Brain Tumour Survivor

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PostPosted: Mon Aug 16, 2010 9:32 am 
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First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Abstract

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59-60 Gy) and 75 mg/m(2)/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59 +/- 10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments.

http://virtualtrials.com/news3.cfm?item=4862


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PostPosted: Mon Aug 16, 2010 9:33 am 
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Repeated treatments with bevacizumab for recurrent radiation necrosis in patients with malignant brain tumors: a report of 2 cases

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Bevacizumab is expected to constitute a new treatment modality for radiation necrosis. In the present cases, we observed a recurrence of radiation necrosis after temporary improvement by bevacizumab treatment. Re-treatment with bevacizumab controlled the necrosis again. A 39-year-old male and a 57-year-old female were diagnosed with glioblastoma and lung cancer metastasis, respectively. The former patient underwent partial resection of the glioblastoma, followed by boron neutron capture therapy (BNCT) and 30 Gy of fractionated X-ray radiotherapy. Eleven months after BNCT, he suffered from left hemiparesis and convulsions with enlargement of a perifocal edema. The latter patient underwent stereotactic radiosurgery twice for the same tumor. Three months after the second radiosurgery, she had an uncontrollable convulsion and right hemiplegia with a massive perifocal edema. Both lesions were suggested to be radiation necroses by positron emission tomography using amino acids as a tracer. Neither patient responded to corticosteroids, anticoagulants, or vitamin E. They underwent treatment with 5 mg/kg bevacizumab biweekly, for a total of 6 cycles. The size of the perifocal edema was clearly reduced in response to the treatments. The neurological status of the patients improved concomitant with therapy. However, the clinical status of both patients was aggravated several months after the bevacizumab was stopped, and the perifocal edemas enlarged again. The patients underwent a second treatment with bevacizumab, and the perifocal edemas again decreased. Although radiation necrosis may recur several months after bevacizumab treatment, repeated bevacizumab treatments also appear to be effective.

http://virtualtrials.com/news3.cfm?item=4861


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PostPosted: Mon Aug 16, 2010 9:35 am 
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A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma

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In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m(2) every 2 weeks for five consecutive administrations (induction phase), and then every 3 weeks at 100 mg/m(2) as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0-10%], 9 partial responses (22.5%, 95% CI: 15-37%), and 16 stable diseases (40%, 95% CI: 32-51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9-9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile.

http://virtualtrials.com/news3.cfm?item=4860


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PostPosted: Wed Aug 25, 2010 9:47 am 
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Drug combination helped kill deadly cancer in mice

(Reuters) - Adding an experimental drug to chemotherapy helped wipe out brain cancer cells in mice, offering a promising new treatment approach for the deadly cancer, U.S. researchers said on Tuesday.

They said a drug called a gamma secretase or Notch inhibitor, combined with Merck & Co's chemotherapy Temodar or temozolomide, dramatically improved survival in mice with glioblastoma multiforme.

Glioblastoma is the most common and most aggressive form of brain cancer in people.

"Glioblastomas are horrendous tumors, and new therapies are desperately needed," said Alonzo Ross of the University of Massachusetts Medical School, whose study appears in the journal Cancer Research.

"We found that this double therapy of combining temozolomide with a Notch inhibitor was highly effective at treating tumor cells in culture and in mice," he added.

The finding is exciting because several drug companies including Eli Lilly and Co and Merck are developing gamma secretase inhibitor drugs that block or inhibit Notch, a cell signaling pathway.

Ross said adding the Notch inhibitor into the mix appeared to make the chemotherapy more potent, apparently permanently stopping the tumor cells from growing..

In half of the mice given the combination treatment, tumors disappeared. In the other half, they shrank.

Lilly last week halted a trial of its drug semagacestat, a notch inhibitor, in Alzheimer's patients because their symptoms got worse.

But Ross said that may not be an issue in brain cancer patients. "They were trying to keep people on the drug for a long period of time whereas we are talking about a transient period," Ross said.

