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Advances in Treatment Planning
Techniques and Technologies
for Esophagus Cancer
Matthew Palmer, MBA, CMD
Outline
• The Flies: X-Ray Beam Angle Study Review
• Advancing the Flies: X-Ray Class Solution and
Benchmark Study
• Advancing Technologies: Proton Treatment Planning
• X-Ray vs. Proton Comparison Study
• Advancing Treatment Options: Dose Escalation
GTV Delineation
• GTV defined based
on all available
imaging :
– EGD/EUS
– PET/CT
– Barium (rare)
GTV Delineation
4D-CT
AVERAGE
Important for the GTV to be delineated with the full 4D dataset.
CTV Delineation
• The CTV presumed to extend 3cm superior and inferior
including into stomach, along walls and out to fascial planes
(i.e. pleura). – Dr. Joe Y. Chang (MDACC)
–
–
–
–
3 cm Superior (Esophagus)
3 cm Left from GE junction to Last Slice of GTV (Stomach Region)
2.5 Inferior from last slice of GTV
1 cm Radially around GTV defined by PET & MIP
Superior CTV- 3 cm Superior
GTV
CTV
Contour the Esophagus Superiorly 3 cm from top slice of GTV.
Use MIP and respiratory phases to modify CTV for motion (ITV).
Stomach Region- 3 cm Left
Stomach
GTV
GTV
Stomach
Region
Stomach
Stomach
Region
Contour into the stomach 3 cm from GE Junction to the
last slice of GTV and stomach overlap.
Mid CTV- 1 cm Radial Exp.
Mid CTV
Sup. CTV
GTV
Expand the GTV and Stomach Region 1 cm Radially
to make Mid CTV
Inferior CTV- 2.5 cm Inferior
Inferior CTV
Expand the Last Slice of GTV Inferiorly 2.5 cm
Total CTV
Combine ALL CTVs (Superior CTV, Mid CTV, & Inferior CTV) to make a Total CTV
Imaging Based PTV Expansion
PTV
PTV Expansion
4D-CT
PTV
CTV
GTV
AVERAGE
Important to analyze contours with motion to ensure accurate coverage in the diaphragm area
Traditional Beam Arrangements
then off
cord
3D/2D
IMRT
IMRT
Effects of Radiation on Heart
• XRT and Cardiac SPECT Study:
• Pre-surgical assessment showed an Increase in LV Ischemia
50Gy
40Gy
20Gy
Gayed el al., J. Nuc. Med. 2006
14 Patients- Acute Cardiac Symptoms
Patient Example #1
Patient Symptoms:
•
•
•
Pneumonia,
Atrial fibrillation,
Shortness of
breath
Decrease in the
inferior apical
segment during
stress and
remains
unchanged
during rest
Suggestive of
mild scar in the
inferior apical
segment.
50.4Gy
45Gy
40Gy
30Gy
Cardiac SPECT Registered w/ Plan
35Gy
30Gy
Worked with Diagnostic Imaging to send Cardiac SPECT images as a volume study
instead of screen captures.
We were able to import with DICOM RT and Register with Tx Plan.
“The Flies” Study Details
• Dosimetric analysis
– Goal: Lower cardiac dose
– Alternative beam arrangements for IMRT planning
– 12 patients
• Carcinoma of the Distal Esophagus
• Planned
– 50.4 Gy in 28 fractions
– 6MV photons
– Step and shoot IMRT
Grosshans, et al., Improving cardiac dosimetry: Alternative beam arrangements for Intensity Modulated
radiation therapy planning in patients with carcinoma of the distal esophagus, Practical Radiation Oncology
(2012) 2, 41-45.
Beam Arrangement Study
350 30 70 110 180
Traditional
Hemi.
350 25 130 165 195
Butterfly
Alternative
290 70 100 180 260
Dragonfly
100 130 180 230 260
Firefly
70
100 150 200 230
Modified Firefly
30o
Cardiac Sparing Study Results
A.
B.
C.
D.
