Italian Court Rules Mobile Phone Use Caused Brain Tumor

A man in Italy who claimed that having to use cell phones for work gave him a brain tumor has been awarded €500 ($535) a month in compensation. Luckily, the tumor was benign, The Guardian reported, although he did lose hearing in his right ear.

In 2011, the WHO’s International Agency for Research on Cancer declared the radiation emitted by cell phones and wireless devices a Group 2B “Possible Carcinogen,” and most recently, the National Toxicology Program, an interagency research program, based at the National Institute of Environmental Health Sciences, concluded that whole body exposure to cell phone radiation likely caused heart and brain tumors in male rats.

Despite such findings, cell phones have become increasingly pervasive and such a common part of our daily lives that most people never think twice about using them — which makes it even more important to start thinking about ways to be safe with your phone and other wearable, wireless devices.

One factor that should no longer be debated is the risk of cell phones to children. Children simply shouldn’t be using them. Keep your own cell phone use to a minimum. Limit wearable device usage to areas with excellent reception, as the weaker the reception, the more power your phone must use to transmit, and the more power it uses, the more radiation it emits.

Never carry your cellphone on your body or sleep with it under your pillow or near your head. And, use a well-shielded wired headset. One of the best kinds of headsets use a combination of shielded wire and air-tube. These operate like a stethoscope, transmitting the sound to your head as an actual sound wave.

Long-term Cell Phone Use Linked to Brain Tumor Risk

Long-term use of both mobile and cordless phones is associated with an increased risk for glioma, the most common type of brain tumor, the latest research on the subject concludes.

The new study shows that the risk for glioma was tripled among those using a wireless phone for more than 25 years and that the risk was also greater for those who had started using mobile or cordless phones before age 20 years.

“Doctors should be very concerned by this and discuss precautions with their patients,” study author Lennart Hardell, MD, PhD, professor, Department of Oncology, University Hospital, Örebro, Sweden, told Medscape Medical News.

Such precautions, he said, include using hands-free phones with the “loud speaker” feature and text messaging instead of phoning.

The study was published online October 28 in Pathophysiology.

Pooled Data

The recent worldwide increase in use of wireless communications has resulted in greater exposure to radiofrequency electromagnetic fields (RF-EMF). The brain is the main target of RF-EMF when these phones are used, with the highest exposure being on the same side of the brain where the phone is placed.

The new study pooled data from two case-control studies on histopathologically confirmed malignant brain tumours. The first included patients aged 20 to 80 years diagnosed from 1997 to 2003, and the second included those aged 18 to 75 years diagnosed between 2007 and 2009. Cases came from six oncology centers in Sweden.

Cases were matched with controls of the same sex and approximate age who were randomly drawn from the Swedish Population Registry.

All participants filled out a questionnaire detailing exposure to mobile phones and cordless desktop phones.

The analysis included 1498 cases of malignant brain tumors; the mean age was 52 years. Most patients (92%) had a diagnosis of glioma, and just over half of the gliomas (50.3%) were the most malignant variety — astrocytoma grade IV (glioblastoma multiforme). Also included were 3530 controls, with a mean age of 54 years.

The analysis showed an increased risk for glioma associated with use for more than 1 year of both mobile and cordless phones after adjustment for age at diagnosis, sex, socioeconomic index, and year of diagnosis. The highest risk was for those with the longest latency for mobile phone use over 25 years.

The risk was increased the more that wireless phones were used. The odds ratios steadily rose with increasing hours of use.

The risk for glioma was greatest in the most exposed part of the brain. The odds ratios were higher for ipsilateral exposure and for glioma in the temporal and overlapping lobes.

Further, the risk was highest among participants who first used a mobile phone (odds ratio, 1.8) or cordless phone (odds ratio, 2.3) before age 20 years, although the number of cases and controls was relatively small.

Developing Brain

As Dr Hardell explained, children and adolescents are more exposed to RF-EMF than adults because of their thinner skull bone and smaller head and the higher conductivity in their brain tissue. The brain is still developing up to about the age of 20 and until that time it is relatively vulnerable, he said.

There was a higher risk for third-generation (3G) mobile phone use compared with other types, but this was based on short latency and rather low numbers of exposed participants, said the authors. 3G universal global telecommunications system mobile phones emit wide band microwave signals, which “hypothetically” may result in higher biological effects compared to other signals, they write.

