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[email protected] PSI Winterschool, January 2012
Proton Therapy Workflow Martijn Engelsman
HollandPTC and TU Delft
Disclaimer: I have no financial interest in any vendor of radiotherapy hardware,
software, or otherwise
[email protected] www.hollandptc.nl 2
Then • Four field box • Historical margins • Lasers + X-ray • Paperwork • 1 plan • Long-term follow-up
Now • IMRT, VMAT, RapidArc • Error analysis -> margins • CBCT • Treatment chain
integration • Adaptive therapy • In-vivo dosimetry + long-
term follow-up
Closed loop
A brief history of photon therapy
[email protected] www.hollandptc.nl 3
Closed Loop: Check and Correct
Check Anatomy
Treatment plan
Check Delivery
[email protected] www.hollandptc.nl 4
300 2 4 6 8 10 12 14 16 18 20 22 24 26 28
160
0
20
40
60
80
100
120
140
Depth (cm)
Dos
e (%
)
Protons: Spread-out Bragg Peak
Protons: Pristine Bragg Peak
Beam Direction
Photons 10MV
Increaseddensity
The Promises and the Peril The Peril: Finite Range ! ! !
The Promises: Lower upstream dose No downstream dose
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Dose degradation in proton therapy
Aafke Kraan et al. IJROBP 2013
Proton therapy needs to: - Detect potential severe dose degradation - Allow effective treatment plan adaptation
[email protected] www.hollandptc.nl 6
General patient complexity
(a.u
.)
Palliative Curative
Photons
Need for IGART
(a.u
.) Photons
Technology Status
(a.u
.)
Photons
The workflow challenge
General patient complexity
(a.u
.)
Palliative Curative
Photons Protons
Need for IGART
(a.u
.) Photons Protons
Technology Status
(a.u
.)
PhotonsProtons
[email protected] PSI Winterschool, January 2012
Patient intake
[email protected] www.hollandptc.nl 8
Patient referral
• Standard indications – Children – Intra-ocular – Base of skull
• Other indications – Head and neck – Prostate – Breast – Lung – Sarcoma – Pancreas – Liver – Etc
We want to / will treat everything …using adaptive
(Intensity modulated) Proton Therapy !
Indication CMS Regence/group Premera/blue/cross Blue/Shield/California Aetna Anthem/blue/cr/blue/sh Humana UnitedHealthCare
Abdominal Investigational Investigational Investigational Investigational Investigational no
Acoustic/neuromas Investigational Investigational Investigational Investigational Investigational no
AVM Investigational Investigational Investigational Investigational Investigational yes yes
Bone/metastasis Investigational Investigational Investigational Investigational no
Breast Investigational Investigational Investigational Investigational Investigational Investigational no
Central/Nervous/System yes children children children yes yes yes yes
Cervix Investigational Investigational Investigational Investigational no
Chordoma///Chondrosarcoma yes yes yes yes yes yes yes yes
Head/and/Neck yes Investigational Investigational Investigational Investigational Investigational no
Hodgking Investigational Investigational Investigational Investigational no
Liver Investigational Investigational Investigational Investigational Investigational Investigational no
Lung Investigational Investigational Investigational Investigational no
Lymphoma Investigational Investigational Investigational Investigational no
Meningioma Investigational Investigational Investigational Investigational Investigational yes no
NonFHodgkin Investigational Investigational Investigational Investigational no
Ocular yes yes yes yes yes Investigational some yes
Paranasal/sinus yes Investigational Investigational Investigational Investigational no
Pediatric yes Investigational Investigational yes yes no
Pituitary yes Investigational Investigational yes yes yes no
Prostate very2few no no no no some some no
Rectum Investigational Investigational Investigational Investigational Investigational no
Retroperitoneal/sarcoma yes Investigational Investigational yes yes no
Sinus/tumors yes Investigational Investigational Investigational Investigational no
Skin/cancer Investigational Investigational Investigational Investigational Investigational no
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Clinical reality Data part of a workflow survey of 12 US-based proton therapy
centers
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Hospital-based or not?
