Dr Kevin PattersonDr Kevin Patterson

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EPIDEMIOLOGYEPIDEMIOLOGYSA CANCER REGISTRY 2003SA CANCER REGISTRY 2003

119 new cases “cancer of the 119 new cases “cancer of the brain”(primary malignant tumours brain”(primary malignant tumours arising in the brain)arising in the brain)

67 male, 52 female67 male, 52 female 9 in the 15-19 age group9 in the 15-19 age group 24 in 20-44 age group24 in 20-44 age group Remainder (86) 45 + age groupRemainder (86) 45 + age group

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50 (42%) in >65 yo age group50 (42%) in >65 yo age group Incidence increases with age Incidence increases with age

particularly for high grade tumoursparticularly for high grade tumours

TYPES OF TUMOURTYPES OF TUMOURRAH neurosurgical data RAH neurosurgical data

1977-981977-98 80 % Astrocytoma80 % Astrocytoma 20% variety of other tumours 20% variety of other tumours

including oligodendroglioma, including oligodendroglioma, ependymoma, medullo blastoma, ependymoma, medullo blastoma, other glial tumours not otherwise other glial tumours not otherwise classified and primary CNS classified and primary CNS lymphomalymphoma

CONT.CONT.

Majority in RAH data (90%) were high Majority in RAH data (90%) were high grade tumours (GLIOBLASTOMA)grade tumours (GLIOBLASTOMA)

In terms of burden of disease in In terms of burden of disease in adults high grade gliomas represent adults high grade gliomas represent the largest single group the largest single group

Treatment OptionsTreatment Options

Surgery cornerstone of initial Surgery cornerstone of initial managementmanagement

Purpose of surgery is diagnostic and Purpose of surgery is diagnostic and therapeutictherapeutic

Increasing evidence that extent of Increasing evidence that extent of resection (biopsy vs sub-total resection (biopsy vs sub-total resection vs total resection) impacts resection vs total resection) impacts on outcomeon outcome

Whats’s New in Surgery?Whats’s New in Surgery?

Functional MRI (fMRI):Functional MRI (fMRI): This newer This newer type of MRI looks for tiny blood flow type of MRI looks for tiny blood flow changes in an active part of the brain. It changes in an active part of the brain. It can be used to determine what part of can be used to determine what part of the brain handles a function such as the brain handles a function such as speech, thought, sensation, or speech, thought, sensation, or movement. Doctors can use this to movement. Doctors can use this to determine which parts of the brain to determine which parts of the brain to avoid when planning surgery or avoid when planning surgery or radiation therapy. radiation therapy.

Awake CraniotomyAwake Craniotomy

In some cases, tumors infiltrate parts of the In some cases, tumors infiltrate parts of the brain involved in movement or language. In brain involved in movement or language. In such cases, functional intraoperative such cases, functional intraoperative mapping can help identify the exact mapping can help identify the exact location of these functions in the brain, location of these functions in the brain, enabling the surgeon to avoid these areas enabling the surgeon to avoid these areas and thereby minimize the risk of harm to and thereby minimize the risk of harm to the patient during surgery. This mapping the patient during surgery. This mapping process often requires that patients remain process often requires that patients remain awake during surgery, especially in the awake during surgery, especially in the case of speech mapping. case of speech mapping.

FGSFGS

Fluorescence-guided surgery. For this Fluorescence-guided surgery. For this approach, the patient drinks a special approach, the patient drinks a special fluorescent dye a few hours before fluorescent dye a few hours before surgery. The dye is taken up mainly by surgery. The dye is taken up mainly by the tumor, which then glows when the the tumor, which then glows when the surgeon looks at it under special surgeon looks at it under special lighting from the operating microscope. lighting from the operating microscope. This lets the surgeon better separate This lets the surgeon better separate tumor from normal brain tissue. tumor from normal brain tissue.

RadiotherapyRadiotherapy

Well established treatment for high Well established treatment for high and lower grade tumours post surgeryand lower grade tumours post surgery

May be primary treatment modality if May be primary treatment modality if surgery inappropriatesurgery inappropriate

Important to avoid radiation exposure Important to avoid radiation exposure to “normal” brain because of to “normal” brain because of TOXICITYTOXICITY

Standard RT delivered to tumour plus Standard RT delivered to tumour plus a margina margin

RT delivery methodsRT delivery methods

Three-dimensional conformal Three-dimensional conformal radiation therapy (3D-CRT)radiation therapy (3D-CRT)

Intensity modulated radiation Intensity modulated radiation therapy (IMRT)therapy (IMRT)

Conformal proton beam radiation Conformal proton beam radiation therapytherapy

RT delivery methodsRT delivery methods

Stereotactic Stereotactic radiosurgery/stereotactic radiosurgery/stereotactic radiotherapy:radiotherapy: This type of This type of treatment delivers a large, precise treatment delivers a large, precise radiation dose to the tumor area in a radiation dose to the tumor area in a single session (radiosurgery) or in a single session (radiosurgery) or in a few sessions (radiotherapy) few sessions (radiotherapy)

RT delivery methodsRT delivery methods

In one approach, radiation beams are In one approach, radiation beams are focused at the tumor from hundreds focused at the tumor from hundreds of different angles for a short period of different angles for a short period of time. Each beam alone is weak, of time. Each beam alone is weak, but they all converge at the tumor to but they all converge at the tumor to give a higher dose of radiation. An give a higher dose of radiation. An example of such a machine is the example of such a machine is the Gamma Knife. Gamma Knife.