Such biological effects, said Dr Hardell, could include an increase in reactive oxygen species, which several articles have linked to cancer. The p53 gene has also been implicated, he said.

The study’s very high participation rate (86% for cases and 87% for controls) makes it unlikely that selection bias influenced the results, said the authors.

Dr Hardell believes the new findings reinforce the message that EF-EMF emissions from wireless phones should be regarded as carcinogenic under International Agency on Research on Cancer (IARC) classifications and that current guidelines for exposure “should be urgently revised” to reflect that.

According to the IARC’s 2013 report, there is a “causal” relationship between use of both mobile and cordless phones and that the risk of glioma is “possible.”

Numerous studies have looked at the link between use of wireless phones and brain tumors. Studies by Dr Hardell and his colleagues dating back to the late 1990s have found a connection with mobile and cordless phones.

But the INTERPHONE study (Int J Epidemiol 2011;39:675-694; Cancer Epidemiol 2011;32:453-464) failed to find strong evidence that mobile phones increase the risk for brain tumors.

In addition, a large prospective study (Int J Epidemiol 2013;42:792-802) found that mobile phone use was not associated with increased incidence of glioma or of meningioma or non–central nervous system cancers in middle-aged British women.

According to Dr Hardell, this last study was limited because it used information at one point in time. “It is not a case-control study and has serious problems with the methods used,” he told Medscape Medical News.

Evidence “Unconvincing”

Reached for a comment, L. Dade Lunsford, MD, Lars Leksell Professor of Neurosurgery, and director, Center for Image Guided Neurosurgery, University of Pittsburgh, Pennsylvania, said the new study provides additional “but as yet unconvincing” evidence of a potential role of cell or cordless phone technologies in the pathogenesis of gliomas.

He noted that some features were not controlled, including ionizing radiation exposure and family history.

As well, he said, the study suffers from recall bias, with results possibly being affected by patients being anxious to solve the question of “why me?”

“It is of interest that the only study that used actual industry data of cell phone use (the Danish study [Lancet Oncol 2011;12:624-626; Rev Environment Health 2012;27:51-58]) was dismissed by the authors as ‘uninformative’,” he said. “Perhaps it was not supportive of the author’s premise.”

Although the study didn’t specify the side of the tumor, Dr Lunsford pointed out that about 90% of the world’s population is right-handed and that most hold their mobile phone to their left ear in order to write with their dominant hand. “One could theorize then that left-sided tumors would predominate with the temporal lobe being most adjacent to the cell phone output.”

Dr Lunsford also commented that both glial and Schwann cells are late-responding tissues and that the oncogenesis of such cells by mobile phone technologies remains unexplained. “If cell phones cause such tumors, why do patients not develop higher rates of ipsilateral basal or squamous cell cancers, or melanomas — these are frequently dividing cell lines that theoretically ought to be even more susceptible.”

While the potential role of cell phones as an additional factor in oncogenesis “can’t be dismissed out of hand,” the use of this technology does save lives, stressed Dr Lunsford.

“Cell phone has provided an amazing safety net for citizens of almost all cultures across the world. The lives saved by the proliferation of cell phone communication is phenomenal — emergency calls, quick first responders, warnings of severe weather are only a few examples.”

Brain tumour genes identified.

The team was led by Professor Brandon Wainwright, Dr Laura Genovesi and Dr Melissa Davis from The University of Queensland’s Institute for Molecular Bioscience.

Professor Brandon Wainwright said these genes provided potential targets for treatment.

Brain tumours are the most common cause of cancer death in children,” Professor Wainwright said.

“Those who do survive often experience significant neurological, intellectual and physical disabilities as a result of their treatment, which involves surgical removal of the tumour followed by radiotherapy and chemotherapy.

“We clearly need more effective and less invasive options to treat medulloblastoma and improve outcomes for both children and adults with this devastating disease.”

There are four different sub-types of medulloblastoma, each with their own molecular signature.

The researchers identified underlying genetic regulatory networks that were present in all of the sub-types, a discovery that Professor Wainwright said was important in advancing treatments.

“We are now searching for existing drugs that may block these gene networks and act as viable treatment alternatives for medulloblastoma.”

The team, which included researchers from Australia, Singapore, Canada, the United Kingdom and the United States, made the discovery after screening 85 tumours.