"I don't think one has to be concerned about the side effects."

More testing is needed before the treatment combination can be tried in people.

The team still needs to test the combination in tumors that have been treated by radiation, which is the standard regimen for patients with glioblastoma tumors.

Ross said it is not clear what effect radiation may have.

"It may enhance it. We just don't know yet," he said.

In addition to Eli Lilly, AVEO Pharmaceuticals is developing a Notch inhibitor drug.

http://www.reuters.com/article/idUSTRE67N4ND20100824


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PostPosted: Sun Sep 05, 2010 6:22 pm 
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Surgeons Use New Tools to Treat Inoperable Brain Tumors

(ST. LOUIS) Washington University neurosurgeons used a new tool for the treatment of braintumors at Barnes-Jewish Hospital for the first time Sept. 1. The tool, the Monteris AutoLITT system is an MRI-guided high-intensity laser probe that “cooks” cancer cells deep within the brain, while leaving surrounding brain tissue undamaged.

Barnes-Jewish is the third hospital in the U.S. to have the tool.

Ralph G. Dacey Jr., MD, chief of neurosurgery at Washington University School of Medicine, and Eric C. Leuthardt, MD, used the Monteris system in a procedure on a patient with a recurrent brain tumor located deep in the brain.

Previous surgeries coupled with the hard-to-reach location of the tumor made a standard tumor resection surgery impossible, said Dr. Leuthardt, director of the Center for Innovation in Neuroscience and Technology at Washington University.

“This tool gives us a treatment for patients with tumors that were previously deemed inoperable,” said Dr. Leuthardt, MD. “It offers hope to certain patients who had few or no options before.”

In Wednesday’s procedure, the surgeons drilled a small burr hole about the diameter of a pencil through the patient’s skull, and then used MRI scans to guide the thin laser probe through the brain into the tumor.

Once inside the tumor, the laser discharged highly focused energy to “cook” and coagulate cancer cells, killing them. The MRI directed positioning of the laser and monitored in real time the discharge of energy to the tumor so healthy surrounding brain tissue was left undamaged.

The Monteris AutoLITT received FDA approval for neurosurgical use in May 2009.

http://virtualtrials.com/news3.cfm?item=4868


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PostPosted: Tue Sep 21, 2010 11:02 am 
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Novel Target for Existing Drug May Improve Success of Radiation Therapy

ScienceDaily (Sep. 20, 2010) — Scientists at Washington University School of Medicine in St. Louis have discovered a new drug target that could improve the effectiveness of radiation for hard-to-treat cancers.

The finding, published in the Journal of the National Cancer Institute, focuses on the role of the enzyme cytosolic phospholipase A2 (cPLA2). This enzyme promotes development and functioning of blood vessel networks that feed malignant tumors, enabling them to overcome the effects of radiation.

They have also identified a drug that stops production of the enzyme. Inhibiting the enzyme can stop the flow of blood tumors need to survive.

Cancers thrive and spread thanks to a unique ability to recruit networks of new blood vessels that penetrate into tumors, bringing oxygen and nutrients and potentially transporting cancer cells to other parts of the body.

Cancer cells start the process of new blood vessel construction, called angiogenesis, by releasing specific molecules into surrounding normal tissue, kicking off a cascade of molecular signals that cause cells lining existing blood vessels to divide and create new vessels. These new vessel networks link the tumor to the circulatory system and its life-sustaining cargo.

Lung cancer and glioblastoma, the most common type of primary brain tumor, are particularly adept at inducing new blood vessel creation via angiogenesis. They are also highly resistant to treatment by radiation.

"Our original objective was to measure the signaling molecules that enable lung and brain cancer to be resistant to radiation," says Dennis Hallahan, MD, the Elizabeth H. and James S. McDonnell III Distinguished Professor in Medicine and chair of the Department of Radiation Oncology at the School of Medicine and senior author of the study.

