Treatment delivery from the Treatment delivery from the patient perspective: potential patient perspective: potential indication, set-up and organ indication, set-up and organ

motion issues at CNAO motion issues at CNAO Piero FossatiPiero Fossati

ESF Exploratory Workshop on Advanced Instrumentation for Cancer Diagnosis and Treatment

Oxford, United Kingdom,

23 – 26 September 2008

We all know how nice it is to have We all know how nice it is to have the Bragg peakthe Bragg peak

Goitein et al, Physics today, 2002 Courtesy of Dr. Ando, NIRS

We all know how nice it is to have a We all know how nice it is to have a high RBE (and only where you need it)high RBE (and only where you need it)

Vertebral osteosarcoma

7 years later

CIRT

Imai et al., Lancet Oncology 2006

We can hope in good clinical results if we We can hope in good clinical results if we are able to deliver this radiation, with nice are able to deliver this radiation, with nice physical and biological properties, to the physical and biological properties, to the targettarget

We have to know where the target isWe have to know where the target is

No matter how good our beam, if the No matter how good our beam, if the target is not where we thought we will not target is not where we thought we will not kill the tumorkill the tumor

Missing the target

Why should the target be Why should the target be elsewhere?elsewhere?

Mispositioning (interfraction)Mispositioning (interfraction)

Organ motion (intrafraction)Organ motion (intrafraction)

Shape change (interfraction)Shape change (interfraction)

Steeper gradientsSteeper gradients

Dose distribution heavily dependent on Dose distribution heavily dependent on tissue densitytissue density

HypofractionationHypofractionation

This issues are much more critical in hadrontherapy This issues are much more critical in hadrontherapy (compared to photons RT) because of:(compared to photons RT) because of:

Organ motion is even more critical when Organ motion is even more critical when active scanning is used (risk of hot and active scanning is used (risk of hot and cold spots):cold spots):

For the CNAO delivery system spot size For the CNAO delivery system spot size will be of millimiters (4 - 10) and time will be of millimiters (4 - 10) and time scale will be of milliseconds.scale will be of milliseconds.

What has been done until now ?What has been done until now ?

What do we plan to do at CNAO ?What do we plan to do at CNAO ?

What would we like to do but do not know What would we like to do but do not know how?how?

Delivery system at CNAODelivery system at CNAO

Fixed vertical and horizontal beamsFixed vertical and horizontal beams

Active spot scanning (no passive spread Active spot scanning (no passive spread beam)beam)

1 - Precise positioning1 - Precise positioning

Always an issue (for all body sites)Always an issue (for all body sites)

Need of fixation devicesNeed of fixation devices

Need of position verification devicesNeed of position verification devices

Need of 6 DOF position correction devicesNeed of 6 DOF position correction devices

The only issue for some body district (limb, The only issue for some body district (limb, head, spine ?)head, spine ?)

Time consumingTime consuming

Precise positioningPrecise positioning

We believe that for “fixed” body sites a We believe that for “fixed” body sites a orthogonal KeV X-Ray imaging coupled to a orthogonal KeV X-Ray imaging coupled to a robotic positioning device is necessary and robotic positioning device is necessary and sufficient. sufficient.

Head and body masks, personalized cushions, Head and body masks, personalized cushions, bite blocks and all such devices employed in bite blocks and all such devices employed in high precision photons RT can be high precision photons RT can be straightforwardly transferd to hadrontherapystraightforwardly transferd to hadrontherapy

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A customized Schaer systyem will be used

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Courtesy of SEAG, RPTC

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2 Shape change2 Shape change

Tumor shrinkageTumor shrinkage

Weight loss or gainWeight loss or gain

Dependent on tumor biologyDependent on tumor biology

Relatively easy to cope with through close Relatively easy to cope with through close clinical monitoring of the patient and clinical monitoring of the patient and frequent off line imaging (e.g. each week for frequent off line imaging (e.g. each week for gynecological malignancy)gynecological malignancy)

Too late if discovered in the treatment room Too late if discovered in the treatment room (a check is anyway most necessary)(a check is anyway most necessary)

3 Organ motion3 Organ motion

The real problemThe real problem

Due to peristalsis, swallowing, heartbeat, Due to peristalsis, swallowing, heartbeat, vessels pulsation but especially vessels pulsation but especially BREATHINGBREATHING

Affects lung treatments, liver treatments, and to Affects lung treatments, liver treatments, and to a lesser extent all abdominal and pelvic a lesser extent all abdominal and pelvic treatments. If the patients is in supine position treatments. If the patients is in supine position (as may be necessary without a gantry) it may (as may be necessary without a gantry) it may also affect retroperitoneal treatmentsalso affect retroperitoneal treatments

