Stereotactic Body Radiotherapy for
Hepatobiliary and Pancraetic Cancer
Anand Mahadevan MD FRCS FRCR
Chairman– Division of Radiation Oncology
Geisinger Health
Geisinger Commonwealth School of Medicine
Disclosure & Disclaimer
• An honorarium is provided by Accuray for this
presentation
• The views expressed in this presentation are
those of the presenter and do not necessarily
reflect the views or policies of Accuray
Incorporated or its subsidiaries. No official
endorsement by Accuray Incorporated or any
of its subsidiaries of any vendors, products or
services contained in this presentation is
intended or is inferred.
Objectives
• Non Surgical Ablative treatment for Liver
and Pancreas tumors
• Techniques and Challenges of SBRT
(Stereotactic Body Radiotherapy)
• SBRT as Primary Treatment
• SBRT for Recurrence and Metastasis
• Future Directions
Fundamental Principles
• Surgery is the primary curative treatment
for Cancer
• Systemic therapy is essential component
in the multimodality management of
cancer
• Radiation therapy is more about protecting
normal tissue than treating cancer
Radiosurgical Ablation
• When not surgical candidates
• Patient preference
• Surgical recovery delays are not ideal
• Systemic therapy (eg. Anti angiogenic
therapy) interferes with surgical recovery
Radiosurgical Ablation
• When not surgical candidates
• Patient preference
• Surgical recovery delays are not ideal
• Systemic therapy (eg. Anti angiogenic
therapy) interferes with surgical recovery
Conventional Stereotactic Radiosurgery
Systems
• Limitations:
– Primarily used for intracranial targets
– Limited scope for tracking movement
– Need rigid Immobilization of target
• Invasive frames
• Discomfort
Moving Targets
• Unpredictable Fixed movements
– Patient Movement
– Internal Organ Movement
– Bowel/Bladder filling/emptying
• Respiratory Movement
Unpredictable Movements
• Conventional
Radiation
Respiratory Movements
Conventional Radiation - PTV
Respiratory Movements - SBRT
• 4D CT and ITV
• Dampening
– Active Breathing Control
• Gating
• Tracking
Respiratory Movements
Conventional Radiation- 4D Imaging
Dampening
Active Breathing Control
Gating
Beam Off
Beam OffBeam On
Beam On
Treatment Field
2.
4.
Gating
Treatment beam is turned on and off
as tumor enters and exits a static
treatment field
= Over-treated healthy tissue
External position sensor
Internal fiducial
Tracking
Modern SBRT Systems
• Allow continuous tracking of the target
– Fiducial based targeting
• Respiratory motion tracking systems
• Examples
– Novalis
– Trilogy
– True Beam
– CyberKnife® System
Fiducial Markers
• Gold Seeds
– 5.0mm x 0.8 mm
– Preloaded in 18-19G
needle
– Free seeds can be
placed at surgery or
laparoscopically
– Easy to place
– 4-7 days from insertion
to scan
Intraoperative
CT Guided
Ultrasound Guided
Endoscopic Ultrasound
Endoscopic Ultrasound
Defining Accuracy
Tumor motion
Patient setup
Patient
movement
Imaging (CT, MRI, etc.)
Treatment planning
Beam delivery
Total
Clinical
Accuracy
Modern SBRT Accuracy
• Mechanical Accuracy = 0.2 mm
• Total Clinical Accuracy
–Stationary lesions: 0.95 mm
–Moving lesions: 1.5 mm
Total
Clinical
Accuracy
Total Clinical Accuracy
Techniques
GANTRY LINAC PARTICLE BEAM ROBOTIC
Pancreas Cancer
Perspective
SBRT in Pancreas Cancer
• Clinical scenarios
– Resected Pancreas cancer
– Locally advanced
– Local recurrence
– Oligometastatic Pancreas Cancer
Locally Advanced Pancreas Cancer
Classic Trials: RT vs. ChemoRT and
Chemo vs. ChemoRT
Gemcitabine Based Chemotherapy
Trials
Modern Chemo-radiation Trials
Trial Treatment No of Pts Med OS
RTOG 9812 50.4Gy+Taxol 122 11.3m
RTOG 0020 50.4Gy+Taxol/Gem 154 11.7m
RTOG0411 50.4Gy+Xeloda/Avastin 94 11.9m
FFCD-SSRO 60Gy+5FU/Cisplat 59 8.6m
ECOG 4201 50.4Gy+Gem 34 11.0m
FFCD-SFRO
• Would Better systemic therapy made a difference – Gem Abraxane,
FOLFIRINOX
• Would earlier Radiation help?
• Shorter radiation (SBRT) without interrupting systemic therapy?
