A very rare case report of long-term survival: A patient operated on in 1994 of glioblastoma multiforme and currently in perfect health

Caruso, Riccardo; Pesce, Alessandro; Wierzbicki, Venceslao

doi:10.1016/j.ijscr.2017.02.025

Cited by 16 publications

(18 citation statements)

References 22 publications

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“…Primary GB, while only rarely metastasising outside brain and central nervous system, has not been shown to exist in a pre-invasive form, hence tumour de-bulking, while alleviating symptoms, should not be considered a curative option 1,4 . Although radiation and chemotherapy in form of the alkylating agent Temozolomide (TMZ) further prolong average patient survival to about 15 months, full remission is exceedingly rare 3,44 . Novel therapeutic approaches, although urgently needed, are frequently hampered by the presence of the blood-brain barrier, which often blocks a dispersal of pharmacological substances throughout the brain.…”

Section: Discussionmentioning

confidence: 99%

The limitations of targeting MEK signalling in Glioblastoma therapy

Selvasaravanan

Wiederspohn

Hadzalic

et al. 2020

Sci Rep

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Glioblastoma (GB) is a highly aggressive, difficult to treat brain tumour. Successful treatment, consisting of maximal safe tumour de-bulking, followed by radiotherapy and treatment with the alkylating agent Temozolomide (TMZ), can extend patient survival to approximately 15 months. Combination treatments based on the inhibition of the PI3K pathway, which is the most frequently activated signalling cascade in GB, have so far only shown limited therapeutic success. Here, we use the clinically approved MEK inhibitor Trametinib to investigate its potential use in managing GB. Trametinib has a strong anti-proliferative effect on established GB cell lines, stem cell-like cells and their differentiated progeny and while it does not enhance anti-proliferative and cell death-inducing properties of the standard treatment, i.e. exposure to radiation or TMZ, neither does MEK inhibition block their effectiveness. However, upon MEK inhibition some cell populations appear to favour cellsubstrate interactions in a sprouting assay and become more invasive in the Chorioallantoic Membrane assay, which assesses cell penetration into an organic membrane. While this increased invasion can be modulated by additional inhibition of the PI3K signalling cascade, there is no apparent benefit of blocking MEK compared to targeting PI3K. Glioblastoma (GB), formerly Glioblastoma multiforme, is the most common primary brain tumour in adults and-due to its aggressive and highly infiltrative nature-among the most lethal malignancies per se 1. The current standard therapy involves maximum safe surgical resection followed by radio-and chemotherapy with the alkylating agent Temozolomide (TMZ) 2 which leads to a mean patient survival of only 15 months 3. Although GB only rarely metastasised outside the neuraxis, upon clinical presentation it will almost invariably have infiltrated the surrounding brain tissue, impeding full surgical resection and resulting in tumour recurrence 4. GB exhibits a rather low mutational burden 5 , with the most consistent alterations found in the PI3K signalling cascade, which is activated in ~88% of all GBs 6,7. Despite intensive efforts to translate modulation of this signalling pathway into a clinical setting, so far, only two mTOR (a downstream modulator of PI3K signalling) inhibitors, Everolimus and Temsirolimus, have been approved for clinical use 8. This might be, at least in part, due to the complexity of the PI3K pathway, while frequently reduced to a "survival pathway" in the context of cancer research, this network has several distinct and somehow competing functions 9,10. In our hands, inhibition of PI3K signalling in differentiated GB cells (DGBCs) only weakly reduces their proliferation and has little effect on their resistance to apoptosis; however, it strongly reduces their motility. In contrast the motility of the corresponding stem cell-like cells (SCs) was not affected, but the increased resistance of SCs compared to DGBCs with regard to apoptosis induction, seems to be mediated, at least in part, by PI...

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Section: Discussionmentioning

confidence: 99%

The limitations of targeting MEK signalling in Glioblastoma therapy

Selvasaravanan

Wiederspohn

Hadzalic

et al. 2020

Sci Rep

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“…The use of substances like 5-Aminolevulinic acid hydrochloride (11), which mark and thus make tumoral tissue easier to identify during an operation, have improved surgery for cerebral gliomas; in fact they allow for a more thorough excision (12), but increased the risk for postoperative complications like neurological deficit, so the using of intraoperative neuromonitoring is mandatory in order to decrease this potential risk. We experienced that in our case, finally we were not able to resect all the amount of tumor revealed by 5-ALA intraoperative visualization because of the electric imperative risk signs for motor deficit.…”

