Different Timing to Use Bevacizumab in Patients with Recurrent Glioblastoma: Early <i>Versus</i> Delayed Administration

Pasqualetti, Francesco; Gonnelli, Alessandra; Molinari, A.; Cantarella, M.; Montrone, S.; Cristaudo, Agostino; Baldaccini, Davide; Mattioni, Roberto; Delishaj, D.; Mazzotti, V.; Morganti, Riccardo; Cocuzza, P.; Fabrini, Maria Grazia; Lombardi, Giuseppe; Rudà, Roberta; Soffietti, Riccardo; Paiar, Fabiola

doi:10.21873/anticanres.12930

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…None of the distally recurrent glioblastoma cases (cases [11][12][13][14] showed concordance in the mutational profiles when compared to primary glioblastoma cases. Acquired mutations were detected in all cases of distally recurrent glioblastoma and included missense FBXW7 mutation (case 12), missense EGFR mutations (cases 13 and 14), CDKN2A deletion (case 11), and PDGFRA amplification (case 11).…”

Section: Histological Features Of Primary and Recurrent Glioblastomasmentioning

confidence: 95%

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Yoon

Kim

Lee

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Glioblastoma is the most malignant form of astrocytoma. The purpose of this study was to analyze the genetic characteristics of primary and recurrent glioblastomas using targeted sequencing and investigate the differences in mutational profiles between the locations of tumor recurrence. Materials and Methods: Fourteen glioblastoma patients who developed local (n=10) or distal (n=4) recurrence were included in the study. Targeted sequencing analysis was performed using the primary (n=14) and corresponding recurrent (n=14) tumor tissue samples. Results: The local and distal recurrence groups showed different genetic evolutionary patterns. Most of the locally recurrent glioblastomas demonstrated concordant mutational profiles between the primary and recurrent tumors, suggesting a linear evolution. In contrast, all cases of distally recurrent glioblastomas showed changes in mutational profiles with newly acquired mutations when compared to the corresponding primary tumors, suggesting a branching evolution. Conclusion: Locally and distally recurrent glioblastomas exhibit different evolutionary patterns. Glioblastoma is the most common malignant tumor of the central nervous system (1-9). The current standard treatment for glioblastoma involves surgical resection, followed by concurrent chemoradiation therapy and adjuvant chemotherapy using temozolomide (8-12). Due to the invasive nature of glioblastoma, surgical resection rarely eliminates all tumor cells, and postoperative treatment is usually necessary to prevent disease recurrence. Despite the advances made in therapeutic strategies, the prognosis of patients with glioblastoma remains very poor, with an average survival of 15 months (13-15) and disease recurrence being the major cause of mortality (16-18). Recurrent glioblastomas tend to be more invasive and resistant to chemotherapy than primary tumors. An understanding of the genetic characteristics of recurrent glioblastoma is crucial for identifying potential targets for drug discovery, stratifying patients for diagnosis, and optimizing an effective treatment strategy. Previous studies have shown the molecular features of recurrent glioblastomas. In particular, the mutational profiles observed in recurrent glioblastomas were compared to those of the corresponding primary tumors (19-21). However, there is a lack of studies exploring the differences in mutational profiles between recurrent glioblastomas at different sites (21, 22). In this study, we investigated the mutational profiles of primary and recurrent glioblastomas using 803 This article is freely accessible online.

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Section: Histological Features Of Primary and Recurrent Glioblastomasmentioning

confidence: 95%

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Yoon

Kim

Lee

et al. 2020

Cancer Genomics Proteomics

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“…1,2 It is estimated that the 5-year survival rate of glioblastoma patients is <4%. 3 The growth manner of glioblastoma is mainly invasive growth, thus aggravating the difficulty of clinical treatment. 4,5 Main treatments for glioblastoma include surgery, radiotherapy, chemotherapy and combined treatment, etc.…”

Section: Introductionmentioning

confidence: 99%

Nucleobindin-2 Promotes the Growth and Invasion of Glioblastoma

Liu

et al. 2019

Cancer Biotherapy and Radiopharmaceuticals

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Background: Glioblastoma is one of the most malignant tumors in the brain with high mortality. In recent years, immunotherapy and targeted therapy show great prospects in the treatments for glioblastoma, whereas more effective therapeutic targets are still urgently needed to be developed. Nucleobindin-2 (NUCB2) is the precursor protein of nesfatin-1, which have a variety of metabolic functions, such as food intake and temperature regulation. In recent years, the potential link between NUCB2 and the development of multiple cancer was gradually revealed; however, the effects of NUCB2 on the progression of glioblastoma are still unclear. Methods: Immunohistochemical assays were performed to explore the NUCB2 expression levels in 94 samples of glioblastoma and corresponding nontumor tissues; patients were divided into NUCB2 high expression group and low expression group. Clinical analysis related to the clinical features, the potential link between NUCB2 expression levels, and clinical features were analyzed; the effects of NUCB2 on cell proliferation and invasion of glioblastoma were detected through colony formation and MTT assay, and transwell assay respectively. The possible effects of NUCB2 on tumor growth and metastasis were measured in mice. Results: In this study, we demonstrated that NUCB2 over-expression was correlated with the high degree of recurrence of patients with glioblastoma. Further, we also revealed that NUCB2 promoted cell proliferation and invasion of glioblastoma in vitro and promoted the growth and metastasis of glioblastoma in mice. Conclusion:This study provided evidence that NUCB2 might be a novel therapeutic target of glioblastoma.

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“…All patients underwent surgery (gross tumor removal or partial tumor removal (including biopsy)), postoperative radiotherapy (60 Gy/30 fractions, delivered using the volumetric modulated arc therapy technique with concomitant daily temozolomide), and sequential chemotherapy with temozolomide (planned up to 12 cycles). After the diagnosis of disease recurrence, every patient was treated with salvage therapies (second-line chemotherapy, with or without second surgery and/or re-irradiation) or the best supportive care [ 3 , 18 , 19 ]. The overall survival (OS) rate was calculated from the beginning of radiotherapy until death or the last follow-up.…”

Section: Patients and Systemic Inflammation Indexesmentioning

confidence: 99%

Old and New Systemic Immune-Inflammation Indexes Are Associated with Overall Survival of Glioblastoma Patients Treated with Radio-Chemotherapy

Pasqualetti

Giampietro

Montemurro

et al. 2022

Genes

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Background. Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods. We tested 12 different SI using blood tests from patients with isocitrate dehydrogenase 1 and 2 wild-type glioblastomas, treated with radio-chemotherapy. The primary endpoint was their overall survival. Results. A total of 77 patients, comprising 43 males and 34 females, with a median age of 64 years (age range 26–84), who were treated between October 2010 and July 2020, were included in the present analysis (approved by a local ethics committee). In the univariate Cox regression analysis, all the indexes except two showed a statistically significant impact on OS. In the multivariate Cox regression analysis, neutrophil × platelet × leukocyte/(lymphocyte × monocyte) (NPW/LM) and neutrophil × platelet × monocyte/lymphocyte (NPM/L) maintained their statistically significant impact value. Conclusions. This univariate analysis confirms the potential of systemic inflammation indexes in patients with glioblastoma, while the multivariate analysis verifies the prognostic value of NPW/LM and NPM/L.

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Different Timing to Use Bevacizumab in Patients with Recurrent Glioblastoma: Early Versus Delayed Administration

Cited by 8 publications

References 23 publications

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Nucleobindin-2 Promotes the Growth and Invasion of Glioblastoma

Old and New Systemic Immune-Inflammation Indexes Are Associated with Overall Survival of Glioblastoma Patients Treated with Radio-Chemotherapy

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