"There are hundreds of signaling molecules, but the enzyme cPLA2 stood out," Hallahan says. "Radiation of tumor cells triggers production of cPLA2 within two minutes and it contributes to tumor survival."

The cPLA2 enzyme is known to regulate the levels of at last three molecules that promote tumor angiogenesis (the creation of new blood vessel networks to feed cancer cells).

The researchers set out to learn if they could enhance the effect of radiation therapy for lung and brain cancers by inhibiting this enzyme.

The idea was to implant tumors into normal mice and into mice that had been genetically engineered to be unable to produce cPLA2 and then compare the effect of radiation therapy on tumor progression in each.

The immense power of cPLA2 became apparent to Hallahan when a graduate student complained that her experiment failed because she could not grow tumors in mice that lacked the gene that produces cPLA2.

"While implanted tumors progressed as expected in normal mice used in the experiment, they were virtually undetectable in cPLA2 deficient mice," Hallahan says. "The 'failed experiment' was actually a significant discovery of the enormous control cPLA2 has in regulating tumor angiogenesis."

The scientists then examined the blood vessels of the cPLA2 deficient mice. While the blood vessels of cPLA2 deficient mice appeared normal, close inspection revealed the absence of a certain type of contractile cell that regulates blood flow.

"Without these cells, blood vessels can still grow into the tumor but blood cannot flow to the tumor," Hallahan says. "Cancer cannot survive without blood flow to feed it."

The central role of cPLA2 in determining the presence or absence of these contractile cells makes it a prime target for interventional therapy.

"Drugs that target cPLA2 have enormous potential for improving the success of radiation against highly angiogenic tumors," Hallahan says.

Hallahan has already identified an existing drug that inhibits cPLA2. It is a compound originally developed by Wyeth, now part of Pfizer, as a treatment for arthritis. The drug had advanced to Phase 2 testing before being discontinued as a potential arthritis treatment.

Reaching Phase 2 testing, however, suggests that a compound has been proven safe, regardless of whether or not it meets performance standards for the specific medical condition for which it was made. These drugs are typically then tested for other uses.

Hallahan learned of the Pfizer compound from an innovative collaboration between Pfizer and Washington University that allows Washington University scientists to view extensive research data on a large array of Pfizer pharmaceutical candidates that are or were in clinical testing.

Don Frail, PhD, chief scientific officer of Pfizer's Indication's Discovery Unit, says the majority of drug candidates tested in development do not give the desired result.

"Yet those drugs that do succeed typically have multiple uses," Frail says. "Hallahan's research has led to an entirely new potential use for one of these compounds in an area of high patient need that otherwise might have been overlooked. This is exactly what our partnership with Washington University is about and is among the first to be funded through the new relationship."

Hallahan is currently partnering with Craig Wegner, PhD, in the Indications Discovery Unit of Pfizer to further understand the pathways impacted by cPLA2 and to evaluate the drug that inhibits its action.

http://www.sciencedaily.com/releases/20 ... 091751.htm


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PostPosted: Wed Sep 22, 2010 12:21 pm 
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Two-pronged therapy shows results against brain cancer

Clinical test could be undertaken after researchers at the University of Massachusetts Medical School have reported early success using a dual therapy targeting one of the most deadly forms of brain cancer.

As they report in the September issue of Cancer Research, a journal of the American Association for Cancer Research, the UMass researchers have been using the combination of two pharmaceuticals, temozolomide and a drug known as a notch inhibitor, against glioblastoma multiforme.

GBM is the most common form of brain cancer and one of the most aggressive and difficult to control.

Temozolomide, which is marketed under the brand names Temodar and Temodal, has already shown some promise against GBM. The two-year survival rate for patients with the brain tumor who received a combination of radiation therapy and temozolomide is around 25 percent, compared to 10 percent for Xray treatments alone.

Temozolomide is thought to inhibit the growth of cancer cells by prevent them from reproducing their DNA.

