John McCain and Glioblastoma

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 to the brain is a known 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.

_________________________

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.

 

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.

_________________________

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>.

Different Brain Tumors Have the Same Origin

What You Need to Know: Glioma is a common name for serious brain tumors. Different types of glioma are usually diagnosed as separate diseases and have been considered to arise from different cell types in the brain. Now researchers at Uppsala University, together with American colleagues, have shown that one and the same cell of origin can give rise to different types of glioma. This is important for the basic understanding of how these tumors are formed and can contribute to the development of more efficient and specific glioma therapies.

The most common primary, malignant brain tumors in adults, called glioma, are formed from cells in the brain that are not nerve cells. These are serious tumors that lack highly effective treatment, and relapses are common. There are different types of glioma, classified according to an established system based on which cell type the tumor arises from. The most common gliomas are astrocytoma, which have their name from astrocytes, and oligodendroglioma, which are believed to arise from oligodendrocytes. Patients with astrocytoma have a poorer prognosis than oligodendroglioma patients, and the two tumor types are considered separate clinical diagnoses.

“Since the tumor types look different and have different prognoses it has been assumed that they arise from different cells of origin in the brain, but the fact is that the exact cell of origin has not been determined for any glioma. We have for a long time been interested in finding out more about the origin of gliomas and how it is associated with the genetic alterations that cause the tumor,” says lead researcher Lene Uhrbom.

In collaboration with colleagues in the United States, Uhrbom’s research group has studied glioma development in mice. Using tumor models for both astrocytoma and oligodendroglioma, which are very similar to human tumors, they showed that one and the same cell type, called oligodendrocyte precursor cells, could give rise to both tumor forms.

The researchers discovered that it is not the cell of origin but rather the genetic aberrations that control which tumor type is formed. By analysing gene activity in a large number of human astrocytoma and oligodendroglioma they could also conclude that the tumors are more similar to one another than was previously believed. This supports their finding that the glioma diagnoses can have the same origin.

“We saw that the same kind of more differentiated cell of origin, which has previously only been shown to give rise to oligodendroglioma, also can give rise to astrocytoma. New findings such as these increase our understanding of the basic mechanisms that cause glioma,” says Lene Uhrbom.

I’m Dr. Michael Hunter.

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: Uppsala University. “Different brain tumors have the same origin, new findings show.” ScienceDaily. ScienceDaily, 28 October 2014. <www.sciencedaily.com/releases/2014/10/141028214055.htm>.

A Trojan Horse for the Deadly Brain Tumor Glioblastoma?

brain tumor cancer Johns Hopkins researchers say they have successfully used stem cells derived from human body fat to deliver biological treatments directly to the brains of mice with the most common and aggressive form of brain tumor, significantly extending their lives. The experiments advance the possibility, the researchers say, that the technique could work in people after surgical removal of brain cancers called glioblastomas to find and destroy any remaining cancer cells in difficult-to-reach areas of the brain. Glioblastoma cells are particularly nimble; they are able to migrate across the entire brain, hide out and establish new tumors. Cure rates for the tumor are notoriously low as a result.

In the mouse experiments, the Johns Hopkins investigators used mesenchymal stem cells (MSCs) — which have an unexplained ability to seek out cancer and other damaged cells — that they harvested from human fat tissue. They modified the MSCs to secrete bone morphogenetic protein 4 (BMP4), a small protein involved in regulating embryonic development and known to have some tumor suppression function. The researchers, who had already given a group of mice glioblastoma cells several weeks earlier, injected stem cells armed with BMP4 into their brains. In a report published in the May 1 issue of Clinical Cancer Research, the investigators say the mice treated this way had less tumor growth and spread, and their cancers were overall less aggressive and had fewer migratory cancer cells compared to mice that didn’t get the treatment. Meanwhile, the mice that received stem cells with BMP4 survived significantly longer, living an average of 76 days, as compared to 52 days in the untreated mice.

“These modified mesenchymal stem cells are like a Trojan horse, in that they successfully make it to the tumor without being detected and then release their therapeutic contents to attack the cancer cells,” says study leader Alfredo Quinones-Hinojosa, M.D., a professor of neurosurgery, oncology and neuroscience at the Johns Hopkins University School of Medicine.

