1. “Finding Facts… Giving Hope” With Radiotherapy
Dr Raphael Chee
Radiation Oncologist
Sir Charles Gairdner Hospital

2. Role of RT in brain tumours RT options
Photon (Xray) therapy
Linac
Radiosurgery
Gamma Knife
Linac based
Tomotherapy
Accuray® Cyberknife
Particle (Hadron) therapy
aka Heavy ion therapy
Proton therapy
Fast Neutron therapy
Boron Neutron Capture therapy
Carbon Ion therapy
Pi meson (Pion) therapy

3. Which brain tumours for RT?
Malignant
Secondary tumours
Glioma
Glioblastoma
Anaplastic
Astrocytoma
Oligoastrocytoma
Ependymoma
CNS lymphoma
Intracranial sarcoma
Hemangiopericytoma
RMS
Benign
Meningioma
Pituitary Adenoma
Craniopharyngioma
*Caveats for paediatric patients – Usually international protocol to standardise management, but in general, withhold RT as long as possible to maximise brain development

4. Prognosis Depends on Tumour type Tumour grade & staging
Location & size of tumour
Determines extent of surgery possible
Curable or not
Determines performance status/deficits
Patient factors
Age
Co-morbidities
Performance status

5. How it works? External Beam Radiation Therapy (EBRT)
Single strand break
Double strand break

6. How it works?
Apoptosis
(cell death)

7. Evolution of RT 1895 - X-rays discovered (W Röntgen, Germany)
1895 – first attempt at therapy (breast cancer, Emil Grubbe, USA)
1903 – first scientific description of the effect of radiotherapy (in lymphoma, Senn & Pusey, USA)
1952 – first linear accelerator (Stanford, California)
1973 – CT scan invented (Hounsfeld, UK)
1990 – first use of CT scan & computers for planning 2D 3D
IMRT

9. Aim of RT
To maximise “rogue” cell kill without harming normal cells

10. LINAC – 3D Conformal

11. LINAC – 3D Conformal

12. LINAC - IMRT
Intensity Modulated Radiation Therapy

13. LINAC - IMRT
Allows coverage of target volume AND avoidance of high doses to adjacent organs at risk
But spreads low doses through more volume of normal tissue
(?) Increase risk of radiation-induced second cancers
Less forgiving if target missed
Importance of quality of patient set up
Greater/more complex QA processes required
IGRT is a pre-requisite

14. LINAC - VMAT Volumetric Modulated Arc Therapy
Upgrade option available on most modern Linacs
First patient treated with VMAT 2008

15. LINAC - VMAT More complexity and hence more stringent QA required
Quality of treatment probably not better than static IMRT
But looks better on “paper”
Uses less monitored units (mu)
Thus treatment can be delivered in less time
More comfortable for patient
Less chance for intra-fraction motion
Theoretical reduction in radiation-induced second cancer risks
“Marketing claims”
Competes with Tomotherapy

16. Tomotherapy “Helical arc IMRT” with image-guidance
First machine in Australia
installed at Royal Brisbane &
Women’s Hospital 2010
“Helical arc IMRT” with image-guidance
Highly conformal & precise
Conformal “avoidance” of normal tissues

17. VMAT vs Tomotherapy

18. VMAT vs Tomotherapy
VMAT can deliver treatment plan 30-40% quicker than Tomotherapy
VMAT uses less monitored units
Tomotherapy plans have slightly better coverage and normal tissue avoidance
No head-to-head studies comparing if one is “clinically better” than the other
Orbits
Optic Nerve
Pituitary Gland
Brainstem
Target Volume

19. Radiosurgery – LINAC based
Maximal size 3cm. Long treatment time – 30-60min

20. Radiosurgery – LINAC based
Frameless – less invasive
Requires real-time IGRT
Requires patient co-operation & compliance

21. Radiosurgery - Gammaknife

22. Radiosurgery - Gammaknife
By Leksell or Elekta
About 200 Cobolt sources
Requires immobilisation frame
Treatment plan conformity similar to others
But cannot fine-tune to place “hot spots” into tumour
Effective working life about 5 years
Treatment time gets longer with increasing age of Cobolt source
Av mins for new source
One machine in Macquarie University in Sydney
Estimated $ more expensive to treat/person vs Linac-based

