Researchers Make Progress in Treatment of Glioblastoma

Technological advances have increased tremendously our understanding of molecular characteristics and genetic drivers for a variety of brain tumors. Although targeted therapies have had a considerable impact on patients outcomes, GBM remains an exception. the identification of targetable driven mutations in GBM has opened new potential treatment options for affected patients. On the basis of these findings, the efficacy of new targeted agents is currently being investigated in clinical trials (Ippen et al, 2018).

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Glioblastoma multiforme (GBM) is the most common type of malignant primary brain cancer in adults. It is composed of highly malignant cells that display metastatic and angiogenic characteristics. This helps to make it resistant to current first-line chemotherapy with temozolomide (TMZ), an alkylating agent. The mechanism of resistance is thought to be a mutation of DNA repair enzymes.

Even with all the research, at present GBM patients still, have a dismal average of one-year survival and a high reoccurrence rate. One of the biggest difficulties noted in treatment is getting the chemotherapy agents to cross the blood-brain barrier (BBB) and reach the lesion while limiting its severe adverse systemic effects. Scientist are now exploring novel methods to deliver the agents including direct insertion of drug-containing discs into the brain, and the use of stem cells as a vector to deliver agents are also being explored (Choi et al, 2018).

GBM is the most common aggressive malignant brain tumor. It arises from the neuroepithelial tissue group of the brain and is one of the most dangerous of cancer family of astrocytoma. It is a malignant tumor that comes from glial cells that serve a supporting role within the nervous system. GBM flourishes under immunosuppressed microenvironment surrounding the tumor and often presents with nonspecific signs and symptoms ranging from headaches to personality changes. It is also known as glioma and comprises 50% of total glioma cases and affects males at a higher rate than females.

In addition, 50% of all cases of GBM are 65 years of age or older showing a correlation between age and occurrence of the disease. The median survival timeline of GBM is 14-15 months with a 10% probability of five-year survival. The reoccurrence nature of GBM garners its resilience and research is being done to reduce the risk of this though through the years has not yielded significant commercial results.

Standard treatment for GBM diagnosis for the first time is surgery to remove the growth followed by radiotherapy and administration of temozolomide (TMZ). It remains impossible to cure GBM leading to patients to opt for other treatment options to alleviate symptoms. The aggressiveness and complexity of GBM in patients call for a dire need of development of noninvasive biomarkers for accurate and early diagnosis of the disease. Despite decades of research to develop an effective biomarker, only a few have shown any promise (Sasmita, 2017).

In 2017, it is estimated that 26,070 patients will be diagnosed with a malignant primary brain tumor in the US. Of these more than half will be diagnosed as glioblastoma. Once the fact of hemorrhage has been ruled out, neurologists will recommend maximal safe debulking surgery initially. MRI is often utilized to give the surgeon a clear view of the tumor prior to the actual procedure. Many patients who were once felt to be a poor candidate for this surgery due to an uncertain risk of neurological compromise are now candidates for more aggressive resection after functional mapping.

In 1990, the Macdonald* response criteria were put forth. Four response categories were proposed. CR-complete response, PR-partial response, SD-stable disease, and PD-progressive disease. These were the first to standardize the assessment of treatment response that used RI and clinical parameters in conjunction with imaging measurements to classify responses. As treatment advances since then has changed how accurate the Macdonald response let to the development of a new set of guidelines.

Clinical trials in the last decade have evaluated bevacizumab in recurrent glioblastoma. More recently, immunotherapies have been introduced for treatment of glioblastoma. An issue with immunotherapy has led to the development of the immunotherapy response assessment. The volume of medical imaging data continues to grow at an exponential rate. As MRI modalities become more widespread, it will become more critical than ever to incorporate advanced imaging and the power of large datasets into the treatment of glioblastoma (Shukla et al,2017 , 2018).

