Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies

Cenciarini, Marta; Valentino, Mario; Belia, Silvia; Sforna, Luigi; Rosa, Paolo; Ronchetti, Simona; D’Adamo, Maria Cristina; Pessia, Mauro

doi:10.3389/fnmol.2019.00065

Cited by 77 publications

(63 citation statements)

References 166 publications

(212 reference statements)

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“…Several studies suggest a detrimental effect of dexamethasone on GBM survival outcomes. 27 Although available data are inconclusive and mainly retrospective with inherent bias, steroids should be used as needed but with caution during the SARS-CoV-2 pandemic. A recent publication outlined the detrimental effects and the clinical outcomes of corticosteroid use in coronavirus and similar outbreaks as a reference.…”

Section: Steroidsmentioning

confidence: 99%

Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas

et al. 2020

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Abstract Background Because of the increased risk in cancer patients of developing complications caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), physicians have to balance the competing risks of the negative impact of the pandemic and the primary tumor disease. In this consensus statement, an international group of experts present mitigation strategies and treatment guidance for patients suffering from high grade gliomas (HGGs) during the coronavirus disease 2019 (COVID-19) pandemic. Methods Sixteen international experts in the treatment of HGG contributed to this consensus-based practice recommendation, including neuro-oncologists, neurosurgeons, radiation oncologists, and a medical physicist. Generally, treatment of neuro-oncological patients cannot be significantly delayed and initiating therapy should not be outweighed by COVID-19. We present detailed interdisciplinary treatment strategies for molecular subgroups in 2 pandemic scenarios, a scale-up phase and a crisis phase. Conclusion This practice recommendation presents a pragmatic framework and consensus-based mitigation strategies for the treatment of HGG patients during the SARS-CoV-2 pandemic.

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Section: Steroidsmentioning

confidence: 99%

Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas

et al. 2020

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“…Using mouse GBM models, we determined that surgical resection alone leads to a reduction in circulating T cells, in addition to the known impact of steroid treatment [18][19][20] , which is also being revisited in terms of its clinical use. Many groups have shown that T cell abundance is one of multiple factors influencing immunotherapy response.…”

Section: Discussionmentioning

confidence: 99%

Preclinical modeling of surgery and steroid therapy for glioblastoma reveals changes in immunophenotype that are associated with tumor growth and outcome

Otvos

Alban

Grabowski

et al. 2020

Preprint

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Recent advances in cancer immunotherapy have created a greater appreciation of potential anti-tumoral impacts by the immune system; however, individual patient responses have been variable. While immunotherapy is often given after standard-of-care treatment, the effects of initial interventions on the ability of the immune system to mount a response are not well understood and this may contribute to the variable response. For glioblastoma (GBM), initial disease management includes surgical resection, perioperative high-dose steroid therapy, chemotherapy, and radiation treatment. While new discoveries regarding the impact of chemotherapy and radiation on immune response have been made and translated to clinical trial design, the impact of surgical resection and steroids on the anti-tumor immune response has yet to be determined. Further, it is now accepted that steroid usage needs to be closely evaluated in the context of GBM and immunotherapy trials. To better model the clinical scenario in GBM, we developed a mouse model that integrates tumor resection and steroid treatment to understand how these therapies affect local and systemic immune responses. Using this model, we observed a systemic reduction in lymphocytes associated with surgical resection and identified a correlation between increased tumor volume and decreased circulating lymphocytes, a relationship that was obviated by dexamethasone treatment. Furthermore, we investigated the possibility of there being similar relationships in a cohort of patients with GBM and found that prior to steroid treatment, circulating lymphocytes inversely correlated with tumor volume. Lastly, correlating GBM patient data and outcomes demonstrated that peripherally circulating lymphocyte content varies with progression-free and overall survival, independent of tumor volume, steroid use, or tumor molecular profiles. These results highlight the systemic immunosuppressive effects that initial therapies can have on patients. Such effects should be considered when designing current and future immunotherapy clinical trials and underscore the importance of circulating lymphocytes as a possible correlate of GBM disease progression.

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“…Our search on drugs used in glioma treatment revealed that Bevacizumab is monoclonal antibody which targets the VEGF pathway via its downstream cascade of PI3K pathway. Also, FGFR2, MAP2K2, MAP3K4, and HSPB1, which are targets to Dexamethasone, are associated with "Regulation of actin cytoskeleton" and "GnRH signaling pathway" (Cenciarini et al, 2019). The study of the drugs, drug targets, and their associated pathway is particularly important to understand what features of cancer can be utilized for treatment.…”

Section: Involvement Of Identified Significant Genes On Different Pmentioning

confidence: 99%

Prediction of survival rate and effect of drugs on cancer patients with somatic mutations of genes: An AI‐based approach

et al. 2020

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The causal role of somatic mutation and its interrelationship with gene expression profile during tumor development has already been observed, which plays a major role to decide the cancer grades and overall survival. Accurate and robust prediction of tumor grades and patients' overall survival are important for prognosis, risk factors identification and betterment of the treatment strategy, especially for highly lethal tumors, like gliomas. Here, with the help of more accurate and widely used machine learning-based approaches, we propose an integrative computational pipeline that incorporates somatic mutations and gene expression profile for survival and grade prediction of glioma patients and simultaneously relates it to the drugs to be administered. This study gives us a clear understanding that the same drug is not effective for the treatment of same grade of cancer if the gene mutations are different. The alteration in a specific gene plays a very important role in tumor progression and should also be considered for the selection of appropriate drugs. This proposed framework includes all the necessary factors required for enhancement of therapeutic designs and could be useful for clinicians in determining an accurate and personalized treatment strategy for individual patients suffering from different life threatening diseases.

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Dexamethasone in Glioblastoma Multiforme Therapy: Mechanisms and Controversies

Cited by 77 publications

References 166 publications

Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas

Neuro-oncology management during the COVID-19 pandemic with a focus on WHO grades III and IV gliomas

Preclinical modeling of surgery and steroid therapy for glioblastoma reveals changes in immunophenotype that are associated with tumor growth and outcome

Prediction of survival rate and effect of drugs on cancer patients with somatic mutations of genes: An AI‐based approach

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