Separate building
Stand-alone Embedded
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Facility layout
1
8 9 13 1 4 5 7 10 12 2 3 11
Gantries 4 4 3 3 3 3 1 1 1 2 2 1
Fixed beam 1 1 2 1 1 1 3 3 3 1 0 0
Interplay? Some Some Some None Some Some Some Some Some Some None None
Only one center with more than two rooms claims no interplay effect.
Typically Pediatric patients, and sometimes SBRT patients, will get priority for beam usage as these are challenging cases.
Although some systems allow prioritization of beam requests, in other cases the rooms will coordinate by means of intercom.
Or one can simply wait, beam delivery time is typically acceptable, room switching is improving. (Only) large PBS fields in a slow scanning solution provide a real challenge.
No advanced scheduling system yet in clinical use, though (some) vendors are actively working on it and promising it to new customers.
Num
ber o
f tre
atm
ent
room
s
0
1
2
3
4
5
(a.u.)
Gantries Fixed beam
[email protected] PSI Winterschool, January 2012
Treatment planning
[email protected] www.hollandptc.nl 13
Treatment planning workflow
1 2 3 4 5 6 7 8 9 10 11 12 Week:
Referral
CT/MRI Info
PTV1
PTV2
Plan 1
Plan 2
27th Tx 1st Tx
Info
1 2 3 4 5 6 7 8 9 10 11 12 Week:
Referral
PTV1 PTV2
CT/MRI
Plan 1 Plan 2 Plan 2‘
CT / Info
Info
Info 1st Tx 27th Tx
Plan 3
34th Tx
PTV3 Plan 1 ‘
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0
2
4
6
8
10
12
14
16
cranial
#"Fields"
2"
4"
6"
8"
10"
12"
14"
16"
0"
Fields per treatment course
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Treatment planning effort
Photons 200 – 300 Protons 60 – 110
Patients planned per FTE dosimetrist
Do I need photon back up planning?
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Treatment Planning
• Commercially available TPS – CMS XiO – Varian Eclipse – Raysearch Raystation – Philips Pinnacle – ( Astroid )
Model your specific
machine?
• Auto-patching and auto-matching • Dose accumulation and deformation • Scripting / auto-planning • Multi-criteria optimization (MCO) • Re-painting strategies
Tools to look for to make life easier
[email protected] www.hollandptc.nl 17
Signatures
1
Treatment(plan Calibra.on Setup(image FieldPhysician 100 83 75 25Physicist 92 100 25 17
Dosimetrist 67 25 25 0
Therapist 17 0 67 92
Perc
ent
0
25
50
75
100
Physician Physicist Dosimetrist Therapist
Treatment plan Calibration Setup image Field
[email protected] www.hollandptc.nl 18
Integration / connectivity
Very few users for each package / combination
TPS OIS TDS Patient
In-House (3)
Hitachi (1)
IBA (7)
Mevion (1)
Varian (1)
In-House (2)
Elekta XiO (4)
Raystation (2)
Varian Eclipse (7) Aria (4)
Mosaiq (8)
Velocity (3)
Mimvista (4)
In-House (1)
Next to using the TPS itself
DIPS (3)
Medcom Verisuite (5)
By proton vendor
In-House (1)
Delineation Treatment planning Record and Verify Proton therapy equipment
Setup verification
Delineation Treatment Planning OIS TDS
Setup verification
[email protected] PSI Winterschool, January 2012
OIS and connectivity
[email protected] www.hollandptc.nl 20
Integration status
For a not yet too difficult treatment / workflow:
• “The integration between TPS and OIS is acceptable. The challenge is mainly in the communication between OIS and TDS.”
• “We do a lot of in-house manipulations to make our OIS work with protons.”
• “There is no integration whatsoever.”
• “No way this system can be integrated.”
“Are you happy about the electronic integration between TPS, OIS and TDS?”
