proton therapy in cancer management

8/13/2019 Proton Therapy in Cancer Management

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PROTON THERAPY INCANCER MANAGEMENT

K.S.REDDY

DIRECTORREGIONAL CANCER CENTREPUDUCHERRY


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Abstract

Introduction : Brachytherapy in the oral cavity is an important alternative to conventionaltreatment and provides a high localized dose and short overall treatment time. A rapid fall ofdose beyond radioactive source makes it possible for increased tumour control and sparingsurrounding tissue while short overall treatment duration reduces risk of tumour repopulation.Moulds are fabricated to hold the catheters in position as closely as possible to tumour surface toprovide adequate dose coverage of tumour volume and increase distance to other normalsurrounding structures. Image based planning and dose optimisation help in better defining

target volume and dose coverage.Materials and Methods: A retrospective analysis of patients of early squamous cell carcinomas oflip and buccal mucosa otherwise not fit for surgery from September 2011 to September 2013 inDepartment of Radiotherapy, RCC, JIPMER, to study response to curative mould brachytherapy.Double plane moulds were prepared for all cases except two cases. Patients were then followedup till disease recurrence. In this study evaluation was done of the technique used, planningdetails, response to therapy and reactions encountered.Results: Six patients treated by mould therapy were reviewed; four cases were of lip and two ofbuccal mucosal cancers. Dose delivered ranged from 12.5-45 Gy in fraction sizes of 250-350cGy.EQD2 ranged from 18-64 Gy. Maximum dose to OAR was 91% of prescribed dose. Localmucositis was only reaction in all cases which resolved in 3-6 weeks. All patients had CR and onlypatient had nodal recurrence at 18 months.Conclusions: Mould therapy is a safe and effective treatment method for selected early andsuperficial squamous cell carcinomas of the oral cavity, although indications are limited.

A retrospective analysis of patients of early squamous cell carcinomas oStudy done from September 2011 to September 2013 in Department of Ra

Double plane moulds were prepared for all cases except two. Patrecurrence. Evaluation was done of technique used, planning deencountered.

Mould preparation:The moulds prepared from thermoplastic + dental wax and customiseoncologist, the physicist makes initial cut out for the mould with thermlayered.

Mould matched with lesion surface and local anatomy; edges trimmedpositions marked into the mould.

Catheters then fixed to mould, and mould again positioned on theplacement and lesion coverage. The lesion was then marked with letreatment position done with mould in place.Oral cancers account for 5-7% of all cancers and brachytherapy is an important alternative to

radical surgery especially in oral cavity. It provides a high localized dose of radiation, with rapidfall-off and short overall treatment time [1].

Mould brachytherapy is technique of delivering brachytherapy by customised applicator toprovide a constant and reproducible frame for source positioning.[2]

Local control rate more than 90% for T1 and T2N0 tumours w ith brachytherapy alone [1].

Mould therapy is indicated: in previously untreated carcinomas of lip, floor of mouth, soft palate, or gingiva, and T1/2 tumours with complete response after external beam radiotherapy.

Integration of imaging and optimization of dose distribution by improved planning systems:better tumour localization with improved dose distribution to the tumour.[3]

But there is paucity of both literature on the use of HDR mould brachytherapy and the optimaltime, dose and fractionation guidelines.[4,5]

CT-Based Mould Brachytherapy in Early Oral Cancers in Patients Unfit Surgery: an Option worth Exploring

Dr. Ashutosh Mukherji, Mr. S Morougan, Mr. K.Saravannan, Dr. S Vivekanandam, Dr. K S Reddy

Department of Radiotherapy, Regional Cancer Centre, JIPMER

Intr

oduction

MaterialsandMethods

MAIN OBJECTIVES

To assess target dose coverage, acute reactions and dose to organs at risk in mouldbrachytherapy.

To assess clinical outcome in patients with early oral cancer treated by mouldbrachytherapy

HYPOTHESIS

Mould therapy is a safe and effective treatment method for selected early and superficial

squamous cell carcinomas of the oral cavity with results comparable to surgery althoughindications are limited.

Aimsand

Objectives

Initial lesion marked outon examination

Lesio

Thermoplastic frame prepared and matched with local

anatomyThermanat

Mould with catheters positioned on patient, edges trimmed, lbefore CT simulation to identify lesion boundar


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CT based 3D image of patient withlead wires marking site of lesion

O

bservations

Dose colour-wash showing lesioncoverage by prescribed isodose

CT-Based Mould Brachytherapy in Early Oral Cancers in Patients Unfit Surgery: an Option worth ExploringDr. Ashutosh Mukherji, Mr. S Morougan, Mr. K.Saravannan, Dr. S Vivekanandam, Dr. K S ReddyDepartment of Radiotherapy, Regional Cancer Centre, JIPMER

Dose delivered ranged from 1250-4500cGy in fraction sizes of 250-350 cGydelivered twice daily.

Two patients who received mould therapyas boost + EBRT for 4-4.5 weeks; two weeksafter completion of mould therapy. EQD2

of these two patients were 18 and 30 Gy.