Hemispheric
Butterfly
Dragonfly
Firefly
Advancing the Flies:
X-Ray Class Solution &
Benchmark
Dosimetric Study
Class Solution & Benchmark Study
• Evaluated dosimetry for 50 patients
• Evaluated multiple correlations and geometric
relationships
• Important Correlations
– Distance from PTV border to Carina (DPC) & TLMD
– % Uninvolved Heart (Heart-PTV/Heart) & Heart MD
DPC and % UIH Data Analysis
DPC
Find the carina bifurcation.
Count the number of
slices between superior
border of PTV and carina.
(+ inferior/ - superior)
DPC = No. of slices * slice
thickness.
PTV-Heart
Overlap
%UIH
PTV typically overlaps
Heart.
Create a Heart – PTV
structure.
%UIH =
(Heart – PTV)/Heart Vol.
Class Solution & Benchmark Study
• Initial data concluded that there was dosimetric variability
based on initial data– Mainly due to different techniques
Reoptimized all of the cases with a “SupaFirefly” technique
www.urbandictionary.com
Man
SupaFirefly Technique
SupaFirefly improved average TLMD, TL-V20, HMD, LMD and Cord
X-Ray Class Solution Study
• Initial data concluded that there was dosimetric variability
based on initial data
• Reoptimized all of the cases with A “SupaFirefly” technique
• Standardized the data and improved the average dosimetric
results and correlations:
– DPC & TLMD: -0.71  -0.83
– %UIH & HMD: -0.67  -0.75
Total Lung
Heart
Mean:
V5:
V10:
V20:
Mean:
V20:
V30:
V40:
-38 cGy
-1.5%
-0%
-1.7%
Liver
-209 cGy
-5.1%
-5.3%
-4.1%
Mean: -252 cGy
V30:
-79cc
V40:
-25cc
DPC (cm) & TLMD (cGy)
Reoptimized
OriginalData
Data
TLMD = 1000 cGy
DPC (cm) & Lung V5-V20 (%)
V5%
V10%
V20%
V5 = 50.5%
V10 = 32%
V20 = 18’%
%UIH (%) & Heart Mean Dose (cGy)
OriginalData
Data
Reoptimized
%UIH (%) & Heart V30-V50 (%)
V30%
V40%
V50%
SupaFirefly Benchmark Calculator
SupaFirefly Class Solution Info.
SupaFirefly Validation Study
• 10 Patients randomly selected from clinical database
• Reoptimized with SupaFirefly beam angles, benchmark calculator,
and objectives
• Compared Clinical Plans (Mod. Firefly) to SupaFirefly Plan
• IMRT techniques for Esophagus are optimal but the SupaFirefly
technique was validated to further improve our clinical practice
Total Lung
Heart
Mean:
V5:
V10:
V20:
Mean:
V20:
V30:
V40:
-134 cGy
-0%
-4%
-5.8%
Liver
-81 cGy
-2.3%
-2.6%
-2.6%
Mean: -751 cGy
V30:
-6.3%
V40:
-1.4%
What about VMAT?
Will it be the SuperFly!
What about VMAT?
IMRT – SupaFirefly
(60, 80, 120, 140, 160, 180, 200)
VMAT – 2 Partial Arcs
(50  180, 180  50)
30Gy
VMAT- Courtesy of Montreal Turner, CMD
What about VMAT?
