The Glioma-IRE project − Molecular profiling in patients with glioma: steps toward an individualized diagnostic and therapeutic approach

Villani, Veronica; Casini, Beatrice; Tanzilli, Antonio; Lecce, Mario; Rasile, Fabrizio; Telera, Stefano; Pace, Andrea; Piludu, Francesca; Terrenato, Irene; Rollo, Francesca; Nicola, Francesca De; Fanciulli, Maurizio; Pallocca, Matteo; Ciliberto, Gennaro; Carosi, Mariantonia

doi:10.1186/s12967-023-04057-y

Cited by 5 publications

(9 citation statements)

References 42 publications

(41 reference statements)

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“…Beyond avoiding toxicities, molecular diagnostics may increase the precision of diagnosis and treatment choice. While molecular profiling and targeting are still relatively new in clinical practice for glioma, several recent studies have supported the notion that molecularly guided therapy is feasible and provides clinical benefit, including in glioblastoma and recurrent glioma ( 24 , 200 , 201 ). A guideline on rational molecular testing of gliomas, glioneural, and neuronal tumors also argued for molecular testing to target therapy but cautioned that only a handful of targets had sufficient evidence available to justify testing for them in standard care ( 202 ).…”

Section: Discussionmentioning

confidence: 99%

High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma

Pöhlmann,

Weller,

Marcellusi

et al. 2024

Front. Oncol.

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Gliomas are a group of heterogeneous tumors that account for substantial morbidity, mortality, and costs to patients and healthcare systems globally. Survival varies considerably by grade, histology, biomarkers, and genetic alterations such as IDH mutations and MGMT promoter methylation, and treatment, but is poor for some grades and histologies, with many patients with glioblastoma surviving less than a year from diagnosis. The present review provides an introduction to glioma, including its classification, epidemiology, economic and humanistic burden, as well as treatment options. Another focus is on treatment recommendations for IDH-mutant astrocytoma, IDH-mutant oligodendroglioma, and glioblastoma, which were synthesized from recent guidelines. While recommendations are nuanced and reflect the complexity of the disease, maximum safe resection is typically the first step in treatment, followed by radiotherapy and/or chemotherapy using temozolomide or procarbazine, lomustine, and vincristine. Immunotherapies and targeted therapies currently have only a limited role due to disappointing clinical trial results, including in recurrent glioblastoma, for which the nitrosourea lomustine remains the de facto standard of care. The lack of treatment options is compounded by frequently suboptimal clinical practice, in which patients do not receive adequate therapy after resection, including delayed, shortened, or discontinued radiotherapy and chemotherapy courses due to treatment side effects. These unmet needs will require significant efforts to address, including a continued search for novel treatment options, increased awareness of clinical guidelines, improved toxicity management for chemotherapy, and the generation of additional and more robust clinical and health economic evidence.

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Section: Discussionmentioning

confidence: 99%

High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma

Pöhlmann,

Weller,

Marcellusi

et al. 2024

Front. Oncol.

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“…The outcome of the developed predictor models with different identified genes was dependent by the choices of the employed feature selection. However, in this context, the great majority of altered genes was previously identified as associated with high grade glioma and contributing in the dysregulation of key pathways involving tumor suppressors or oncogenes [ 25 , 44 – 51 , 53 ]. In particular, a role for gene mutations of BRAF was highlighted by the ML modeling.…”

Section: Discussionmentioning

confidence: 99%

Machine learning to improve interpretability of clinical, radiological and panel-based genomic data of glioma grade 4 patients undergoing surgical resection

Polano

Ius

et al. 2023

J Transl Med

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Background Glioma grade 4 (GG4) tumors, including astrocytoma IDH-mutant grade 4 and the astrocytoma IDH wt are the most common and aggressive primary tumors of the central nervous system. Surgery followed by Stupp protocol still remains the first-line treatment in GG4 tumors. Although Stupp combination can prolong survival, prognosis of treated adult patients with GG4 still remains unfavorable. The introduction of innovative multi-parametric prognostic models may allow refinement of prognosis of these patients. Here, Machine Learning (ML) was applied to investigate the contribution in predicting overall survival (OS) of different available data (e.g. clinical data, radiological data, or panel-based sequencing data such as presence of somatic mutations and amplification) in a mono-institutional GG4 cohort. Methods By next-generation sequencing, using a panel of 523 genes, we performed analysis of copy number variations and of types and distribution of nonsynonymous mutations in 102 cases including 39 carmustine wafer (CW) treated cases. We also calculated tumor mutational burden (TMB). ML was applied using eXtreme Gradient Boosting for survival (XGBoost-Surv) to integrate clinical and radiological information with genomic data. Results By ML modeling (concordance (c)- index = 0.682 for the best model), the role of predicting OS of radiological parameters including extent of resection, preoperative volume and residual volume was confirmed. An association between CW application and longer OS was also showed. Regarding gene mutations, a role in predicting OS was defined for mutations of BRAF and of other genes involved in the PI3K-AKT-mTOR signaling pathway. Moreover, an association between high TMB and shorter OS was suggested. Consistently, when a cutoff of 1.7 mutations/megabase was applied, cases with higher TMB showed significantly shorter OS than cases with lower TMB. Conclusions The contribution of tumor volumetric data, somatic gene mutations and TBM in predicting OS of GG4 patients was defined by ML modeling.

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“…Among the most important genetic variants, mutations in the isocitrate dehydrogenase (IDH) gene identify IDH-mutant gliomas that demonstrate a better prognosis than wildtype IDH gliomas [11,12]. Other molecular alterations include mutations in the tumor-suppressor gene tumor protein 53 (TP53), the alpha-thalassemia/mental retardation x-linked (ATRX) syndrome, and the epidermal growth factor receptor (EGFR) pathway [13].…”

Section: Epidemiology and Classification Of Gliomasmentioning

confidence: 99%

Advancements in Glioma Care: Focus on Emerging Neurosurgical Techniques

De Simone,

Conti,

Palermo

et al. 2023

Biomedicines

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Background: Despite significant advances in understanding the molecular pathways of glioma, translating this knowledge into effective long-term solutions remains a challenge. Indeed, gliomas pose a significant challenge to neurosurgical oncology because of their diverse histopathological features, genetic heterogeneity, and clinical manifestations. Relevant sections: This study focuses on glioma complexity by reviewing recent advances in their management, also considering new classification systems and emerging neurosurgical techniques. To bridge the gap between new neurosurgical approaches and standards of care, the importance of molecular diagnosis and the use of techniques such as laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) are emphasized, exploring how the integration of molecular knowledge with emerging neurosurgical approaches can personalize and improve the treatment of gliomas. Conclusions: The choice between LITT and FUS should be tailored to each case, considering factors such as tumor characteristics and patient health. LITT is favored for larger, complex tumors, while FUS is standard for smaller, deep-seated ones. Both techniques are equally effective for small and superficial tumors. Our study provides clear guidance for treating pediatric low-grade gliomas and highlights the crucial roles of LITT and FUS in managing high-grade gliomas in adults. This research sets the stage for improved patient care and future developments in the field of neurosurgery.

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The Glioma-IRE project − Molecular profiling in patients with glioma: steps toward an individualized diagnostic and therapeutic approach

Cited by 5 publications

References 42 publications

High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma

High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma

Machine learning to improve interpretability of clinical, radiological and panel-based genomic data of glioma grade 4 patients undergoing surgical resection

Advancements in Glioma Care: Focus on Emerging Neurosurgical Techniques

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