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Title: Common Strategy for Adult and Pediatric Medulloblastoma: A Multicenter Series of 253 Adults

Abstract

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-riskmore » 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.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [8];  [9];  [10];  [11];  [12];  [8];  [2];  [13];  [2]
  1. Department of Radiation Oncology, Hopital de la Timone, Marseille (France). E-mail: laetitia.padovani@free.fr
  2. Department of Radiation Oncology, Centre Leon Berard, Lyon (France)
  3. Department of Biostatistics, Centre Leon Berard, Lyon (France)
  4. Department of Medical Oncology, Hopital de la Timone, Marseille (France)
  5. Department of Radiation Oncology, Institut Curie, Paris (France)
  6. Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France)
  7. Department of Radiation Oncology, Centre Alexis Vautrin, Nancy (France)
  8. Department of Radiation Oncology, Hopital de la Timone, Marseille (France)
  9. Department of Radiation Oncology, Centre Val D'aurelle, Montpellier (France)
  10. Department of Radiation Oncology, Clinique de l'Orangerie, Strasbourg (France)
  11. Department of Radiation Oncology, Hopital Henry Mondor, Creteil (France)
  12. Department of Radiation Oncology, Hopital Saint Andre, Bordeaux (France)
  13. (France)
Publication Date:
OSTI Identifier:
20951662
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2006.12.030; PII: S0360-3016(06)03639-X; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ADULTS; BRAIN; CARCINOMAS; CHEMOTHERAPY; CHILDREN; METASTASES; MULTIVARIATE ANALYSIS; PATIENTS; PEDIATRICS; PERFORMANCE; RADIATION DOSES; RADIOTHERAPY; VERTEBRAE