IMRT – 7 Beams
(60, 80, 120, 140, 160, 180, 200)
Liver Mean
Heart Mean
Total Lung Mean
■ IMRT
731
1753
749
VMAT – 2 Partial Arcs
(50  180, 180  50)
▲VMAT
681
1794
767
VMAT- Courtesy of Montreal Turner, CMD
Advancing Technologies:
Esophagus Proton
Treatment Planning Basics
Influential Parameters on Proton Planning
• User-Defined Parameters
– Beam Angles
– Beam Weights
– Lateral Margins
• Beam Specific & Calculated Parameters
– Range Uncertainties (3.5%)
• Distal and Proximal Margins (CTV+)
– Setup uncertainties (5mm)
– Compensator Smearing (Motion) (6mm-10mm)
Beam Angle Limit Criteria
• Influential factors on Beam Angles
–
–
–
–
Table Edge
Parallel beams to sharp tissue gradients
Movable objects/Fleshy Tissue, i.e. breast, fat
Distal critical structures to beam
• Others
– Length of Lung tissue
– Tumor motion
• GTV Overrides for compensator design
• Verification Plans
Beam Angles Issue- Distal End
Individual Beam Analysis
Beam Angle Issue- Table Edge
Individual Beam Analysis
AP/PA (Original Technique)
AP- 100%
PA- 100%
AP/PA/Lt Lat (2nd Technique)
AP- 100%
PA- 100%
LL- 100%
No Smear
9mm Smear
Smoothed
T0%
T50%
AP/PA vs. 2 Fld (LPO/PA)
■ AP/PA vs. ▲ LPO/PA
LPO/PA
LLat-100%
HEART
LUNG
LIVER
CORD
Lung
Heart
Liver
Cord (Max)
AP/PA
1428
3196
1057
3066
LPO/PA
1524
2139
615
4137
Effects on Protons of 4D Motion
Image Courtesy of David Lege, CMD
Proton vs. X-Ray
Comparison Study
Effectiveness of Proton Therapy for
Esophageal Cancer
• Stephen Lin, MD (MDACC) analyzed more than 100
patients which documents protons effectiveness and
technique
– “Utility of Proton Beam Therapy with Concurrent
Chemotherapy for the Treatment of Esophagus Cancers”
• Suggest Left Lateral or LPO with PA
– Optimal for sparing lungs, heart and liver
• Protons reduces the mean lung and heart dose
compared to photon therapy
• Question:
– Are there any situations in which Protons does not have
the best dosimetric results, if any?
X-Ray vs. Proton Comparison Study
• Evaluated 54 patients, 42- GEJ, 11- Mid, 2- Cervical
• Purpose: investigated potential patient specific
parameters that can statistically indicate which
modality should be used on a case-by-case basis
– Emphasis on the LUNG and HEART
• Questions:
– Are there any anatomical characteristics that would
indicate a different proton planning technique than the
standard approach?
– Why are some cases suboptimal based on expected
results?
X-Ray Correlative Factors
applicable to Protons?
• X-Ray technique has been refined and specific
correlations have been defined to estimate the lung
and heart doses
– DPC & TLMD
– %UIH & Heart MD
• Question: Do these parameters apply to protons?
X-Ray vs. Proton Comparison Study
Dosimetric Results
Proton (All Sites)
Minimum Differences
Lung Mean*:
-290 cGy+
Cord Max*:
-545 cGy+
Liver Mean*:
-517 cGy+
Heart Mean*:
-667 cGy+
*Statistically Significant (p<0.01)
DPC (cm) & TLMD (cGy)
X-Rays
Protons
%UIH (%) & HMD (cGy)
Suboptimal Proton
Plans
X-Rays
Protons
Optimal X-Ray
Plans
Suboptimal X-Ray
Plans
Mean Dose Comparison Analysis
• The DPC and %UIH matched up similarly for each modality
– Trends are consistent and the linear regression estimations do not
cross anywhere
• The results indicate that PROTONS has superior results for
both the LUNG and HEART Mean Doses
• PROTONS has some statistical outliers for both LUNG and
HEART
– Zero LUNG outliers cross the x-ray best-fit line
– 5 HEART outliers cross the x-ray best-fit line
• Conclusion: PROTONS will have superior LUNG, HEART, &
LIVER Mean Doses in 95% of all cases
Total Lung: Volumetric Analysis (GEJ)
Average DVHs of all Patients
X-Rays
Protons
Heart: Volumetric Analysis (GEJ)
Average DVHs of all Patients
X-Rays
Protons
Volumetric Analysis Summary (GEJ)
• Lung:
– Protons is statistically better from 5Gy-30Gy
– X-Rays are statistically better from 40Gy-50Gy
• Heart:
– Protons is statistically better from 5Gy-20Gy
– X-Rays are statistically better from 40Gy-50Gy
• Analysis:
– IMRT- modulated and more conformal
– Protons- 3D-conformal
– Protons- each beam adds 3.5%*Range +3mm for
each beam to the distal range which minimizes
conformality
– IMPT may be able to help proton conformality
Esophagus Comparative Estimator
Outlier Analysis
• The DPC and %UIH are strong predictive parameters used to
estimate dosimetric results.