The results were published in the highly prestigious scientific journal Proceedings of the National Academy of Sciences USA.

300% Increased brain cancer risk for long-term users of cell phones and cordless phones.

A Swedish study on the use of wireless phones, including cell phones and cordless phones, has uncovered a link between electromagnetic radiation exposures and the risk of malignant and non-malignant brain tumors.

Cell phones and cordless phones emit a form of non-ionizing electromagnetic radiation, radiation which can be absorbed by tissues and cells that come into close contact with the phone, e.g., the head and neck. The most conclusive evidence as to the dangers of cell phone and similar radiation exposures come from studies on long-term exposure (ten years or more) like this Swedish study.


300% increased risk for long term users

This new study reveals that people who used cell phones and cordless phones for more than a year were at a 70% greater risk of brain cancer compared to those who used cell phones and cordless phones for a year or less. Those who used cell phones and cordless phones for more than 25 years were found to have a 300% greater risk of brain cancer than those who used cell phones and cordless phones for a year or less.

The total number of hours of cell phone and cordless phone use was found to be as important as the number of years of use. A quarter of the study’s subjects were found to have lifetime cell phone or cordless phone use of 2,376 or more hours, which corresponds to about 40 minutes a day over ten years. Heavier users were found to have a 250% greater risk of brain tumors compared to those who’d never used cell phones or cordless phones or used them for less than 39 hours in their lifetime.

Brain cancer risk highest on side of head used to phone

This new study echoes the previous study findings of the decade long 13-nation Interphone study, which found a 180% greater risk of brain cancer among those who used cell phones for 1,640 or more hours in their lifetime. But it also goes further.

In this latest study, for all types of cell phone and cordless phone use, brain cancer risk was found to be greater in the part of the brain where the exposure to cell phone and cordless phone radiation was highest, on the side of the head where people predominantly used their phones.

Wireless safety standards inadequate

Given the consistent results from these studies, public health bodies from around the world are asking that the current wireless safety standards be reviewed.

The World Health Organization (WHO) recently classified radio frequency electromagnetic fields as a Group 2B possible carcinogen. Doctors groups are also sounding the alarm. The American Academy of Environmental Medicine, the International Society of Doctors for the Environment (ISDE) and the Irish Doctors Environmental Association (IDEA) are all calling for improved standards.

Practice safe use of wireless phones

In the absence of sufficiently protective standards and legislation, individuals need to act now. This means:

  • Limiting calls to those that are absolutely necessary on wireless devices
  • Using a speaker phone or air tube headset whenever possible
  • Keeping cell phones away from the body
  • Turning your cell phone off when not in use
  • Texting instead of talking
  • Alternating from one side of the head to the other when phoning
  • Avoiding using a cell phone when reception is poor
  • Using a corded land line whenever possible
  • Removing cordless phones from bedrooms

Minimizing the effects of these wireless exposures now instead of later is timely and crucial.

Sources :

Polio Injection Shrinks Woman’s Brain Tumor.

Stephanie Lipscomb, 22, used to have a cancerous tumor the size of a lime in her brain. Monday, she learned that it’s the size of a pea, and it’s still shrinking even though she hasn’t had any chemotherapy or radiation in more than a year.

Doctors at Duke University Medical Center attribute the shrinkage to the modified polio virus they injected into her tumor in May 2012, causing it to shrink without damaging surrounding healthy brain cells.

“Throughout this whole process, I never thought I was going to die,” she said, adding that she’s a religious person. “This is just another part of my story.”

Lipscomb was finishing up her freshman year at the University of South Carolina Upstate in 2010 when headaches began to plague her as she juggled nursing classes and waitressing. At first, doctors told her she had chronic migraines and gave her caffeine pills. Later, they said she had a sinus infection and gave her antibiotics.

Nothing worked.

“I was pitiful,” she said. “By that point, my migraines were so bad, I couldn’t eat anything without throwing it back up. I couldn’t bathe myself. I couldn’t dress myself.”

So she called her grandparents, who were nearby. They took her to the emergency room, fearing meningitis.

When Lipscomb’s CT brain scans came back, they found a tumor the size of a tennis ball behind her right eye. It was a glioblastoma – the most aggressive kind of brain cancer. She was only 20 years old and told she would live five more years at best.

