Breakthroughs in Brain Tumor Treatment
Brain
Posted on: Aug 16
Brain
Posted on: Aug 16
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Tags: proton therapy, cancer, epilepsy, surgery, article

Breakthroughs in Brain Tumor Treatment

Glioblastoma multiforme, or GBM, has long frustrated clinicians with its resistance to treatment and dire prognosis. GBM is both the most common and lethal of all primary brain tumors. In fact, of the estimated 22,000 new cases of primary brain cancer diagnosed annually in the United States, 80 percent are gliomas, and the majority of these are GBM.

Median GBM survival is just 15 months. And the prognosis for patients with recurrent GBM is even more discouraging, with median survival less than a year. Because recurrence rates are so high, many clinicians take a palliative, rather than curative, approach to treating GBM. But that need not be the case, said brain tumor specialists with Indiana University Health Neuroscience.

“In the past, there has been a lot of nihilism in the medical community regarding treatment of GBM,” said James Miller, MD, Assistant Professor of Neurological Surgery at Indiana University School of Medicine. “Physicians in the past may have tended to think of GBM treatments as futile; but things are changing, and there are some exciting new treatment approaches and opportunities for patients with GBM.”

Research is increasing scientists’ understanding of genetic and cellular pathways. In addition, a better understanding of how therapeutic agents cross the blood-brain barrier is leading to new delivery techniques and more targeted treatment. There are also various ongoing vaccine studies that are showing promise in improving the overall survival of these patients.

Through clinical trials, patients today have access to a variety of these promising new therapies. Early referral to a research center like IU Health provides both newly diagnosed and recurrent patients more treatment options and the chance of a better outcome.

“We’re working with the nation’s leading researchers to translate the latest discoveries into treatment breakthroughs,” said Stephanie Wagner, MD, clinical associate professor of medicine at IU School of Medicine and Director of the neuro-oncology program at IU Simon Cancer Center.

What's exciting to me is that we are using the patient's own immune system to fight the brain tumor...

James Miller, MD

Brain cancer vaccine

One of the most exciting breakthroughs in brain tumor treatment is a vaccine made from a patient’s own tumor cells. Vaccines have been the focus of research for decades, as they offer a less-toxic approach than traditional chemotherapy. However, most vaccines to date have fallen short—delivering positive results for a small group of patients, but proving less effective when tested across multiple sites.

Now, with phase I trials showing very positive results for a new GBM vaccine, a phase II, randomized, multicenter study is underway. IU Health is the only center in the region offering access to the DCVax-Brain trial for newly diagnosed GBM.

“What’s exciting to me is that we are using the patient’s own immune system to fight the brain tumor,” Dr. Miller said. “The vaccine is created by taking a patient’s tumor proteins and combining them in the laboratory with the patient’s immune cells to ‘activate’ them. When those activated immune cells are re-injected, they help attack the residual brain tumor cells. It’s a highly personalized treatment.”

The vaccine involves purifying a patient’s dendritic cells from a blood draw. These cells help to direct the entire immune system. Once activated with proteins from a patient’s own tumor, the dendritic cells are returned to the patient as a vaccine work to recruit and mobilize other cells against the cancer cells. The dendritic cells direct the immune system to specifically attack the cancer cells, without the toxicity or side effects of chemotherapy.

In Phase I trials, median survival for patients receiving the vaccine was 33.8 months, and median time to recurrence was more than two years, compared with 6.9 months with standard care. Of patients receiving the vaccine, 33 percent reached four-year survival, 27 percent reached six-year survival, and the longest surviving patient to date exceeds 10 years.

“I don’t think this is going to work for everybody,” Dr. Miller said. “But for the people who it has worked, it’s worked phenomenally. If we’re able to figure this out a little bit more and refine it, it could really be a game changer for treatment of GBM.”

The wave of the future is multi-targeted therapy and tailoring one's treatment based on molecular markers.

Investigational therapies for newly diagnosed

In the past, most clinical trials focused on recurrent GBM. Given that there is recurrence in nearly all cases, the lack of alternative therapies was frustrating for physicians and patients alike. Today, a number of trials are focused specifically on the newly diagnosed, and IU Health is playing a key role in bringing these therapies to patients. In addition to the DCVax-Brain study, this summer IU Health will begin offering newly diagnosed GBM patients another vaccine therapy, as well as study that inhibits TGF-beta.

