clinical concept and history of protons relevance and … · 2010-01-25 · gg 01/10 - psi winter...

Center for Proton Therapy

GG 01/10 - PSI Winter School

Center for

Proton Therapy

PSI Winter School January 2010

Bad Zurzach

and PSI, VilligenSwitzerland

Clinical Concept and History of ProtonsClinical Concept and History of Protons

Relevance and Limitations of ConformalityRelevance and Limitations of Conformality

Gudrun Goitein

schuetz

Notiz

Marked festgelegt von schuetz



Center for

Proton Therapy

Who came first: The Clinical Concept or Protons ?

PP++



Center for

Proton Therapy

Clinical Concept Clinical Concept and History of Protonsand History of Protons

Clinical concepts”

developed in simple forms

shortly after the discovery of x-rays, when effects of radiation on human tissues were observed.

Stopping uncontrolled cellular and tissue activities was the goal. 1896 treatment of a hairy nevus; 1897 irradiation for trigeminal

neuralgia, rheumatic pain; 1899 irradiation of a SCC of the skin; ….

Irradiation until the desired effect occurred was the “logical”

approach; the term tolerance dose

was introduced as late as 1925

The understanding of the underlying biology developed during decades until to date

Observation of toxicities (1896 skin toxicity) led to the introduction of shielding blocks very early on; this was the first, important step to conformation (first individually shaped blocks as late as 1973)

Technical innovations and increasingly sophisticated tools (treatment devices) allowed to translate the growing understanding and knowledge into

medical praxis



1896: Emil

Grubbe, a Chicago electrician

and metallurgist, first treated

the recurrent

breast

cancer

of a 55-year-old woman in the last

days of January

1896 -

only

weeks

after the

announcement

of Roentgen's discovery.1897: Note that

the eyes

are

shielded

for

protection.

1895: R1895: Rööntgen ntgen discoversdiscovers

xx--raysrays



Center for

Proton Therapy


Clinical concepts for radiation treatments of malignancies (and Clinical concepts for radiation treatments of malignancies (and nonnon--malignant malignant conditions) has been growing on the grounds ofconditions) has been growing on the grounds of

understanding of diseases, pathophysiology, biochemistry, pathology, ...knowledge about spread and dynamics of diseasesthe idea of defined target volumesradio-biological knowledge about target-

and normal tissues

developments and improvements of other than radiation treatments

and their interaction with radiation therapy

physical knowledge about

different kinds of radiationtechnical progress -

not to forget imaging

The clinical concepts for the use of therapeutic radiation were The clinical concepts for the use of therapeutic radiation were (and still(and still are) strongly based on limitations through normal tissue toleranare) strongly based on limitations through normal tissue tolerancece

Where combination of radiotherapy with other modalities (local/ systemic) did/do not increase local tumor control and cure rates, outcomes

are to date unsatisfactory for many diseases and conditions



Center for

Proton Therapy


The desire and necessity to focus radiation to target volumes anThe desire and necessity to focus radiation to target volumes and d the physical knowledge about particle beams led Prof. Robert Wilthe physical knowledge about particle beams led Prof. Robert Wilson son to write his landmark paper to write his landmark paper Radiological Use of Fast Protons Radiological Use of Fast Protons in 1946in 1946

““These properties (These properties (of protons, as described beforeof protons, as described before) make it possible ) make it possible to irradiate to irradiate intensilyintensily a strictly localized region within the bodya strictly localized region within the body, with but little skin dose., with but little skin dose.””

““One naturally asks what are the advantages of fast protons over One naturally asks what are the advantages of fast protons over highhigh--energy energy electrons such as those from a electrons such as those from a betatronbetatron. This question can be answered only by . This question can be answered only by medical workers, and the answers will probably be different for medical workers, and the answers will probably be different for different kinds and different kinds and sizes of tumors.sizes of tumors.””

