomized study should be performed to confirm these results, but because frequency is very low, such a study would be difficult.
Journal of Clinical Oncology, 2005
Objective The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. Patients and Methods Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m2 per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. Results Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% ± 7.6% and 64.8% ± 8.1%, respectively. Radiologic review showed that 4% of patients were wrong...
Journal of Neurosurgery, 1995
EDULLOBLASTOMA is the most common malignant central nervous system tumor of childhood. Standard management has included surgical resection followed by craniospinal radiation therapy. Over the past decades, the survival rate of patients with medulloblastoma has progressively increased as diagnostic, surgical, anesthetic, and radiotherapy techniques have improved. These developments have been previously reviewed. 11 Recent reports indicate 5-year survival rates of 50% to 70%, but the quality of life for survivors is impaired by neurointellectual and endocrinological sequelae, which are mainly due to whole-brain irradiation. The role of chemotherapy in the adjuvant setting was demonstrated by randomized studies. 14,35 The potential benefits of protocols including chemotherapy prior to craniospinal irradiation have been summarized by Packer. The rationale for this treatment schedule is that ߜ The aim of this study was to evaluate the feasibility and efficacy of a protocol that includes "sandwich" chemotherapy, that is, chemotherapy alternated with radiotherapy, and reduced doses of supratentorial irradiation in children with medulloblastoma. Between March 1985 and September 1988, 70 successive children with newly diagnosed medulloblastoma from eight centers were treated in this prospective nonrandomized study. Patients were assigned to two risk groups. Group A included patients with macroscopically complete or subtotal excision, no brainstem involvement, no atypical cells in the cerebrospinal fluid, normal myelography, and who were more than 2 years of age. Group B patients encompassed those who did not fit the criteria for Group A. Two children were excluded from analysis after histological review confirmed ependymoma. Thus, a population of 68 children was selected, with 31 in Group A and 37 in Group B.
International Journal of Radiation Oncology*Biology*Physics, 2000
Purpose: The German Society of Pediatric Hematology and Oncology (GPOH) conducted a randomized, prospective, multicenter trial (HIT '91) in order to improve the survival of children with medulloblastoma by using postoperative neoadjuvant chemotherapy before radiation therapy as opposed to maintenance chemotherapy after immediate postoperative radiotherapy. Methods and Materials: Between 1991 and 1997, 158 patients were enrolled and 137 patients randomized. Seventy-two patients were allocated to receive neoadjuvant chemotherapy before radiotherapy (arm I, investigational). Chemotherapy consisted of ifosfamide, etoposide, intravenous high-dose methotrexate, cisplatin, and cytarabine given in two cycles. In arm II (standard arm), 65 patients were assigned to receive immediate postoperative radiotherapy, with concomitant vincristine followed by 8 cycles of maintenance chemotherapy consisting of cisplatin, CCNU, and vincristine ("Philadelphia protocol"). All patients received radiotherapy to the craniospinal axis (35.2 Gy total dose, 1.6 Gy fractionated dose / 5 times per week followed by a boost to posterior fossa with 20 Gy, 2.0 Gy fractionated dose). Results: During chemotherapy Grade III/IV infections were predominant in arm I (40%). Peripheral neuropathy and ototoxicity were prevailing in arm II (37% and 34%, respectively). Dose modification was necessary in particular in arm II (63%). During radiotherapy acute toxicity was mild in the majority of patients and equally distributed in both arms. Myelosuppression led to a mean prolongation of treatment time of 11.5 days in arm I and 7.5 days in arm II, and interruptions in 35% of patients in arm I. Quality control of radiotherapy revealed correct treatment in more than 88% for dose prescription, more than 88% for coverage of target volume, and 98% for field matching. At a median follow-up of 30 months (range 1.4-62 months), the Kaplan-Meier estimates for relapse-free survival at 3 years for all randomized patients were 0.70 ؎ 0.08; for patients with residual disease: 0.72 ؎0.06; without residual disease: 0.68 ؎ 0.09; M0: 0.72 ؎ 0.04; M1: 0.65 ؎ 0.12; and M2/3: 0.30 ؎ 0.15. For all randomized patients without M2/3 disease: 0.65؎ 0.05 (arm I) and 0.78 ؎ 0.06 (arm II) (p < 0.03); patients between 3 and 5.9 years: 0.60 ؎ 0.13 and 0.64 ؎ 0.14, respectively, but patients between 6 and 18 years: 0.62 ؎ 0.09 and 0.84 ؎ 0.08, respectively (p < 0.03). In a univariate analysis the only negative prognostic factors were M2/3 disease (p < 0.002) and an age of less than 8 years (p < 0.03). Conclusions: Maintenance chemotherapy would seem to be more effective in low-risk medulloblastoma, especially in patients older than 6 years of age. Neoadjuvant chemotherapy was accompanied by increased myelotoxicity of the subsequent radiotherapy, causing a higher rate of interruptions and an extended overall treatment time. Delayed and/or protracted radiotherapy may therefore have a negative impact on outcome. M2/3 disease was associated with a poor survival in both arms, suggesting the need for a more intensive treatment. Young age and M2/3 stage were negative prognostic factors in medulloblastoma, but residual or M1 disease was not, suggesting a new stratification system for risk subgroups. High quality of radiotherapy may be a major contributing factor for the overall outcome.