Noting the notch signaling pathway appears to be operating in overdrive in tumor cells, a team UMass Medical School team led by Alonzo H. Ross, a professor of biochemistry and molecular pharmacology, decided to test a combination of temozolomide and the experimental notch inhibitor drug against GBM cells in laboratory cultures and lab mice.

The Notch pathway is a way cells exchange signals and is thought to help regulate cell growth.

So far, the results have been encouraging.

"We found that this double therapy of combining temozolomide with a Notch inhibitor was highly effective at treating tumor cells in culture and in mice," Ross said.

The problem Ross and his colleagues are trying to overcome is the ability of GBM tumors to begin growing again after surgery, radiotherapy and chemotherapy have appeared to tame them. Researchers believe that these forms of therapy can get rid of GBM cancer cells but aren't nearly as effective against cancer stem cells.

Cancer stem cells are immature cells found within cancerous tumors that can mature into a variety of cancer cells types.

In both cultured cells and lab mice, the combination of temozolomide and the Notch inhibitor were more successful than either agent alone in slow the recurrence of GBM cells.

"The effect of the two together is very dramatic," Ross said.

Patrick M. O'Connor, a member of the Cancer Research editorial board, says the UMass study provides preclinical proof-of-concept evidence that the Notch pathway confers a survival advantage to glioma cells treated with temozolamide alone.

"These results help lay the groundwork for future clinical research and are yet another stepping stone towards a future era dominated by 'precision therapeutics' designed to specifically target the underlying molecular drivers of cancer growth and spread," said O'Connor, who is the founder and chief science officer of Selexagen Therapeutics, a San Diego-based biotech firm.

http://suncoastpinellas.tbo.com/content ... n-ca/news/


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PostPosted: Fri Sep 24, 2010 12:11 pm 
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Toward the First Nose Drops to Treat Brain Cancer

ScienceDaily (Sep. 23, 2010) — Scientists are reporting the development and successful initial testing of a new form of methotrexate -- the mainstay anticancer drug -- designed to be given as nose drops rather than injected. It shows promise as a more effective treatment for brain cancer, they say.

The report appears in ACS' Molecular Pharmaceutics.

Tomotaka Shingaki and colleagues note that brain cancer is difficult to treat, partly because current anticancer drugs have difficulty reaching the brain. That's because the so-called blood-brain barrier (a protective layer of cells surrounding the brain) prevents medication in the blood from entering the brain. But new evidence indicates that some drugs administered through the nose, either as nose drops or nasal spray, can bypass this barrier and travel directly into the brain. Among them are drugs for migraine headaches. Until now, however, nobody knew if methotrexate might do the same.

The scientists tested methotrexate nose drops on laboratory rats with brain cancer. Compared to cancer treated with an injectable form of the drug, the nose drop drug reduced the weight of tumors by almost one-third, the scientists said. "The strategy to utilize the nose-brain direct transport can be applicable to a new therapeutic system not only for brain tumors but also for other central nervous system disorders such as neurodegenerative diseases," the article noted.

http://www.sciencedaily.com/releases/20 ... 121949.htm


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PostPosted: Sun Sep 26, 2010 10:21 am 
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How heat helps in cancer treatment

Heat – whether from a carefully created and controlled fever or from hyperthermia delivered by microwaves, radio frequency or ultrasound – is increasingly being used as a cancer treatment.

There are two theories as to why this might work. First, a fever within the body produces a state in which the immune system becomes hypersensitive, detects that the cancer cells are not normal and attacks them. It may be that, if we have a strong immune system, it is destroying cancer cells every day but, on occasion, some cells are missed and cancer develops. In the USA scientists are experimenting with giving cervical cancer patients a bio-engineered form of listeria (not the actual disease) - both it and salmonella are instantly recognisable by the body as enemy bacteria – thus hoping to spark the immune system into rising up to fight it and the cancer.

