“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 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 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

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 First patient treated with VMAT 2008

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 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 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

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

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 Closest machines in Indonesia, Malaysia, India, Thailand.

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 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 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 About $100 million to built a proton centre, takes up about 2 football fields

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 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

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