Researchers are also exploring the effect of multi-targeted therapies on GBM, and a number of clinical trials are focused on how these new drugs might aid the newly diagnosed. “Historically, GBM has been treated with surgery, radiation, more surgery, more radiation. But the therapies were behind the times because they were more localized therapies and didn’t treat the disease in a systemic fashion,” Dr. Wagner said. “I think we have been naïve in thinking that single-agent therapy will work on a tumor that has multiple growth pathways. The wave of the future is multi-targeted therapy and tailoring one’s treatment based on molecular markers.”

One such therapy is bevacizumab, the only drug approved for GBM patients in the last decade. Bevacizumab works by targeting blood vessels and blocking cells that are important for cancer cell growth. Because it targets only those cells important to tumor growth, the drug spares healthy tissue and results in fewer side effects. The FDA approved bevacizumab in 2009 for treatment of recurrent GBM, making it the first antiangiogenic therapy approved for cancer patients.

Bevacizumab is routinely prescribed for patients with recurrent disease, and now researchers think there is potential benefit for newly diagnosed patients, as well. Three phase II studies have shown that bevacizumab in the newly diagnosed patient increases progression-free survival, though its impact on overall survival remains to be determined. In addition, two phase III trials recently closed, though survival data is not yet available.

“Independent of any survival benefit, bevacizumab seems to improve quality of life in newly diagnosed patients by reducing side effects through tightening the blood-brain barrier and decreasing vasogenic edema,” Dr. Wagner said. “There is also evidence that it improves neurocognitive function in recurrent GBM patients.”

Access to trials

For all GBM patients, prompt referral to a research center is important, Dr. Wagner said. “Trial eligibility is very rigid and patients may miss an opportunity to participate in a trial if not referred soon after diagnosis. After a patient starts radiation, it’s usually too late,” she explained

By connecting patients to a research center and the full range of treatment options, physicians can offer their patients the highest level of care and hope in the face of a grim diagnosis.

Tags: proton therapy, cancer, epilepsy, surgery, article
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Breakthroughs in Brain Tumor Treatment

Glioblastoma multiforme, or GBM, has long frustrated clinicians with its resistance to treatment and dire prognosis. GBM is both the most common and lethal of all primary brain tumors. In fact, of the estimated 22,000 new cases of primary brain cancer diagnosed annually in the United States, 80 percent are gliomas, and the majority of these are GBM.

Median GBM survival is just 15 months. And the prognosis for patients with recurrent GBM is even more discouraging, with median survival less than a year. Because recurrence rates are so high, many clinicians take a palliative, rather than curative, approach to treating GBM. But that need not be the case, said brain tumor specialists with Indiana University Health Neuroscience.

“In the past, there has been a lot of nihilism in the medical community regarding treatment of GBM,” said James Miller, MD, Assistant Professor of Neurological Surgery at Indiana University School of Medicine. “Physicians in the past may have tended to think of GBM treatments as futile; but things are changing, and there are some exciting new treatment approaches and opportunities for patients with GBM.”

Research is increasing scientists’ understanding of genetic and cellular pathways. In addition, a better understanding of how therapeutic agents cross the blood-brain barrier is leading to new delivery techniques and more targeted treatment. There are also various ongoing vaccine studies that are showing promise in improving the overall survival of these patients.

Through clinical trials, patients today have access to a variety of these promising new therapies. Early referral to a research center like IU Health provides both newly diagnosed and recurrent patients more treatment options and the chance of a better outcome.

“We’re working with the nation’s leading researchers to translate the latest discoveries into treatment breakthroughs,” said Stephanie Wagner, MD, clinical associate professor of medicine at IU School of Medicine and Director of the neuro-oncology program at IU Simon Cancer Center.

What's exciting to me is that we are using the patient's own immune system to fight the brain tumor...

