Multiform Glioblastoma GBM Brain Cancer New treatments or polymorphic glioblastoma is the most aggressive type of brain cancer, called gliomas, which are tumors derived from the central nervous system glia.
Histologically, the gliomas are divided into four categories (I-IV) and unfortunately, the most aggressive one is the GBM-Glioblastoma Multiforme-Grade IV, which is common in humans. Unfortunately, the survival rate in most patients with polymorphic glioblastoma is poor; thus, this kind of tumor has gathered the attention of the scientific community.
One of the reasons for the treatment complexity of the Multiform Glioblastoma GBM Brain Cancer New treatments, is as its name implies, its histological diversity. It is "multiform" microscopically and consists of areas of necrosis with pleomorphic nuclei and cells with intense microvascular proliferation.
Moreover, the polymorphic glioblastoma is genetically multiform, with various deletions, amplifications and point mutations that lead to the activation of the stimulation mechanisms such as of the epidermal growth factor receptor (EGFR) and of the platelet receptor growth factor (PDGFR), as well as causing Cell cycle disorders, or mutations in p53 associated with the CDK4 amplification or loss of Rb. These tumors also depict intracellular genetic heterogeneity with subclones located within the cancer cell population itself.
Hence, one comprehends the diverse complexity in confronting and successfully treating this kind of tumors.
Fortunately, research and application of new technologies have taken a leap forward towards the successful treatment direction and in conjunction with surgery, radiotherapy and chemotherapy, a light of hope emerges from the dark tunnel of this so aggressive disease.
Therefore, it is important to be aware of the latest therapeutic advancements in treating GBM-Glioblastoma Multiforme, as well as to be aware of the alternative therapies already offered in aiding to the treatment of the Multiform Glioblastoma GBM Brain Cancer New treatments or polymorphic glioblastoma.
INITIAL TREATMENT OF GLIOBLASTOMA
Surgical removal – Biopsy
Brain decompression and restoration of neurological disorders (as far as feasible).
Maximum possible tumor removal with maximum surgical ablation limits on healthy tissue.
Removal of the tumor prior to treatment with radiotherapy and chemotherapy
Getting a tissue sample for:
Biopsy – Confirmation of Diagnosis.
Examination of positivity in bio-indicators.
Possibility of developing a vaccine against Multiform Glioblastoma GBM Brain Cancer.
Extension of survival and preservation of quality of life.
***It is crucial to comprehend the importance of a surgical intervention in the course, management and course of the illness. The greater the extent of the tumor removal, the better the prognosis.
*** Removal of 98% or more of the tumor has been associated with a significantly better survival rate. The chances of an almost complete tumor removal may be increased if the surgery is guided by a fluorescent dye known as 5-aminolevulinic acid.
Continuously improved surgical techniques (Microsurgery, Neuro-intracutaneous or Neuroendocannula or Neuro endocannula) and the evolution of technology (Robotic-guided Microsurgery) have led to the possibility of full tumor removal, leading to an increased survival rate and thus maintaining an optimum quality of life for the patient.
Post surgery, radiotherapy is considered as a necessary component of treatment for people with Multiform Glioblastoma GBM Brain Cancer. On average, post surgery radiotherapy significantly reduces the size of a tumor. Nowadays, the targeted three-dimensional conformal radiotherapy is considered a treatment of choice, with a total radiation dose of 60-65 Gy as the optimal and most effective form of treatment.
The combination of radiotherapy (60 Gy in the tumor area only) combined with chemotherapeutic drugs such as temozolamide and lomustine (CCNU) is able to substantially increase the survival rate of patients.
The common and mostly used treatment nowadays for polymorphic glioblastoma is radiotherapy in combination with temozolamide. The addition of lomustine appears to contribute significantly to the patient survival rate.
Temozolomide (Temondal): 45% of most polymorph glioblastomas respond positively to the hypermethylation of the promoter of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), which results in the gene's "inactivation", thereby minimizing the ability of the cancerous cell to repair its DNA. This results in an increased sensitivity effect to Temozolomide.
It is noteworthy that patients who were positive to the methylation of the MGMT promoter and were treated with Temolomide had an average survival rate of 21.7 months compared to 12.7 months survival rate of patients found negative to methylation, and survival rates of 2 years were 46 % Vs. 13.8%, respectively.