Robert Wilson, 1946Robert Wilson, 194627 years prior to the introduction of individually shaped blocks



DO

SE

DEPTH (CM)

depth of penetration depends on the proton’s energy

narrow peak (few mm)

low entrance dose

“no”

exit dose



Clinical ConceptClinical Concept

and History of Protonsand History of Protons

Robert Wilson had understood one main principle of radiation therapy:Put the dose where the target isPut the dose where the target is.

This meansthe right = necessary amount of dosenecessary amount of dosein optimized = most efficient and best tolerable fractionationmost efficient and best tolerable fractionationto the correct = medically appropriate, large enough, but medically appropriate, large enough, but

as small and conformal as possible volumeas small and conformal as possible volumeThe clinical concept of delivering sufficiently high radiation dose clinical concept of delivering sufficiently high radiation dose to the targetto the target

was and still is supported by the fact thatsupported by the fact that

protons offer a geometrical protons offer a geometrical advantage in dose depositionadvantage in dose deposition

as compared to photons and electrons

dose conformationdose conformationDose conformation can allow for increased target doses which are

resulting in

different biological effects, supposedly in better local tumor control without increase in, or even with reduction of, normal tissue toxicities



Center for

Proton Therapy

Clinical Concept andClinical Concept and

History of ProtonsHistory of Protons

(1954 (1954 ––

ongoing)ongoing)

The first large field treatment with protons at the Harvard Cyclotron in 1976, for a pediatric pelvic rhabdo-myosarcoma.

The patient died several years later from probably a marginal tumor progression or relapse

The second large field treatment, for a chondrosarcoma of the

base of skull. The patient is alive and active, though diagnosed with local relapse more than 30 years after

proton radiation therapy

HCLHCL--MGH pioneers of proton radiation therapyMGH pioneers of proton radiation therapy

Slides courtesy of M. Goitein



The

preparation

for

proton

treatment

of a skullbase tumor

has changed

over

the

decades; however, the

goal

has remained the

same: local

tumor

control

and minimal

treatement

related

toxicity

Pioneers of proton radiation therapyPioneers of proton radiation therapy

HCL 1976

The

patient

has explicitely

agreed

to be

recognized

on instructive

photographs

PSI 2005



(1954 (1954 ––

ongoing)ongoing)



α+β

rotation for

cranial/intracranial and

c-spine treatmentsα

rotation for treatments in the trunk

The first compact gantry and the first gantry providing spot scaThe first compact gantry and the first gantry providing spot scanning technology,nning technology, a PSIa PSI--product, designed by E. product, designed by E. PedroniPedroni; 1996 ; 1996 --

2009: >500 patients treated 2009: >500 patients treated



(1954 (1954 ––

ongoing)ongoing)

β

rotation






(1954 (1954 ––ongoing)ongoing)

The first 3The first 3--d treatment planning program, including DRR and BEV, by M. Goited treatment planning program, including DRR and BEV, by M. Goitein in

Patients’

position

Num

ber o

f tre

atm

ents

Motion (mm)Slides courtesy of M. Goitein






(1954 (1954 ––

ongoing)ongoing)

Dynamic beam application, 3Dynamic beam application, 3--d dose calculation;d dose calculation; discrete spot scanning, IMPT at PSIdiscrete spot scanning, IMPT at PSI

+

+ +

Treatment planning for spot scanning protons and IMPT

IMPT IMPT IMPTIMPT




Center for

Proton Therapy



(1954 (1954 ––

ongoing)ongoing)MEEIMEEI--MGHMGH--HCLPioneersHCLPioneers

of proton radiation therapy for ocular melanomasof proton radiation therapy for ocular melanomas

The first proton irradiation of a choroidal melanoma took place at the Harvard Cyclotron in 1976 –

a collaboration between MEEI, MGH, HCL

The first collimator – not yet computer fabricated,

with a tiny shield for the macula



PSI introduced proton radiation therapy for ocular melanomas to PSI introduced proton radiation therapy for ocular melanomas to Europe in 1984;Europe in 1984;~~4700 4700 ptspts, , ~ 230~ 230--250 250 pts./ypts./y, , largestlargest

numbernumber

of of patientspatients

worldwideworldwide

OPTIS installation at the beam line of the injector 1 cyclotron

at PSI

Robotic chair for patient positioning in the OPTIS2 facility, to open in late spring 2008