[email protected] PSI Winterschool, January 2012
Image-guidance
[email protected] www.hollandptc.nl 22
IGRT and ART, until now
• State of the art – Daily Orthogonal X-rays (plus some off-line imaging)
• Auxiliary positioning systems – Ultrasound – VisionRT – Fiducial markers – Electromagnetic Transponder Tracking
• Treatment adaptation – Off-line CT – Slow adaptation -> TPS vendors picking up the pace
• Remote positioning • E.g. Fava et al. Radiother Oncol.103, p.18, “In-gantry or remote patient
positioning? Monte Carlo simulations for proton therapy centers of different sizes.”
[email protected] www.hollandptc.nl 23
Orthogonal X-ray alignment
Pro • On-line setup protocol • 6-DOF setup correction
Con • Time-consuming • Intra-operator variability • Rotations are difficult • No treatment adaptation
• Dose degradation remains unknown !
Aligning the tumor is not even half the solution !
[email protected] www.hollandptc.nl 24
Cone-beam CT at isocenter (photons, 2009)
Slide courtesy of J-J. Sonke, NKI
Room entrance to first
“beam-on”: 6 minutes
+
VMAT / RapidArc 4 minutes
=
10 minute fraction
[email protected] www.hollandptc.nl 25 1
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
Setup times 0 10 35 16 10 2 3 3 0 4 1 0 2 0 0 1 0
Cou
nt (#
)
0
10
20
30
40
Patient setup time (minutes)
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
Fraction times in proton therapy (2014)
1
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
Setup times 0 10 35 16 10 2 3 3 0 4 1 0 2 0 0 1 0
Cou
nt (#
)
0
10
20
30
40
Patient setup time (minutes)
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
1
0 10 20 30 40 50 60 70 80 90 100 110 120
Fraction times 0 6 24 34 12 2 6 0 0 2 0 0 1
Cou
nt (#
)
0
10
20
30
40
Total in-room time (minutes)
0 10 20 30 40 50 60 70 80 90 100 110 120
Setup time (minutes) Fraction time (minutes)
Anesthesia or SBRT Anesthesia or SBRT
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Frequency of setup verification
1
Peadiatric Intra+cranial Gastro Prostate H&N Thoracic SBRT
Every field 67% 58% 58% 67% 58% 58% 88%
Every fraction 33% 42% 42% 33% 42% 42% 13%
Perc
ent
0%
20%
40%
60%
80%
100%
Peadiat
ric
Intra-
crania
l
Gastro
Prostat
eH&N
Thorac
icSBRT
Every field Every fraction
[email protected] www.hollandptc.nl 27
3D in-room imaging
CBCT
• Volumetric matching • Visualize anatomy changes
• Dose recalculation
In-room CT
Having on-line 3D imaging is not even half the solution !
Need for decision protocols and software to (semi-)automate these
[email protected] PSI Winterschool, January 2012
Treatment adaptation
[email protected] www.hollandptc.nl 29
Repeat CT: Examples of clinical application
Chang et al. IJROBP2014, p.809
- Adaptive IMPT at MD Anderson - Weekly repeat CT and recalculation - 9/34 patients had to be replanned - In two cases to ensure OAR sparing - 3 days to start of new plan
most of these patients, IMPT was the only option fortreatment because of the need for normal tissue sparing.Typically, IMPT was chosen because of a significant dosi-metric advantage over other modalities (Fig. 2B) or becauseit was the only option for definitive treatment to sparespinal cord, esophagus, and lung (Fig. 2C), or because ofrecurrent disease that had been treated previously with ra-diation therapy (Fig. 2D).
Analyses of tumor motion, WET, beam angleselection, and plan robustness
Beam angle‒specific tumor motion and WET analyseswere performed for each patient as described in Methods.The absolute WETs of the pixels within the ITV forevery tested beam angle were calculated on T0 and T50phases. The WETs of the pixels on the distal surface of
the ITV orthogonal to the beam (beam angle Z 0) wereprojected to a plane and shown as a 2D map (Fig. 3).Figure 3A shows the WET change between T0 and T50as a function of incident proton beam angle, andFigure 3B shows an example of the same patient at abeam angle of 160!. The S5mm for this beam angle was95.1%. Optimal beam angles that minimized the effect ofrespiratory motion were then selected based on theseanalyses. Findings from patient-specific tumor motionand WET analyses are summarized in Table 2. The datashowed a median 86.2% of the voxels in the IGTV thattraveled in perpendicular to the beam axis by "5 mm.The data also met our acceptability limit of #80% of thevoxels in the ITV in which the WET differences are notmore than 5 mm (S5mm).
