Results of a Randomized Study of Preradiation Chemotherapy Versus Radiotherapy Alone for Nonmetastatic Medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study

Taylor, Roger; Bailey, Chris; Robinson, Kath; Weston, Claire; Ellison, David W.; Ironside, James W.; Lucraft, Helen; Gilbertson, Richard J.; Tait, Diana; Walker, David; Pizer, Barry; Imeson, John; Lashford, L. S.

doi:10.1200/jco.2003.05.116

Cited by 317 publications

(191 citation statements)

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“…In 2000, Greenberg et al noted in a series of 17 adults that adults had higher rates of toxicity from chemotherapy, and 100% of adults required dose reductions during their course of treatment compared with 4.4% of children who were unable to complete treatment. 30,31 Thus, different treatment protocol and other unrecorded variables may be the source of the differences observed in this study.…”

Section: Discussionmentioning

confidence: 89%

“…Other studies have indicated that, for various reasons, between 5% and 10% of patients did not receive radiotherapy after it was offered. 29,30 The SEER data do not provide information about why radiation was not received. It is important to remember that the SEER database collects information at a population level, as distinct from a controlled clinical environment; therefore, other factors may contribute to the lower uptake of radiotherapy, such as socioeconomic status or performance status.…”

Section: Discussionmentioning

confidence: 99%

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Relative survival of childhood and adult medulloblastomas and primitive neuroectodermal tumors (PNETs)

Smoll

2011

Cancer

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BACKGROUND: Medulloblastomas are 1 of the most common brain tumors in children but can affect individuals of all ages. For this report, the author investigated the impact of medulloblastomas/primitive neuroectodermal tumors (PNETs) on the US population with a focus on age differences. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database were used to describe cumulative relative survival (CRS) using crude, period, and longitudinal period approaches for patients diagnosed with all medulloblastoma subtypes and PNETs. CRS estimates were obtained using SEER expected mortality data and the Ederer II method for expected survival estimation. These data were applied to the construction of rational follow-up scheduling protocols. RESULTS: The 5-year period CRS for all patients who were followed between 2001 and 2006 was 69%. Adults had a worse overall prognosis, but this difference in excess hazard rates appeared only after 4 years of follow-up. Furthermore, the 5-year and 10-year CRS has improved a minimum of 11% in children, adolescents, and adults over the past 25 years. CONCLUSIONS: The survival difference between children, adolescents, and adults with medulloblastomas and PNETs depended on the length of follow-up, which was described in this report as an age-by-follow-up interaction and observed as a ''fork'' on Kaplan-Meier curves. Differences in survival between children and adults emerged only 4 years after diagnosis, and adults fared worse. There has been significant improvement in survival from medulloblastomas/PNETs since the late 1970s and early 1980s. Cancer 2012;118:1313-

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Relative survival of childhood and adult medulloblastomas and primitive neuroectodermal tumors (PNETs)

Smoll

2011

Cancer

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“…There have been many advances in the treatment of medulloblastoma including improved surgical resection techniques, radiation, and chemotherapy (Zeltzer et al, 1999;Packer et al, 2003a;Taylor et al, 2003). These changes have greatly improved overall survival with current treatment strategies achieving up to 70 -75% 5-year disease-free survival (DFS) (Evans et al, 1990;Packer et al, 1994;Leonard et al, 2001).…”

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confidence: 99%

Survivin, Survivin-2B, and Survivin-deItaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome

et al. 2005

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Survivin is an apoptotic inhibitor that is expressed at high levels in a variety of malignancies. Survivin has four known alternative splice forms (Survivin, Survivin-2B, Survivin-deltaEx3, and Survivin-3B), and the recent literature suggests that these splice variants have unique functions and subcellular localisation patterns. We evaluated 19 fresh-frozen paediatric medulloblastomas for the expression of three Survivin isoforms by quantitative PCR. Survivin was most highly expressed when compared with normal cerebellar tissue. We also investigated Survivin protein expression in 40 paraffin-embedded paediatric medulloblastoma tumours by immunohistochemistry. We found a statistically significant association between the percentage of Survivin-positive cells and histologic subtype, with the large-cell-anaplastic variant expressing Survivin at higher levels than the classic subtype. We also found a statistically significant relationship between the percent of Survivin-positive cells in the tumours and clinical outcome, with higher levels of Survivin correlating with a worse prognosis. In summary, our study demonstrates a role for Survivin as a marker of tumour morphology and clinical outcome in medulloblastoma. Survivin may be a promising future prognostic tool and potential biologic target in this malignancy.

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“…The 5 year event-free survival of 83.0% ± 5.3% and 5 year cumulative incidence of local failure of 4.9% is similar to results reported for similar patients treated with 23.4 Gy CSI and adjuvant chemotherapy where the entire posterior fossa was irradiated to 55.8 Gy. [15][16][17] The targeting guidelines for this study, in addition to 23.4 Gy CSI, included irradiation of the anatomic PF to 36 Gy and treatment of the postoperative tumor bed with a margin of 2cm to 55.8 Gy. These guidelines were responsible for a reduction in the volume of the PF receiving the prescription dose, which averaged 13% and a lack of difference between the planning target volume and the volume of the PF which were not statistically different.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 The evolved standard for average-risk MB in North America includes post-operative CSI to 23.4 Gy, irradiation of the anatomic PF to 55.8 Gy and 12 months of combination chemotherapy as evidenced by the recently completed trial of the Children's Oncology Group. 17 Reducing the neuraxis dose in the absence of chemotherapy has met with limited success 18 and attempts to further reduce the neuraxis dose to 18 Gy with chemotherapy have not been made in a large prospective trial.…”

Section: Introductionmentioning

confidence: 99%

Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

Merchant¹,

Kun²,

Krasin³

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

152

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Purpose/Objective-Limiting neurocognitive sequelae of radiation therapy (RT) has been an objective in the treatment of medulloblastoma (MB). Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation (CSI) may reduce neurocognitive sequelae and requires evaluation. October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk MB were treated on a prospective, IRB-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of CSI (23.4 Gy), conformal PF RT (36.0 Gy) and primary site RT (55.8 Gy). The planning target volume for the primary site included the post-operative tumor bed surrounded by an anatomically confined margin of 2 cm which was then expanded with a geometric margin of Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Materials/Methods-Between CONFLICT OF INTEREST NOTIFICATION:There are no conflicts of interest with the authors or materials in this manuscript. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included 4 cycles of high-dose cyclophosphamide, cisplatin and vincristine.Results-With a median follow-up of 61.2 months (5.2-115.0 months), the estimated 5-year eventfree survival and cumulative incidence of PF failure were 83.0% ± 5.3% and 4.9% ± 2.4% (±SE), respectively. Targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses above 55Gy compared to conventionally planned RT. Reductions in dose to the temporal lobes, cochleae and hypothalamus were statistically significant.Conclusions-This prospective trial demonstrates that irradiation of less than the entire PF after 23.4 Gy CSI for average-risk MB results in disease control comparable to treatment of the entire PF.

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Results of a Randomized Study of Preradiation Chemotherapy Versus Radiotherapy Alone for Nonmetastatic Medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children’s Cancer Study Group PNET-3 Study

Cited by 317 publications

References 26 publications

Relative survival of childhood and adult medulloblastomas and primitive neuroectodermal tumors (PNETs)

Relative survival of childhood and adult medulloblastomas and primitive neuroectodermal tumors (PNETs)

Survivin, Survivin-2B, and Survivin-deItaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome

Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma

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