• There are outliers that do not fit the best-fit predictions.
• Analyzed additional correlations to see if the outliers were
consistent.
TLMD vs. HMD
Original Data
Proton
Outlier
X-Ray
Outlier
X-Rays
Protons
Suboptimal Protons
Suboptimal X-Rays
TLMD vs. HMD
Reoptimized Results
Remaining
suboptimal Proton
cases (5)
Suboptimal X-Ray
cases (8)
Optimal X-Ray
cases (9)
Optimal Proton
cases (8)
X-Rays
Protons
Suboptimal Protons
Suboptimal X-Rays
TLMD vs. HMD: Suboptimal Proton Results
Analysis
• The following categories were identified:
–
–
–
–
–
AP/PA beam arrangement (6) [old technique]
PA/Lt Lat beam arrangement but suboptimal weight to PA (1) [1:1]
Suboptimal beam arrangement with 3 beams (1) [AP/PA/Lt Lat]
Patients with unique anatomy (2) [heart wraps around CTV]
Patients with small lung volumes which skew the expected results (2)
• Suboptimal Proton plans reoptimized and majority improved
– Trade-offs: Spared LUNGS at the expense of the HEART
• 5 remaining outliers
– Were outliers for both X-rays and Protons
– Protons were still superior despite suboptimal anatomy
Suboptimal Anatomy or Contours
X-Ray & Proton TLMD Comparison
• TLMD for each patient graphed with each other as a
scatter plot.
• The trend will identify the superior technique.
• If modalities are identical then the data points will be
along the grey line.
X-Ray & Proton TLMD Comparison
Protons Advantageous- All Data Points
below Equivalent Best-fit Line (grey line)
Note: Same patient data graphed against each other
X-Ray & Proton TLMD Comparison
• TLMD for each patient graphed with each other as a
scatter plot.
• The trend will identify the superior technique.
• If modalities are identical then the data points will be
along the grey line.
• Results indicate that the TLMD is consistently lower
with proton therapy.
• The outliers in this graph match the outliers in the
DPC vs. TLMD and TLMD vs. HMD graph.
X-Ray & Proton HMD Comparison
• HMD for each patient graphed with each other as a
scatter plot.
– The colors represent optimal or suboptimal plans from the
TLMD comparison
X-Ray & Proton HMD Comparison
5 Cases- Protons suboptimal for TLMD
and HMD
* same patients in other analysis graphs
3 Cases- Protons optimal for TLMD,
Suboptimal for HMD
Green dots are optimal TLMD data
Red dots are suboptimal TLMD data
X-Ray & Proton HMD Comparison
• HMD for each patient graphed with each other as a
scatter plot.
– The colors represent optimal or suboptimal plans from the
TLMD comparison
• Results indicate that the HMD is consistently lower
with proton therapy.
• The outliers in this graph match the outliers in the
%UIH vs. HMD and TLMD vs. HMD graph.
• Tradeoffs between HMD and TLMD are evident.
• 5 suboptimal cases for both modalities are evident.
Proton & Photon Suboptimal Expected Results
Anatomy/Contouring (CTV overlapping Heart)
Proton & X-Ray Suboptimal Plans
Anatomy/Contouring (CTV)
■ X-Rays vs. ▲ Protons
HEART
LUNG
Lung
Heart
X-Rays Protons
396
256
2041
1341
Suboptimal Photon Plan
Hemispheric Beam Angles
Suboptimal Photon Plan
Hemispheric Beam Angles
■ X-Rays vs. ▲ Protons
HEART
LUNG
Lung
Heart
X-Rays Protons
729
363
2151
797
Suboptimal Proton Plan
AP/PA Beam Angles
Suboptimal Proton Plan
AP/PA Beam Angles
■ Protons vs. ▲ X-Rays
HEART
LUNG
Lung
Heart
X-Rays
1431
2354
Protons
410
2502
Suboptimal Proton Plan
Reoptimized: Lt Lat/PA
Suboptimal Proton Plan
Reoptimized: Lt Lat/PA
■ Protons vs. ▲ X-Rays
HEART
LUNG
Lung
Heart
X-Rays
1431
2354
Protons
410  728
2502  1171
Advancing Treatment Options:
Dose Escalation
Analysis Summary
• Advances in treatment planning techniques have
significantly reduced Heart, Lung, and Liver doses
have facilitated advanced techniques and
technologies….