Read about the former Phillies catcher with brain cancer.

The typical glioblastoma patient has between 14 and 18 months to live from the time he or she is diagnosed, said Dr. Annick Desjardins, Lipscomb’s neuro-oncologist at the Preston Robert Tisch Brain Tumor Center at Duke University Medical Center. Even after surgery, these types of tumors usually return, signaling that the patient will die in three to eight months.

So when Lipscomb’s tumor returned two years after her initial surgery to remove it, Desjardins gave her the option of enrolling in a clinical trial that would use the polio virus’s scariest feature: it’s ability to unlock a cell, enter it and kill it.

Not all brain cancer patients were eligible, Desjardins said. Lipscomb’s tumor was in the right frontal lobe, the area of the brain the controls planning and social skills. Had it been in the area that controls motor skills, vision or language, doctors wouldn’t have offered the treatment because it would have been too dangerous to tamper with those areas of the brain.

Lipscomb’s mom was on the fence about using the virus.

“She was like, ‘What? They’re gonna put polio in my daughter? What the heck are they thinking?'” Lipscomb said. “I had to break it down a little more for my mom since I’m a nursing major.”

Using polio to treat cancer has been Duke neurosurgeon Dr. Mattias Gromeier’s goal for two decades, during which he created and studied a modified version of the virus under a microscope and in monkeys.

Lipscomb became Gromeier’s first human patient, and so far, she has survived longer than she would have with standard treatment, Desjardins said.

“It has been most gratifying,” Gromeier said.

The standard polio virus uses a receptor molecule present on brain cells to “unlock” them. The virus then enters the cell and replicates until the cell dies. Gromeier’s modified version of polio is spliced with a rhinovirus, which causes the common cold. This allows it to enter healthy brain cells using the same receptor molecule – which is also found in most cancers – but the virus is unable to replicate, so it can’t hurt the cells.

However, because cancer cells have a different biochemical makeup than regular brain cells, the modified virus is able to enter them, replicate and kill them much like normal polio does. As such, the virus leaves healthy brain tissue unharmed, but it targets and destroys cancer.

Once Lipscomb and her mom were on board, doctors used a catheter to enter Lipscomb’s brain and slowly inject the virus over six and a half hours.

It took several months for the virus to start killing Lipscomb’s cancer cells, but on Monday, she learned that the tumor was only the size of a pea. Desjardins told her it could come back, but the tumor was still shrinking.

“It was probably one of the most exciting scans I have ever seen of my brain,” Lipscomb said. “I don’t think it’s going to come back.”

Of the eight patients treated with the modified polio virus, two have not responded well. Three patients have been improving over the last few months and it is too soon to tell how well three other patients will respond, Gromeier said. He does not know why the tumors didn’t shrink in two of the patients.

Another clinical trial is in the works so Gromeier can continue his research.

Since even non-glioblastoma cancer cells have the receptor polio needs to unlock it, Gromeier has been able to shrink melanoma, prostate, colorectal and pancreas cancers in a lab. Still, he has yet to do trials on animals or humans.


Targeting Invasive Glioma Cells.

Name of the Trial
Phase I Trial of AZD7451, a Tropomyosin-Receptor Kinase (TRK) Inhibitor, for Adults with Recurrent Gliomas (NCI-12-C-0005). See the protocol summary.

Principal Investigators
Dr. Katharine McNeill, NCI Center for Cancer Research, and Dr. Howard Fine, New York University Cancer Institute

Why This Trial Is Important

Glioblastoma is the most common malignant brain tumor in adults, with about 12,000 new cases diagnosed each year in the United States. It is also one of the deadliest, with a median survival following diagnosis of about 14 months.

Surgery to remove as much of the tumor as possible is the standard primary treatment for glioblastoma. After surgery, doctors use radiation therapy and treatment with the chemotherapy drug temozolomide to try to delay the growth of the remaining cancer. Although these measures may delay disease progression for a while, they cannot prevent it, and death usually occurs within a few months. Currently, the only therapy that has proven effective in delaying death in patients with progressive glioblastoma is bevacizumab, which helps block the tumor’s ability to induce the formation of new blood vessels.

Glioblastoma is particularly difficult to treat because of its highly invasive nature. Although the bulk of the tumor may be well defined, malignant cells have usually migrated away from the tumor by the time it is discovered. Some of these cells inevitably remain behind after surgery and, if left unchecked, will eventually kill the patient.