The results of a robustness analysis of an MFO IMPTplan for a representative patient are shown in Figure 4.The maximum deviation from the nominal dose-volume
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80
Lung V5 (%)
Lung V20 (%)
MLD (Gy)
Heart V40 (%)
Esophagus V60 (%)
CTV D5 (Gy)
CTV D95 (Gy)
GTV D5 (Gy)
GTV D95 (Gy)
IMRT
PSPT
IMPT
Esoph 60Gy
PSPT IMPT
IMRT IMPT
IMPT:solid PSPT:dotted IMRT:dashed
CTV
A
B CTV
Esophagus
Lung
IMPT vs IMRTMLD reduction: 4.4 Gy
IMPT vs PSPTMLD reduction: 4.3 GyEsophagus V65: 3% vs 10%
10020.0
Mean Lung Dose
PSPT IMRT IMPT IMPT IMPT SFO MFO Robust
15.0
10.0
Dose (cGy)
Norm
aliz
ed V
olum
e (%
)
Norm
aliz
ed V
olum
e (%
)
Dose (cGy)
80
60
40
20
0
0
2000 4000 6000 8000 10000 0 2000 4000 6000 8000 10000
100
80
60
40
20
0
Fig. 2. (A) Comparison of dosimetric variables for intensity modulated proton therapy (IMPT), passive scattering protontherapy (PSPT), and intensity modulated radiation therapy (IMRT). Values shown are means of all patients. (B) Comparisonsof dose-volume histogram (DVH), isodose distributions, and total mean lung dose for a representative patient who receivedchemotherapy with IMPT to 74 Gy(relative biological equivalence [RBE]) for stage III NSCLC.
Volume 90 $ Number 4 $ 2014 IMPT in thoracic malignancies 813
[email protected] www.hollandptc.nl 30
Clinical reality: Adaptive proton therapy
1
Peadiatric Intra-cranial Gastro Prostate H&N Thoracic SBRT
never 33.3% 66.7% 50.0% 75.0% 25.0% 33.3% 62.5%
1x 50.0% 33.3% 25.0% 25.0% 41.7% 16.7% 0.0%
2x 8.3% 0.0% 8.3% 0.0% 16.7% 16.7% 0.0%
3x 0.0% 0.0% 0.0% 0.0% 8.3% 8.3% 25.0%
4x 0.0% 0.0% 0.0% 0.0% 0.0% 0.0% 12.5%
5x 8.3% 0.0% 16.7% 0.0% 8.3% 16.7% 0.0%
6x 0.0% 0.0% 0.0% 0.0% 0.0% 8.3% 0.0%
0%
25%
50%
75%
100%
Peadiatric
Intra-cranial
Gastro
Prostate
H&N
Thoracic
SBRT
never 1x 2x 3x 4x 5x 6x
a) # of re-calculations per patient
0.0%
25.0%
50.0%
75.0%
100.0%
Peadiatric
Intra-cranial
Gastro
Prostate
H&N
Thoracic
SBRT
never 1x 2x 3x 4x 5x 6x
b) # of re-plannings per patient
On average: 75% never or once On average: 85% never or once
[email protected] www.hollandptc.nl 31
Adaptive Therapy Vision (2013 PTCOG)
• 0 years – Off-line, next 2-3 days
• 5 years – On-line evaluation of plan adequacy and choice of plan
of the day
• 10 years – 10 second automated on-line plan re-optimization
[email protected] www.hollandptc.nl 32
Example: online adaptive PT
2. Daily plan selection on the basis of in-room CT scanning plus dose-recalculation
1. Create treatment plan library using individualized motion model and/or variable plan robustness
Fast on-line dose recalculation is at the moment proton therapy’s best bet for validating continued plan adequacy!