BreathingBreathing

A complex caotic phenomenonA complex caotic phenomenonIntervals of more or less regular breathing that each 5- 15 minutes Intervals of more or less regular breathing that each 5- 15 minutes change pattern and through a highly unpredictable phase reach a change pattern and through a highly unpredictable phase reach a new temporary steady statenew temporary steady stateNo reliable correlation betwen body surface and internal No reliable correlation betwen body surface and internal displacement during change of patternsdisplacement during change of patternsFrequency, Tidal volume, relative role of thoracic muscles and Frequency, Tidal volume, relative role of thoracic muscles and diaphragm and end expiration volume are among the parameters diaphragm and end expiration volume are among the parameters that can change in minutesthat can change in minutesElevated inter-patient and intra-patient variabilityElevated inter-patient and intra-patient variabilityPain and emotional status can influence breathing patternPain and emotional status can influence breathing patternDisplacements up to 3-4 cm can take placeDisplacements up to 3-4 cm can take placeNot possible to predict a priori direction and amplitude of a lung Not possible to predict a priori direction and amplitude of a lung nodule displacementnodule displacement

How to deal with respiratory organ How to deal with respiratory organ motionmotion

Breathhold, gating, tracking, coaching, abd. pressureBreathhold, gating, tracking, coaching, abd. pressureWhichever you choose you need to measure motion Whichever you choose you need to measure motion (target position or surrogate marker)(target position or surrogate marker)Once you know how the target moves you can steer the Once you know how the target moves you can steer the beam, or decide to enlarge the irradiated volume (a beam, or decide to enlarge the irradiated volume (a simple CTV simple CTV PTV approach is not adequate) PTV approach is not adequate)It is mandatory to check what you are doing (a real time, It is mandatory to check what you are doing (a real time, in vivo dosimetry would be appreciated)in vivo dosimetry would be appreciated)Robustness of the treatment plan should be considered Robustness of the treatment plan should be considered (ideally as a parameter for inverse planning optimization)(ideally as a parameter for inverse planning optimization)Everything should happen in real timeEverything should happen in real time

StrategiesStrategies

Breath hold: requires active cooperation, Breath hold: requires active cooperation, you cannot avoid measuring target you cannot avoid measuring target position (to be sure it is performed position (to be sure it is performed correctly)correctly)

Gating: (in my opinion probably the best Gating: (in my opinion probably the best solution) solution)

Tracking: much more complicated with Tracking: much more complicated with only a small gain on time efficiencyonly a small gain on time efficiency

Measuring target displacementMeasuring target displacement

Breathing is a caotic phenomenonBreathing is a caotic phenomenon

Surrogate markers: air flow, body surface Surrogate markers: air flow, body surface position (simple 1D marker option cfr position (simple 1D marker option cfr NIRS, or optoeletronic surface NIRS, or optoeletronic surface reconstruction with or without passive reconstruction with or without passive markers)markers)

Measuring the real thing: implanted Measuring the real thing: implanted markers and fluoroscopy, or frequent X-markers and fluoroscopy, or frequent X-ray (how often ?)ray (how often ?)

Surrogate markersSurrogate markers

Only the phase… probably not enough for spot scanning (and for stack layer?)

More advanced surface More advanced surface reconstructionreconstruction

Body markers

Surface reconstruction

From the camera images to the surface or From the camera images to the surface or marker positionmarker position

From the marker position to the target From the marker position to the target positionposition

How many msec ?How many msec ?

At the end it is only a guess (caotic At the end it is only a guess (caotic behaviour, hysteresis)behaviour, hysteresis)

NOT ENOUGHNOT ENOUGH

You have to look at what you doYou have to look at what you do

Fluoroscopy (radioprotection issues)Fluoroscopy (radioprotection issues)Periodic x-ray check during dose delivery to verify the Periodic x-ray check during dose delivery to verify the external external internal model, i.e. you trust the model for a internal model, i.e. you trust the model for a short time between cheks (how often have I to check ? short time between cheks (how often have I to check ? Regular interval vs. adaptive interval cfr. Isaksson et al, Regular interval vs. adaptive interval cfr. Isaksson et al, Med Phys 2005)Med Phys 2005)

What has been done until now (by us)?What has been done until now (by us)?

X-ray Exac trac with a custom made BH X-ray Exac trac with a custom made BH system (together with EIO and Politecnico system (together with EIO and Politecnico di Milano). Accuray Synchrony (together di Milano). Accuray Synchrony (together with CDI) ….. with CDI) ….. not precise enough for spot scanningnot precise enough for spot scanning

What do we plan to do at CNAO ?What do we plan to do at CNAO ? ?? …. In the beginning only fixed ?? …. In the beginning only fixed targetstargets

What would we like to do but do not What would we like to do but do not know how?know how?

