High Precision Radiation Therapy for Cancers of the Upper Abdomen - PowerPoint PPT Presentation

High Precision Radiation Therapy for Cancers of the Upper Abdomen Laura A Dawson M D Laura A. Dawson, M.D. Princess Margaret Hospital, University of Toronto, Toronto Ontario Canada Toronto, Ontario, Canada

Elekta Oncology Disclosures Funding from Bayer y

Outline: RT for Upper Abdominal Ca pp Historical (dismal) role of RT Overcoming challenges Example – RT for hepatocellular carcinoma Future (promising) role of RT

Historical (Dismal) Role of RT – Why? • Challenging to select appropriate patients – Local, regional and distant occult metastases • Tumorcidal dose RT not possible to deliver – Tumor delineation – Moving organs – Many critical normal tissues • Normal tissue toxicity – Parallel fn organs – liver, kidneys – S Serial fn organs - stomach, small bowel, spinal cord… i l f t h ll b l i l d – Low whole organ RT tolerances – Partial organ tolerances not established Partial organ tolerances not established

Potential Toxicities • Hepatic injury – Radiation induced liver disease (RILD) • Anicteric ascites, hepatosplenomegaly A i t i it h t l l • Elevated liver enzymes (ALP > AST/ALT) – Non-RILD hepatic toxicity Non RILD hepatic toxicity • Elevation of transaminases • Reactivation of viral hepatitis • Liver decompensation • Liver decompensation • Biliary stricture • Renal failure • Renal failure • Stomach, duodenal, colon bleeding, obstruction, fistula, … fistula, …

How to Deliver RT Safely • Requires RT technological advances – Imaging – Breathing motion management – Planning – Image guidance I id • Understand normal tissues tolerances • Appropriate patient selection A i t ti t l ti • Improve integration of RT with other therapies

Technological Advances • Improved imaging – Tumor definition – Image fusion (CT, MRI) – Respiratory sorting – Motion measurement • Conformal, computer aided RT planning • Breathing motion management • Image guided radiotherapy (IGRT)

Imaging Imaging • Multi-modal imaging: CT MR PET • Multi-modal imaging: CT, MR, PET • Multi-phasic imaging: CT, MR – Arterial - HCC Venous - portal vein thrombus – Arterial - HCC, Venous - portal vein thrombus • Image registration and fusion

Radiation Planning • Geometric conformation of dose • Intensity modulated radiation therapy Intensity modulated radiation therapy • Automated computer optimization Volume to be irradiated Prescription dose 50% dose

Breathing Motion Management Breathing Motion Management • Breathing motion measurement (1 – 3 cm) – Fluoroscopy, cine MR, respiratory sorted CT • Motion management strategies – Increase volume irradiated – Breath hold Planning target – G ti Gating beam b volume, PTV – Track beam Free breathing Breath hold RT

Image Guided Radiation Therapy, IGRT Image Guided Radiation Therapy, IGRT • IGRT = Daily imaging immediately before or during RT delivery to position patient more accurately and precisely accurately and precisely • Changes in upper abdo Changes in upper abdo organ position day-to-day – Free breathing – Breath hold • IGRT increases likelihood of dose being delivered • IGRT increases likelihood of dose being delivered as planned – Improved tumor control & less toxicity p y

IGRT Is Not New 1951 Johns & Cunningham, Canada Co60 & xray designed 1958 Co60-xray implemented 1958 Lokkerbol, Netherlands Linac & retractable xray tube designed Li & t t bl t b d i d 1961 Linac-xray implemented Canadian stamp demonstrating image guided Cobalt from 1951

IGRT Is Not New 1951 Johns & Cunningham, Canada Co60 & xray designed 1958 Co60-xray implemented 1958 Lokkerbol, Netherlands Linac & retractable xray tube designed Li & t t bl t b d i d 1961 Linac-xray implemented Why didn’t IGRT catch on previously? - Not efficient - Less rationale, since other challenges limited RT doses Canadian stamp demonstrating image guided Cobalt from 1951

IGRT 2008 MV EPID MV EPID kV Fluoroscopy + markers Ultrasound kV CT kV Fl k Ult d kV CT MV cone MV CT MV CT kV Cone-beam CT beam CT beam CT kV Cone beam CT MR Integration, … Dawson, Jaffray, JCO, 2007

4D (Temporal) IGRT R Respiratory Sorted kV i t S t d kV kV Fl kV Fluoroscopy Cone Beam CT Free Breathing Free Breathing CBCT CBCT CBCT CBCT • Improved accuracy • Improved precision Planned doses = delivered doses Exhale Exhale Inhale Inhale

Understanding Normal Tissue RT Tolerances Liver Toxicity Liver Toxicity 1.0 Liver volume Veff Veff irradiated irradiated 0.8 0 8 3/3 icity 2/3 0.6 1/3 1/3 of Toxi 0.4 Risk 0.2 0.0 0 20 40 60 80 100 120 Dose (G ) 1 5 G bid Dose (Gy), 1.5 Gy bid Dose (Gy) Dawson LA et al. IJROBP 2002

