Glioblastoma multiforme in a child with tuberous sclerosis complex

Lesma, Elena; Alfano, Rosa Maria; Peron, Angela; Scornavacca, Giulia Federica; Massimino, Maura; Schiavello, Elisabetta; Ancona, Silvia; Cerati, Michele; Bulfamante, Gaetano; Gorio, Alfredo; Canevini, Maria Paola

doi:10.1002/ajmg.a.37158

Cited by 16 publications

(11 citation statements)

References 19 publications

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“…Due to the extremely low number of each malignancy, a comparison with data in the general population was not possible. With respect to each type of cancer encountered in our cohort, we found only two other patients with Wilm's tumor [Grether et al, ; Spreafico et al, ], six with glioblastoma multiforme besides the one previously described by our team [Cristofori et al, ; Brown, ; Padmalatha et al, ; Al‐Saleem et al, ; Matsumura et al, ; Reyes and Prayson, ; Vignoli et al, ], two with uterine cancer [Jaffe and Chambers, ; Wataya‐Kaneda et al, ], and one with a possible abdominal sarcoma [Bonetti et al, ]. Although there seems to be an association between chordomas and TSC [McMaster et al, ], we did not find any patients with this malignancy in our cohort.…”

Section: Discussionmentioning

confidence: 91%

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Do patients with tuberous sclerosis complex have an increased risk for malignancies?

Peron

Vignoli

Briola

et al. 2016

American J of Med Genetics Pt A

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Tuberous Sclerosis Complex (TSC) is generally characterized by the presence of benign tumors, but some patients with malignancies have been reported in the literature. We examined a large Italian TSC population (240 individuals followed from 2001 to 2015, aged 3 months-74 years), assessing the frequency of malignancies to determine whether there is an increased risk for cancer in this disorder, and looking for possible features associated with the development of neoplasia. Fifteen patients had malignancies (6.25%); median age at diagnosis was 37.5 years (range of 1.6-58). Five of seven renal tumors were renal cell carcinomas. Eight patients had a non-renal malignancy (3.3%), but we did not find a more prevalent type of cancer. No patient developed more than one malignancy. The prevalence of all malignant tumors was compatible with the prevalence in the general population (5.6%, 95%CI 2.99-9.31%, vs. 4.4% in Italy). Median age at cancer diagnosis was lower (37.5 years, 95%CI 28.6-44.7, vs. 66.0 years). Two patients (13.3%) died of their cancer, while outcome was favorable in the remaining individuals. Malignant tumors were more frequently diagnosed in patients with mutations in TSC1 when compared to TSC2 and patients with no mutation identified (P = 0.032). Our study demonstrated that TSC patients do not seem to have an increased risk for malignancies besides renal cell carcinoma. However, when cancer develops, age at diagnosis is lower than in the general population, and malignant tumors are more frequently diagnosed in patients with mutations in TSC1. Further studies are needed to confirm these data. ©2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 91%

“…The clinical, genetic, and histological characteristics of each patient are reported in Table . Patient 10 was previously described by our group [Vignoli et al, ]. Eleven individuals (73.3%) were female; four (26.7%) were male.…”

Section: Resultsmentioning

confidence: 99%

Do patients with tuberous sclerosis complex have an increased risk for malignancies?

Peron

Vignoli

Briola

et al. 2016

American J of Med Genetics Pt A

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“…Of note, loss of TSC1 accelerates malignant glioma genesis when it is combined with oncogenic signals [20]. Patients with tuberous sclerosis have a bi-allelic loss of TSC1/TSC2 and a few clinical cases have been reported on the occurrence of GBM in such patients [21], but further investigations related to this association are needed.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme

Alkharusi

Landázuri

et al. 2016

Oncotarget

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Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high levels in U251-MG, at low levels in U87-MG and barely detectable in U373 cell lines and in 66% of brain tumor tissues from 32 GBM patients by immunohistochemical technique. In addition, stimulation of U251-MG and U87-MG cells but not U373 with Prl resulted in increased STAT5 phosphorylation and only in U251-MG cells with increased cellular invasion. Furthermore, STAT5 phosphorylation and cellular invasion induced in Prl stimulated cells were significantly reduced by using a Prl receptor antagonist that consists of Prl with four amino acid replacements. We conclude that Prl receptor is expressed at different levels in the majority of GBM tumors and that blocking of PrlR in U251-MG cells significantly reduce cellular invasion.

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“…This article was referenced 28 times (Web of Science, retrieved 9-1-2017) and none of the referencing manuscripts mentioned other cases of induced malignant brain tumor. A case of a potentially radiation-induced meningioma was mentioned by Shepherd et al as the cause of death of a patient 19 years after radiation (15).Seven more malignant gliomas were reported in TSC patients that never received therapeutic radiation(16)(17)(18)(19)(20)(21)(22).An article specifically looking at the incidence of malignant tumors in TSC patients examined 240 patients over 14 years and concluded that there was only an increased risk in renal cancer but not of intracranial tumors(23)…”

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Radiotherapy for subependymal giant cell astrocytoma: time to challenge a historical ban? Case report and review of the literature.

Kamel

Berge

2020

Preprint

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Background Subependymal giant cell astrocytoma is a deep-seated benign but life-threatening brain tumor that occurs in patients with the tuberous sclerosis complex. Resection is the traditional treatment and expert opinion is strongly against the use of radiotherapy. Systematic epidemiological studies, however, demonstrate high rates of complications and recurrences. The need for efficient non-surgical treatment is best illustrated by the considerable enthusiasm about the activity of the mTOR inhibitor everolimus in reducing tumor volume. Unfortunately regrowth is frequent after dose reduction or cessation and continued tumor control requires continued administration of the drug, leading to concerns about its metabolic and immunosuppressive side effects and cost of treatment. Results We successfully treated a case with growing bilateral subependymal giant cell astrocytoma with fractionated stereotactic radiotherapy before everolimus became available. After a follow-up of 8 years, everolimus was administered for renal angiomyolipoma and the patient was followed up until 13 years after radiotherapy. Successive MRI's demonstrated an 80% volume reduction after radiotherapy that further increased to 90% during everolimus administration. In order to review the basis for the strong expert opinion against radiotherapy, we performed an exhaustive literature study regarding efficiency, potential dangers and side effects of radiation. 1298 article references and 780 full-text articles in search of evidence for contra-indicating radiotherapy. Varying short-term tumor control of single-fraction radiosurgery were described in a total of 13 cases. Only in two published cases the radiation dose of fractionated radiotherapy was mentioned. A single publication mentions an induced secondary brain tumor 8 years after total brain irradiation. Conclusion There is no evidence for contra-indicating fractionated radiotherapy in subependymal giant cell astrocytoma. Our experience demonstrates that these tumors, as other benign intracranial tumors, responds slowly to radiotherapy and suggests that fractionated stereotactic radiotherapy holds promise to consolidate responses obtained with mTOR inhibitors avoiding regrowth after cessation. This combined treatment would avoid costs and complications of long-term treatment with everolimus and deserves to be studied as a definitive non-surgical treatment.

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Glioblastoma multiforme in a child with tuberous sclerosis complex

Cited by 16 publications

References 19 publications

Do patients with tuberous sclerosis complex have an increased risk for malignancies?

Do patients with tuberous sclerosis complex have an increased risk for malignancies?

Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme

Radiotherapy for subependymal giant cell astrocytoma: time to challenge a historical ban? Case report and review of the literature.

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