The second theory, which ties in with several stories recently about patients whose cancers have simply disappeared overnight, is that it is the high temperature itself which destroys the cancer. Also in the USA, cancer patients are being placed in an infra-red “hot box” for eight hours – under sedation – two days after chemotherapy and having taken immune system boosting drugs. This treatment is much gentler than radiotherapy, means less chemotherapy is required and, therefore, the patient will have fewer side-effects. It appears that primary malignant tumours have a bad blood circulation, which makes them more sensitive to changes in temperature. So, the experimental theory is that a 40 degree centigrade controlled fever will wake-up the immune system.

Hyperthermia tends to be used in combination with radio or chemotherapy but at a private clinic in Mexico – called the Hope4Cancer Institute – the doctors are using it as an “aggressive but natural approach to treatment” without the conventional therapies. The Medical Director is Dr Antonio Jiminez, who is an oncology researcher and determined to find non-invasive, non-surgical and painless treatments without side-effects. He explains that hyperthermia, using specific sound wave frequencies to heat the cancer cells and destroy them does not affect normal cells – so there are no side effects.

To eliminate the detox symptoms which occur when cancer cells die off quickly, the Hope4Cancer Institute uses infrared light therapy, infrared saunas, massage therapy, organic coffee enemas and IV therapy to flush out the dead cells. Whole body or local hyperthermia is combined with SonoPhoto Dynamic Therapy and patients are encouraged to follow the Hallelujah Acres Diet (vegan and raw food).

Dr Jiminez says: “We address all aspects of the cancer – spiritual, emotional and physical. We address the cause of the cancer and help the immune system fight the disease.” The institute employs six medical doctors with varying specialities, treats 200 patients each year and claims to be particularly successful with cases of breast cancer. His argument is that “cancer mutates, like flu mutates but our conventional cancer treatments are much the same today as they were 25 years ago. We make new flu vaccines every year but we don’t change our approach to cancer.”

Ancient civilisations used heat to treat tumours – particularly those of the breast – and it seems that, once again, we are looking back to the less invasive treatments of the past. The spotlight seems to fall onto the role of the immune system and, as I wrote last week, the need to tailor treatment to the individual patient.

Could it be that the ever-growing number of people developing cancer are doing so because, nowadays, we have fewer infections and, therefore, fewer fevers? Does this mean that the immunisation programme, antibiotics and better hygiene have created the cancer monster?

http://blogs.telegraph.co.uk/news/judit ... treatment/

[comment - cancer cells have a lower temperature tolerance. Lifestyle is the greatest contributor to the cancer explosion in the past 40 years. Heat is easy to apply without the risks of invoking a fever]


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PostPosted: Thu Sep 30, 2010 11:46 am 
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New Treatment for Most Common Cancer in Babies

(CBS) Neuroblastoma is the most commonly diagnosed cancer for babies in the first year of life. It's an aggressive disease and less than half of its victims survive. But there's new hope in a new treatment. CBS News Contributor and Neurosurgeon CNN's Dr. Sanjay Gupta reports on this promising therapy that's already saving young lives.

Kindergarten was supposed to mean new friends and ballet for 6-year-old Hayley Kudro. But she said she wasn't eating well because of her tumor. "It filled up my whole belly," Hayley replied.

Instead, she's spent the past year enduring toxic treatments for a cancer her family had never even heard of.

"We didn't really have a choice," said Haley's mom, Karen. "It was do this, or lose her."

Last year, Hayley was diagnosed with neuroblastoma - a cancer of the nervous system. It was the most aggressive form: she had a softball-sized tumor in her belly that choked her liver and pancreas.

"Without treatment it will grow and spread and kill the child within a matter of months," said Dr. John M. Maris, of The Children's Hospital of Philadelphia.

Hayley had the standard treatment including chemotherapy, major surgery and radiation. But she's also receiving a drug treatment called immunotherapy - designed to rev up her own immune system to kill the cancer. The immunotherapy drug not only stimulates the child's immune system, it attacks tumor cells.

