John McCain and Glioblastoma

brain tissue.jpg

US Senator John McCain recently had removal of an aggressive brain tumor known as glioblastoma multiform. It is a highly aggressive form of cancer that often returns quickly to the same spot, even with surgery, radiation therapy, and chemotherapy. McCain;s tumor was associated with a small blood clot above the Arizona Republican’s left eye, and surgeons removed it using a minimally invasive procedure. A statement from the senator’s office explains that imaging suggests that the neurosurgeon successfully removed the abnormality, at least the gross, measurable tumor.

What is Glioblastoma?

A brain tumor is a mass of abnormal cells that originated in the brain itself. GMB arises from supportive tissue (not the nerves themselves) in the brain (glial cells). Rarely, glioblastoma runs in families, but most individuals with GBM have no family history of the disease. While cancer can spread to the brain from other organs such as the lungs, GBM begins in the brain and only uncommonly spreads outside of it. For most individuals, we do not know the cause of GBM, but exposure to radiation tot he brain is a know risk factor for the future development of cancer of the brain.

Next steps?

Following a recovery period of 3 to 4 weeks, patients typically proceed to radiation therapy (RT). The RT targets the tumor (or where it use to be) and often the surrounding edema (water) plus an inch or so. Often, those with GBM also have an oral chemotherapy known as temozolamide at the same time as radiation therapy (and sometimes after it). This approach of fractionated (for example, Monday through Friday for 6 weeks) radiotherapy plus oral chemotherapy is a category 1 recommendation of the National Comprehensive Cancer Network, a group of some of the top cancer treatment facilities in America. For those over 70, one may consider this approach versus a shortened course of radiation therapy versus chemotherapy with deferred radiation therapy.

In 2011, the Food and Drug Administration approached a portable medical device that generates low-intensity electric fields termed Tumor Treating Fields (TTF) for GBM. The use of this device (placed on the head) may yield results similar to chemotherapy, but with lower toxicity and improved quality of life.

Prognosis

Half of patients will survive beyond about 18 months. While 10 year survival is quite uncommon, it is possible. We need better treatments, and clinical trials are an important part of achieving this. I’m Dr. Michael Hunter.

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The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minutes. Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

 

Brain Tumors: New Hope?

What You Need to Know: Targeted therapies are a growing and groundbreaking field in cancer care in which drugs or other substances are designed to interfere with genes or molecules that control the growth and survival of cancer cells. Now, scientists have identified a novel interaction between a microRNA and a gene that could lead to new therapies for the most common and deadly form of brain tumor, malignant glioma.

Background: Scientists at Virginia Commonwealth University (USA) have identified a novel interaction between a microRNA and a gene that could lead to new therapies for the most common and deadly form of brain tumor, malignant glioma.

Details, details: Investigators provided the first evidence of an important link between a specific microRNA, miR-184, and a cancer promoting gene, SND1, in the regulation of malignant glioma. miR-184 is known to suppress tumor development by regulating a variety of genes involved in cancer growth, while SND1 has been shown to play a significant role in the development of breast, colon, prostate and liver cancers. Through a variety of preclinical experiments, the team demonstrated that increasing the expression of miR-184 slows the growth and invasive characteristics of glioma cells through direct regulation of SND1. Additionally, they showed that reduced levels of SND1 led to reduced levels of STAT3, a gene that has been shown to promote the most lethal characteristics of brain cancer.

“Patients suffering from brain tumors are in desperate need of improved therapies,” says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine and director of the VIMM. “We’re hopeful that this new understanding of the relationship between miR-184 and SND1 ultimately will lead to the development of new drugs that reduce SND1 expression and improve patient outcomes.”

Prior studies have shown that levels of miR-184 are unusually low in tissue samples from patients with malignant gliomas. Using advanced computer analysis techniques designed to study and process biological data, the researchers identified SND1 among a handful of other genes that miR-184 helps regulate. Knowing SND1 is implicated in a variety of cancers and having previously defined its role in liver cancer, Emdad, Fisher and their colleagues explored this relationship further. They confirmed low levels of miR-184 expression in human glioma tissue samples and cultured cell lines as well as an increase in the expression of SND1 compared to normal brain tissue. Using data from a large public brain tumor database called REMBRANDT, the researchers confirmed that patients with lower levels of SND1 survived longer than those with elevated SND1 expression.