Progress in the treatment of glioblastoma has been hampered by the absence of preclinical tumor models that mimic the invasiveness of the cancer. However, NCI researchers recently developed new cell lines from a subset of glioblastoma tumor-initiating cells that more accurately replicate the invasiveness of human glioblastoma in animal models. Using the new models, they were able to determine that cells near the edge of glioblastoma tumors express a set of proteins that help make them highly invasive. Subsequently, they identified a compound that may be effective in blocking the function of one of these key proteins.

A protein called tropomyosin-receptor kinase, or Trk, is commonly found on brain cells and helps regulate the development, function, and survival of nerve cells. In glioblastoma, Trk is highly expressed on the cells around the edges of the tumor and on the infiltrative cells that have migrated away from the tumor mass, whereas those cells in the bulk of the tumor show lower levels of Trk expression. Doctors want to see if inhibiting the function of Trk will help block the invasiveness of glioblastoma cells and reduce the likelihood that the tumor will progress.

In this first-in-class phase I trial, patients with glioblastoma that has not responded to standard postoperative therapy or that has progressed will be treated with varying amounts of a Trk inhibitor called AZD7451 to determine the maximum tolerated dose and the side effects of this drug. Doctors will also look for signs of clinical activity.

“Regardless of the extent of tumor resection, there are always residual tumor cells because these cells are highly invasive and infiltrate normal brain tissue,” said Dr. Fine, former chief of NCI’s Neuro-Oncology Branch. “So surgery is never curative in this disease; some type of postoperative therapy is always required to try to address these remaining infiltrative tumor cells.

“We became interested in trying to study this invasive process in the laboratory in hopes of identifying new molecular targets for therapy,” he continued. “We were able to find that this molecule called Trk was expressed specifically on glioblastoma cells that were invading and [that] Trk was signaling to these tumor cells in a way that was important for the cells to move within the brain. Further, by inhibiting Trk we were able to shut off the invasive process in these models.”

The trial is taking place at the NIH Clinical Center in Bethesda, MD, and at the New York University Cancer Institute in New York City.


AZD7451 for Recurrent Gliomas

Basic Trial Information






Protocol IDs

Phase I Biomarker/Laboratory analysis, Treatment Active 18 and over NCI 120005
12-C-0005, NCT01468324

Trial Description



  • AZD7451 is a drug that may help interfere with brain tumor cell growth. It can prevent glioma cells from entering into normal brain tissue, and slow or stop the growth of additional tumors. Researchers want to see if AZD7451 is effective against gliomas that have not responded to surgery, radiation, or chemotherapy.


  • To see if AZD7451 is a safe and effective treatment for gliomas that have not responded to standard treatments.


  • Individuals at least 18 years of age who have gliomas that have not responded to standard treatments.


  • Participants will be screened with a physical exam, medical history, blood and urine tests, heart function tests, an eye exam, and imaging studies.
  • Participants will take AZD7451 daily by mouth for 28-day cycles of treatment.
  • Participants will keep a medication diary and record any side effects. Treatment will be monitored with frequent blood tests and imaging studies.
  • Treatment will continue as long as there are no serious side effects and the tumor does not start growing again….

Further Study Information


Recurrent glioma patients have very limited treatment options. A major cause of gliomarelated morbidity and mortality is the extensive infiltrative and invasive nature of glioma cells. Thus, inhibition of glioma invasion is a potentially promising strategy.

Work in the laboratory of Dr. Howard Fine has identified TrkA as an important signaling receptor for mediating glioma cell invasion. Both genetic and pharmacological inhibition of Trk potently inhibits glioma invasion and tumor progression in vitro and in vivo.

AZD7451 is a first in-class inhibitor of Trk.


To establish the maximally tolerated dose (MTD) of continuous once daily AZD7451 in patients with recurrent malignant gliomas not on enzyme-inducing anti-epileptic drugs (EIAED).

To generate pharmacokinetic data on continuous twice a daily AZD7451 dosing.


Patients with histologically proven glioblastoma are eligible for this study. Patients should have failed prior standard treatment with radiotherapy.