The remaining four patients who receivedmould therapy as the definitive treatmentcompleted their schedules in 11 15fractions over six to eight days. EQD2 ofthese patients ranged from 54 Gy forrecurrent disease cases to 64 Gy forradically treated cases.

Acute skin reactions immediate postbrachy

Lesion characteristics

Results&Conclusions All patients had com

initial lip lesion had have maintained th

All patients are undmonths (range 3-23

Three patients haveand the rest below 6

Local mucositis (gwas only reaction in

There were no latstrictures in any case

CT-based planning dose greater than 1

Plans optimised so awithin the mould.

Mould therapy isselected early anoral cavity, thoug

It can be a cosboosting early ca

CT based treatmemore accuratelytreatment sequela

References

1) Mazeron JJ, Ardirecommendations focarcinomas. Radioth

2) Ariji E, Hayashi N, Kimmould brachytherapremote afterloadingRadiol Endod 1999;87

3) Nag S. High dose rtreatment guidelines

4) Fietkau R. BrachytheBrachytherapy J. 199

Author reports no

SITE INVOLVEDSite involved Number

Lip 4Tongue 0

Floor of Mouth 0Buccal mucosa 2

TYPE OF LESION

Primary 4

Recurrent 2

Healed reactions at 4weeks post brachy

Dose was prescribed to 80-85% isodose line in most cases to keep volume of tissue receivinggreater than 200% of prescribed dose to less than 5% and further higher doses to withinsubstance of the mould. In all cases the organ at risk was the mandible. Maximum dose to OARwas 91% of prescribed dose to 2cc of OAR with median dose being 68% (range 48-91%).

BED for 3 and 10 Gy doseswere less than 100 Gy in all

cases for late toxicities.


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Treatments of Cancer

Surgery,

Radiation therapy and

Chemotherapy

are the first line treatments.


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RT - Past, Present & Future - Perspec


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The Evolution of Radiation Therapy1950s 1960s 1970s 1980s 1990s

Standard

Collimator

The linac reducedcomplicationscompared to Co60

Cerrobend Blocking

Electron Blocking

Blocks were usedto reduce thedose to normaltissues

MLC leads to 3D

conformal

therapy whichallows the firstdose escalationtrials.

Dynamic MLC

and IMRT

ComputerizedIMRT introducedwhich allowedescalation ofdose andreduced

compilations

Hig

IMRT Esmalleand hialong of new

techno

Computerized3D CTTreatmentPlanning


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Particle therapyElectrons

Protons

NeutronsCarbon ionsParticle therapy works in a

similar manner as x-rays; except

since they are bigger and more

powerful, they can destroy the

DNA more than x-rays, which

often ruins the ability of the cell

to repair itself.


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A Man - A Vision In 1946 Harvard physicist

Robert Rathbun Wilson

(1914-2000) first proposed*:

Protons can be used clinically

Accelerators are available

Maximum radiation dose can

be placed into the tumor

Proton therapy providessparing of normal tissues

Modulator wheels canspread narrow Bragg peak

*Wilson, R.R. (1946), Radiological useprotons, Radiology 47, 487.


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History of Proton Beam Therapy1946 R. Wilson suggests use of protons

1954 First treatment of pituitary tumors1958 First use of protons as a neurosurgical to

1967 First large-field proton treatments in Swe

1974 Large-field fractionated proton treatme

program begins at HCL, Cambridge, MA

1990 First hospital-based proton treatment copens at Loma Linda University MedicalCenter, California


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Why protons ? Protons are attractive to radiotherapy because of their

dose distribution

The RBE of protons are indistinguishable from 250 kV X-rameans that they are 10-15% more effective than 60Co (

The OER of proton beams is not distinguishable from X-ra

Protons are sparsely ionizing, except for a region at the eparticles range

In the entrance plateau, the average LET is about 0.5 keto a max of 100 keV/

This high LET component is restricted to a tiny portion of terminal track, it does not have any significant effect (thbe kept in mind when planning treatment close to critic

structures)


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Just Remember!!!

As protons traverse matter, their maximum

energy is not distributed at first interactioncausing them to scatter in a different direcleaving a void down range. THINK MASS.

Protons stay on relatively straight paths.

Interactions along that path simply slow dthe proton and shorten its distance.

Maximum energy is still delivered at the enthe proton beams path.


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Benefits from Protons in TreatmentPlanning

Finite depth (No dose beyond givendistance)

Sharp penumbra

Highest dose is delivered at end ofbeam path.

Allows for a lower integral dose


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RADIOBIOLOGY

Protons have a relatively low LET

Not much difference from photons

RBE = 1.1 and believed to be slightly higheat distal end of peak

Cobalt Gray Equivalent (CGE) = Gy x 1.1

Neutron dose from patient and Nozzle(can be reduced with spot scanning)


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Range = Depth

Controlled by maximum energy ofproton beam

Represents the initial peak in a SOBP

Maximum range for 230 MV proton:- Passive scattering beam = 28 cm

- Active scanning beam = 34 cm


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Pristine peak and SOBP

Pristine peak is a Pure single Bragg peak

SOBP is Spread Out Bragg peak

SOBP is defined as 90% - 90% on depth docurve

Beam energy is degraded by a modulatio

wheelBeam current is also modulated for a smo

useful dose plateau

Zero to Full modulation is possible


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Proton Accelerators

Cyclotron

Mono-energetic

Continuous beam

Smallerfootprint

Synchrotron

Poly- energe

Pulse beam

Largerfootp


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Production of Clinical Proton Beam

Cyclotron: 230 MeV proton beams

(~33 cm depth in water)Energy degrader: reduce energy

to the desired value

Beam line:

guide the

proton beam

to the treat-

ment room


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Energy Degrader

Made of Carbon.