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
This study was undertaken to determine the effect of adjuvant chemotherapy combined with reduced-dose craniospinal irradiation (CSI) on survival and neurocognitive sequelae of radiotherapy (RT) in patients with average- risk medulloblastoma above the age of 3 years. Thirty-three children between 3 and 10 years of age with average-risk medulloblastoma were treated with postoperative reduced-dose CSI (24.0 Gy) and 30.6 Gy of local RT (total of 54.6 Gy) and then with adjuvant chemotherapy consisting of cisplatin, vincristine, and cyclophosphamide every 4 weeks for 8 cycles. At 5 years, event-free survival (EFS) was 79%, while overall survival (OS) was 85%. Sites of relapse were local in 3%, neuraxis in 9% and both local and neuraxis in 9% of the patients. Chemotherapy was well tolerated. Hematopoietic toxicity was the most predominant side effect followed by vomiting and ototoxicity. No grade III or IV nephrotoxicity or neurotoxicity and no treatment-related deaths were encountered. In...
Children
Craniospinal irradiation (CSI) has been a major component of the standard of care treatment backbone for childhood medulloblastoma. However, chemotherapy regimens have varied based on protocol, patient age, and molecular subtyping. In one of the largest studies to date, we analyzed treatment outcomes in children with newly-diagnosed medulloblastoma treated with pre-irradiation chemotherapy followed by risk-adapted radiotherapy and maintenance chemotherapy. A total of 153 patients from the Polish Pediatric Neuro-Oncology Group were included in the analysis. The median age at diagnosis was 8.0 years, and median follow-up time was 6.4 years. Sixty-seven patients were classified as standard-risk and eighty-six as high-risk. Overall survival (OS) and event-free survival (EFS) for standard-risk patients at 5 years (±standard error) were 87 ± 4.3% and 84 ± 4.6%, respectively, while 5-year OS and EFS for high-risk patients were 81 ± 4.3% and 79 ± 4.5%, respectively. Only one patient had dis...
Treatment results for 149 medulloblastoma patients from one institution
International Journal of Radiation Oncology Biology Physics, 1996
Purpose: Retrospective analysis of patients with medulloblastoma to determine the effectiveness of previous treatments for medulloblastoma and plan for future management strategies. Methods and Materials: During the period March 1976 to December 1991, 172 patients with cerebellar medulloblastoma were referred to King Faisal Specialist Hospital and Research Center. One hundred and forty-nine patients were treated with curative intent. There were six postoperative deaths, and 10 patients planned for radiotherapy treatment failed to complete the prescribed course. One hundred and thirty-three patients completed a course of radiotherapy after surgery. Adjuvant chemotherapy was not used routinely (six patients only). Tumors were staged retrospectively according to the Chang staging system. There were no T1 patients, 32 patients had T2 tumors, 76 had T3 tumors, and 29 had T4 tumors. The T stage could not be allocated in 12 patients. Ninety-nine patients required a shunting procedure either pre-or postoperatively. Forty-six patients had complete resection of tumor, 91 had incomplete resection, and 6 patients had biopsy only. The extent of resection could not be determined in six patients. The median radiation dose for the whole brain was 34 Gy, spine 32.5 Gy, and posterior fossa 52.8 Gy. Fraction sizes ranged from 1.7-1.8 Gy for craniospinal fields and 2 Gy for the posterior fossa boost. Seventy percent completed the prescribed course within 7 weeks. Results: Actuarial survival for the whole group of 149 patients was 53% at 5 years and 38% at 10 years. On univariate analysis, patients with T2 tumors did significantly better as compared to patients with T3 and T4 tumors. Survival of patients who had clinical and radiological complete resection of tumor at surgery was significantly better than patients with incomplete tumor removal. The presence of a ventriculoperitoneal (VP) shunt had a significant negative impact on survival. Treatment failure by site was analyzed with respect to the radiation dose. Doses greater than 50 Gy for the posterior fossa, and greater than 30 Gy for craniospinal axis, resulted in significantly better survival. On multivariate analysis, the only significant prognostic factor was the presence of a VP shunt in patients with T2 tumors. Conclusion: T stage, VP shunt, radiation doses and extent of surgery were important prognostic factors. In this study, radiation doses of more than 50 Gy to the posterior fossa and 30 Gy to the craniospinal axis resulted in improved survival.
Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma
Journal of Neurosurgery, 1991
✓ Between 1975 and 1989, 108 children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor (MB/PNET) of the posterior fossa were treated at the authors' institution. The patients were managed uniformly, and treatment included aggressive surgical resections, postoperative staging evaluations for extent of disease, and craniospinal radiation therapy with a local boost. Beginning in 1983, children with MB/PNET were prospectively assigned to risk groups; those with “standard-risk” MB/PNET were treated with radiation therapy alone, while those in the “poor-risk” group received similar radiation therapy plus adjuvant chemotherapy with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), vineristine, and cisplatin. The 5-year actuarial disease-free survival rate for all patients treated between 1975 and 1982 was 68%, and 73% when patients who died within 2 weeks after operation were excluded. This survival rate was statistically better for patients treated after 1982 (8...