Understanding Normal Tissue RT Tolerances • Collaboration and consensus Michigan, hyper# Colorado, 3 # Liver DVHs with no liver toxicity Pan, Kavanaugh, Dawson et al, QUANTEC IJROBP, 2008

HCC Radiotherapy Planning CT at simulation kV cone beam CT at treatment treatment

Hepatocellular Carcinoma Hepatocellular Carcinoma • HCC - third cause of global cancer mortality • Increasing in N America w increasing Hepatitis C g g p – 18 000 cases / year US in 2006 • Local therapy can cure – Resection 50% 5 yr survival – Transplant 70% 5 year survival • Predominantly hepatic recurrence • < 15% of patients have resection/ transplant • Overall 5 year survival < 10% WHO and American Cancer Statistics 2003-2006

Carbon Ions for HCC: Japan n=69 • Phase II Study HCC: 52.8 Gy/ 4 # / 4 days Ph II St d HCC 52 8 G / 4 # / 4 d • Med follow-up of 5.4 years Local control 94% LOCAL CONTROL 94% 1 < 3 cm 100% 3-5 cm 90% .8 < = 5 cm (n=53) 5-10 cm 93% .6 > 5 cm (n=16) >10 cm >10 cm 100% 100% .4 .2 G Gr. 3 toxicity n=3 3 t i it 3 0 0 1 2 3 4 5 6 Time (years) (y ) Courtesy of H Tsujii, Japan Kato H, Tsujii H, et al: ICLA 06 2007, Barcelona; Tsuji et al, New Journal of Physics 10, 2008

Carbon Ions for HCC: Japan n=69 • Phase II Study HCC: 52.8 Gy/ 4 # / 4 days Ph II St d HCC 52 8 G / 4 # / 4 d • Med follow-up of 5.4 years Survival 3yr 5yr OVERALL SURVIVAL 1 < 5 cm 5 cm 62% 36% 62% 36% .8 8 > 5 cm 64% 17% .6 < = 5 cm .4 4 .2 > 5 cm 0 0 0 1 2 3 4 5 6 Time (years) (y ) Courtesy of H Tsujii, Japan Kato H, Tsujii H, et al: ICLA 06 2007, Barcelona; Tsuji et al, New Journal of Physics 10, 2008

PMH Phase I Study • 41 patients – 31 HCC (52% portal vein thrombosis) – 10 intrahepatic cholangiocarcinoma (IHC) • Median volume 172 cc ( 9 – 1913) • Individualized therapy – Breath hold, IGRT, SBRT • Median dose 36 Gy (24 – 54 Gy), 6 fractions M di d 36 G (24 54 G ) 6 f ti • No radiation induced liver disease (RILD) Tse, JCO, 2008

Toxicity: PMH • Grade 3 nausea/vomiting G d 3 / iti 1 1 • Grade 3 platelets 1 • Radiation Liver Disease, RILD R di ti Li Di RILD 0 0 • Grade 3 liver enzymes 10 (8 preexisting) • Decline in Child score Decline in Child score 7 (5 with PD) 7 (5 with PD) • 1 small bowel obstruction: 24 mo post RT p • 1 duodenal perforation: 15 mo post RT Pre RT Pre RT 15 mo post RT 15 mo post RT Tse, JCO, 2008

Response: PMH 45 y o man – Hepatocellular carcinoma 36 Gy/ 6 # 45 y.o. man Hepatocellular carcinoma, 36 Gy/ 6 # Baseline 9 months

Overall Survival: PMH Med. Surv 95% CI 1.0 Cholangioca 15.0 mo 6.5 - 29.0 HCC 11.7 mo 9.2 - 21.6 0.8 urvival ability of Su Survival 0.6 S Proba 0.4 0 2 0.2 HCC HCC CH Cholangiocarcinoma 0.0 0 5 10 15 20 25 30 35 Months Months Tse, JCO, 2008

Future (Promising) Role of RT • Biologic & image based improved patient selection – Micro-metastases identification – Treatment predictive biologic signatures Treatment predictive biologic signatures • Tumorcidal doses of RT to high risk targets only – Biologic highest risk tumor delineation – Individualized doses – – Multiple strategies to control organ motion Multiple strategies to control organ motion • Avoidance of normal tissue toxicity • Improved integration of RT with other therapies • I Improved outcomes for upper abdominal cancers d t f bd i l

Acknowledgements PMH GI site group, HCC tumor board, referring physicians and patients PMH GI it HCC t b d f i h i i d ti t High Precision Liver RT Image Guidance Mark Lee David Jaffray Maria Hawkins Doug Moseley Regina Tse Mike Sharpe Robert Case Kristy Brock Cynthia Eccles Cynthia Eccles Tom Purdie Tim Craig Patricia Lindsay John Kim Rob Dinniwell Rob Dinniwell NKI / AvL Amsterdam Jim Brierley Jan Jakob Sonke Jolie Ringash Marcel van Herk Rebecca Ringash g Bernard Cummings Jean-Pierre Bissonnette ASCO CDA (Dawson) Kristy Brock NCIC Gina Lockwood Canadian Cancer Society Andrea Marshall Elekta