Brain Tumours: An overview on current clinical care and research
Dr Brindha Shivalingam, Keynote
Hosted by Cure Brain Canc...
Brain Tumours
An overview on current clinical
care and research
Dr Brindha Shivalingam
Neurosurgeon
Royal Prince Alfred Ho...
Introduction
Brain cancer compared to other cancers
Cancer incidence
Breast
Brain
Prostate
Melanoma
Bowel
Other
Current Clinical care
Most patients present to hospital or their GP with new symptoms
that concern them :
Headache (new on...
New onset of
symptoms
• Referral to
Neurosurgeon
or present to
ED
Stabilisation
of symptoms
and
investigations
• Potential...
Stabilisation of symptoms
Dexamethasone.
Strong steroid that reduces swelling (oedema)
in the brain.
Can dramatically reve...
Stabilisation of symptoms
Anticonvulsants.
Many available.
Traditionally used drug is phenytoin.
Newer agents are better t...
Investigations
CT
MRI
PET
fMRI/DTI
Surgery
When ever possible, the general consensus now is to
offer maximal surgery.
Benign tumours
complete curative resect...
Surgery
Many techniques are used to resect tumours
¤  craniotomy with frameless stereotactic navigation
¤  Endoscopic re...
Post operative care
¤  Hospital stay for an uncomplicated course is in the order of 2-7
days
¤  Mobility
¤  Attending t...
Diagnosis
¤  The final diagnosis is made by the pathologist analysing the
tumour tissue.
¤  Once a name is given to the ...
Radiotherpy
¤  Given in fractions (small doses) to maximise brain recovery
between doses.
¤  Overall 6 weeks of treatmen...
Chemotherapy
¤  Temozolomide – alkylating agent that impairs DNA repair
enzymes.
¤  Oral agent
¤  Given daily for 6 wee...
Benign Tumours
¤  If a complete resection has been achieved, then a cure has
been achieved.
¤  Some benign tumours have ...
Benign Tumours
¤  Some small benign tumours can be treated purely with SRS
¤  Others can just be watched with regular MR...
Patient
Neurosurgeon
and team
Radiation
oncology
Medical
oncology
Case
managers/
CNS/nurses
Rehabilitation
OT/Physio/
spee...
Ideal set up
Centres that are optimally set up for management of these cancers, should
have:
¤  Surgical expertise and sp...
Current situation
At present in NSW there are ~ 20 hospitals where Neurosurgery is
possible.
~520 new gliomas are diagnose...
Current situation
¤  Dilution and fragmentation is good for no body.
¤  Surgeons are unable to develop skills and knowle...
Current situation
Lack of cohesive care of the patient and their families
Patients and families feeling out of depth and u...
Research
1898-1937.
Died aged 39 of
Glioblastoma
multiforme
History
For many decades, there was very little research or development in
the treatment of GBM.
First real change came wi...
History
¤  After under going the usual trial process, the drug was
authorised for use in recurrent GBM in 2001
¤  2005 –...
Basic tumour biology
Uncontrolled growth of cells
Due to genetic abberations
Cell cycle is very
tightly regulated
by numer...
Basic Tumour Biology
Genetic functions involved in tumour formation:
Stimulate cell division.
Suppress cell division
Promo...
The era or targeted therapies
¤  1956 – Watson and Crick described DNA
¤  Human genome project started in 1995 and was c...
Era of targeted therapies
¤  Most other previously deadly cancers are now treated with
targeted therapies.
¤  Resulted f...
Targeted therapies
¤  Agents that target specific tumour cellular functions in order to
kill the tumour cell.
¤  There a...
Brain Cancer and targeted therapy
¤  Bevacizumab (Avastin) – anti VEGF targeted drug
¤  Shown not to be of value when gi...
Trial process
Ensures safety
¤  Phase I – <10 patients. Aim is to look for significant toxicity.
¤  Phase II – 30 patien...
Funding and research pitfalls
Every step of cancer research requires funding.
Current model is to apply for grants to vari...
Funding and research pitfalls
Rare Cancers and conditions are even harder to research due to
lack of funding
being less co...
The Future
¤  Specialist neuro oncology centres
¤  Cohesive care and support through these centres
¤  Establish functio...
