“Finding Facts… Giving Hope” With Radiotherapy

Dr Raphael CheeRadiation 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• 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?

*Caveats for paediatric patients – Usually international protocol to standardise management, but in general, withhold RT as long as possible to maximise brain development

Benign• Meningioma• Pituitary Adenoma• Craniopharyngioma

Malignant• Secondary tumours• Glioma

– Glioblastoma – Anaplastic – Astrocytoma – Oligoastrocytoma – Ependymoma

• CNS lymphoma• Intracranial sarcoma

– Hemangiopericytoma– RMS

PrognosisDepends 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)– 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

• “Helical arc IMRT” with image-guidance

• Highly conformal & precise

• Conformal “avoidance” of normal tissues

• First machine in Australia installed at Royal Brisbane & Women’s Hospital 2010

VMAT vs Tomotherapy

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

BrainstemTarget Volume

Pituitary Gland

Radiosurgery – LINAC based

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

Radiosurgery - Gammaknife

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 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• 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 RevolutionImproving 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

• 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”

• 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