This study will accrue up to 60 evaluable patients. Cohorts of 3 to 6 patients will receive continuous AZD7451 twice a day orally for 28 days. The MTD will be based on the tolerability observed during the first 4 weeks of treatment only. Up to three patients may be enrolled simultaneously at each dose level. The dose of AZD7451 can be progressively escalated if only 0/3 or 1/6 patients experience a dose limiting toxicity at the prior dose level.

At the end of Cycle 1, patients may choose to continue to receive AZD7451 until disease progression or until they experience unmanageable drug related toxicity, as long as they are continuing to derive clinical benefit and do not fulfill any of the criteria for removal from protocol therapy. Each cycle during this extension period will last 28 days.

Eligibility Criteria

  • Patients with histologically proven malignant primary gliomas who have progressive disease after radiotherapy will be eligible for this protocol.
  • Patients must have an MRI scan performed within 14 days prior to registration and on a fixed dose of steroids for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MRI is required.
  • Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:

1. Patients will be eligible four weeks after surgery if they have recovered from the effects of surgery.

2. Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease postoperatively, an MRI should be done:

  • no later than 96 hours in the immediate post-operative period or
  • at least 4 weeks post-operatively, and
  • within 14 days of registration, and
  • on a stable steroid dosage for at least 5 days.

If the 96 hour scan is more than 14 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required on a stable steroid dosage for at least 5 days.

  • Patients must have failed prior radiation therapy.
  • Ability of subject or Legally Authorized Representative (LAR) (if the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of this study.
  • Patients must be greater than or equal to18 years old, and must have a life expectancy > 8 weeks. Because no dosing or adverse event data are currently available on the use of AZD7451 in patients < 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
  • Patients must have a Karnofsky performance status of greater than or equal to 60
  • Patients must be at least 4 weeks from radiation therapy. Additionally, patients must be at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from procarbazine, 2 weeks from vincristine and 2 weeks from last bevacizumab administration. Patients must be at least 4 weeks from other cytotoxic therapies not listed above and 2 weeks for non-cytotoxic agents (e.g., interferon, tamoxifen) including investigative agents. With the exception of alopecia, all toxicities from prior therapies should be resolved to CTCAE less than or equal to grade 1.
  • Patients must have adequate bone marrow function (WBC less than or equal to 3,000/microl, ANC > 1,500/mm(3), platelet count of > 100,000/mm(3), and hemoglobin greater than or equal to 9 gm/dl), adequate liver function (AST, ALT and alkaline phosphatase less than or equal to 2.5 times ULN and bilirubin less than or equal to 1.5 times ULN), and adequate renal function (creatinine less than or equal to 1.5 times ULN and/or creatinine clearance less than or equal to 50 cc/min calculated by Cockcroft-Gault) before starting therapy. Patients must also have serum potassium greater than or equal to 3.5 mmol/L, magnesium greater than or equal to 0.75 mmol/L, phosphate and calcium levels within normal levels; supplementation is allowed. In cases where the serum calcium is below the normal range, 2 options would be available: 1) the calcium adjusted for albumin is to be obtained and substituted for the measured serum value. Exclusion is to then be based on the adjusted for albumin values falling below the normal limit. 2) Determine the ionized calcium levels. Exclusion is then to be based on whether these ionized calcium levels are out of normal range despite supplementation. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
  • Patients must either not be receiving steroids, or be on a stable dose of steroids for at least five days prior to registration.
  • The effects of AZD7451 on the developing human fetus are unknown. For this reason and because AZD7451 is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or herpartner is participating in this study, the treating physician should be informed immediately.
  • A 12 lead electrocardiogram (ECG) to be performed within 2 weeks of trial entry with QTc less than or equal to 470 msec.
  • Patients must have normal left ventricular ejection fraction (LVEF greater than or equal to 55% or normal by NIH Clinical Center criteria).