• Can we deliver safe, effective dose escalation
techniques with Simultaneous Integrated Boosts?
RTOG 94-05(INT 0123)
• RTOG 94-05 (INT 0123)- High Dose (64.8 Gy) vs. Conventional
(50.4 Gy) Dose with 3D Techniques
RTOG 94-05(INT 0123)
Patterns of Failure & Treatment Related Deaths
MDACC Patterns of Failure Study
• 15/66 (23%) pts failed in GTV
• 2/66 (3%) pts failed in CTV without GTV
• 1/66 (1.5%) pts failed in PTV only
• 4/66 (6%) pts failed outside PTV as site of first failure
alone
• 2/66 (3%) failed outside PTV simultaneously with infield failure.
• No patients failed in non-targeted esophagus
• Median dose at site of failure: 5250cGy
Modified Firefly
Dose Escalation Feasibility
Modified Firefly
Dose Escalation Feasibility
Conv. w/ Bst: V30 = 65%
Esophagus
Lung
Liver
Spinal cord
Heart
X-Ray SIB Techniques
IMRT- SIB – SupaFirefly
(60, 80, 120, 140, 160, 180, 200)
VMAT- SIB – 2 Partial Arcs
(50  180, 180  50)
63Gy
VMAT- Courtesy of Montreal Turner, CMD
X-Ray SIB Techniques DVHs
■ SupaFirefly vs. ▲ VMAT
LUNG
PTV
GTV
HEART
LIVER
■ SupaFirefly-SIB vs. ▲ VMAT- SIB
**Minimal changes
with higher doses
VMAT- Courtesy of Montreal Turner, CMD
Proton SIB Techniques
Protons- IB – Lt Lat/LPO/LPO
(100, 150, 190)
63Gy
IMPT- SIB – RPO, PA, LPO
(150, 180, 210)
63Gy
Proton SIB Techniques DVHs
■ Protons vs. ▲ Protons-IB
HEART
LUNG
LIVER
■ IMPT- SIB vs. ▲ Protons-IB
Heart Lower for IIMPT
PTV
GTV
All SIB Technique Comparison
IMRT- SIB – SupaFirefly
VMAT- SIB
63Gy
Protons- IB
IMPT- SIB
63Gy
All SIB Technique DVH Comparison
■ IMRT- SIB
▲ IMPT-SIB
LUNG
VMAT- SIB
✪ Protons- IB
PTV
GTV
HEART
LIVER
Liver Mean
Heart Mean
Total Lung Mean
IMRT-SIB
769
1948
825
VMAT- SIB
704
1839
788
Protons-IB IMPT- SIB
53
48
1157
741
488
295
Summary
• New X-Ray Beam Angles have improved cardiac doses without
sacrificing other structures.
• SupaFirefly technique is more optimal than traditional
Modified Firefly.
• SupaFirefly combined strengthened correlations and created
the ability to estimate lung and heart doses.
• New esophagus class solutions have been validated and was
used for the proton comparison study.
• VMAT Superfly technique is a comparable option to SupFirefly.
• Protons are superior to x-rays for the LUNG, HEART, and LIVER
Mean doses.
Summary
• Suboptimal planning techniques or anatomy explained the
outliers for both modalities.
• Physicians should evaluate CTV margins around the heart.
• The distance from PTV to carina and % Uninvolved heart can
be used to estimate the lung and heart doses for both
modalities.
• Extensive parameter analysis indicates that protons is
superior to photons for almost all scenarios.
• Advances in techniques have facilitated dose escalation to the
GTV.
• Intensity Modulated Proton Therapy (IMPT) has significant
advantages if used with minimal motion (current).
