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1 Understanding Radiation Therapy and its Role in Treating Patients with Pancreatic Cancer Presented by Pancreatic Cancer Action Network August 18, 2014 If you experience technical difficulty during the presentation: Contact WebEx Technical Support directly at: US Toll Free: Toll Only: or Submit a question to the Event Producer via the Q&A Panel For international support numbers visit: Questions may be submitted anytime during the presentation. To submit questions: Type your questions in the text entry box Click the Send Button Please direct your questions to All Panelists in the drop down 1

2 Understanding Radiation Therapy and its Role in Treating Patients with Pancreatic Cancer Christopher Crane, MD Associate Professor Department of Radiation Oncology Outline How does radiation work? How is radiation given? 2

3 How does radiation work? Types of Radiation Non-ionizing Do not produce ions in matter Microwaves, ultrasound, radio waves Ionizing Eject orbital electrons and produce ions Directly ionizing Charged particles (electrons, protons, alpha particles) Indirectly ionizing Uncharged particles (neutrons, gamma rays, x-rays) 3

4 Effects of Ionizing Radiation Radiation Ionizations Free Radicals DNA Damage Biologic Effects Radiation and DNA Free radicals produce DNA strand breaks Single strand breaks are repaired easily Double strand breaks difficult to repair Most important lesion produced by radiation Can lead to cell death, mutation or carcinogenesis Affects tumor and normal tissue 4

5 Factors Affecting Biologic Effects of Radiation Fraction Size A lower total dose in large fractions can have the same biologic effect as a higher total dose in small fractions Single Fractions vs. Multiple Fractions/ Day Randomized trials in head and neck cancers Dose Rate High Dose Rate vs. Low Dose Rate brachytherapy Overall Treatment Time Head and neck cancers, anal cancer Factors Affecting Biologic Effects of Radiation Type of tissue Bone marrow cells most sensitive Early responding vs. late responding tissues Oxygenation Enhances effects of radiation Radiosensitization Chemotherapy agents: 5-FU, cisplatin Biologic agents: Cetuximab Multiple randomized trials 5

6 How is radiation given? Goals Maximize damage to tumor cells Minimize damage to normal tissues 6

7 Simulation: Positioning and Immobilization Simulation: Imaging 7

8 Treatment Planning Contour radiation targets, other organs Design beam arrangement Number, size, orientation Design blocks to protect normal structures Cerrobend, Multi-leaf collimators (MLC) Treatment Machines Cobalt-60 Linear Accelerators Photons Electrons 8

9 Localized Pancreatic Cancer: Role of XRT vs Arterial Involvement T 1-3 T4 borderline T4 Surgery helpful? Yes Maybe No XRT helpful? Maybe HELPS the MOST Yes MS Borderline Resectable Healthy 52yo man, no past medical history. Painless jaundice Nov with weight loss. CA19-9: 168 T4 borderline 9

10 Borderline Resectable Pancreatic Cancer MDACC Results for All Patients Not resected (MS = 13 mos.) Finished NAJ Tx and Resected (MS = 41 mos.) Time from Initial Dx (months) Survival of all borderline patients (156), resected (40%) v. not resected (60%) Katz, et al 2008 Case Study: Pancreatic Ca 66 yo man, borderline resectable pancreatic ca Plan: Pre-op chemo-rt Surgery CT simulation Supine, arms up, body cradle Contouring Tumor, LN, kidneys, liver, spinal cord 4-field technique 10

11 Fields AP LAT Dosimetric Plan 11

12 DVH Tumor/LN Right Kidney Liver Spinal Cord Left Kidney Case#2: 74 y.o. male, NED at 7 years (72 Gy, no surgery or maintenance chemotherapy) Initial Scan 50months 12

13 13

14 IMRT Intensity Modulated Radiation Therapy Computer aided optimization Reverse Planning Multiple beams, Multi-Leaf Collimation Highly conformal RT to targets Minimizes dose to normal tissues Dose painting of targets IMRT MLC Shape Cumulative Dose Courtesy of Dr. Boyer 14

15 IMRT IMRT Beams 15

16 Why use IMRT? Reduce toxicity Anal cancer - genitalia Gastric and GE junction Ca heart and liver Rectal cancer? bowel? Increase dose tumor control Selected pancreatic cancers Liver cancers MDACC Dose Escalation LAPC (BED Gy) N=30 Median 31mo 3 yr OS 34% (95% CI 13 to 49mo) Crane, unpublished 16

17 67 yo WM with Neck/Body LAPC 63 Gy in 28 fx IGRT - Monitoring Stomach Position IMRT PancCa 63Gy - 28fx - 55Gy 17

18 What is steriotactic body radiotherapy (SBRT)? Increased precision Organ motion control Higher doses per treatment Ablates surrounding tissue Great for CNS, lung, liver tumors Not for tumors near the GI tract cyberknife SBRT Blue ITV Colon Red PTV Yellow 25Gy Isodose line Liver Duo Kidney Small Bowel Kidney Green Isodose line Lt. Blue 12.5 Gy Isodose line 1. An ITV using a 4DCT, a CT-PET and end expiration CT scans 2. Gold fiducials were placed and respiratory gating with 9 Field IMRT Schellenberg, ASTRO,

19 Fractionated SBRT (All retrospective) Study N stages Regimen MS >G2 Late GI tox Mahadevan, III 8-12Gy x mo 5% crude G3 Polistna, Italy III Gem, 10 x mo 0% Didolkar, mixed Gy /4 fx Rwigema, mixed 20-24Gy /1fx 8.7mo 22.3% crude G2/3 10.3mo 2% G2 Phase II Trial: SBRT / LAPC JHU/Stanford/MSKCC (33Gy/1 week) Overall survival: 13.9 Months (95% CI months) Herman, pastr0,

20 MDACC Dose Escalation LAPC (BED Gy) N=30 Median 31mo 3 yr OS 34% (95% CI 13 to 49mo) OS: 13.9 mos (95% CI mos) RTOG 1201: SMAD4 Directed Treatment Approved Trial: Stratification Variable LAPC Stratify: SMAD4 Status Ca 19-9 < 90 Gem x 3 mo Gem x 3 mo FOLFIRINOX x 3 mo IMRT 63Gy 50.4 Gy 3D CRT 50.4 Gy Eligibility: Locally Advanced Unresectable No prior Chemotherapy or RT, PS

21 RTOG 1201 modification LAPC Gem/Abraxane x 3 mo IMRT 63Gy Stratify: SMAD4 Status Ca 19-9 < Gy 3D CRT *Maintenance chemo until progression in all arms Eligibility: Locally Advanced Unresectable No prior Chemotherapy or RT, PS 0-1 Complications from RT Complications mainly occur locally, in organs that are in the RT field Some complications occur during treatment or within days or weeks Some complications appear after months or years 21

22 Examples of Complications Fatigue Skin: Erythema, desquamation CNS: Somnolence, cognitive loss Head & Neck: Mucositis, xerostomia Lung: Pneumonitis Upper GI: Nausea, esophagitis Lower GI: Diarrhea, proctitis GU: Cystitis, urethritis Hem: Myelosuppression Cardiovascular toxicity Second malignancies Indications for Urgent RT Spinal cord compression Brain metastasis with symptoms SVC syndrome with progression Uncontrolled bleeding Peripheral nerves with symptoms 22

23 Thank you for your participation! Pancreatic Cancer Action Network If you have questions, please contact our Patient and Liaison Services (PALS) programat (877) or 23