A new study of 226 high-risk patients like Hayley found that adding the immunotherapy to the standard therapy improved the survival rates by 20 percent. It was so effective, the trial was stopped early.

Gupta asked Maris, "How often do you get to say in cancer research, 'wow, we've found something that works, maybe even cures?'"

"This is one of those moments where we've proven a therapy makes a major difference," he replied.

This is an expensive treatment, costing up to $40,000. Its side effects are relatively mild, just severe flu symptoms once a month during the treatment.

Immunotherapy will be added to traditional treatments in a variety of cancers including breast cancer, melanoma, and kidney cancer.

Hayley is back in first grade. Doctors believe her tumor is gone. Thanks to immunotherapy, it may not come back.

http://www.cbsnews.com/stories/2010/09/ ... 2677.shtml


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PostPosted: Sat Oct 02, 2010 8:53 am 
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Genetic Changes That Make Some Forms of Brain Cancer More Aggressive Identified

ScienceDaily (Sep. 30, 2010) — A multi-institutional team led by investigators from Memorial Sloan-Kettering Cancer Center has published a study that provides new insight into genetic changes that make some forms of glioblastoma, the most common type of primary brain cancer, more aggressive than others and explains why they may not respond to certain therapies. The research was led by senior author Eric C. Holland, MD, PhD,--an MSKCC surgeon, researcher and the Director of the Brain Tumor Center--and was published in the October 1 issue of the journal Genes & Development.

Glioblastoma has several subtypes, which are characterized by different genetic changes found in the tumor cells. One common subtype is characterized by cells with increased signaling from a protein called platelet-derived growth factor receptor (PDGFR). In this study, which involved screening patients' tumor samples for PDGFR mutations, the researchers were surprised to find that almost half of all glioblastomas with excess copies of the PDGFR gene also had rearrangements in the gene itself, creating proteins that are continually turned on. These rearrangements were either shortened forms of the protein or involved the fusion of the protein to another receptor. Fusion genes have not been found in brain tumors previously but are well studied in certain types of leukemia, and more recently have been found in some solid tumors as well.

Much of the team's work was made possible by data coming from The Cancer Genome Atlas (TCGA), an effort funded by the National Institutes of Health to understand the molecular basis of cancer. Glioblastoma is one of three forms of cancer that has been studied in detail as part of TCGA's initial pilot phase, along with ovarian cancer and lung cancer.

The presence of the rearrangements in the PDGFR gene suggest that these specific tumors have evolved to be dependent on signaling through this receptor, a target for several drugs under development. According to the researchers, the recent study suggests that more effort needs to be put into identifying exactly which subtype of glioblastoma a patient has in order for therapies to be targeted appropriately.

http://www.sciencedaily.com/releases/20 ... 105608.htm


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PostPosted: Tue Oct 05, 2010 9:38 am 
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Brain cancer vaccine doubles survival

Patients with the brain cancer glioblastoma treated with a vaccine lived nearly twice as long as those who received radiation and chemotherapy, an encouraging result for a cancer that often kills patients within a year, U.S. researchers said Monday.

The Celldex Therapeutics Inc vaccine works by targeting a mutation in a gene called the epidermal growth factor receptor, which fuels cancer growth.

"It does appear to help patients live much longer than we could have expected," said Dr. John Sampson of Duke University in North Carolina, whose team worked on the study published in the Journal of Clinical Oncology.

Working with researchers at The University of Texas MD Anderson Cancer Center, Sampson's team showed the vaccine killed cancer cells carrying the mutation in all but one patient.

Immune response tests showed patients who developed antibodies after being vaccinated were most likely to respond, giving doctors a good way to see which patients might benefit, Sampson said in a telephone interview.

He said many patients in the study are still alive after five years. "That is pretty unusual with this disease."

Glioblastoma multiforme typically kills half its victims within a year and patients rarely survive more than three years. Sampson remains cautious and says the treatment still needs to be proven in a large-scale clinical trial.