RT delivery methodsRT delivery methods

Another approach uses a movable linear Another approach uses a movable linear accelerator (a machine that creates accelerator (a machine that creates radiation) that is controlled by a computer. radiation) that is controlled by a computer. Instead of delivering many beams at once, Instead of delivering many beams at once, this machine moves around the head to this machine moves around the head to deliver radiation to the tumor from many deliver radiation to the tumor from many different angles. Several machines with different angles. Several machines with names such as X-Knife, CyberKnife, and names such as X-Knife, CyberKnife, and Clinac are used in this way for stereotactic Clinac are used in this way for stereotactic radiosurgery radiosurgery

RT delivery methodsRT delivery methods

Brachytherapy (internal radiotherapy): Brachytherapy (internal radiotherapy): Unlike the external radiation approaches Unlike the external radiation approaches above, brachytherapy involves inserting above, brachytherapy involves inserting radioactive material directly into or near the radioactive material directly into or near the tumor. The radiation it gives off travels a tumor. The radiation it gives off travels a very short distance, so it affects only the very short distance, so it affects only the tumor. This technique is most often used tumor. This technique is most often used along with external radiation. It provides a along with external radiation. It provides a high dose of radiation at the tumor site, high dose of radiation at the tumor site, while the external radiation treats nearby while the external radiation treats nearby areas with a lower dose. areas with a lower dose.

ChemotherapyChemotherapy

Commonly used as an adjunct to Commonly used as an adjunct to surgery/RT (concurrent surgery/RT (concurrent Temozolomide/RT in GBM) or salvageTemozolomide/RT in GBM) or salvage

Problem with drug delivery is the Problem with drug delivery is the BBBBBB

Progress has been slow with a Progress has been slow with a number of negative trials reported in number of negative trials reported in recent yearsrecent years

Angiogenesis inhibitorsAngiogenesis inhibitors

Bevacizumab (Avastin) most well Bevacizumab (Avastin) most well establishedestablished

Approved and funded in USA for Approved and funded in USA for treatment of relapsed GBM (not treatment of relapsed GBM (not funded in Australia)funded in Australia)

First line trials in combination with First line trials in combination with standard CT/RT have standard CT/RT have notnot demonstrated a survival advantagedemonstrated a survival advantage

Local DeliveryLocal Delivery

Gliadel (carmustine) wafersGliadel (carmustine) wafers Implanted at time of surgery and Implanted at time of surgery and

slowly release chemotherapy locallyslowly release chemotherapy locally Randomised trial has demonstrated Randomised trial has demonstrated

benefit over surgery/RT alone in GBMbenefit over surgery/RT alone in GBM No data to compare with standard No data to compare with standard

RT/TemozolomideRT/Temozolomide

Local deliveryLocal delivery

For a newer method called For a newer method called convection convection enhanced deliveryenhanced delivery, small tubes are placed , small tubes are placed into the tumor in the brain through a small into the tumor in the brain through a small hole in the skull during surgery. The tubing hole in the skull during surgery. The tubing extends through the scalp and is connected extends through the scalp and is connected to an infusion pump, through which chemo to an infusion pump, through which chemo drugs can be given. This may be done for drugs can be given. This may be done for hours or days and may be repeated more hours or days and may be repeated more than once, depending on the drug used. This than once, depending on the drug used. This is still an investigational method, and studies is still an investigational method, and studies are continuing. are continuing.

New approachesNew approaches

““Targeted” therapies, recognise a Targeted” therapies, recognise a unique genetic defect in the tumour unique genetic defect in the tumour that drives growth or prevents cell that drives growth or prevents cell death eg activating EGFR mutationsdeath eg activating EGFR mutations

Currently small molecule TKI’s and Currently small molecule TKI’s and monoclonal AB’s most well monoclonal AB’s most well developeddeveloped

ImmunotherapyImmunotherapy

Need to “persuade” the immune Need to “persuade” the immune system to recognise tumour as system to recognise tumour as foreign and mount an immune foreign and mount an immune response against the tumourresponse against the tumour

Personalised vaccines use tumour Personalised vaccines use tumour from individual patients to prime from individual patients to prime immune cells which are re-injected immune cells which are re-injected (dendritic cells)(dendritic cells)

ImmunotherapyImmunotherapy

Protein vaccines which provoke an Protein vaccines which provoke an immune response against a immune response against a particular molecule on the tumour eg particular molecule on the tumour eg EGFR VIIIEGFR VIII

This is a mutation of the EGFR This is a mutation of the EGFR receptor present on 1/3 of GBMreceptor present on 1/3 of GBM

Phase 3 trial currently ongoingPhase 3 trial currently ongoing

Other approachesOther approaches

Hypoxic cell sensitisersHypoxic cell sensitisers Therapeutic virusesTherapeutic viruses

Trials in AustraliaTrials in Australia

http://www.cancertrialsaustralia.com/http://www.cancertrialsaustralia.com/Clinical-Trials-Register.aspxClinical-Trials-Register.aspx

Calvary North Adelaide, relapsed Calvary North Adelaide, relapsed GBM, carboplatin or lomustine in GBM, carboplatin or lomustine in combination with Buparlisib (PI3K combination with Buparlisib (PI3K inhibitor)inhibitor)

Support and Community Support and Community ServicesServices

Adelaide Brain Cancer Support groupAdelaide Brain Cancer Support group Cancer Council………….Cancer Council…………. Huge unmet need for brain cancer Huge unmet need for brain cancer

co-ordinatorco-ordinator

THANKYOUTHANKYOU