Risk factors of recurrence in 157 MB/PNET patients treated in one institution

Perek, Danuta; Perek-Polnik, Marta; Drogosiewicz, Monika; Dembowska-Bagińska, Bożena; Roszkowski, Marcin; Barszcz, Sławomir

doi:10.1007/s003810050276

Cited by 9 publications

(5 citation statements)

References 14 publications

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“…1,7,30,31 Among these patients, 2 had early relapse in the spinal axis despite more aggressive therapy. In agreement with other reports on adults 1,4,19,32,36,40 and children, 17,37,48 we found that the presence of metastatic disease at presentation was an important prognostic factor for overall and event-free survival times. In a larger multicenter series, 7 metastatic disease did not appear to be correlated with a worse prognosis, but data were available for only 61% of the patients, and half of the patients with Stage M0 medulloblastomas received chemotherapy either before or after, or both before and after, radiotherapy.…”

Section: Prognostic Factorssupporting

confidence: 82%

Survival and prognostic factors in a series of adults with medulloblastomas

Riffaud

Saïkali

Leray

et al. 2009

JNS

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Object In this article, the authors report their experience in the management of adult patients with medulloblastoma at their institution to identify prognostic factors important for survival and disease control. Methods Between 1977 and 2005, 27 patients who were ≥ 16 years old and had medulloblastoma were treated consecutively. There were 16 women and 11 men with a median age of 21 years (range 16–54 years). Gross-total resection was performed in 21 patients, subtotal (≥ 90%) in 2, incomplete in 1, and biopsy in 3 patients. Six patients had the desmoplastic variant, and 21 patients presented with classic medulloblastoma. Staging according to the Chang classification showed 4 patients with tumors invading the brainstem (2 with Stage T3b and 2 with Stage T4), 3 patients with metastases (2 with Stage M2 and 1 with Stage M3), and 1 patient in whom the stage was unknown (Stage MX) who died 10 days postoperatively. Twenty patients were assigned to the standard-risk group and 7 to the high-risk group. All patients except the one whose status was classified as Stage MX underwent craniospinal radiotherapy at our institution. Seven patients received chemotherapy before radiotherapy. Results The 5- and 10-year overall survival rates for the present study were 81 and 62%, respectively. The median overall survival time was 17.7 years. The 5- and 10-year event-free survival rates were 72 and 57%, respectively. The median event-free survival time was 17.9 years. Univariate analysis showed that survival was significantly correlated with sex (women had a better prognosis than men) and M stage (patients without metastases had a better outcome). Patient age, duration of symptoms, Karnofsky Performance Scale score at presentation, hydrocephalus, tumor location, brainstem invasion, extent of resection, histological subtype, preradiotherapy chemotherapy, risk group, and period of presentation were not significant variables. Multivariate analysis identified sex and M stage as well as the period of presentation as independent prognostic factors for overall and event-free survival times. Eleven patients suffered tumor recurrence within a median time of 4.2 years. The posterior fossa was not the most common site of recurrence, and delayed recurrence was not rare. All patients in whom the tumor recurred have died despite aggressive treatments. The median survival time after diagnosis of recurrence was 2.5 years. Questionnaires on quality of life and cognition showed high scores in favor of limited negative effects in the perception of mental and physical health after treatment. The authors observed 1 supposed second malignancy (thyroid carcinoma) and no evidence of pituitary dysfunction. Conclusions Long-term survival is possible in adults treated for medulloblastoma. Although rare, metastasis seeding at presentation is a poor prognostic factor. The possibility of delayed recurrence necessitates close follow-up of all patients. Tumor recurrences should be treated with aggressive therapies as some patients may have sustained response. Adjuvant chemotherapy should be given to high-risk patients, but its role in reducing recurrences, particularly distant ones, remains unclear in the standard-risk group.

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Section: Prognostic Factorssupporting

confidence: 82%

Survival and prognostic factors in a series of adults with medulloblastomas

Riffaud

Saïkali

Leray

et al. 2009

JNS

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“…Treatment of patients with MB, the most common pediatric brain cancer, poses an additional problem. Current therapies for MB cause dramatic impairment of cognitive function and predispose patients to future treatment-associated neoplasms [2]. Hence, there is a pressing need to identify novel proteins and signaling pathways that can serve as new targets for improved treatment of GB and MB.…”