“We still have a long way to go and many challenges to overcome before we will have therapies that are ready for clinical use, but this is a significant first step in the process,” says Emdad, member of the Cancer Molecular Genetics research program at Massey, assistant professor in the VCU Department of Human and Molecular Genetics and member of the VIMM. “Future studies will aim to explore the relationship between SND1 and STAT3, identify additional microRNAs that may be relevant to malignant glioma and explore the effects of drugs that block SND1 expression in more advanced preclinical models.”

I’m Dr. Michael Hunter.

Journal Reference:
L. Emdad, A. Janjic, M. A. Alzubi, B. Hu, P. K. Santhekadur, M. E. Menezes, X.-N. Shen, S. K. Das, D. Sarkar, P. B. Fisher. Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness. Neuro-Oncology, 2014; DOI: 10.1093/neuonc/nou220

Virginia Commonwealth University. “Important gene interaction defined that drives aggressive brain cancer.” ScienceDaily. ScienceDaily, 11 December 2014. <www.sciencedaily.com/releases/2014/12/141211162501.htm>.

Progress on Deadly Brain Cancer?

English: Gliobastoma (astrocytoma) WHO grade I...
English: Gliobastoma (astrocytoma) WHO grade IV – MRI sagittal view, post contrast. 15 year old boy. Deutsch: Glioblastom (Astrozytom) WHO Grad IV – MRT sagittale Schnittführung, nach Kontrastmittel. 15 Jahre alter Junge. (Photo credit: Wikipedia)

Eight of 16 patients participating in a study of an experimental immune system therapy directed against the most aggressive malignant brain tumors — glioblastoma multiforme — survived longer than five years after diagnosis, according to Cedars-Sinai researchers, who presented findings Nov. 23 at the Fourth Quadrennial Meeting of the World Federation of Neuro-Oncology.

Seven of the 16 participants still are living, with length of survival ranging from 60.7 to 82.7 months after diagnosis. Six of the patients also were “progression free” for more than five years, meaning the tumors did not return or require more treatment during that time. Four participants still remain free of disease with good quality of life at lengths ranging from 65.1 to 82.7 months following diagnosis. One patient who remained free of brain cancer for five years died of leukemia. The original clinical trial — a Phase I study designed to evaluate safety — included 16 patients with glioblastoma multiforme enrolled between May 2007 and January 2010 by researchers at Cedars-Sinai’s Johnnie L. Cochran, Jr. Brain Tumor Center.

Results published in January at the end of the study showed median overall survival of 38.4 months. Typically, when tumor-removal surgery is followed by standard care, which includes radiation and chemotherapy, median length of survival is about 15 months. Median progression-free survival — the time from treatment to tumor recurrence — was 16.9 months at study’s end. With standard care, the median is about seven months.

The experimental treatment consists of a vaccine, ICT-107, intended to alert the immune system to the existence of cancer cells and activate a tumor-killing response. It targets six antigens involved in the development of glioblastoma cells.

According to information presented at the scientific meetings, all eight long-term survivors had tumors with at least five antigens, 75 percent had tumors with all six, and 100 percent had tumors with at least four antigens associated with cancer stem cells — cancer-originating cells that appear to enable tumors to resist radiation and chemotherapy and even regenerate after treatment.

“Our findings suggest that targeting antigens that are highly expressed by cancer stem cells may be a viable strategy for treating patients who have glioblastomas. Long-term remission of disease in this group of patients was correlated with the expression of cancer stem cell tumor-associated antigens,” said Surasak Phuphanich, MD, director of the Neuro-Oncology Program at the Cochran Brain Tumor Center and professor of neurology with Cedars-Sinai’s Department of Neurosurgery and Department of Neurology.

Based on results of the Phase I study, the ICT-107 vaccine entered a Phase II multicenter, randomized, placebo-controlled trial in 2011.

The vaccine is based on dendritic cells, the immune system’s most powerful antigen-presenting cells — those responsible for helping the immune system recognize invaders. They are derived from white blood cells taken from each participating patient in a routine blood draw. In the laboratory, the cells are cultured with synthetic peptides of the six antigens — essentially training the dendritic cells to recognize the tumor antigens as targets. When the “new” dendritic cells in the vaccine are injected under the patient’s skin, they are intended to seek and destroy lingering tumor cells. Vaccine is administered three times at two-week intervals after standard radiation and chemotherapy.

My Take: While the results are promising, they are preliminary (? selection bias). Still, vaccines are an innovative approach, and we really need to have an approach to glioblastoma that is paradigm-shifting.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Cedars-Sinai Medical Center (2013, November 24). Update: 50 percent of patients in new brain cancer study alive after five years. ScienceDaily. Retrieved November 24, 2013, from http://www.sciencedaily.com­/releases/2013/11/131124093517.htm

Brain Tumor Surgery: Could a New Laser Dramatically Improve Accuracy?