  • Patients who, in the view of the treating physician, have significant active hepatic, renal, pulmonary or psychiatric diseases are ineligible.
  • 2 Prior treatment with AZD7451.
  • History of hypersensitivity to active metabolites or excipients of AZD7451.
  • Clinically significant cardiovascular event (e.g. myocardial infarction, angina pectoris, coronary artery bypass graft, angioplasty, vascular stent, superior vena cava syndrome (SVC), New York Heart Association (NYHA, Appendix I) classification of heart disease > 2 within 6 months before entry; or presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.
  • Hemorrhagic or ischemic stroke, including transient ischemic attacks and other central nervous system bleeding in the preceding 6 months that were not related to glioma surgery. History of prior intratumoral bleeding is not an exclusion criterion; patients with history of prior intratumoral bleeding, however, need to undergo a non-contrast head CT to exclude acute blood.
  • Ventricular arrhythmias requiring continuous therapy or asymptomatic sustained ventricular tachycardia within 12 months before study entry. Continuous or intermittent atrial fibrillation requiring treatment. Patients with significant ECG abnormalities such as complete left bundle block and third degree heart block are not eligible.
  • QTc prolongation with other medications that required discontinuation of that medication.
  • Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age. QTc with Bazett’s correction that is unmeasurable, or > 470 msec on screening ECG. (Note: If a subject has a QTc interval > 470 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be less than or equal to 470 msec in order for the subject to be eligible for the study. Patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is greater than or equal to 460 msec.
  • Any concurrent medication that may cause QTc prolongation or induce

Torsades de Pointes 1) Drugs listed in Appendix H, Table 2, that in the investigator’s opinion cannot be discontinued are allowed; however, must be monitored closely.

  • Concomitant medications that are moderate or potent inducers or inhibitors of CYP3A4 are not permitted within the specified wash-out periods prior to or during treatment with AZD7451
  • Patients with a history of corneal disease such as corneal ulcers, corneal dystrophies, keratoconus.
  • Refractory nausea and vomiting or significant gastrointestinal impairment, as judged by the investigator, that would significantly affect the absorption of AZD7451, including the ability to swallow the oral solution.
  • Patients known to have active hepatitis B or C (testing not required for entry on study).
  • Other concomitant anti-cancer therapy except corticosteroids.
  • Patients with a peripheral neuropathy CTCAE > 1 in the prior 4 weeks or active muscle diseases (including dermatomyositis, polymyositis, inclusion body myositis, muscular dystrophy and metabolic myopathy) or family history of myopathy. Patients with pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi syndrome or renal tubular acidosis.
  • Evidence of active infection or active bleeding diatheses.
  • Pregnant women are excluded from this study because AZD7451 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD7451, breastfeeding should be discontinued if the mother is treated with AZD7451. Female patients must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
  • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
  • Patients known to have a malignancy (other than their malignant glioblastoma) that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except for non-melanoma skin cancer, carcinoma in situ in the cervix or ductal carcinoma in situ).
  • Major surgery within 4 weeks or incompletely healed surgical incision before starting therapy.
  • Patients known to be HIV-positive (testing is not required for entry on study) and on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD7451. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Howard A Fine, M.D. Principal Investigator


Tracy Cropper, R.N. Ph: (301) 402-6298


Howard A Fine, M.D. Ph: (301) 402-6298


Source: NCI




Intraoperative subcortical electrical mapping of optic radiations in awake surgery for glioma involving visual pathways.

Preservation of the visual field in glioma surgery, especially avoidance of hemianopia, is crucial for patients‘ quality of life, particularly for driving. Recent studies used tractography or cortical occipital stimulation to try to avoid visual deficit. However, optic radiations have not been directly mapped intraoperatively. The authors present, for the first time to their knowledge, a consecutive series of awake surgeries for cerebral glioma with intrasurgical identification and preservation of visual pathways using subcortical electrical mapping.


Fourteen patients underwent awake resection of a glioma (1 WHO Grade I, 11 WHO Grade II, 2 WHO Grade III) involving the optic radiations. The patients had no presurgical visual field deficit. Intraoperatively, a picture-naming task was used, with presentation of 2 objects situated diagonally on a screen divided into 4 quadrants. An image was presented in the quadrant to be saved and another image was presented in the opposite quadrant. Direct subcortical electrostimulation was repeatedly performed without the patient’s knowledge, until optic radiations were identified (transient visual disturbances). All patients underwent an objective visual field assessment 3 months after surgery.


All patients experienced visual symptoms during stimulation. These disturbances led the authors to stop the tumor resection at that level. Postoperatively, only 1 patient had a permanent hemianopia, despite an expected quadrantanopia in 12 cases. The mean extent of resection was 93.6% (range 85%–100%).


Online identification of optic radiations by direct subcortical electrostimulation is a reliable and effective method to avoid permanent hemianopia in surgery for gliomas involving visual pathways.

Source: Journal Of Neurosurgery.