CANCER IMMUNOTHERAPY

The finding is yet another example of the potential of cancer immunotherapies -- treatments that recruit the immune system to fight cancer.

Earlier this year, the U.S. Food and Drug Administration approved the first cancer vaccine, Dendreon Corp's prostate cancer therapy Provenge.

And a team in June said Bristol-Myers Squibb Co's immune system treatment ipilimumab helped extend the lives of patients with aggressive melanoma, the deadliest form of skin cancer for which there are few treatment options.

For the midstage brain cancer study, researchers enrolled 35 people with glioblastoma who had undergone radiation and were treated with the chemotherapy drug temozolomide, sold by Merck under the brand name Temodar, which is thought to boost immune response.

Of those, 18 people got the vaccine and 17 were in a control group. Those who got the vaccine lived an average of 26 months, compared with 15 months for those in the control arm.

Sampson said the vaccine is the first to target proteins only present in cancer cells, which could mean it would have fewer side effects than other cancer vaccines.

He said he has no current financial ties to Celldex, but has received research funding from the company in the past.

Epidermal growth factor receptor mutations are found in many other cancers, and the teams say the vaccine should be tested in other cancers as well. But funding the large studies it will take to prove the vaccine works may be a challenge.

Last month, Celldex's partner Pfizer Inc pulled out of a strategic partnership to develop the vaccine, and the company said it now plans to develop it on its own.

The National Cancer Institute is spending $14 million over five years to develop a network of clinics to test cancer immunotherapy treatments.

http://www.msnbc.msn.com/id/39505662/ns/health-cancer/


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PostPosted: Wed Oct 13, 2010 1:59 pm 
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Long-Term Benefits of Transcranial Magnetic Stimulation for Depression Supported by New Study

ScienceDaily (Oct. 11, 2010) — In a study to determine the durability and long-term effects of transcranial magnetic stimulation (TMS), psychiatric researchers at Rush University Medical Center have found the non-invasive, non-drug therapy to be an effective, long-term treatment for major depression.

Results of the study were published in the October 2010 issue of Brain Stimulation, a journal published by Elsevier.

TMS therapy is a non-invasive technique that delivers highly focused magnetic field pulses to a specific portion of the brain, the left prefrontal cortex, in order to stimulate the areas of the brain linked to depression. These pulses are of a similar intensity to the magnetic field produced during an MRI imaging scan. The repeated short bursts of magnetic energy introduced through the scalp excite neurons locally and in connected areas in the brain.

TMS received clearance from the U.S. Food and Drug Administration (FDA) in October 2008. This novel treatment option is a safe and effective, acute antidepressant therapy, but there is limited information on its long-term benefits.

"This is the only prospective, maintenance, follow-up study which assesses the durability of acute TMS benefit in patients with major depression," said Dr. Philip G. Janicak, study principal investigator and professor of psychiatry at Rush University Medical Center.

In the study, 301 patients suffering from major depression were randomly assigned to receive active or sham TMS in an acute, six-week, controlled trial. Patients who responded then underwent a three-week, transition period where they were tapered off of active or sham TMS treatment and started on a standard antidepressant for maintenance. After any successful acute treatment for depression such as TMS, antidepressant medications or electroconvulsive (ECT) therapy, it is usual practice to introduce maintenance medication to lessen the chance of relapsing.

In the acute, randomized trial, 142 patients who received active TMS therapy responded and entered the three-week, transition phase. One hundred twenty-one patients completed this phase without relapse. Of those patients, 99 (81.8 percent) then agreed to be followed for an additional 24-week period during which only 10 patients relapsed.

In addition, TMS was successfully used as an intermittent rescue strategy to preclude impending relapse in 32 of 38 (84 percent) patients. This indicated that the therapeutic effects of TMS are durable in the majority of acute responders and that reintroduction of TMS as an adjunct to medication was effective and safe in preventing relapse.