Brain tumour patient forum Brinda Shivalingam keynote speech
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Brain Tumours: An overview on current clinical care and research. By Dr Brindha Shivalingam, Neurosurgeon,
Royal Prince Alfred Hospital

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Brain tumour patient forum Brinda Shivalingam keynote speech

  1. 1. Brain Tumours: An overview on current clinical care and research Dr Brindha Shivalingam, Keynote Hosted by Cure Brain Cancer Foundation
  2. 2. Brain Tumours An overview on current clinical care and research Dr Brindha Shivalingam Neurosurgeon Royal Prince Alfred Hospital
  3. 3. Introduction
  4. 4. Brain cancer compared to other cancers Cancer incidence Breast Brain Prostate Melanoma Bowel Other
  5. 5. Current Clinical care Most patients present to hospital or their GP with new symptoms that concern them : Headache (new onset or change in pattern) Seizures (generalised or partial) weakness of limbs speech problems visual problems Confusion Incidental finding
  6. 6. New onset of symptoms • Referral to Neurosurgeon or present to ED Stabilisation of symptoms and investigations • Potential diagnosis. Discussion of plan of management. Surgery (biopsy or resection) • Post operative care in hospital Confirmation of diagnosis • Referral to radiation oncology and medical oncology Commence radio/chemo • Ongoing followup Benign tumours Communication
  7. 7. Stabilisation of symptoms Dexamethasone. Strong steroid that reduces swelling (oedema) in the brain. Can dramatically reverse symptoms Side effects : Short term – appetite, restlessness, agitation, sleeplessness, delirium Long term – weight gain, muscle atrophy, thin fragile skin, decreased immunity, osteoporosis, diabetes.
  8. 8. Stabilisation of symptoms Anticonvulsants. Many available. Traditionally used drug is phenytoin. Newer agents are better tolerated with fewer side effects. Side effects : lethargy, dizziness, unsteadiness, headache, nausea, insomnia, rash, liver toxicity. Is there a role for prophylactic anticonvulsants? No.
  9. 9. Investigations CT MRI PET fMRI/DTI
  10. 10. Surgery When ever possible, the general consensus now is to offer maximal surgery. Benign tumours complete curative resection is possible. Location is always the issue. Metastatic tumours complete resection is generally possible. Gliomas Gross total resection/radical resection/subtotal resection/biopsy
  11. 11. Surgery Many techniques are used to resect tumours ¤  craniotomy with frameless stereotactic navigation ¤  Endoscopic resections ¤  iMRI ¤  5- ALA ¤  awake surgery
  12. 12. Post operative care ¤  Hospital stay for an uncomplicated course is in the order of 2-7 days ¤  Mobility ¤  Attending to personal care ¤  Weaning off medication ¤  Pain management ¤  Discharge planning
  13. 13. Diagnosis ¤  The final diagnosis is made by the pathologist analysing the tumour tissue. ¤  Once a name is given to the tumour, we can then be more definitive about what the future holds.
  14. 14. Radiotherpy ¤  Given in fractions (small doses) to maximise brain recovery between doses. ¤  Overall 6 weeks of treatment. ¤  Side effects (short term) ¤  Hair loss ¤  Fatigue ¤  Headache, nausea ¤  Side effects (long term) ¤  Short term memory loss, cognitive decline ¤  Unsteady gait ¤  Radiation necrosis
  15. 15. Chemotherapy ¤  Temozolomide – alkylating agent that impairs DNA repair enzymes. ¤  Oral agent ¤  Given daily for 6 weeks with radiation ¤  Adjuvant 6 cycles ¤  Well tolerated in general ¤  Can cause pseudoprogression which can be very confusing.
  16. 16. Benign Tumours ¤  If a complete resection has been achieved, then a cure has been achieved. ¤  Some benign tumours have a propensity to recur. ¤  Location is the key. ¤  Residual tumour : ¤  Watch and wait ¤  Radiotherapy/SRS
  17. 17. Benign Tumours ¤  Some small benign tumours can be treated purely with SRS ¤  Others can just be watched with regular MRIs ¤  Some benign tumours in difficult locations should be managed as a chronic disease.
  18. 18. Patient Neurosurgeon and team Radiation oncology Medical oncology Case managers/ CNS/nurses Rehabilitation OT/Physio/ speech pathology Palliative care Neurologist Family/friends Psychologist GP Go To Person????