23. Cyberknife
Closest machines in Indonesia, Malaysia, India, Thailand.

24. Cyberknife By Accuray Has real-time IGRT Does not need frame
Probably not as accurate as Gammaknife, similar to Linac-based (but no studies available to test/compare)
Long treatment time – about 60min +
Over 150 machines world-wide
Nearest Malaysia, Thailand, India

25. Reminder
Aim of radiation therapy is to maximise lethal effects to cancer cells, without harming normal cells
By conformally treating cancer targets, and by conformally missing normal organs at risk
But uncertainties
Microscopic disease
Changes in internal anatomy during course of treatment
Differences in daily set-up
Tolerances in technology

26. Evolution Rather Than Revolution
Improving technology
Hardware upgrades
Better (faster, more accurate) software/planning algorithm
Better screen resolution
More sensitive imaging modalities
CT scan resolution
PET scan
MRI planning scan
IGRT (image guidance)

27. New Revolution? – Improving Conformity

28. Particle Therapy
Little good quality evidence to prove better (or at least not worse) than photon (Xray/gamma) therapy
Advantages are theoretical
High LET (Linear Energy Transfer) thought to be more effective in causing irreparable DNA damage to cells (Xrays have low LET)
But must be certain target is being treated, otherwise high risk of normal tissue toxicity
Not enough experience
Very expensive ventures
Currently, treatment facilities need loads of space
Need very specialised (& rare) skills
Most clinical experience with proton therapy
“tune-able”
Probably has variable LET, depending on energy
Main advantage is dosimetric

29. Proton Therapy

30. Proton Therapy

31. Proton Therapy
Majority machines in North America & Europe (about 25 worldwide)
A few in Japan, one each China & South Africa
Australian Proton Therapy facility in Sydney, approx
Mixed therapy & research facility
Mounting clinical evidence of therapeutic benefits/efficacy
About $100 million to built a proton centre, takes up about 2 football fields

32. Carbon Ion Therapy Has one of the highest LET for particle therapy
Does not require O2, so effective in hypoxic cancers
One of the factors for poor radiosensitivity
3 therapy centres worldwide (Japan, Germany & Italy)
More planned, all in Europe
No clinical studies to suggest better than conventional Xray therapy
Majority of studies are physics-based
Risk of significant toxicity
Very expensive; inadequate data to warrant/risk financial investment

33. Fast Neutron Therapy

34. Fast Neutron Therapy
Limited centres – most built in 1970s; USA, Europe & Japan
Clinical studies showed disappointing results, mainly because of unexpected (at that time due to naïve knowledge of radiobiology) late toxicity
No image guidance
Difficult to guide due to lack of charge in particle, necessitating higher doses
Mostly abandoned as cancer therapy but on-going research – some centres still provide therapy

35. Pi Meson (Pion) Therapy
A pion particle is short-lived (≈26x10-7 sec)
Damage to DNA only occurs at the “end of
it’s life”
Is considered as intermediate LET
More “forgiving” to adjacent normal tissue

36. Pi Meson (Pion) Therapy
Currently not available for therapy
First pion centre at Los Alamos, New Mexico closed in 1981 after about 200 patients, second (Paul Scherrer Institute) in Switzerland closed in 1993, after having treated 500 patients
Another has opened in BC, Canada – TRIUMF
But this is only for clinical research, currently
Early results showed no better or worse than conventional Xray therapy

37. Caution Complexity of treatment increasing Greater number of processes
Beware of over-reliance on “blackbox”
Greater number of processes
More things can go wrong
More mistakes can be made
Varying number of commercial hardwares & softwares
May not be compatible
Not all equipment are made the same
QA & Audit important
QA results are site & equipment specific

38. Thank You
Brain Tumour Expo 2010

39. Alternative therapy UHF (“microwave”) therapy aka Tronado machine
Thermotherapy
NHMRC review of local practice & available scientific evidence in 2005 reported “no scientific evidence to support the use of microwaves in treating cancer, either alone or when combined with other therapies.”
Audit of Dr J. Holt’s practice
Initial response rate 50% RT alone, 34% RT + UHF, 17% UHF + GBA
Following surgery RR 44% RT alone, 25% RT +UHF, 11% UHF + GBA
No “good scientific studies” to support & explain UHF phenomena on cancer cells
Not accepted as standard of care for cancer treatment