Bevacizumab (Αvastin): Bevacizumab is a monoclonal antibody (a type of protein) designed to be able to recognize and to adhere to the vascular endothelial growth factor (VEGF), a protein that circulates in the blood and contributes to the growth of blood vessels. Through its attachment to VEGF, Bevazijumab prevents cancer cells from developing their blood supply mechanism and thus depletes them from oxygen and nutrients and hence decreases the growth and spread of glioblastoma.
Other chemotherapeutic agents used inter alia for relapse include nitrosoureas, Vinka alkaloids and cytosine.
In certain cases, patients benefit from the implantation of topical targeted chemotherapy with carmustine polymers (Gliadel wafers).
IMMUNOLOGICAL THERAPIES - VACCINES
Glioblastoma vaccines are designed to elicit a tumor-specific immune response or towards directly related to tumor-associated antigens. In this way, the patient's immune system attacks the cancer cells carrying these antigens.
Clinical studies currently underway are many but accessible treatments are the following:
ERC 1671 (Gliovac): It is a promising treatment against glioblastoma with extremely interesting results from the clinical studies that have taken place. It is in a Phase II clinical trial of the FDA and the vaccine is prepared from cancerous cells of the patient (autologous antigens) which are also combined with allogenic antigens, ie cancer cells taken from other Glioblastoma patients. The first clinical results of Gliovac treatment for patients resistant to other treatments are very encouraging, with minimal toxicity and improved overall survival (OS). The mean survival for patients treated with Gliovac at six month (26 weeks) was 100% vs 33% in the control group. At 40 weeks, overall survival was 10% in patients who did not receive Gliovac, while in the Gliovac group, survival at 40 weeks was 77%. These data show that Gliovac has low toxicity and is a promising treatment.
Rindopepimut-Rintega®, CDX-110): It is a vaccine that targets a mutant peptide called Rintega® CDX-110, which is expressed in about one-third of glioblastomas. It is intended to be used in EGFRvIII-positive patients in the FDA Clinical Phase II study and the evidence is that Rhindopimus reduces the mean survival of patients with recurrent glioblastoma.
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Note: Of course there are many other immune experimental studies (DCVax-L, ICT-107, HSPPC-96, SL-701, ICT-121, HSV1-TK, Flt3L, imiquimod, Montanide. We mention here only those in which treatment is accessible.
APPLICATION OF NOVO TTF - 100A ELECTRICAL TREATMENT (Optune ™):
The Novo TTF-100A is a portable device designed to treat glioblastoma. It is approved by the FDA, and uses TTF (Tumor Treating Fields) electromagnetic fields. Unfortunately, the Novo TTF-100A is not provided free of charge by the fund, so the patient should be informed of the cost of the entire procedure.
The device is intended for continuous use at home or away from home, from patients with glioblastoma. Results from the studies that have been carried out indicate that treatment can slow down progression of the disease and increase the median overall survival compared to standard chemotherapy in patients with recurrent glioblastoma. It can also be used at the initial diagnosis phase of the disease, but in this case the duration of treatment is longer.
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THERAPIES UNDER DEVELOPMENT - RESEARCH FIELD
The use of MRgLITT-guided laser therapy is becoming increasingly important for the treatment of brain tumors and, in the case under discussion, of glioblastoma. It is a minimally invasive approach with wide application to many types of tissues. For glioblastoma in the brain, the laser is stereotaxically applied through a chilled optical fiber so as to produce as much heat into the tumor as to kill it. The treatment is performed by real-time intraoperative control of thermal damage to the tumor tissue but also to the surrounding brain, by temperature imaging throughs magnetic resonance (MRTI). It is a promising treatment for many types of brain tumors, including glioblastoma.
An exemplary approach is experimental treatment with nanoparticles. These consist of a core of iron oxide and a shell, which will facilitate the penetration of iron oxide particles into cancer cells. The nanoparticles are introduced directly into the tumor by injection. Thereafter, alternating magnetic fields produce heating to about 46 ° C. The results of randomized controlled trials in humans are not yet available.
Tumors can be heated and destroyed in an accurate way by nanotechnology. The Phase II clinical study has been completed and the method is expected to be applied across Europe after approval (Nano-Cancer® therapy).
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