"The results of the follow-up study further support TMS as a viable treatment option for patients with major depression who have not responded to conventional antidepressant medications," said Janicak. "After acute response to TMS, a standardized regimen of antidepressant medication maintained the acute benefit in the majority of patients over a six-month period."

The FDA-approved TMS device was developed by Neuronetics, Inc. Patients treated with TMS therapy do not require anesthesia or sedation and remain awake and alert. It is a 40-minute outpatient procedure that is prescribed by a psychiatrist and performed in an outpatient setting. The treatment is typically administered daily for four-to-six-weeks.

Depression affects at least 14 million American adults each year. Researchers estimate that by the year 2020, depression will be the second leading cause of disability worldwide. About two-thirds of those who experience an episode of depression will have at least one other episode in their lives. Depression is a debilitating illness, and existing treatment options are frequently ineffective or intolerable due to side effects. Current antidepressant therapies are not beneficial for at least a third of depressed individuals, leaving many with a lack of adequate treatment options.

http://www.sciencedaily.com/releases/20 ... 114052.htm

[comment - although a cancer diagnosis can lead to depression, I was thinking about the use in those who have been left disabled by our cancer/treatment]


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PostPosted: Tue Oct 19, 2010 9:14 am 
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Scottish scientists trial brain cancer vaccine

Scientists in Scotland are to test a new vaccine to treat a deadly form of brain cancer.
Cancer Research UK and Cancer Research Technology - the charity's development and commercialisation arm - have launched the first clinical trial of a promising cancer vaccine to treat glioblastoma.

The treatment, IMA950, will direct and boost the body's immune system to enable it to fight cancer.

The vaccine will be used together with the standard treatments of surgery, radiotherapy and chemotherapy.

The trial is taking place at the Beatson West of Scotland Cancer Centre in Glasgow and up to four other hospitals yet to be confirmed across the UK.

Professor Roy Rampling, from the University of Glasgow who will lead the study, said: "Glioblastoma can be challenging to treat because there are limited options for therapy; there's a real need for new treatments for this disease."

http://news.scotsman.com/health/Scottis ... 6587478.jp


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PostPosted: Tue Nov 02, 2010 8:31 am 
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Compound in Daffodils Targets Brain Cancer

ScienceDaily (Nov. 1, 2010) — When looking for new ways to treat aggressive brain cancers, an international team of scientists turned a new leaf and "discovered" the lowly daffodil. A new research study published in the November 2010 print issue of The FASEB Journal offers hope that a natural compound found in daffodil bulbs, called narciclasine, may be a powerful therapeutic against biologically aggressive forms of human brain cancers.

"We are planning to move a narciclasine derivative toward clinical trials in oncology within a three to four year period in order to help patients with brain cancers, including gliomas, as well as brain metastases," said Robert Kiss, Ph.D., co-author of the study from the Laboratory of Toxicology at the Institute of Pharmacy at the Université Libre de Bruxelles in Brussels, Belgium. "We hope narciclasine could be given to brain cancer patients in addition to conventional therapies."

To make this discovery, Kiss and colleagues used computer-assisted techniques to identify targets for narciclasine in cancer cells. The strongest potential candidate to emerge was the eEF1A elongation factor. Researchers then grafted human melanoma brain metastatic cells into the brains of genetically altered mice. Results showed that the injected mice survived significantly longer when treated with narciclasine than those mice left untreated. The researchers believe that narciclasine selectively inhibits the proliferation of very aggressive cancer cells, while avoiding adverse effects on normal cells. Narciclasine could be used in the near future to combat brain cancers, including gliomas, and metastases such as melanoma brain metastases.

"Scientists have been digging in odd corners to find effective treatments for brain cancer for decades, and now they've found one in daffodils." said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "It doesn't mean that you should eat daisies or daffodils for what ails you, but that modern medicinal chemistry can pluck new chemicals from stuff that grows in the garden. This is a good one!"

http://www.sciencedaily.com/releases/20 ... 115612.htm


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