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Stereotactic Body Radiotherapy for Hepatobiliary ... Stereotactic Body Radiotherapy for Hepatobiliary and Pancraetic Cancer Anand Mahadevan MD FRCS FRCR Chairman – Division of Radiation

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  • 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

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