– Robust optimization will solve motion issues
Acknowledgements
•
•
•
•
•
•
•
•
•
•
•
•
Shari Greer, CMD
Stephen Bilton, CMD
Khoi Vu, CMD
Rebecca Frame, CMD
Chris Spicer, CMD
Rolly Erice, CMD
Steven Lin, MD
James Welsh, MD
David Grosshans, MD
James Cox, MD
Steve Settle, MD
Kara Bucci, MD
•
•
•
•
•
•
•
•
•
•
Cody Crawford, CMD
Thi Nguyen, CMD
Mayank Amin, CMD
David Lege, CMD
Rola Georges, CMD
Kit Ciura, CMD
Jaques Bluett, CMD
Beverly Riley, CMD
Bill Umfleet, CMD
Cody Wages, CMD
Publication References
•
•
•
•
Isacsson, et al., Comparative Treatment Planning between Proton and X-Ray Therapy in
Esophageal Cancer (IJROBP, Vol. 41, No. 2, pp. 441-450, 1998)
Chandra, et al., Feasibility of Using Intensity Modulated Radiotherapy to Improve Lung Sparing
in Treatment Planning for Distal Esophagus Cancer (Radiotherapy and Oncology, Vol. 77, pp.
247-253, 2005)
Sugahara, et al., Clinical Results of Proton Beam Therapy for Cancer of the Esophagus (IJROBP,
Vol. 61, No. 1, pp. 76-84, 2005)
Zhang, et al., 4-D Computed Tomography-based Treatment Planning for Intensity Modulated
Radiation Therapy and Proton Therapy for Distal Esophagus Cancer (IJROBP, Vol. 72, No. 1, pp.
278-287, 2008)
•
Bucci, Palmer et al., PET/CT Fusion with Treatment Planning CT (TP CT) Shows Predominant
Pattern of Locoregional Failure in Esophageal Patients Treated with Chemoradiation (CRT) is in
GTV (ASTRO Presentation, IJROBP, Vol. 72, No. 1, Supplement: S72, 2008)
•
Welsh, et al., Intensity Modulated Proton Therapy Allows Dose Escalation and Normal Tissue
Sparing in Locally Advanced Distal Esophagus Tumors; A Dosimetric Study (IJROBP, Vol. 81, No.
5, pp. 1336-1342, 2011)
•
Turner, et al., Exploring the Feasibility of Dose Escalation Positron Tomography- Positive
Disease with Intensity Modulated Radiation Therapy and the Effects of Normal Tissue
Structures for Thoracic Malignancies (Medical Dosimetry, Vol. 36, No. 4, pp. 383-388, 2011)
Publication References
•
Welsh, et al., Failure Patterns in Patients with Esophageal Cancer Treated with definitive
Chemoradiation (Cancer, pp. 2632-2640, 2012)
•
Pottgen, et al., Radiotherapy Versus Surgery within Multimodality Protocols for Esophageal
Cancer- A Meta-analysis of the Randomized Trials (Cancer Treatment Reviews, Vol. 38, pp. 599604, 2012)
•
Welsh, et al., Esophageal Cancer Dose Escalation Using Simultaneous Integrated Boost
Technique (IJROBP, Vol. 82, No. 1, pp. 468-474, 2012)
•
Grosshans, et al., Improving Cardiac Dosimetry: Alternative Beam Arrangements for Intensity
Modulated Radiation Therapy Planning in Patients with Carcinoma of the Distal Esophagus
(Practical Radiation Oncology, 2, pp. 41-45, 2012)
•
Monjazeb, et al., The Impact of Multimodality Therapy of Distal Esophageal and
Gastroesophageal Junction Adenocarcinomas on Treatment-Related Toxicity and
Complications (Seminars in Radiation Oncology, 23: 60-73, 2013)
•
Echeverria, et al., Proton Therapy Radiation Pneumonitis Local Dose –Response in Esophagus
Cancer Patients (Radiotherapy and Oncology, Vol. 106, pp. 124-129, 2013)
Questions?
Email: mpalmer@mdanderson.org
Please email me if you would like the
Esophagus Estimator Spreadsheet.