Progress Against Brain Cancer
This timeline of advances against brain cancer was developed by the American Society of Clinical Oncology (ASCO),
which represents nearly 30,000 physicians who treat people with cancer and research new cures. An interactive
version, which includes timelines of advances against a range of common cancers, is available online at
www.CancerProgress.Net.
Overview
Brain tumors are particularly challenging because they arise within one of the body’s most critical organs. The risk
of harming healthy brain tissue can severely limit doctors’ ability to use surgery, radiation or other treatments. Yet
researchers are steadily overcoming these challenges to extend survival and improve patients’ quality of life. For
example, in recent years:
• Advances in the use of chemotherapy, including drugs that can cross the protective “blood-brain-barrier” and
radiation, have helped triple (from 8 percent to 25 percent) the percentage of patients who survive at least
two years with glioblastoma, one of the most common brain tumors
• Refined imaging technologies have led to improved tumor diagnosis and monitoring, and enable doctors to
precisely focus radiation treatment to protect healthy brain tissue
• Recent genetic discoveries have led to the identification of distinct sub-types of brain tumors, making it
possible for doctors to personalize care to individual patients and providing potential targets for new
treatments
Although more than 50 types of brain tumors are known, nearly half of cases fall within a related group of tumors
called gliomas. These tumors are the primary focus of this section of CancerProgress.Net.
Timeline
1970s CT scanning provides first clear image of brain tumors
Researchers perform the first computed tomography (CT) scan on a human patient – a woman with a
suspected brain tumor. With CT scanning, which uses X-rays to create images of “slices” of the brain,
doctors are for the first time able to clearly see tumors arising in the soft tissue of the brain. Over the
following decades, this technology continues to be refined and used in combination with other
imaging approaches, such as MRI.
1970s First promising chemotherapy for glioma
Researchers report the first data on efficacy of the chemotherapy drug carmustine (BCNU). Unlike other
chemotherapy drugs available at the time, carmustine is able to cross the blood-brain barrier and
directly attack gliomas. Although this drug can cause significant side effects, the first trials show that it
shrinks some tumors. Later trials show that carmustine and other similar drugs also provide a small but
significant increase in long-term survival when used with other treatments.
Progress Against Brain Cancer
2
1975-1980 Radiation established as standard treatment for glioblastoma
Radiation therapy becomes a mainstay of treatment for glioblastoma, a highly aggressive form of
glioma, based on data showing it extends median survival from 3 months to about 9 months. This is
the first time a treatment is proven effective against any brain cancer. Today, radiotherapy is used
alone or with chemotherapy, both before and after surgery, and in patients with inoperable tumors.
1980s MRI greatly improves ability to diagnose and monitor brain tumors
MRI (magnetic resonance imaging) quickly gains widespread use following its introduction in the mid-
1980s, replacing CT scanning as the primary imaging tool for brain tumors. This new technology
provides the clearest-ever image of brain tumors and, for the first time, enables doctors to see small,
low-grade tumors. Today, refined MRI technologies are widely used to diagnose brain tumors, assess
their size and specific location, and non-invasively monitor whether a tumor is responding to therapy.
Unlike a CT scan, which uses X-rays to create an image, MRI uses magnetic fields to create detailed
pictures of the brain and other tissue.
Mid-1980s Gamma Knife therapy introduced for treating brain tumors
After nearly two decades of research, doctors begin using a non-invasive technique known as Gamma
Knife to treat certain brain tumors. Also called stereotactic radiosurgery, the approach utilizes precisely
focused radiation waves to disrupt cancer cell function and replication, while leaving the brain tissue
surrounding the tumor largely untouched. Gamma Knife may also be combined with other forms of
cancer therapy, including surgery. The approach continues to be refined today.
1993 Adding chemotherapy to radiation after surgery increases survival for malignant
gliomas
A large analysis of the results of several studies shows that adding chemotherapy to radiation therapy
helps patients with surgically treated malignant gliomas live longer compared to radiation therapy
alone. Randomized trials had previously found that this approach yielded only marginal benefits, yet
when the data from these individual studies were assessed in combination, the survival advantage
became more pronounced. Despite this result, the still-modest benefits of the combination approach,
and the potential for serious side effects, have led to continued debate about its use.
1993 World Health Organization develops universal system for classifying brain tumors
New international standards for classifying brain and nervous system tumors give doctors and
researchers a common language for describing and sharing knowledge about tumor staging and
characterization, genetics and treatment. Before this time, many different classification systems were in
use around the world, making it difficult to communicate and translate research findings and improve
patient care. Experts now reconvene every several years to update the WHO system based on growing
knowledge about tumor classification and identification of new sub-types.
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1994 National Cancer Institute establishes brain tumor research networks
Spurred by emerging understanding about the complexity involved in treating brain tumors and the
urgent need for improved therapies, the NCI establishes major brain tumor clinical research networks
for adults and children. These groups are comprised of the nation’s top brain cancer experts from
academic centers who collaborate to evaluate novel therapies for patients with newly diagnosed and
recurrent brain tumors.