Variable steps ofthickness.

Decreases energy levelto desired maximum.

Dirty producesneutron contamination(contained indegrading area by 15

feet thick walls)


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Why protons ? An advanced form of targeted radiation therapy

reduction in integral dose to normal tissues comparconventional radiation including IMRT which may trinto reduced toxicities

Dose escalation to tumorsincreased local contro

Treat tumors close to critical organseye, spinal co

More safely & effectively combine with chemotherasurgery


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A Simple Comparison with Photons


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Patient Positioning for ChargedParticles

High precision in patient

positioning is even moreimportant for charged particletherapy, because of the sharpBragg Peaks.

Depending on the disease siteextensive immobilisationprocedures need to beadopted


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Body mould immobilisation forpelvic sites


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PracticalProtonRadiotherapyBeams

Rangemodulator

i i


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Practical Proton Radiotherapy BeamsCollimators and beam shaping

Irregular apertures a

to conform the bethe shape of the tuprojected along thdirection of the inc

beamthey need to be thienough to expend incident energy (ththan the range)


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Snout:10 cm, 18 cm,25 cm

Lucite CoAperture


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Si l ti


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Simulation

CT scans of volume of interest,without contrast, 1 mm thick slices

CT scans of same volume, withcontrast

MR scans of volume to include targetand adequate for image fusion

4D-CT used to ascertain motion


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P t Th


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Proton Therapy

Not the silver bullet Protons are another tool and will not totally

replace other modalities

Can be combined with other modalities

Immobilization, some beam arrangements andtreatment schemas can be similar to

conventional radiation therapy (building onto

current knowledge)

U t i ti i P t Th


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Uncertainties in Proton TherapyPatient related: Physics related:

Patient setup CT number conv

Patient movements Dose calculatOrgan motion

Body contour

Target definition

Biology related: Machine relatedRelative biological Device tolera

effectiveness (RBE) Beam ene

T t t Pl i


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Treatment Planning

Acquisition of imaging data (CT, MRI)

Conversion of CT values into stoppingpower

Delineation of regions of interest

Selection of proton beam directions

Design of each beam

Optimization of the plan


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Areas where (high energy) physics may


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Areas where (high-energy) physics may

contribute to proton radiation therapy:

Development of proton computed tomograNuclear data evaluation and benchmarking

Radiation transport codes for treatment plan

In vivo localization and dosimetry of proton

beams

Influence of nuclear events on RBE


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Maxillary Sinus


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Maxillary Sinus

P

Prostate cancer


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Prostate cancer

Two-field Protons Six-field IMRT planPlanning comparison for Prostate cancer

Non small cell lung cancer (NSCLC


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Non-small cell lung cancer (NSCLC

Phot

Proto

Glioma


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Glioma

Proton IMRT plans

Planning comparison of a brain tumour


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Para-spinal tumour


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Para spinal tumour

Proton IMRTPlanning comparison of a juxtaspinal tumou


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Medulloblastoma- CSI


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Proton Therapy Worldwide


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Estimated 45

centers by 2013

As of August 2013, there were 43 particle therap


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As of August 2013, there were 43 particle therapin the world, representing a total of 121 treatmenavailable to patients on a regular basis.

They are located in Canada, China, Czech RepuFrance, Germany, Italy, Japan, South Korea, PolRussia, South Africa, Sweden, Switzerland, the UKUS.

28% of the proton therapy facilities are located iand 23% are located in Japan and

More than 96,537 patients had been treated.

Clinical Studies of Proton Therapy With at Least 20


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Patients and With a Follow-Up Period of at Least 2Years (>36 Studies)

Challenges


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Challenges


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Incidence of second malignancies in


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gpatients treated with protons

558 patients treated with Protons between1973-200Harvard cyclotron, Cambridge, MA were comparematched surveillance

Median duration of follow-up was 6.7 yrs.

Second malignancies occurred in 29 proton patien

and in 42 photon patients(7.5%)

Proton therapy was not associated with increased second malignancies (adjusted hazard ratio: 0.52;


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The emerging technology committee (2007)ofthe American Society of Radiation Oncology


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y gy(ASTRO)

This report reflects evidence collected up to Novem

Data was reviewed for PBT in central nervous systemgastrointestinal malignancies, lung, head and neck, and pediatric tumors.

Proton beam therapy (PBT) is a novel method for tremalignant disease with radiotherapy.

Current data do not provide sufficient evidence to rPBT in lung cancer, head and neck cancer, GI maligand pediatric non-CNS malignancies.

Radiotherapy and Oncolog


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