J. VerweyOPTIS

E. Egger

H. Staeuble, proband



(1954 (1954 ––

ongoing)ongoing)


GG 01/10 - PSI Winter SchoolGG03/07



(1954 (1954 ––

ongoing)ongoing)Pioneers of proton radiation therapy for ocular melanomasPioneers of proton radiation therapy for ocular melanomasEyePlanEyePlan

(by M. Goitein), first used in 1976, meanwhile modernized, and (by M. Goitein), first used in 1976, meanwhile modernized, and still in still in

use for many hundred patients every year use for many hundred patients every year

If the clinical concept and, in this case, the model are correct

and performance is standardized at a high level, treatment outcomes can be as excellent as for ocular melanomas: 98% LC@10ys; OMs are the by far largest the by far largest tumor entity treated with protons tumor entity treated with protons ––

about 18about 18’’000 worldwide000 worldwide



Center for

Proton Therapy

Clinical Concept and History of ProtonsClinical Concept and History of Protons

(1954 (1954 ––

ongoing)ongoing)

The users of medical proton facilities were wise to restrict the

indications according to the available technologies: limited energies; fixed horizontal beam lines; collimated and, where

necessary, compensated = range-modulated broad beams; devices for stereotactic irradiation; equipment for “large field”

treatments

Main indications since the early times of proton radiation therapy were therefore intra-cranial lesions (benign and malignant); choroidal melanomas; skull base, spinal and para-spinal tumors (mostly sarcomas); and later prostate cancer

The local control rates of proton radiotherapy for sarcomas of the skullbase and for ocular melanomas were a “proof of principle”

that dose

conformation with the consequence of target dose escalation can improve outcomes significantly

The clinical concept from the very beginning was proton irradiatThe clinical concept from the very beginning was proton irradiation for localized ion for localized and well definedand well defined

lesions in radiation sensitive environments lesions in radiation sensitive environments

(e.g. skull base, brain), and histologies which require relative(e.g. skull base, brain), and histologies which require relatively high ly high radiation doses for local tumor control (e.g. sarcomas)radiation doses for local tumor control (e.g. sarcomas)



Center for

Proton Therapy


History of Protons (1954 History of Protons (1954 ––

ongoing)ongoing)

Combination treatmentCombination treatment

with surgery and proton irradiation for sarcomas was one of the important foci of the medical program at the HCL/MGH

Learning about normal tissue tolerance in case of partial or nonnormal tissue tolerance in case of partial or non--uniform dose uniform dose load to organs at risk (OARs)load to organs at risk (OARs)

has allowed to modify clinical concepts

to including higher than traditional target doses and special fractionation schemes (e.g. for ocular melanoma, since recent years

for NSC lung cancer)The impact of local control rates on survivalimpact of local control rates on survival

has been shown mainly with the

excellent outcomes of proton radiation therapy for choriodal

melanoma and sarcomas of the base of skull –

both diseases for which the results

of conventional irradiation and brachytherapy

were unsatisfactory

There is no publication available which states inferior outcomes after prno publication available which states inferior outcomes after proton oton radiation therapyradiation therapy

as compared to conventional radiation therapies

(x-rays, electrons, both combined, brachytherapy)



Center for

Proton Therapy


History of Protons (1954 History of Protons (1954 ––

ongoing)ongoing)

The spectrum of indications for proton treatments has been extended spectrum of indications for proton treatments has been extended with with improving technologiesimproving technologies

-

e.g. gantries, variable and higher energies,

beam scanning (at PSI only), and with increasing capacities in hospital based facilities and dedicated projects

Modern treatment planning tools for both proton and conventional

radiotherapy led to numerous studies comparing 3-d dose distributions to targets,

dose loads to OARs and integral dose to anatomical compartments

There are no comparative treatment planning studies no comparative treatment planning studies ––

virtual or for real patients virtual or for real patients –– which show a disadvantage for proton beamswhich show a disadvantage for proton beams.