James Miller, MD

Brain cancer vaccine

One of the most exciting breakthroughs in brain tumor treatment is a vaccine made from a patient’s own tumor cells. Vaccines have been the focus of research for decades, as they offer a less-toxic approach than traditional chemotherapy. However, most vaccines to date have fallen short—delivering positive results for a small group of patients, but proving less effective when tested across multiple sites.

Now, with phase I trials showing very positive results for a new GBM vaccine, a phase II, randomized, multicenter study is underway. IU Health is the only center in the region offering access to the DCVax-Brain trial for newly diagnosed GBM.

“What’s exciting to me is that we are using the patient’s own immune system to fight the brain tumor,” Dr. Miller said. “The vaccine is created by taking a patient’s tumor proteins and combining them in the laboratory with the patient’s immune cells to ‘activate’ them. When those activated immune cells are re-injected, they help attack the residual brain tumor cells. It’s a highly personalized treatment.”

The vaccine involves purifying a patient’s dendritic cells from a blood draw. These cells help to direct the entire immune system. Once activated with proteins from a patient’s own tumor, the dendritic cells are returned to the patient as a vaccine work to recruit and mobilize other cells against the cancer cells. The dendritic cells direct the immune system to specifically attack the cancer cells, without the toxicity or side effects of chemotherapy.

In Phase I trials, median survival for patients receiving the vaccine was 33.8 months, and median time to recurrence was more than two years, compared with 6.9 months with standard care. Of patients receiving the vaccine, 33 percent reached four-year survival, 27 percent reached six-year survival, and the longest surviving patient to date exceeds 10 years.

“I don’t think this is going to work for everybody,” Dr. Miller said. “But for the people who it has worked, it’s worked phenomenally. If we’re able to figure this out a little bit more and refine it, it could really be a game changer for treatment of GBM.”

The wave of the future is multi-targeted therapy and tailoring one's treatment based on molecular markers.

Investigational therapies for newly diagnosed

In the past, most clinical trials focused on recurrent GBM. Given that there is recurrence in nearly all cases, the lack of alternative therapies was frustrating for physicians and patients alike. Today, a number of trials are focused specifically on the newly diagnosed, and IU Health is playing a key role in bringing these therapies to patients. In addition to the DCVax-Brain study, this summer IU Health will begin offering newly diagnosed GBM patients another vaccine therapy, as well as study that inhibits TGF-beta.

Researchers are also exploring the effect of multi-targeted therapies on GBM, and a number of clinical trials are focused on how these new drugs might aid the newly diagnosed. “Historically, GBM has been treated with surgery, radiation, more surgery, more radiation. But the therapies were behind the times because they were more localized therapies and didn’t treat the disease in a systemic fashion,” Dr. Wagner said. “I think we have been naïve in thinking that single-agent therapy will work on a tumor that has multiple growth pathways. The wave of the future is multi-targeted therapy and tailoring one’s treatment based on molecular markers.”

One such therapy is bevacizumab, the only drug approved for GBM patients in the last decade. Bevacizumab works by targeting blood vessels and blocking cells that are important for cancer cell growth. Because it targets only those cells important to tumor growth, the drug spares healthy tissue and results in fewer side effects. The FDA approved bevacizumab in 2009 for treatment of recurrent GBM, making it the first antiangiogenic therapy approved for cancer patients.

Bevacizumab is routinely prescribed for patients with recurrent disease, and now researchers think there is potential benefit for newly diagnosed patients, as well. Three phase II studies have shown that bevacizumab in the newly diagnosed patient increases progression-free survival, though its impact on overall survival remains to be determined. In addition, two phase III trials recently closed, though survival data is not yet available.

“Independent of any survival benefit, bevacizumab seems to improve quality of life in newly diagnosed patients by reducing side effects through tightening the blood-brain barrier and decreasing vasogenic edema,” Dr. Wagner said. “There is also evidence that it improves neurocognitive function in recurrent GBM patients.”

Access to trials

For all GBM patients, prompt referral to a research center is important, Dr. Wagner said. “Trial eligibility is very rigid and patients may miss an opportunity to participate in a trial if not referred soon after diagnosis. After a patient starts radiation, it’s usually too late,” she explained

By connecting patients to a research center and the full range of treatment options, physicians can offer their patients the highest level of care and hope in the face of a grim diagnosis.

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