Gliomas are a diverse group of neoplasms that the primary treatment is surgical removal or resection followed by radiation and/or chemotherapy. Despite ongoing efforts to advance treatment, practically all adult gliomas eventually progress and have an overall poor prognosis [Sen. John McCain]. MRI is fundamental to the characterization of brain tumors and is used to guide surgical strategies and is required to monitor treatment response.

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Differences in scanning protocols, whether in the same institution or between institutions, may affect image interpretation, assessment of contrast enhancement and changes in follow-up examinations. Key changes have occurred in the understanding of glioma, which is reflected in recent WHO classification. MRI protocols must account for new approaches to glioma classifications and should aim to complement and add value in the diagnostic workup.
This study’s aim was to provide the best clinical practice recommendations on conventional and advanced MRI of glioma patients and assess their feasibility. Relatively easy adaptation towards the standard best clinical practice recommendations can be expected though some variation throughout Europe is likely to remain. For advanced techniques lack of facility, software, and experience is likely to hamper their introduction at some institutions. The neuroradiological community has an important role to include technical aspects in their various training programs. In addition, the introduction of structured reports which could also have other advantages in terms of accuracy and effectiveness have been discussed. Advanced imaging methods may offer crucial diagnostic information and should be utilized where possible within the constraints of currently available data and local expertise (Thust et al, 2018).

Efficient tumor-specific biomarkers are in high demand as they are important in expediting diagnosis at initial stages and can further facilitate personalized treatment regime and prognosis protocols. Personalized biomarkers based clinical trials are now becoming a necessity as they have helped immensely in achieving reliable outcomes that contribute to a greater probability of prolonging and improving quality-of-life of patients. CNST-tumors in the central nervous system requires a central objective of investigating different aspects of CNSTs is to determine potential biomarkers and gene expression change that could be clinically leveraged for diagnosis, prognostic, and therapeutic applications.

The discovery of new and novel therapeutic agents for CNSTs are often influenced by biomarkers-based research. For CNSTs most of the targeted toxins are usually recombinant polypeptides. There are also several small molecule inhibitors currently in clinical trials for CNSTs. While a number of challenges remain for treatment of CNSTs, significant advances have been made in the molecular classification of these tumors and have led to valuable insights into the development of safe effective and improved therapeutic strategies. The focus of current research is shifting toward the development of personalized neuro-oncology protocols (Khan et al, 2017).

Work Cited
Choi, P.J. et al (2018). Emerging cellular therapies for Glioblastoma Multiforme. Cureus, 10(3). The Cureus Journal of Medical Science. Doi:10.7759/cureus.2305

Ippen, F.M. et al (2018). Precision medicine for primary CNS tumors: Are we there yet? American Society of Clinical Oncology. ASCO Educational Book. Doi:10.1200/EDBK_199247

Khan, I.N. et al (2017). Current and emerging biomarkers in tumors of the central nervous system (CNS): Possible diagnostic, prognostic, and therapeutic applications. Seminar in Cancer Biology. http://dx.doi.org/10.1016/j.semcancer.2017.07.004

*Macdonald, D.R. et al. (1990). Response criteria for Phase II studies of supratentorial malignant Glioma. Journal of Clinical Oncology, 8. https://doi.org/10.1200/JCO.1990.8.7.1277

Sasmita, A.O. (2017). Biomarkers and therapeutic advances in glioblastoma multiforme(GBM).Asia-Pacific Journal of Clinical Oncology, 14(1). Doi:10.1111/ajco.12756

Shukla, G. et al. (2017). Advanced magnetic resonance imaging (MRI) in glioblastoma: A review. Chinese Clinical Oncology,6(4). http://dx.doi.org/10.21037/cco.2017.06.28
Also published as:
Shukla, G. et al. (2018). Advanced MRI in glioblastoma: A review. JHN Journal,13(1), Article 5. http://jdc.jefferson.edu/jhnj/vol1/iss1/5

Thust, S.C. et al (2018). Glioma imaging in Europe: A survey of 220 centers and recommendations for best clinical practice. Springer Berlin Heidelberg. https://doi.org/10.1007/s0033-018-5314-5

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