Present and Future of Radiation Therapy

ICTP School on Medical Physics

March 25 – April 5, 2019
Miramare, Trieste

Yakov Pipman, DSc

Overview
• Then
• Now
• Tomorrow
• Summary
 Radiotherapy 1-D

KiloVoltage therapy for breast

Radiation therapy simulation… a note and a diagram in the chart
Radiotherapy 1-D and 2-D
Typical dosimetric calculation
=
Computation of Beam- ON
time for a Co-60 treatment

BOTi=PDi/100 x T100,d,FS
 The 90’s – the era of 3D

Perez and Brady - Principles and Practice of Radiation Oncology-1998, and others…
Cranio- spinal Irradiation
 RFS vs. DOSE - RT alone

From: M.J.Zelefsky et. al.; IJROBP June 1998

 RFS vs. DOSE - RT alone
657 patients treated in 1994-95

From: P. Kupelian et. al.; IJROBP Feb 2005

 Dose Response

• From: G.E.Hanks et. al., IJROBP, June 1998

 Morbidity vs. Dose

From:G.E.Hanks et. al., IJROBP, June 1998

Hypothesis … for new technologies
Basic Strategy
More accurate • Reduce treatment volume
dose delivery & better - Irradiate a smaller volume of
normal tissue
dose distributions yield
better clinical
… allows dose escalation
outcomes! - higher doses to tumours

Tumour Control
Probability
(TCP)

Normal Tissue
Toxicity (NTCP) Courtesy: Dr Jacob (Jake) Van Dyk
 Radiation Oncology Historical Trends
Clinical Benefit
(Survival)
(Conformality)
1.0
1895-1940s 1950s 1960s-70s 1970s-80s 1990s-2019 >2020s
100-400 kV x-rays Cobalt-60 Multi-energy CT, 3D-CRT IMRT, IGRT, ART, PET, MR-
0.9
Non-uniform dose MV x-rays linacs Brachytherapy IGRT, Protons, Carbon ions
Next??
High skin dose Skin sparing Computerized afterloading
0.8 Brachytherapy Uniform dose TPSs
Radium & radon Manual treatment Simulators
??
Calculation systems planning
0.7

0.6 CT

0.5 2010s
Linear
“Real data” Survival=67%
0.4 accelerators
1970s
Cobalt-60
0.3 Brachytherapy
Survival=50%
Discovery of x-
Fractionation
rays &
0.2 radioactivity

0.1

0.0
1895 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040
Year Courtesy: Dr Jacob (Jake) Van Dyk
USA 5-yr Survival: 1970s [] to 2010s []
• All cancers up
• 50% 67%
• Except cervix &
uterus
• Prostate
• 68% 99%
• “early detection
and improved
Our World in Data, University of Oxford
https://ourworldindata.org/uploads/2018/03/Five
treatment”
-year-cancer-survival-rates-USA-v2-01.png

Courtesy: Dr Jacob (Jake) Van Dyk

Prostate Cancer EBRT

Thariat et al. Nat Rev Clin Oncol 10: 52–60; 2013

Image guidance over the years
• Portal Imaging (film and digital)
• Fluoroscopic tracking (range of motion)
 Fiducial based 2D/2D match

Gold coils implanted in the prostate are shown on a DRR (a) and on an MV portal
image (b). Image matching structures obtained from the DRR are superimposed on
the EPID to target the coils, rather than the bony anatomy.
Image guidance over the years
• On Board imagers (kV and MV)
Localization and 4D RF Tracking of Implanted Markers
Optical System

4D Localization System
Infrared Cameras

4D Electromagnetic
Array

4D Tracking Station

Optical Targets

4D Console
Implanted
Beacon® Electromagnetic
Transponders
Image guidance over the years
• U-Sound targeting (mainly
distance or interface)
Image guidance over the years
• Optical surface
matching (Visionrt)
 Multimodality image registration

Acoustic neuroma not Mass clearly seen on reformatted

clearly visible on CT image MRI image after fusion with CT
Current
Image-Guided Radiation Therapy (IGRT)
4-D Radiation Therapy
Meyer et al 2007

Reduction of systematic and random uncertainties

Adapted from Dr Jacob (Jake) Van Dyk
• Do We Deliver the Correct Dose
Distribution for every Treatment?

