Glioblastoma Multiforme (GMB) is the most common form of primary malignant brain tumor in adults. With the current standard therapy, median survival time hovers just over 12 months. This incurable disease is devastating with a median survival time of 6-8 months from time of recurrence (J10). The current standard of therapy at first diagnosis consists of surgery followed by radiotherapy with concommittant and adjuvant chemotherapy using the agent temozolamide (TMZ) (Multiple sources). In 2003, the United States Food and Drug administration approved the Gliadel Wafer (GW) for treatment of newly diagnosed GBM (C3). The monoclonal antibody Bevacizumab (BEV) was first used to treat recurrent GBM in 2005 and has a significant survival benefit for patients with grade IV glioma (E5). Many more promising avenues for new treatment have been and are currently being studied. Such areas include the use of antiepileptic drugs, using Convection-Enhanced Delivery of chemotherapeutic agents, and targeting specific molecular markers and pathways such as the epidermal growth factor receptor (EGFR), O6-methylguanine-DNA-methyltransferase (MGMT), and the PI3K/Akt/mTOR pathway.
CURRENT STANDARD OF THERAPY
The current standard of therapy is resection of the tumor plus radiotherapy and TMZ (E5). Multiple studies performed between 1976 and 1991 have led postoperative radiotherapy to be accepted as standard treatment (L12). The universal dosing schedule for radiotherapy in GBM is fractionated irradiation over 6-7 weeks for a total of 60 gray (Gy) (G7,M13). TMZ is an oral alkylating agent that can be used concomitant with radiotherapy and as an adjuvant. The European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) organized a study showing that adding TMZ to standard radiotherapy is beneficial to overall survival. This study enrolled 573 patients from 85 institutions and randomly assigned eligible patients to receive either standard radiotherapy alone or radiotherapy plus concomitant and adjuvant TMZ. There was a 37% decrease in relative risk of death and a median increase in survival of 2.5 months in patients treated with TMZ and radiotherapy when compared to radiotherapy alone (P<0.001). There are adverse effects with both RT and chemotherapy, but hematologic toxicities are more likely to occur in patients treated with both TMZ and RT (M13). This study maintained its validity after accounting for recursive partitioning analysis classifications (L12). The current standard dose of TMZ is 75 mg per square meter of body surface area daily during radiotherapy and then a dose of 150-200 mg per square meter of body surface area for 5 days of each 28-day cycle following RT (G7,M13).
... in glioma cells (suppression of autophagy, mentioned above, is often accompanied by activiation of apoptosis). Silencing eEF-2 kinase expression with the inhibitors (NH125) remarkably increased the TMZ-activated apoptosis in human glioma cells. One other important discovery of this experiment was that the combination of TMZ and NH125 did not cause TMZ to destroy normal human astrocytes. Essentially, co-treatment of TMZ with NH125 made TMZ more effective against glioma and produced a better survival benefit for the mice, but could not cure the mice. This may be because the amount of NH125 (eEF-2 inhibitor) used was not enough, or the dosages of TMZ and NH125 were not optimal. Nonetheless, development of better and more effective inhibitors of eEF-2 kinase may help in finding the cure for glioblastoma multiforme, the malignant and extremely aggressive brain tumor.
Further research on this alternative model could lead to therapies that not only target the properties of the primary tumor but also those of the secondary tumor and save many from the burden of fighting cancer again.
Glioblastoma Multiforme (GBM) is known as the most aggressive form of malignant brain tumor in adults [1,2,4,5]. Patients who are diagnosed with Glioblastoma Multiforme have an extremely poor rate of survival. Glioblastoma multiforme has been found to be sporadic and doesn’t have any linkage or genetic pre-dispositions. The prognostic of GBM is poor and there has been little improvement of the patients overall survival rates for the past three decades [5]. Although patients undergo surgical resection along with chemotherapy and high-dose radiotherapy the survival rate after diagnosis is still low at the survival time of 14-15.5months [1,2,4,5]. There has been hope that immunotherapy may contribute as a beneficial treatment to this malignant brain tumor [1]. Treatments that would be effective in GBM patients are desperately needed. Three studies were reviewed to get a better understanding of what treatments or combination of treatments would be more beneficial to GBM patients.
U.S. Congress, Office of Technology Assessment. 1990. Unconventional Cancer Treatments, OTA-H-405. Washington, D.C.: U.S. Government Printing Office.
According to the Central Brain Tumor Registry of the United States (CBTRUS), the incidence rate of all primary malignant and non-malignant brain and central nervous system tumors (CNS) for 2005 to 2009 was 20.6 cases per 100,00 (7.3 per 100,000 for malignant tumors and 13.3 per 100,000 for non-malignant tumors) (Fig. 1) [1].