Even though IMXT may offer comparable dose conformality to target volumes, the use of protons results generally in significant reduction of irruse of protons results generally in significant reduction of irradiationadiation

of normal tissues; this is the strongest argument for proton radof normal tissues; this is the strongest argument for proton radiotherapyiotherapy in pediatrics, where localized outsidein pediatrics, where localized outside--target dose and integral dose have target dose and integral dose have

particular impact on the growing organismparticular impact on the growing organism



Center for

Proton Therapy

Clinical Concept Clinical Concept and History of Protons (1954 and History of Protons (1954 ––

ongoing)ongoing)

The clinical concept of high precision radiotherapy with protons

has not changed in principle, though today’s applications may include diseases that are

less well circumscribed than e.g. oc. melanomas or skullbase chordomas

For instance, H&N tumors, NSC lung cancer, esopageal

cancer, pediatric CNS malignancies and other diseases may require target volumes extending substantially further than the gross tumor

(e.g. cranio-spinal axis irradiation in pediatric patients)

The potential of protons to reduce outside-target dose makes them THE radiation therapy modality for large volumes -

as the volume which receives

integral dose increases with increasing target volume - and for multi-modality treatments in oncology

Conformality Conformality --

Relevance and LimitationsRelevance and Limitations




Relevance and LimitationsRelevance and LimitationsThe amount and the geometry of dose reduction in OARs is relevanThe amount and the geometry of dose reduction in OARs is relevant for the t for the

applicable total doseapplicable total dose; the dose gradient matters: conformality does not necessarily mean zero dose outside a target or inside an OAR

3 “fields”

IMPT

Sacral chordoma, 10 year old girl

OAR:

cauda equina

Skull base chordoma

4 “fields”

IMPT

OAR:

brainstem & center




Relevance Relevance and Limitationsand LimitationsThe therapeutical dose for a radiation treatment consists usually of partial doses

to defined target volumes, which are delivered via individual plans; the sum of the partial doses is the total dose. Applied dose levels have to be balanced with dose constraints for OARs

sacral

chordoma

GTV

CTV1

(68 Gy RBE)

= risk

CTV for

unclear

microscop.

tumor spread

PTV 1

= CTV1 + 7mm

CTV2

(74 Gy RBE)

= CTV1 reduced

to avoid

toxicity

in the pelvicpelvic

nervnerv--vesselvessel

bundlebundle)

PTV 2

= CTV2 + 7mm

OAR rectalOAR rectal mucosamucosa



Center for

Proton Therapy

Multi-modality cancer treatments are inevitably always multi-toxicity treatmentsReduced toxicity for one modality will influence overall toxicity and may

allow for dose escalation of this or/and other modalities (e.g. less dose to oral mucosa allows for higher radiation dose and/or stronger chemotherapy)

In case of radiation being the single agent cancer treatment, protons can be the tool to overcome dose limitations through normal tissue constraints; this may result in re-designing treatment concepts which have unsatisfactory outcomes due to insufficient radiation dose (e.g. inoperable NSC lung cancer, inoperable sarcoma in adult patients, H&N tumors...)