Approach similar to Accuray synchrony Approach similar to Accuray synchrony but with better surface detection and but with better surface detection and adaptive chek intervals (optimizing what adaptive chek intervals (optimizing what already exist) already exist) Problem our orthogonal X Problem our orthogonal X ray flat panels cannot be both in position ray flat panels cannot be both in position when the terapeutic beam is onwhen the terapeutic beam is on

Something new??Something new??

Can we detect in real time without extra dose to Can we detect in real time without extra dose to the patient the position of a lung nodule ?the patient the position of a lung nodule ?

Can we avoid invasive fiducial marker placement Can we avoid invasive fiducial marker placement ? (I believe ? (I believe NONO))

Could we measure the position of an implanted Could we measure the position of an implanted marker in some other way ? Maybe measuring marker in some other way ? Maybe measuring the influence of an implanted coil on an external the influence of an implanted coil on an external magnetic field makes sense or is it only an magnetic field makes sense or is it only an ignorant’s dreor measuring the change in ignorant’s dreor measuring the change in electric capacitance? Is anybody working on electric capacitance? Is anybody working on this? Does it am? Would it work with a ion beam this? Does it am? Would it work with a ion beam on?on?

If you have an idea you like be sure somebody If you have an idea you like be sure somebody else had already had it quite a while ago !else had already had it quite a while ago !

Meas. Sci. Technol. 19 (2008) 024006 (9pp) doi:10.1088/0957-0233/19/2/024006Tracking of internal organ motion with a six degree-of-freedom MEMS sensor: concept and simulation studyManuel Bandala and Malcolm J Joyce

30 mm × 20 mm × 10 mm

Implantable with 14 gauge needleAccuracy 0.2 mmRead out rate 10 HzNot yet tested in clinics

Balter et al, IJROBP 2005

We are the ones who could We are the ones who could benefit most of such sensorsbenefit most of such sensors

Hadrontherapy as a community should Hadrontherapy as a community should support those researchessupport those researches

Probably not too ambitious a goal but Probably not too ambitious a goal but investment and focusing are requiredinvestment and focusing are required

Steering the beam is easier than Steering the beam is easier than measuring the motionmeasuring the motionNovel approaches are welcomeNovel approaches are welcomeWe should strive for a continuous real time We should strive for a continuous real time measurment of the target positionmeasurment of the target positionAt present I believe we need implanted At present I believe we need implanted markersmarkersIn the end active spot scanning may turn In the end active spot scanning may turn out to be simply not the best way to treat out to be simply not the best way to treat lung and liver and we may have to go back lung and liver and we may have to go back to passive spreadingto passive spreading

Quality assurance and in vivo Quality assurance and in vivo dosimetrydosimetry

Organ motion is difficult to deal with, we Organ motion is difficult to deal with, we have to check what we are doing and how have to check what we are doing and how effective it iseffective it is

In vivo dosimetry is mandatoryIn vivo dosimetry is mandatory

In vivo dosimetry can detect also shape In vivo dosimetry can detect also shape changes that eluded clinical monitoringchanges that eluded clinical monitoring

What has been done until now (not by us)?What has been done until now (not by us)?

In beam PET In beam PET

In beam PET (cfr. FP7 call) In beam PET (cfr. FP7 call)

AQUAAQUA

What do we plan to do at CNAO ?What do we plan to do at CNAO ?

Those approaches have much in common:Those approaches have much in common:They mesure something that would have They mesure something that would have happened anyway (and so no extra dose is happened anyway (and so no extra dose is delivered to the patient)delivered to the patient)If the result is positive you can be sure that If the result is positive you can be sure that everything went well, if it is negative you are not everything went well, if it is negative you are not sure of what went badsure of what went badThe signal that can be detected bears less The signal that can be detected bears less information respect to the actual dose information respect to the actual dose distributions and therefore cold spots may be distributions and therefore cold spots may be masked by a blurring effectmasked by a blurring effectYou know the result after the treatment session You know the result after the treatment session is ended, for hypofractionated treatments it may is ended, for hypofractionated treatments it may be too latebe too late

Different dose

Same β+ activity ?

What would we like to do but do not What would we like to do but do not know how?know how?

When a fiducial marker is inserted, have a When a fiducial marker is inserted, have a dosimeter inside it (it should be read dosimeter inside it (it should be read without extracting the fiducial from the without extracting the fiducial from the patient body). Science fiction ?patient body). Science fiction ?

Have a proton portal imaging (or part of it) Have a proton portal imaging (or part of it) to check position during dose deliveryto check position during dose delivery

Proton portal imaging ?Proton portal imaging ?

(CNAO can accelerate C12 to 400 MeV/u (CNAO can accelerate C12 to 400 MeV/u so protons could be much faster)so protons could be much faster)

Would it be possible to put the Bragg peak Would it be possible to put the Bragg peak beyond the patient and measure the range beyond the patient and measure the range without delivering a high dose ? without delivering a high dose ?

How much dose ?

Can we build this black box ?

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-OK-Abort-Correct online?