English: TAC_Brain_tumor_glioblastoma-Coronal_...
TAC_Brain_tumor_glioblastoma-Coronal_plane Italiano: Immagine TAC della zona cerebrale, identificando un tumore di tipo glioblastoma (Photo credit: Wikipedia)

Background: Everyone loves a laser (I can almost hear my mom addressing the childhood me: “It’s all fun and games, until someone loses an eye…”). Now comes news that a new laser-based technology may improve the accuracy of brain tumor surgery, allowing the surgeon to better discern cancer tissue from normal tissue while they are operating. This can help avoid leaving cancer cells behind. Unfortunately, with current techniques, less than 1 in 4 patients with the aggressive brain tumor glioblastoma can have a complete gross resection.

Investigators from Harvard and University of Michigan describe a technique to distinguish health tissue from tumor in the brains of living mice. They showed that the technique worked with glioblastoma multiforme (GBM), one of the most aggressive forms of brain tumors. The technique is known as SRS microscopy, and the team is looking to test it in a clinical trial at Michigan.

Basics: SRS stands for stimulated Rama scattering. C.V. Raman was one of the Indian scientists who co-discovered the effect and shared a 1930 Nobel Prize (physics) for it. More recently, Sunney Xie, PhD (Harvard) amplified the Raman signal by more than 10,000 times. This makes it possible to create multicolor SRS images of living tissue or other materials. The team can create 30 new images every second, allowing for the creation of videos of tissue in real time!

The key is to identify the margin of a tumor, or the boundary area where tumor cells infiltrate normal cells.This can be a zone quite difficult in which to operate. The new technique allows for the detection of the difference between the signal given off by the dense cellular structure of tumor tissue, and the normal healthy gray and white matter.

So how good is this technique? In their hands, the investigators found it to be as effective as the current technology (looking at the tissue under the microscope with something called H&E staining). But here’s the great thing: The SRS microscopy can be done in real time, without the use of dyes (and without the removal and processing of the tissue, as is currently necessary).

Next steps: A smaller laser (one that is small and stable enough for use in the operating theater). Then clinical trials, perhaps as soon as next year! I’m Dr. Michael Hunter, and I thank you for joining me in sharing this exciting news.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minuteable now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Science Translational Medicine, September 2013 DOI:10.1126/scitranslmed.3005954.

Primary Brain Cancer: Any Progress?

brain tumor glioma coronal

In spite of advances in imaging and treatment, life expectancy for patients with primary tumors of the brain remain low at about 15 to 18 months. So are we making progress? Today, we hear from Dr. Steven Brem, the Chief of Neurosurgery at the Hospital of the University of Pennsylvania (Philadelphia, Pennsylvania, USA).

Is survival improving? Patients with malignant gliomas are living longer than ever before and they have better quality of life. Overall survival used to be 9 months, and it now averages 15 to 18 months. While not spectacular, the trend is unmistakable. And we now have a subgroup of perhaps 20% of patients who are living over 3 years, with an occasional very long-term survival. The combination of temozolomide chemotherapy and radiation therapy as been a major advance. And the use of bevacizumab [which starves a tumor of its blood supply] for recurrent glioblastomas is changing the neuro-oncology landscape. This is because we previously didn’t think such large molecules would be able to cross the blood-brain barrier and be effective. In addition, it shows us that targeted therapies will likely have a greater role in the future.

Current research: Several lines of research are being pursued. A better understanding of the genes (cancer genomics) will allow for breakthroughs in management. Immunotherapies are being pursued (currently for glioblastoma multiforme, or GBM). In addition, the neural pathways of the brain are being mapped, with the findings translating to the operating room. Using advanced mathematical modeling, surgeons can visualize what was formerly invisible to the eye, and even invisible under the microscope – the brain’s “wiring diagram.” Eventually, surgery will be tailored to the region of the tumor boundary, reducing the risk of neurologic complications such as cognitive impairment, paralysis, language deficits, and others. As glioblastoma cells follow white fiber matter paths, we should be able to better predict tumor growth and strategically plan therapy using newer mathematical models that provide a roadmap for each tumor. We also are pursuing the causes of malignant brain tumors.

My take: We will see improvement in survival rates among those with malignant brain tumors. Over the next 10 years, we should make more progress than we have over the last 30 to 40 years, given a better understanding of genomics, better neuroimaging, and better treatment.

The ASCO Post, June 25, 2013

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minuteable now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.