The use of protons in combined treatments should lead to a critical review of those oncological concepts, where the component of local therapy

might be improved (e.g. H&N cancer, pediatric malignancies)

Protons may even allow to include radiation therapy in treatment

concepts, which have so far excluded radiation due to unacceptable toxicity

(e.g. pre-op RT)




Relevance and LimitationsRelevance and LimitationsConformality of radiation dose in a patient is a 3-d factum –

there is no such thing as

“irradiating a field”, which is 2-d

Dose conformation has two aspects:dose which is supposed to be deposited and

dose which is supposed to be avoided; both are key issues in all clinical concepts which include radiotherapy

Physics law does not allow to deliver any “wanted dose”

without some level of “unwanted dose”

Dose conformation can therefore only be optimized (not idealized) physically / technically by

choosing “the best suited”

radiation quality (x-rays, e-, p+, other particles) appropriate energy

sophisticated technology

andmedically by

target definition and dose prescription and other details of a clinical concept





Bowel

and intestines

Kidneys

Tumor

Liver

Passive scattering Spot scanning

Beam application techniques can have strong impact on 3-d dose distribution; site, size and shape of a target may require scanning beams to improve conformality




Relevance and LimitationsRelevance and LimitationsUltimately, the degree of possible dose conformation depends on the physics

of protons in matter and the size and/or shape of the structure(s) which should be conformally

treated and/or avoided

Spot scanning

1 field

Passive scattering

3 fields

1 field

3 fields

Slide courtesy

of M. Goitein

schuetz

Notiz





Relevance and LimitationsRelevance and LimitationsDose conformation has two aspects:

dose which is supposed to be deposited

and dose which is supposed to be avoided

The dose to dose to bebe

avoidedavoided

in the

inner ear/cochlea

is

the differencedifference

betweenbetween

the the twotwo

dose levels dose levels in this

plan, represented

by

red (>90%) and blue

(80-90%)

Undifferentiated sarcoma, 30 y/o

male

total dose 74 Gy RBE

OAR: inner ear

schuetz

Notiz





Relevance andRelevance and

LimitationsLimitations

The degree of possible dose conformation when using scanning beams is influenced by the fact, that spots cannot be made infinitely small

Avoiding structures of about spot size, which are embedded in a target, or covering such small volumes (mini target) exclusively -

which would

be the ultimate conformality –

is illusionary

However, beam application technique and treatment performance help to increase 3-d dose conformation by e.g. (additional) collimation, choice of energy, beam angles, optimized beam scanning, patient set-up, sophisticated treatment planning (e.g. IMPT)

Mini target or mini OAR


GG 01/10 - PSI Winter School2nd

series plans, delivered in 2002, for skull base chordomas, total dose 74 Gy RBE)


Relevance and LimitationsRelevance and LimitationsSophisticated treatment planning for spot scanning proton therapy of skull base

chordomas: IMPT (second series plans) using 3 beam directions (“fields) to reduce dose to small structures: chiasm, optic nerves, brainstem/center




Relevance andRelevance and

LimitationsLimitations

TargetTarget--

and/or organ motion are and/or organ motion are ““the antidotethe antidote””

to dose conformalityto dose conformality

Physiological motion –

respiration, pulsation, peristalsis –

cannot be suppressed; if compensation by gating, triggering or other (upcoming) technologies

is not possible, uncertainties in dose amount and deposition have to be estimated and taken care of in treatment planning and clinical concept

Accidental and arbitrary motions can be reduced by immobilisation

devices and comfortable, pain-free patient position

Motion control by sensors or image guidance/visually can deliver

qualitative and quantitative information about mal-position and deformation of targets and non-target tissues, which result in altered tissue densities along the beam paths and in miss-match between target volume and high dose volume

The effect of altered and/or changing tissue densities on proton

beams is increasing with atomic numbers of the tissue materials; broad beams are less sensitive to tissue motion than scanned beams



SummarySummary

Clinical Concept and History of Protons Clinical Concept and History of Protons

Clinical concepts in oncology are primarily not protonClinical concepts in oncology are primarily not proton--specific,specific, and they have not changed substantially since the very earlyand they have not changed substantially since the very early

radiotherapy adventuresradiotherapy adventures

However, as protons are excellent tools in radiation therapy, However, as protons are excellent tools in radiation therapy, clinical concepts have been developed which focus on protons clinical concepts have been developed which focus on protons as single agent or as component in multi modality regimens as single agent or as component in multi modality regimens