Section: Discussionmentioning

confidence: 99%

Unusual aggressive and rapidly growing glioblastoma multiforme – case presentation

Dabija¹,

Eva²,

Poeată³

et al. 2017

Romanian Neurosurgery

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Glioblastoma multiform is one of the most rapidly progressing cerebral tumors and the most aggressive one in our neurosurgical experience. We present the case of a 45 year old patient with very aggressive type of tumor who had come to our service for the following: intense headache, confusion, right hemiparesis installed approximately one month before. IRM scan shows up the presence of a large tumoral mass without a precise border in the left temporal-parietal region which had extended all the way down to the thalamus. The planned intervention used 5-aminolevulinic acid (5-ALA) for the precise removal of the tumor mass, suboptimal because of the risk of lesioning the motor tractsindicated by the intraoperative electrophysiological monitoring. After surgery the outcome was good with the partial regression of the motor deficit, but only after 3 weeks due to the unexpected tumor growth the neurological status started to decay and even worsened. The patient underwent surgery again with the partial remission of the symptoms although following imagistic controls showed up fast tumor growth once more. He was recommended to oncology service for the beginning of radiotherapy. We consider the evolution and invasion of this tumor in only a 3 weeks period being impressive.

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“…Nowadays with the innovations introduced by molecular biology, the effect on overall survival (OS) of many molecular parameters has been investigated, such as p53, epidermal growth factor receptor (EGFR), IDH and MGMT. Some of these parameters demonstrated an interaction with the adjuvant treatment, thus significantly influencing survival [14]. The role surgery, or more precisely of the extent of resection (EOR), to date, remains unquestioned [15], although surgery can obtain totally different results in regards to the EOR, depending on the plethora of different techniques developed and introduced to maximize the resection while sparing the function, such as awake surgery, intraoperative neuromonitoring (IoN) and intraoperative neuropsychological testing (IoNT), intraoperative imaging methods and even hypnosis aided awake surgery (HAS).…”

Section: Background and Rationalementioning

confidence: 99%

Long Term Survival in Patients Suffering from Glio-blastoma Multiforme: A Single-Center Observational Cohort Study

et al. 2019

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Background: Glioblastomas (GBM) are generally burdened, to date, by a dismal prognosis, although long term survivors have a relatively significant incidence. Our specific aim was to determine the exact impact of many surgery-, patient-and tumor-related variables on survival parameters. Methods: The surgical, radiological and clinical outcomes of patients have been retrospectively reviewed for the present study. All the patients have been operated on in our institution and classified according their overall survival in long term survivors (LTS) and short term survivors (STS). A thorough review of our surgical series was conducted to compare the oncologic results of the patients in regard to: (1) surgical-(2) molecular and (3) treatment-related features. Results: A total of 177 patients were included in the final cohort. Extensive statistical analysis by means of univariate, multivariate and survival analyses disclosed a survival advantage for patients presenting a younger age, a smaller lesion and a better functional status at presentation. From the histochemical point of view, Ki67 (%) was the strongest predictor of better oncologic outcomes. A stepwise analysis of variance outlines the existence of eight prognostic subgroups according to the molecular patterns of Ki67 overexpression and epidermal growth factor receptor (EGFR), p53 and isocitrate dehydrogenase (IDH) mutations. Conclusions: On the grounds of our statistical analyses we can affirm that the following factors were significant predictors of survival advantage: Karnofsky performance status (KPS), age, volume of the lesion, motor disorder at presentation and/or a Ki67 overexpression. In our experience, LTS is associated with a gross total resection (GTR) of tumor correlated with EGFR and p53 mutations with regardless of localization, and poorly correlated to dimension. We suppose that performing a standard molecular analysis (IDH, EGFR, p53 and Ki67) is not sufficient to predict the behavior of a GBM in regards to overall survival (OS), nor to provide a deeper understanding of the meaning of the different genetic alterations in the DNA of cancer cells. A fine molecular profiling is feasible to precisely stratify the prognosis of GBM patients.

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A very rare case report of long-term survival: A patient operated on in 1994 of glioblastoma multiforme and currently in perfect health

Cited by 16 publications

References 22 publications

The limitations of targeting MEK signalling in Glioblastoma therapy

The limitations of targeting MEK signalling in Glioblastoma therapy

Unusual aggressive and rapidly growing glioblastoma multiforme – case presentation

Long Term Survival in Patients Suffering from Glio-blastoma Multiforme: A Single-Center Observational Cohort Study

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