1999 New oral chemotherapy drug, temozolomide, increases glioma survival
The FDA grants accelerated approval to the oral chemotherapy drug temozolomide (Temodar) to treat
anaplastic astrocytoma (a form of high-grade glioma) that recurs following other therapy. The
approval is based on early-stage data suggesting that the drug shrinks tumors and is generally well
tolerated. In 2005, temozolomide receives full approval for this and other high-grade gliomas, based
on data showing that adding the drug to initial radiation therapy increases two-year survival by as
much as 50 percent.
2003 Chemotherapy “wafer” active against malignant gliomas
Use of a surgically implanted biodegradable wafer containing the anticancer medication carmustine
(BCNU) is found to delay tumor growth and improve overall survival in some patients with gliomas. The
wafer provides continuous chemotherapy directly to the tumor site to kill remaining cancer cells and to
prevent or slow regrowth of the cancer. Today it is used in patients with recurrent malignant glioma
and newly diagnosed glioblastoma, a highly aggressive form of glioma.
2005 MGMT gene alteration predicts response to chemotherapy
Researchers discover that patients with tumors carrying a specific alteration in a gene known as MGMT
benefit from temozolomide (Temodar) therapy. The MGMT gene is involved in repairing DNA damage
in cancer cells, including damage caused by chemotherapy. Tumors with a genetic alteration that
silences this gene are unable to repair the damage caused by temozolomide, and therefore are more
susceptible to the drug. On the other hand, tumors without this gene alteration are more resistant to
the drug. Researchers continue to explore how to use this and other genetic information to identify
which patients are most likely to benefit from chemotherapy.
2005, 2008 Researchers begin mapping the genome of glioblastoma
In 2005, the National Cancer Institute and the National Genome Research Institute launch The Cancer
Genome Atlas Project, with the goal of mapping the genetic changes involved in glioblastoma and
other cancers. In 2008, researchers report the identification of several key mutations – in the ERBB2,
NF1 and TP53 genes – that are involved in triggering the development and spread of glioblastoma. It is
hoped that these findings will help pinpoint new targets for drug therapies.
Progress Against Brain Cancer
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2006 Genetic mutations affect survival for oligodendroglioma
Two studies find that patients with oligodendroglioma tumors (a form of glioma) that lack certain
parts of chromosomes 1 and 19 are more sensitive to treatment and have better survival than patients
whose tumors are not missing this genetic material. Both studies also evaluated the benefit of adding
chemotherapy to standard radiation, finding that this approach caused significant side effects and did
not improve survival in the overall population.
2006 Chemically “illuminating” glioma tumors during surgery postpones recurrence
The use of 5-aminolevulinic acid, a substance that reacts with and illuminates malignant glioma cells, is
shown to improve surgeons’ ability to remove tumor tissue. Patients treated with this technique during
surgery were significantly less likely to have any tumor growth after six months, compared to those
who underwent conventional surgery.
2006 Molecular sub-classification of high-grade gliomas predicts prognosis
Using advanced molecular classification techniques to examine tumor samples, researchers discover
distinct subtypes of high-grade astrocytoma tumors (a form of glioma). They find that each subtype
has unique biological features that appear to influence the tumor’s behavior and response to certain
therapies. The findings pave the way for future research that may help personalize therapy for each
tumor and patient, ensuring better outcomes and avoiding unnecessary side effects.
2008 Bevacizumab (Avastin) receives FDA approval for glioblastoma
Two early-stage trials suggest that giving the targeted therapy bevacizumab (Avastin), alone or with
the chemotherapy drug irinotecan (Camptosar), may cause tumor shrinkage in patients with
glioblastoma whose disease progresses after previous therapy. Based on these findings, the FDA grants
accelerated (or early, conditional) approval for bevacizumab to treat glioblastoma. Bevacizumab is an
“anti-angiogenic” drug, meaning it works by interfering with the development of blood vessels that
tumors need to grow and spread. This marks the first new drug approved for treating brain tumors in
a decade, and studies are ongoing to determine if initial treatment with bevacizumab improves overall
survival.
2009 Gene mutations linked to tumor aggressiveness
Scientists learn that brain tumors with an alteration in the IDH1 or IDH2 genes are less aggressive than
those without this mutation – a finding that may eventually enable some patients to safely undergo
less intense therapy. The study also offers researchers a potential new clue regarding how some
tumors form in the first place. The IDH1 and IDH2 genes are located on a pathway that governs the
metabolic function of cells, and mutations to these genes may enable abnormal, or cancerous, cells to
form. Continued research may guide future development of targeted therapies that interfere with the
IDH1 and IDH2 genes in order to halt tumor growth.
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2010 Nine-gene test can predict glioblastoma outcome
Researchers identify a set of nine genes that predict the likelihood that a glioblastoma tumor will
respond to therapy. The research is used to create a test called DecisionDX-GBM. If validated in future
trials, this test has the potential to help doctors choose the most effective therapy for a patient, and
could be used to help identify new treatments targeting tumors that do not respond to standard
therapies.
http://www.cancerprogress.net/downloads/timelines/progress_against_brain_cancer_timeline.pdf