33--d dose conformation is condition for optimized = sufficiently d dose conformation is condition for optimized = sufficiently high high dose levels and clinically appropriate target volumes as well asdose levels and clinically appropriate target volumes as well as

for for

avoiding unnecessary dose to normal tissues; this was and is theavoiding unnecessary dose to normal tissues; this was and is the guideline in proton radiation therapy as in every other RTguideline in proton radiation therapy as in every other RT



Center for

Proton Therapy

Clinical Concept and History of Protons Clinical Concept and History of Protons

The pioneers were right, their guideline has never proven to be The pioneers were right, their guideline has never proven to be wrongwrong

Good thinking, broad knowledge in physics, technology and Good thinking, broad knowledge in physics, technology and medicine, and good performance are all together timeless andmedicine, and good performance are all together timeless and

lead to successlead to success

Excellent and never before reached treatment outcomes for Excellent and never before reached treatment outcomes for sarcomas of the skull base and for ocular melanomas have sarcomas of the skull base and for ocular melanomas have paved way for ongoing technical developments and triggeredpaved way for ongoing technical developments and triggered

““newnew””

medical needsmedical needs

SummarySummary



Center for

Proton Therapy

Conformality Conformality ––

relevance and limitationsrelevance and limitations

ImprovedImproved

dose conformation as compared to any other radiation dose conformation as compared to any other radiation treatment modality was the precondition for the medical use of treatment modality was the precondition for the medical use of protonsprotons

Conformality is a most relevant element in all clinical conceptsConformality is a most relevant element in all clinical concepts which include radiation; higher target doses and reduced nonwhich include radiation; higher target doses and reduced non--target target

dose levels are supposed to make treatments more efficient and dose levels are supposed to make treatments more efficient and less toxicless toxic

Limitations of conformality are based on physics laws, availableLimitations of conformality are based on physics laws, available technologies (hardtechnologies (hard--

and soft ware), and on conditions of the humanand soft ware), and on conditions of the human

body body

SummarySummary



Center for

Proton Therapy

Conformality Conformality ––

relevance and limitationsrelevance and limitations

Wherever possible, information about limitations should be Wherever possible, information about limitations should be qualitative qualitative andand

quantitative; this is particularly important in case of quantitative; this is particularly important in case of

motions of targets and/or normal structures motions of targets and/or normal structures

Limitations of conformality need to be recognized, understood anLimitations of conformality need to be recognized, understood anddtaken care of in all procedures of proton radiotherapytaken care of in all procedures of proton radiotherapy

The ultimate, ideal conformality does not existThe ultimate, ideal conformality does not exist

Therefore, we must not promise perfect conformation in proton Therefore, we must not promise perfect conformation in proton radiation therapy; radiation therapy; honesty has to characterize promotion of protons honesty has to characterize promotion of protons ––

not businessnot business

We have to continuously work on improving proton therapy byWe have to continuously work on improving proton therapy by thinking, learning, critical reflection and serious performancethinking, learning, critical reflection and serious performance

SummarySummary



Center for

Proton Therapy

Thank you for listeningThank you for listening

““These properties (of protons, as described before) make it possiThese properties (of protons, as described before) make it possible ble to irradiate to irradiate intensilyintensily

a strictly localized region within the bodya strictly localized region within the body, , ……”……”

““One naturally asks what are the advantages of fast protons over One naturally asks what are the advantages of fast protons over highhigh--energy energy electrons such as those from a electrons such as those from a betatronbetatron. This question can be answered only by . This question can be answered only by medical workers (medical workers (who are all professionals involved in proton radiation therapy), ), and the answers will probably be different for different kinds aand the answers will probably be different for different kinds and sizes of tumors.nd sizes of tumors.””

Enjoy the PSI Winter School 2010Enjoy the PSI Winter School 2010

stay on Robert Wilsonstay on Robert Wilson’’s ways way

and

clinical concept and history of protons relevance and … · 2010-01-25 · gg 01/10 - psi winter...

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