Standard treatments for glioblastoma include chemotherapy, radiation and surgery, but even a combination of all three rarely leads to more than 5 years of survival after diagnosis. Finding a way to get biologic therapy to mop up what other treatments can’t get is a long-sought goal, says Quinones-Hinojosa, who cautions that years of additional studies are needed before human trials of fat-derived MSC therapies could begin.

Quinones-Hinojosa, who treats brain cancer patients at Johns Hopkins Kimmel Cancer Center, says his team was heartened by the fact that the stem cells let loose into the brain in his experiments did not transform themselves into new tumors. The latest findings build on research published in March 2013 by Quinones-Hinojosa and his team in the journal PLOS ONE, which showed that harvesting MSCs from fat was much less invasive and less expensive than getting them from bone marrow, a more commonly studied method. Ideally, he says, if MSCs work, a patient with a glioblastoma would have some adipose tissue (fat) removed from any number of locations in the body a short time before surgery. The MSCs in the fat would be drawn out and manipulated in the lab to secrete BMP4. Then, after surgeons removed the brain tumor, they could deposit these treatment-armed cells into the brain in the hopes that they would seek out and destroy the cancer cells.

I’m Dr. Michael Hunter.

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.

References: Q. Li, O. Wijesekera, S. J. Salas, J. Y. Wang, M. Zhu, C. Aprhys, K. L. Chaichana, D. A. Chesler, H. Zhang, C. L. Smith, H. Guerrero-Cazares, A. Levchenko, A. Quinones-Hinojosa. Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are Nononcogenic, Suppress Brain Cancer, and Prolong Survival. Clinical Cancer Research, 2014; 20 (9): 2375 DOI: 10.1158/1078-0432.CCR-13-1415; Johns Hopkins Medicine. “Human fat: Trojan horse to fight brain cancer?.” ScienceDaily. ScienceDaily, 1 May 2014. <www.sciencedaily.com/releases/2014/05/140501075055.htm>.

Deadly Brain Tumor: Gross Total Resection Prolongs Survival

English: TAC_Brain_tumor_glioblastoma-Transver...
English: TAC_Brain_tumor_glioblastoma-Transverse_plane Italiano: Immagine TAC della zona cerebrale, indicante un tumore di tipo glioblastoma. Piano Trasverso (Photo credit: Wikipedia)

Gross total resection of glioblastoma may prolong survival with modern radiation therapy and chemotherapy, according to new research from the German Glioma Network. However, incomplete resection appears no better than a biopsy.

“There is no linearity such as ‘70% resection is better than 50%,'” said Dr. Joerg-Christian Tonn from University of Munich LMU, who led the new work. “The goal must be (if anatomically and clinically feasible) to resect all the solid tumor mass — this makes the difference.”

Among the 222 patients (64.2%) who underwent radiotherapy plus chemotherapy, median overall survival was significantly longer after gross total resection (21.0 months) than after incomplete resection (15.2 months) or biopsy (15.7 months). In multivariate Cox regression analyses, independent predictors of better overall survival included gross total resection, age 60 years or less, Karnofsky performance score of 80 or higher, MGMT promoter methylation, and radiotherapy plus chemotherapy. Incomplete resection was no better than biopsy.

for those unable to have a complete resection, Dr. Samuel Ryu from Gachon University Gil Hospital in Inchon, Korea, made a case for incomplete resection, even if it has no survival benefits: “The role of surgical resection also includes removal or reduction of mass effect,” he told Reuters Health by email. “Although there is no survival benefit, there can be some neurological benefit by reducing the pressure to the adjacent brain parenchyma.”

And there is this eloquent criticism of the paper, too:

Dr. Sonia Tejada from Universidad de Navarra in Spain, questioned whether there are meaningful conclusions to be drawn from the new work. “I am surprised that this article that does not give any new data in the field has been published in this journal,” she said. “Nowadays,” Dr. Tejada noted, “a paper about resection in glioblastoma without volumetric analysis is incomplete and should not have been published. Indeed, the data about overall survival in the group of incomplete resection was 11.7 (10.0-13.5) months and in the group of biopsy was 8.7 (6.3-11.2) months. Although not statistically significant, there is a difference; the absence of significance does not mean an absence of difference.”

I’m Dr. Michael Hunter.

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: http://www.medscape.com/viewarticle/814079; Annals of Oncology 2013