[email protected] www.hollandptc.nl 33
Clinical reality: Moving tumors
1
Margins Breath-hold Gating Repainting
100% 50% 8.3% 8.3%
Perc
enta
ge o
f ins
titut
es
0%
25%
50%
75%
100%
Margins Breath-hold Gating Repainting
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The other workflow
Not patient-specific but
indication specific
[email protected] www.hollandptc.nl 36
Margins • Range error • Setup error • Number and direction of
beams • Use of ITV • Dual-Energy CT • …
IGART • Frequency of imaging • Kind of imaging (X-ray,
CBCT, in-room CT • Plan of the day • Prompt-gamma imaging • …
4D error simulation platform for do-it-yourself analysis.
What we need
The balance in proton therapy
[email protected] www.hollandptc.nl 37
Rescanning variables
• Spot size • Lateral spot overlap • Distal spot overlap • Volumetric or layer repainting • Number of rescans • Number of treatment fractions • Number of beams in the plan • Simultaneous gating or breath-hold • Iso-layer or scaled-rescanning • Spot-, line- or contour-scanning • Uniform, phase-controlled, random, time-delay, … • Layer changing time (vendor dependent) • Re-image and re-plan approach • …
Different answer for: - Each indication? - Each patient?
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Quality Assurance
[email protected] www.hollandptc.nl 39
Dosimetric quality assurance
• Extent depends on: – Facility layout (e.g. # rooms) – Your beamline(s) (e.g. PSPT, universal nozzle, PBS) – Patient mix (gating, tracking, …) – Experience – Patient specific?
• No standard approaches (yet) – QA tools and QA program – Technically demanding (who can do it)
• Night-time and morning work
Imaging QA to 1st order similar to photon therapy
[email protected] www.hollandptc.nl 40
QA time needed:
QA Time Daily 10 – 30 minutes per room Weekly 5 hours per week Monthly 5 – 25 hours per month Modality switch Followed by daily QA Fields: Hardware (PSPT) 0.5 – 1.0 FTE Fields: Dosimetric 5 – 15 hours per week
Overall QA time in % of yearly clinical operational hours:
Photons: Protons:
10% 20%
60% of PSPT 100% of PBS
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Facility start-up
[email protected] www.hollandptc.nl 42
Indications treated
Pedia
tric
Sarco
mas
Gastro
-intes
tinal
Pros
tate
Head a
nd ne
ck
Lung
Pe
lvis
Breast
1
Prostate Pediatric H&N Sarcoma's Gastro-intestinal Lung Pelvis Breast
1st year 100 100 50 50 40 50 50
2nd year 50 25 40 50 50
3rd year 25 50
4th year 20 50
Perc
ent
0
25
50
75
100
Prostat
e
Pediat
ricH&N
Sarcom
a's
Gastro-
intest
inalLun
gPelv
isBrea
st
1st year 2nd year 3rd year 4th year
[email protected] www.hollandptc.nl 43
Staffing (for 500 patients per year)
Phys
ician
s
Phys
icists
Ther
apist
s
Dosim
etrist
s
Full-
time
Empl
oym
ent (
FTE)
5
10
15
20
[email protected] www.hollandptc.nl 44
Closed Loop: Check and Correct
Check Anatomy
Treatment plan Check Dose
Check Delivery
Improved treatment plan design
Best possible imaging
Dose recalculation
In-vivo dosimetry
[email protected] www.hollandptc.nl 45
The workflow challenge
General patient complexity
(a.u
.)
Palliative Curative
Photons Protons
Need for IGART
(a.u
.) Photons Protons
Technology Status
(a.u
.)
PhotonsProtons
Technology Status
(a.u
.)
PhotonsProtons
[email protected] www.hollandptc.nl 46
Conclusions
We are here
Quality, integration and efficiency of proton therapy
• More and better tools • More and better use • More patient benefit