Management of glioblastoma after recurrence: A changing paradigm

Mallick, Supriya; Benson, Rony; Hakim, Abdul; Rath, G.K.

doi:10.1016/j.jnci.2016.07.001

“…For recGB, there is no standard treatment. Despite intensive efforts in the past decade to define therapeutically effective treatments for recGB none of the regimens tested yielded significant results [5,19,20]. Most of investigational therapies tested so far in recGBs have been based on a hypothesistesting approach aiming at addressing the following possibilities 1) Improving clinical outcomes through repeated application of the principle modules of standard unspecific therapy (surgery, RT or TMZ) in recGBs 2) Improving clinical outcomes through targetoriented treatments interfering with intrinsic (angiogenesis, invasion/ adhesion/ECM remodelling, proliferation) or extrinsic (tumourassociated immunosupression) mechanisms in recGB.…”

Section: Glioblastoma: General Factsmentioning

confidence: 99%

Perspectives and Challenges in Molecular-Based Diagnostics and Personalized Treatment for Recurrent High-Grade Gliomas

Kalasauskas¹,

Renovanz²,

Bikar³

et al. 2017

View full text Add to dashboard Cite

Glioblastoma is the most common and most malignant type of intrinsic brain tumor in adults. The standard of care for glioblastoma consists of surgical debulking followed by combined radiochemotherapy. The clinical efficacy of standard therapies for newly diagnosed glioblastomas is rather modest with the highest survival rate at 5-years being less than 10%. Inevitable recurrence after cytotoxic therapies poses the major challenge in the clinical management of high grade gliomas. For recurrent glioblastomas, there is no standard therapy with lack of level one evidence for treatment efficacy. Recent evidence indicates that post-therapy recurrence in gliomas is a consequence of a plethora of molecular and cellular factors including intratumoural heterogeneity, functional hierarchy of distinct types of glioma cells, dynamic changes in the molecular landscapes and cellular composition of the tumour during therapy and the impact of particular treatment modalities. There is an emerging consensus that molecular distinctions within and between individual tumours is an important factor determining clinical outcomes. Consequently, integrated approaches based on the combination of molecular profiling with traditional methods such as immunohistochemical phenotyping, karyotyping and/or non-quantitative methylation-specific PCR have emerged as a promising venue towards increasing the predictive value of diagnostics for malignant brain tumors. The high level of inter-and intra-tumoural molecular diversity in gliomas underscores the need of integrating high throughput molecular profiling and pharmacogenomics into a diagnostic paradigm for gliomas and raises the possibility that molecular-instructed personalized treatments may provide clinical benefit to patients with glioblastoma, particularly in the setting of post-treatment recurrence. Here we discuss potential prospects and challenges of patient-tailored diagnostics and personalized treatment strategies for recurrent glioblastomas.

show abstract

“…A direct relationship between the level of genetic complexity and poor efficacy of therapeutic strategies based on the "one-treatment-for-all" principle can be seen in glioblastoma, a genetically complex cancer characterized by a high degree of molecular and cellular heterogeneity. The promise of high-throughput molecularbased diagnostics as a strategy for more accurate patient stratification and prognostic staging has been recognized as a matter of urgent priority for improving the efficacy of glioblastoma therapy [4,5]. In this article, we discuss the current state, perspectives and specific challenges in molecular characterization and development of personalized approaches for treatment-refractory glioblastoma.…”

Section: Personalized Approach To Cancer Treatmentmentioning

confidence: 99%

“…An inevitable recurrence after standard therapy is the ultimate cause of death from glioblastoma. Currently, there are no treatments for recurrent glioblastoma (recGB), with the lack of therapeutic options precluding any chance of disease control after recurrence [5,18].…”

Section: Glioblastoma: General Factsmentioning

confidence: 99%

“…Immunotherapeutic approaches based on autologous vaccination with dendritic cells have yielded some encouraging preliminary results in both ndGB and recGBs in a series of Phase I/II trials [21,22] but their confirmation in Phase III is still awaited. A comprehensive discussion of the outcomes of all completed trials on recGB has been covered in several recent reviews [5,19,20].…”

Section: Glioblastoma: General Factsmentioning

confidence: 99%

See 1 more Smart Citation

Assessment of Anti-Proliferative Activities of Selected Medicinal Plant Extracts Used for Management of Diseases around Lake Victoria Basin

Swaya¹,

Aduma²,

Chelimo³

et al. 2017

J Carcinog Mutagen

2

0

View full text Add to dashboard Cite

Glioblastoma is the most common and most malignant type of intrinsic brain tumor in adults. The standard of care for glioblastoma consists of surgical debulking followed by combined radiochemotherapy. The clinical efficacy of standard therapies for newly diagnosed glioblastomas is rather modest with the highest survival rate at 5-years being less than 10%. Inevitable recurrence after cytotoxic therapies poses the major challenge in the clinical management of high grade gliomas. For recurrent glioblastomas, there is no standard therapy with lack of level one evidence for treatment efficacy. Recent evidence indicates that post-therapy recurrence in gliomas is a consequence of a plethora of molecular and cellular factors including intratumoural heterogeneity, functional hierarchy of distinct types of glioma cells, dynamic changes in the molecular landscapes and cellular composition of the tumour during therapy and the impact of particular treatment modalities. There is an emerging consensus that molecular distinctions within and between individual tumours is an important factor determining clinical outcomes. Consequently, integrated approaches based on the combination of molecular profiling with traditional methods such as immunohistochemical phenotyping, karyotyping and/or non-quantitative methylation-specific PCR have emerged as a promising venue towards increasing the predictive value of diagnostics for malignant brain tumors. The high level of inter-and intra-tumoural molecular diversity in gliomas underscores the need of integrating high throughput molecular profiling and pharmacogenomics into a diagnostic paradigm for gliomas and raises the possibility that molecular-instructed personalized treatments may provide clinical benefit to patients with glioblastoma, particularly in the setting of post-treatment recurrence. Here we discuss potential prospects and challenges of patient-tailored diagnostics and personalized treatment strategies for recurrent glioblastomas.

show abstract

“…Perhaps one of the most immediate applications for this technology is the treatment of GBM following surgical resection of the tumor bulk. GBM is a notoriously aggressive and invasive cancer, with 90% of patients experiencing tumor recurrence and five-year survival rates hovering below 15% 295 . Invasive tumor cells often lie within normal tissue protected by the BBB and beyond the reach of traditional therapies.…”

Section: Future Directionsmentioning

confidence: 99%