  19. 19. Ideal set up Centres that are optimally set up for management of these cancers, should have: ¤  Surgical expertise and specialisation ¤  Surgical technology ¤  Dedicated specialists in Radiation oncology, Medical oncology ,Neuroradiology and Neuropathology departments with regular MDT meetings ¤  Strong supportive staff for case management and coordination of care ¤  Access to trials – both local and international ¤  Onsite tissue banking facilities and research facilities
  20. 20. Current situation At present in NSW there are ~ 20 hospitals where Neurosurgery is possible. ~520 new gliomas are diagnosed every year. Therefore each hospital may see about 26 gliomas a year. This causes incredible fragmentation and dilution.
  21. 21. Current situation ¤  Dilution and fragmentation is good for no body. ¤  Surgeons are unable to develop skills and knowledge ¤  Difficulty with setting up tissue banks and research labs ¤  Difficult to recruit patients into trials ¤  Funding bodies can’t identify where to infuse funds ¤  Difficulty attracting allied health professionals with a specialty interest
  22. 22. Current situation Lack of cohesive care of the patient and their families Patients and families feeling out of depth and unsupported. This is most true for patients from rural areas and sadly other small states in Australia
  23. 23. Research 1898-1937. Died aged 39 of Glioblastoma multiforme
  24. 24. History For many decades, there was very little research or development in the treatment of GBM. First real change came with temozolomide in 1997. Prof Malcolm Stevens (Birmingham UK): I don’t think there was ever a ‘Eureka’ hats-in-the-air moment,” said Professor Stevens. “There was no particular moment in time when temozolomide was ‘discovered’”. ….. it was funding from Cancer Research UK that was vital
  25. 25. History ¤  After under going the usual trial process, the drug was authorised for use in recurrent GBM in 2001 ¤  2005 – Stupp et al showed benefit of concurrent radiation and chemo. 2 yr survival rate of 26.5% ¤  All of the above was what was achieved in the pre genetic era
  26. 26. Basic tumour biology Uncontrolled growth of cells Due to genetic abberations Cell cycle is very tightly regulated by numerous genes
  27. 27. Basic Tumour Biology Genetic functions involved in tumour formation: Stimulate cell division. Suppress cell division Promote cell death cell migration or spread What causes these mutations ???? inherited factors environmental factors
  28. 28. The era or targeted therapies ¤  1956 – Watson and Crick described DNA ¤  Human genome project started in 1995 and was completed in 2003 ¤  DNA sequencing technology has significantly improved and developed and become affordable.
  29. 29. Era of targeted therapies ¤  Most other previously deadly cancers are now treated with targeted therapies. ¤  Resulted from identifying crucial genetic mutations. ¤  Significant improvement in survival even with advanced cancer.
  30. 30. Targeted therapies ¤  Agents that target specific tumour cellular functions in order to kill the tumour cell. ¤  There are several of these on the market. ¤  They target various cellular functions and immune functions ¤  Small molecules ¤  Monoclonal antibodies
  31. 31. Brain Cancer and targeted therapy ¤  Bevacizumab (Avastin) – anti VEGF targeted drug ¤  Shown not to be of value when given upfront with standard Stupp protocol ¤  CABARET study will reveal its effects at recurrence ¤  Current study by Celldex (US) ¤  ACT IV – rindopepimut . EGFR vIII positive. ¤  ReACT – recurrent GBM
  32. 32. Trial process Ensures safety ¤  Phase I – <10 patients. Aim is to look for significant toxicity. ¤  Phase II – 30 patients. Ongoing assessment of toxicity but start to assess for benefit. ¤  Phase III – 300 patients. Randomised to assess for benefit when compared to current standard therapy.
  33. 33. Funding and research pitfalls Every step of cancer research requires funding. Current model is to apply for grants to various bodies. This has problems : competition time consuming project comes to a halt when the money is used up lack of job security for researchers Result : inefficient research with low productivity
  34. 34. Funding and research pitfalls Rare Cancers and conditions are even harder to research due to lack of funding being less competitive with the grant process difficulty enrolling patients into trials due fragmentation of care
  35. 35. The Future ¤  Specialist neuro oncology centres ¤  Cohesive care and support through these centres ¤  Establish functional tissue banks ¤  Neuropathological diagnosis ¤  Genetic profiling of all tumours ¤  Data collection ¤  Increased funding for research with funding channeled to research laboratories set up in these specialist centres. ¤  Funding for laboratories should ideally come form sources other than the grant system.

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