SBRT
• Stanford Phase I
• Stanford EBRT+ Boost
• Stanford Gem SBRT
• Danish Phase II
• UPMC
• Sinai, Baltimore
• BIDMC Upfront SBRT
• BIDMC Gem SBRT
• Tampa
Tolerance Based Approach
Stereotactic body radiotherapy and gemcitabine for
locally advanced pancreatic cancer
Mahadevan A1, Jain S, Goldstein M, Miksad R, Pleskow D, Sawhney M, Brennan D, Callery
M, Vollmer C.
Department of Radiation Oncology, Beth Israel Deaconess Medical Center and Harvard
Medical School, Boston, MA
Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):735-42
Toxicity
• Acute(3m)
– 3(8%) Grade 3 Toxicity
• 2 GI Bleed (one associated with Tumor
Progression)
• 1 Gastric outlet Obstruction (with tumor
progression)
Toxicity
Borderline Resectable
Modern Single Institution Studies
Trial Treatment No. of
Pts
Med OS
MD Anderson 50.4Gy+Xeloda/Avastin 47 14.4m
UCSF 50.4Gy+Avastin 17 17.0m
MSKCC 50.4Gy+Gem/Erlotinib 20 18.7m
U of Michigan 50-60Gy+Gem 27 23.1m
MD Anderson 50.4Gy+Gem/Cetuximab 69 18.8m
Total Neoadjuvant Therapy
Total Neoadjuvant
Therapy
(TNT)
Chemo
SBRT
Surgery
Neoadjuvant Chemo
and Surgery (NeoC-S)
Chemo
Surgery
Neoadjuvant Chemo and
SBRT (NeoC-SBRT)
Chemo
SBRT
Results – Overall Survival
Treatment
Group
Number Median Overall
Survival (Months)
TNT 25 36.5
NeoC-SBRT 49 19.3
NeoC-
Surgery
6 22.2
p=0.03
p=0.98
p=0.1
7
Results – Local Regional Recurrence
FOLFIRINOX SBRT
FOLFIRINOX SBRT
J Clin Oncol. 2016 Aug 1;34(22):2654-68
Locally Advanced, Unresectable Pancreatic Cancer:
American Society of Clinical Oncology Clinical
Practice Guideline
Balaban EP1, Mangu PB1, Khorana AA1, Shah MA1, Mukherjee S1, Crane CH1, Javle
MM1, Eads JR1, Allen P1, Ko AH1, Engebretson A1, Herman JM1, Strickler JH1, Benson AB
3rd1, Urba S1, Yee NS1.
Resected Pancreas Cancer
R1 Resection
Resected Pancreas Cancer
ChemoRT vs. Observation
• “ChemoRT Improves Overall Survival vs
Observation”
– GITSIG Study
• Significant Increase in Med Survival (20m vs 11m)
• Significant increase in 5-yr Survival (18% vs 8%)
ESPAC 4
• Adjuvant Gem vs GemCAP
• Primary endpoint OS
• 2008-2014, 730 pts, Med age 65yrs
• 60%R1, 80% N=, 40% Poorly differentiated
• Med OS: 28m v 25.5m p=0.032
• 5% yr Survival: 29% vs 16 %
• No diff in Grade ¾ Toxicity.
• Is this the end of adjuvant Radiation therapy for
resected Pancreas Cancer?
Local Control after
Whipple+ChemoRT
+ve margin (%) Local Failure (%)
GITSG 0 47
EORTC 19 51
ESPAC 28 63
CONKO 19 37
RTOG 34 25
Impact of resection status on pattern of failure and
survival after pancreaticoduodenectomy for pancreatic
adenocarcinoma
Raut CP, Tseng JF, Sun CC, Wang H, Wolff RA, Crane CH, Hwang R, Vauthey JN, Abdalla EK,
Lee JE, Pisters PW, Evans DB
Ann Surg. 2007
Jul;246(1):52-60
Post OP R1 Resection
• Fiducials placed at surgery
• One planning CT with oral and IV contrast
• 1000cGy to +ve margins 3-4 weeks post
OP
• 5040cGy 5-6 field IMRT6-8 weeks postOP
• Concurrent Xeloda
• Adjuvant Gemcitabine
Overall Survival – Median 22m
Survival By Margin
• R1: 62pts (40%)
• R0: 95 Pts (60%)
• Median Survival
– 19.5m vs. 27m
• 2yr Survival
– 36m vs.51m
• 5yr Survival
– 17% vs.28%
R1(Pos. Margin)- Survival by Treatment
Negative Margins vs. Positive
Margins + CK Boost
• Median Survival
– 27m vs. 29.5m
• 2yr Survival
– 51.3% vs.50.4%
• 4yr Survival
– 37% vs. 42%
• p=0.7881
Local Control
P=0.0002
