“Finding Facts… Giving Hope”
With Radiotherapy
Dr Raphael Chee
Radiation Oncologist
Sir Charles Gairdner Hospital
• Role of RT in brain tumours
• RT options
– Photon (Xray) therapy
• Linac
• Radiosurgery
– Gamma Knife
– Linac based
• Tomotherapy
• Accuray® Cyberknife
– Particle (Hadron) therapy
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aka Heavy ion therapy
Proton therapy
Fast Neutron therapy
Boron Neutron Capture therapy
Carbon Ion therapy
– Pi meson (Pion) therapy
Which brain tumours for RT?
Malignant
• Secondary tumours
• Glioma
– Glioblastoma
– Anaplastic
– Astrocytoma
– Oligoastrocytoma
– Ependymoma
Benign
• Meningioma
• Pituitary Adenoma
• Craniopharyngioma
• CNS lymphoma
• Intracranial sarcoma
– Hemangiopericytoma
– RMS
*Caveats for paediatric patients – Usually international protocol to
standardise management, but in general, withhold RT as long as
possible to maximise brain development
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
How it works?
External Beam Radiation Therapy (EBRT)
Single strand
break
Double strand
break
How it works?
Apoptosis
(cell death)
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
Aim of RT
• To maximise “rogue” cell kill without
harming normal cells
LINAC – 3D Conformal
LINAC – 3D Conformal
LINAC - IMRT
• Intensity Modulated Radiation
Therapy
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
LINAC - VMAT
• Volumetric Modulated Arc Therapy
• Upgrade option available on most
modern Linacs
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)
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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
Tomotherapy
• 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
VMAT vs Tomotherapy
VMAT vs Tomotherapy
Orbits
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
Optic
Nerve
Pituitary
Gland
Brainstem
Target
Volume
Radiosurgery – LINAC based
Radiosurgery – LINAC based
• Frameless – less invasive
• Requires real-time IGRT
• Requires patient co-operation & compliance
Radiosurgery - Gammaknife
Radiosurgery - Gammaknife
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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 30-45 mins for new source
• One machine in Macquarie University in
Sydney
• Estimated $500-1000 more expensive to
treat/person vs Linac-based
Cyberknife
Cyberknife
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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
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
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)
New Revolution? – Improving Conformity
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
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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
Proton Therapy
Proton Therapy
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 2013-2014
• Mixed therapy & research facility
• Mounting clinical evidence of
therapeutic benefits/efficacy
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
Fast Neutron Therapy
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
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
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
Caution
• Complexity of treatment increasing
– Beware of over-reliance on “blackbox”
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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
Thank You
Brain Tumour Expo 2010
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