Citation Formats

Padovani, Laetitia, Sunyach, Marie-Pierre, Perol, David, Mercier, Cedric, Alapetite, Claire, Haie-Meder, Christine, Hoffstetter, Sylvette, Muracciole, Xavier, Kerr, Christine, Wagner, Jean-Philippe, Lagrange, Jean-Leon, Maire, Jean-Philippe, Cowen, Didier, Frappaz, Didier, Department of Neuro-oncology, Centre Leon Berard, Lyon, and Carrie, Christian. Common Strategy for Adult and Pediatric Medulloblastoma: A Multicenter Series of 253 Adults. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.12.030.
Padovani, Laetitia, Sunyach, Marie-Pierre, Perol, David, Mercier, Cedric, Alapetite, Claire, Haie-Meder, Christine, Hoffstetter, Sylvette, Muracciole, Xavier, Kerr, Christine, Wagner, Jean-Philippe, Lagrange, Jean-Leon, Maire, Jean-Philippe, Cowen, Didier, Frappaz, Didier, Department of Neuro-oncology, Centre Leon Berard, Lyon, & Carrie, Christian. Common Strategy for Adult and Pediatric Medulloblastoma: A Multicenter Series of 253 Adults. United States. doi:10.1016/j.ijrobp.2006.12.030.
Padovani, Laetitia, Sunyach, Marie-Pierre, Perol, David, Mercier, Cedric, Alapetite, Claire, Haie-Meder, Christine, Hoffstetter, Sylvette, Muracciole, Xavier, Kerr, Christine, Wagner, Jean-Philippe, Lagrange, Jean-Leon, Maire, Jean-Philippe, Cowen, Didier, Frappaz, Didier, Department of Neuro-oncology, Centre Leon Berard, Lyon, and Carrie, Christian. Fri . "Common Strategy for Adult and Pediatric Medulloblastoma: A Multicenter Series of 253 Adults". United States. doi:10.1016/j.ijrobp.2006.12.030.
@article{osti_20951662,
title = {Common Strategy for Adult and Pediatric Medulloblastoma: A Multicenter Series of 253 Adults},
author = {Padovani, Laetitia and Sunyach, Marie-Pierre and Perol, David and Mercier, Cedric and Alapetite, Claire and Haie-Meder, Christine and Hoffstetter, Sylvette and Muracciole, Xavier and Kerr, Christine and Wagner, Jean-Philippe and Lagrange, Jean-Leon and Maire, Jean-Philippe and Cowen, Didier and Frappaz, Didier and Department of Neuro-oncology, Centre Leon Berard, Lyon and Carrie, Christian},
abstractNote = {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.},
doi = {10.1016/j.ijrobp.2006.12.030},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 68,
place = {United States},
year = {Fri Jun 01 00:00:00 EDT 2007},
month = {Fri Jun 01 00:00:00 EDT 2007}
}
  • Purpose: To evaluate the potential influence of radiotherapy quality on survival in high-risk pediatric medulloblastoma patients. Methods and Materials: Trial 9031 of the Pediatric Oncology Group (POG) aimed to study the relative benefit of cisplatin and etoposide randomization of high-risk patients with medulloblastoma to preradiotherapy vs. postradiotherapy treatment. Two-hundred and ten patients were treated according to protocol guidelines and were eligible for the present analysis. Treatment volume (whole brain, spine, posterior fossa, and primary tumor bed) and dose prescription deviations were assessed for each patient. An analysis of first site of failure was undertaken. Event-free and overall survival rates weremore » calculated. A log-rank test was used to determine the significance of potential survival differences between patients with and without major deviations in the radiotherapy procedure. Results: Of 160 patients who were fully evaluable for all treatment quality parameters, 91 (57%) had 1 or more major deviations in their treatment schedule. Major deviations by treatment site were brain (26%), spinal (7%), posterior fossa (40%), and primary tumor bed (17%). Major treatment volume or total dose deviations did not significantly influence overall and event-free survival. Conclusions: Despite major treatment deviations in more than half of fully evaluable patients, underdosage or treatment volume misses were not associated with a worse event-free or overall survival.« less
  • Purpose: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. Methods and Materials: Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI. Results: p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had >5% weightmore » loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P<.001). p-CSI patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts. Conclusions: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.« less
  • Purpose: To compare quality of survival in “standard-risk” medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Methods and Materials: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Results: Data were provided by 151 ofmore » 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Conclusions: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life.« less
  • Ataxia telangiectasia (AT) is a genetic disorder with a predisposition to malignancy. Cells from patients with AT demonstrate an increased sensitivity to ionizing radiation which creates a problem when these patients require treatment for their malignant disease. An eleven-year-old boy with a previous diagnosis of AT was seen in consultation following partial resection of medulloblastoma in the posterior fossa. To estimate how much the conventional radiation dose might have to be reduced, we compared the radiosensitivity of bone marrow myeloid progenitor cells from this patient to that of cells from the marrow of normal individuals, using colony formation in anmore » agar culture assay system as the endpoint (CFU-Cs). Neither radiation dose-survival curve exhibited a shoulder--each displayed an extrapolation number of 0.99. The survival curve of normal cells displayed a steep slope with a D0 of 0.98 Gy (0.83-1.19 Gy, 95% confidence limits); the slope for the AT cells was considerably steeper with a value for D0 of 0.32 Gy (0.29-0.35 Gy). The ratio of D0's indicated that these AT cells were approximately 3X more radiosensitive than normal cells. Based on this, the daily dose was reduced from 1.8 to 0.6 Gy and the radiation was restricted to 25 treatments to the posterior fossa rather than the conventional cranio-spinal treatment. An additional 5 treatments at 1.0 Gy per day were given to the whole brain. The patient's skin responded to these reduced fraction sizes and doses to a similar degree as normal patients' skin following a standard schedule and the patient is doing well nine months after initiation of treatment.« less
  • Purpose: Model the effects of radiation dosimetry on IQ among pediatric patients with central nervous system (CNS) tumors. Methods and Materials: Pediatric patients with CNS embryonal tumors (n = 39) were prospectively evaluated with serial cognitive testing, before and after treatment with postoperative, risk-adapted craniospinal irradiation (CSI) and conformal primary-site irradiation, followed by chemotherapy. Differential dose-volume data for 5 brain volumes (total brain, supratentorial brain, infratentorial brain, and left and right temporal lobes) were correlated with IQ after surgery and at follow-up by use of linear regression. Results: When the dose distribution was partitioned into 2 levels, both had amore » significantly negative effect on longitudinal IQ across all 5 brain volumes. When the dose distribution was partitioned into 3 levels (low, medium, and high), exposure to the supratentorial brain appeared to have the most significant impact. For most models, each Gy of exposure had a similar effect on IQ decline, regardless of dose level. Conclusions: Our results suggest that radiation dosimetry data from 5 brain volumes can be used to predict decline in longitudinal IQ. Despite measures to reduce radiation dose and treatment volume, the volume that receives the highest dose continues to have the greatest effect, which supports current volume-reduction efforts.« less