Section: Introductionmentioning

confidence: 99%

The SOX2-Interactome in Brain Cancer Cells Identifies the Requirement of MSI2 and USP9X for the Growth of Brain Tumor Cells

et al. 2013

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Medulloblastomas and glioblastomas, the most common primary brain tumors in children and adults, respectively, are extremely difficult to treat. Efforts to identify novel proteins essential for the growth of these tumors may help to further our understanding of the biology of these tumors, as well as, identify targets for future therapies. The recent identification of multiple transcription factor-centric protein interaction landscapes in embryonic stem cells has identified numerous understudied proteins that are essential for the self-renewal of these stem cells. To identify novel proteins essential for the fate of brain tumor cells, we examined the protein interaction network of the transcription factor, SOX2, in medulloblastoma cells. For this purpose, Multidimensional Protein Identification Technology (MudPIT) identified >280 SOX2-associated proteins in the medulloblastoma cell line DAOY. To begin to understand the roles of SOX2-associated proteins in brain cancer, we focused on two SOX2-associated proteins, Musashi 2 (MSI2) and Ubiquitin Specific Protease 9x (USP9X). Recent studies have implicated MSI2, a putative RNA binding protein, and USP9X, a deubiquitinating enzyme, in several cancers, but not brain tumors. We demonstrate that knockdown of MSI2 significantly reduces the growth of DAOY cells as well as U87 and U118 glioblastoma cells. We also demonstrate that the knockdown of USP9X in DAOY, U87 and U118 brain tumor cells strongly reduces their growth. Together, our studies identify a large set of SOX2-associated proteins in DAOY medulloblastoma cells and identify two proteins, MSI2 and USP9X, that warrant further investigation to determine whether they are potential therapeutic targets for brain cancer.

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“…Pediatric central nervous system tumors are the second most common malignancy in children (second only to leukemia), of which, medulloblastoma is the most common type. While the 5-year survival of medulloblastoma patients is nearly 80%, a treatment regime involving resection, radiotherapy and chemotherapeutics is associated with significant co-morbidities, including growth and endocrine abnormalities, as well as impairment of cognitive function [2], [3]. Moreover, the use of chemotherapeutics and radiation treatments predisposes young patients to future treatment-induced neoplasms and malignancy.…”

Section: Introductionmentioning

confidence: 99%

“…The expression and requirement of SOX2 in central nervous system tumors is not surprising, given that SOX2 is expressed in neural progenitor cells and their progeny [9]. In brain tumor initiating cells [10], [11], hypomethylation of the SOX2 promoter has been directly correlated with SOX2 expression, and the SOX2 promoter is hypomethylated in aggressive glioblastoma patient samples [12]. Additionally, it has recently been reported that the SOX2 gene is amplified in nearly 10% of glioblastomas and overexpressed in over 85% of these tumors [12].…”

Section: Introductionmentioning

confidence: 99%

Elevating SOX2 Levels Deleteriously Affects the Growth of Medulloblastoma and Glioblastoma Cells

et al. 2012

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Medulloblastomas and glioblastomas are devastating tumors that respond poorly to treatment. These tumors have been shown to express SOX2 and overexpression of SOX2 has been correlated with poor prognosis. Although knockdown of SOX2 impairs the growth and tumorigenicity of brain tumor cells, it was unclear how elevating SOX2 levels would affect their fate. Interestingly, studies conducted with neural stem cells have shown that small increases or decreases in the level of this transcription factor significantly alter their fate. Here, we report that elevating SOX2 3-fold above endogenous levels in U87 and U118 glioblastoma, and DAOY medulloblastoma cells significantly impairs their ability to proliferate. We extended these findings and determined that elevating SOX2 in DAOY cells remodels their cell-cycle profile by increasing the proportion of cells in the G1-compartment, and induces the expression of genes associated with differentiation. Furthermore, we show that elevating SOX2 leads to a dramatic induction of CD133 expression in DAOY cells, yet inhibits the ability of both CD133+ and CD133− cells to form neurospheres. Together, these findings argue that SOX2 levels must be carefully controlled in glioblastomas and medulloblastomas to maintain their fate. Equally important, our data suggests that increases in the expression of SOX2 during brain tumor progression are likely to be linked closely with changes in other critical genes that work in concert with SOX2 to enhance the tumorigenicity of brain tumors. Importantly, we demonstrate that this is also likely to be true for other cancers that express SOX2. Moreover, these studies demonstrate the advantage of using inducible promoters to study the effects of SOX2 elevation, as compared to gene expression systems that rely on constitutive expression.

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Risk factors of recurrence in 157 MB/PNET patients treated in one institution

Cited by 9 publications

References 14 publications

Survival and prognostic factors in a series of adults with medulloblastomas

Survival and prognostic factors in a series of adults with medulloblastomas

The SOX2-Interactome in Brain Cancer Cells Identifies the Requirement of MSI2 and USP9X for the Growth of Brain Tumor Cells

Elevating SOX2 Levels Deleteriously Affects the Growth of Medulloblastoma and Glioblastoma Cells

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