The most common type of radiation therapy that is used involves exposure of patients to external radiations. In this method, a beam containing high-energy X-rays is directed to a specific region of the body to irradiate the main tumors. However, the problem with this technique is that the ability to hit normal tissues of adjacent organs (Noda et al., 2009). Different from this, targeted radionuclide therapy functions like chemotherapy. A radionuclide labeled molecule is administered either orally or intravenously such that it delivers radiations that are sufficiently toxic to the site of the disease to kill the target cells (Bolus & Brady, 2011). However, the main difference with chemotherapy is that the drugs or toxins only...
At this day in age we are constantly trying to improve the field of medicine in any way that we possibly can. We cherish every birthday and continually try to prolong life. Not only through every field of medicine, especially in terms of cancer. The American Cancer Society is “the official sponsor of birthdays” and is making leaps and bounds in the types of care that cancer patients receive. One of these many breakthroughs is the practice of Stereotactic (Body) Radiotherapy or S(B)RT. SBRT and other radiation therapies have the ability to greatly improve the way that we treat the issue of cancer and the variation of treatment options; however, they have raised the concerns of long term effects from radiation and cost-effectiveness. As research has begun to show, radiation therapies are having great success in curing cancer.
Radiation therapy is a growing field that has not been around very long. This field works with patients that have many different types of cancer ranging from leukemia, lung cancer, prostate cancer, cervical cancer, and brain cancer among others. Cancer can be effectively treated using surgical, chemical and radiation treatment or a combination of the three. Many advantages and disadvantages have emerged when considering the use of radiation therapy and these pros and cons should be discussed thoroughly between the Oncologist and patient before a decision has been made on a course of action. Special licensing is required to enter this specialized field of radiation therapy and can be obtained through special programs.
Susan G. Komen for the Cure, (2009). Radiation Therapy and Side Effects. Susan G. Koman for the Cure. Retrieved from:
Cancer in one way or another touches all of us, whether as a patient or through the diagnosis of the people you love around you. Millions of patients who are faced with cancer are depending on oncologists everywhere to cure cancer so others will not suffer like they had to. Optimistically, sooner rather than later this international problem will come to an end. There are a number of drug companies that have been coming out with cancer treatment drugs. “Oncology has been one of the hottest and most active therapeutic areas for drug development, drug makers may want to take note of a finding that new cancer drugs have proven far more difficult to gain approval than medicines for infectious and autoimmune diseases.” (nature.com) Unfortunately, these drugs cannot cure the cancer but it sure makes it a load easier o...
Meyer, John L., ed. IMRT, IGRT, SBRT: Advances in the Treatment Planning and Delivery of Radiotherapy. New York: Karger, 2007.
According to SEER Statistics, 23,380 people are estimated to get a brain or nervous system cancer diagnosis. Out of those people, 14,320 people are estimated to die from their brain or nervous system cancer diagnosis (National Cancer Institute). Cancer is a type of dangerous tumor, or a buildup of extra cells that form a mass of tissue, that can be life threatening (National Cancer Institute). The term for a tumor that is cancerous is a malignat tumor, whereas a benign tumor does not contain cancer cells (National Cancer Institute). According to the National Cancer Institute, the causes of brain cancer are unknown, but risk factors include family history and excessive radiaton exposure. Although they are not always due to a brain tumor, comon symptoms include headaches, nausea, speech, hearing, vision, and mood changes, problems with balance and mamories, seizures, and numbness in arms and legs (National Cancer Institute). MRI and CT scans as well as surgical biposies (or the removal of part of the tumor to be examined) are used to diagnose brain cancer (National Cancer Institute). Different types of treatment options include radiation therapy, surgery to remove the tumor, and chemotherapy. According to Charles Davis, MD, PhD and Nitin Tandon, MD of WebMD.com, chemotherapy is “ the use of powerful drugs to kill tumor cells”. There are a few different types of chemotherapy, but all of which bring out the same kinds of side effects. Although the physical side effects of chemotherapy are commonly known, few people know of the emotional toll chemotherapy can take on a patient and his or her family as they go though this process.
Radiation therapists work closely with patients to fight cancer. According to Health Care Careers, Oncologists, Dosimetrists and nurses are some of the professionals that a radiation therapist works with while caring for a cancer patient. This group of professionals will determine a specialized treatment plan. The first step usually includes a CT scan performed by a radiologist to find the exact area that needs to be targeted with x-rays. Next, the therapist uses a special machine that emits radiation called a Linear Accelerator. They use this machine during a treatment called external beam therapy. During this process, the Linear Accelerator will project x-rays at targeted cancer cells or tumors. Another therapist will be in a different room monitoring the patient’s viral signs until the procedure is over. The external therapy l...
Another treatment that is used to help a cancer patients overcome the disease is radiation therapy. Although very affective and used commonly, thi...
“NINDS Brain and Spinal Tumors Information Page.” Brain and Spinal Tumors Information Page: National Institute of Neurological Disorders and stroke (NINDS N.P., 10, Feb. 2005. Web. 15 Apr. 2014.