For many anatomical sites we have

limited control of the internal organ
motion
 Effects of Intra-Fraction Organ Motion on the
Delivery of IMRT with an MLC

IMRT treatment: summation of small

Conventional treatment beams
Effect of organ motion
on GTV is accounted for No organ motion with organ motion
by PTV, which is always delivered = planned delivered  planned
inside the beam
aperture.
Courtesy of Dr C. S. Chui
Hybrid Technologies-Imaging and Therapy
• Linac/CBCT
In Room Radiographic guidance
Hybrid Technologies-Imaging and Therapy
• Tomotherapy
• Halcyon
Hybrid Technologies-Imaging and Therapy
Cobalt/MR
Hybrid Technologies-Imaging and Therapy
• →Linac/MR
 Hybrid Technologies-Imaging and Therapy
• Linac/MR

Alberta, Canada (G. Fallone)

UMC Utrecht ELEKTA/Philips

Figures from: Uwe Oelfke, Paul Keall
Hybrid Technologies- Anatomy and Function
• PET/CT
• PET/MR
• Other advances

Autocontouring

Adaptive Radiation Therapy (ART)

Computing advances

Computer hardware (Moore’s “law”):

Size ↓ , Density ↑ (Doubling time < 2y)
Processor Speed ↑
Software:
Parallel processing
Optimization
Processing capability ↑↑↑
• Real-time adaptive RT
• 4-D
• Real-time replanning
• Dose accumulation
Advanced algorithms
• Monte Carlo planning calculations, but much faster!
• Boltzmann transport
• Radiobiological models
• Accounting for Uncertainties (Robust Optimization)
Example of Robust Optimization
End of PTV?

Big Little
difference difference

From:
Moe Siddiqui
April 08, 2017
RaySearch Labs
http://pubs.medicaldosimetry.org/pub/e5a
d0d52-782b-cb6e-2763-e6a918540f5c
Adaptive technologies
• Image warping
• Daily-re-optimization
• Daily dose accumulation
• Real-time tracking of tumor markers
• Real-time tracking and correction of MLC
apertures
More Adaptation … example
• Tissue voxels move/change from day to day

Planning CT Treatment day CT

Schaly et al, PMB 49: 791-805, 2004

Deformable Image Registration
Thin-Plate Spline Image Warping

Source Target

Courtesy: Jeff Kempe

Deformable Image Registration
Thin-Plate Spline Image Warping

46

Result Target

Courtesy: Jeff Kempe

Warping Example: 6-Field Prostate
Note rectal
distention …
pushes
prostate up

Treatment fraction 1
Planned

47

Warped fraction 1 Difference: warped ̶ planned

Schaly et al, PMB 49: 791-805, 2004

 Will image guidance & dose warping
improve treatment outcome?
IGRT

Laser

Best dose escalation strategy:

Combine margin reduction (low 48
NTCP) with daily IGRT technique Laser
(high TCP) to localize the daily
moving/deforming target IGRT

volume.

Song et al: Med Phys 32: 2193-203, 2005

IGRT Impact on Clinical Outcomes

Rectal distension not a predictor of

Rectum: if distended @ planning … urological toxicity … due to IGRT
But not @ treatment …
Prostate moves down out of high
dose volume

2005
2005
From Dr Jacob (Jake) Van Dyk
 Technology advantages
• More efficient
Halcyon
• VMAT, TomoTherapy, Halcyon
Example: Installation, commissioning, training

TrueBeam

Courtesy
T.F. Atwood, UCSF
Sept 2018
 Technology advantages
• More efficient
Halcyon
• IMAT, TomoTherapy, Halcyon
Example: Patient throughput

6 pts/hr
TrueBeam

3.5 pts/hr
Courtesy
T.F. Atwood, UCSF
Sept 2018
 Trends Over the Next 10 Years
• More particles
70
Proton Therapy Facilities
60

Number of proton facili es

• Protons, carbon ions, … 50
y = 4E-56e0.0652x

• Proton therapy
40

30

• 92 operational (Feb 2019) 20

• 45 under construction (Jan 2019) 10

• Source Physics World, 25 Feb 2019 0

1950 1960 1970 1980 1990 2000 2010 2020
• Carbon ion therapy Year

• 11 carbon ion facilities (2017) Figure courtesy Thomas Bortfeld … source: PTCOG

• 6 in Japan
“Conservative Estimate”
• 10% of the patients who require radiation
would benefit from proton therapy
• From Thomas Bortfeld, MGH (2018)
• “… 10-20% of patients receiving radiotherapy
might benefit from charged particle beams.”
• From Jones & Burnet, BMJ 330: 979-980; 2005
More Compact … Shrinking Proton Accelerators
US FDA Cleared
Proton Therapy
Systems

1946
Harvard
(700 tons)
1996

IBA/Sumitomo
(220 tons)
2000
Varian/Accel
(90 tons) 2012
Courtesy: Mevion Mevion Medical
Slide courtesy Thomas Bortfeld Systems (<20 tons)
Trends Over the Next 10 Years
• More hypofractionation (higher
doses/fraction, SBRT)
• Breast cancer
Timeline of UK Breast RT Trials

Yarnold BJR 92: 20170849; 2019 Fisher JCO 32:2894-2901; 2014

From Dr Jacob (Jake) Van Dyk
Brachytherapy
LDR HDR
e-Brachytherapy
X-Ray Tube HV Cable
Professional Communication
• Radiation Oncologists and Radiation Therapists
• Radiologists
• Interventional Radiologists (Cardiology, ENT, Gynecologists)
• Surgeons (Breast, Gynecology, H&N, s
• Neurosurgeons
• Administration
• Engineers
• Computer Scientists