27 th Annual Management of Colon and Rectal Diseases 2.23.2019 Radiation Therapy: From Fallacy to Science Hadi Zahra, MD, DABR Radiation Oncologist CHI Health Henry Lynch Cancer Center Assistant Clinical Professor Creighton University School of Medicine Adjunct Clinical Assistant Professor Radiation Oncology Department University of Nebraska Medical Center Disclosures None 1
Learning Objectives Identify current indications for radiotherapy in colorectal malignancies Gain an understanding of the evolution of radiation therapy Learn about latest advances in treatment design and delivery Recognize techniques for reducing RTinduced toxicities Incidence of Cancer In 2018, approx 1.7 million people will be diagnosed with cancer in the U.S. Estimated New Cancer Cases for 2018 https://seer.cancer.gov/statfacts 2
Incidence of Cancer Deaths Estimated New Cancer Cases and Cancer Deaths for 2018 https://seer.cancer.gov/statfacts Multidisciplinary Approach Colorectal Surgery Medical Oncology Radiation Oncology Evidence Based national guidelines (ex. NCCN, ASCO, ASTRO, ASCRS) Multidisciplinary tumor board conferences 3
History of Radiation Therapy 1895 Wilhelm Roentgen discovers X rays 1896 Becquerel discovers natural radioactive decay 1952 1 st LINAC used for treatment 1968 Leksell invents stereotactic radiosurgery 1980 Proton therapy in U.S. 1988 Development of IMRT 2000 s Image guided RT WILHELM ROENTGEN 1845 1923 MARIE CURIE 1867 1934 The Evolution of Radiation Therapy 1950 s 1970 s 1980 s 1990 s 2000 s The First LINAC Computerized 3D CT Treatment Planning Standard Collimator Cerrobend Blocking Electron Blocking Multileaf Collimator Dynamic MLC and IMRT Functional Imaging High resolution IMRT Linac reduced complications compared to Co- 60 Blocks used to reduce dose to normal tissues MLC leads to 3D conformal therapy and allows dose escalation Computerized IMRT allows further dose escalation and reduced normal tissue doses IMRT evolves along with introduction of new imaging technologies 4
Historical Treatment Strategy Initially treated by surgery alone High curability with T1 T2 node negative cancers T3 T4 or N+ tumors showed high LR rates The addition of postop RT improved LRC No change in OS The addition of chemo to postop RT improved LRC and OS Postop RT Prolongs DFS 227 pts from 1975 1980 (T3 T4 or node +) underwent surgical resection, randomized to: Surgery alone: TR 55% LRR 24% Postop RT: TR 48% LRR 20% Postop chemo: TR 46% LRR 27% Postop chemo RT: TR 33% LRR 11% 8 yr FU: Postop chemo RT improved OS compared to surgery alone GITSG GI 7175. N Engl J Med, 1985 Douglass HO et al. N Engl J Med, 1986 5
Postop RT vs Postop Chemo RT 204 pts from 1980 1986 (T3 T4 or node +) underwent surgical resection, randomized to: Postop RT: TR 63% LRR 25% Postop chemo RT: TR 41% LRR 13% 5 yr OS Postop RT: 40% Postop chemo RT: 55% Krook JE et al. NCCTG 79 47 51. N Engl J Med, 1991 Preop vs Postop Chemo RT 823 pts from 1995 2002 (T3 T4 or node +) randomized to: Preop chemo RT: LR 6% Postop chemo RT: LR 13% (SS) 5 yr OS Preop chemo RT: 76% Postop chemo RT: 74% (NS) Toxicity: Fewer acute (27% vs 40%) and late toxicities (14% vs 24%) in preop arm Increased rate of sphincter preserving surgery (39% vs 19%) 10 yr LR results: Preop chemo RT: 7.1% Postop chemo RT: 10.1% (p = 0.048) Sauer, et al. German CAO/ARO/AIO 94. N Engl J Med, 2004 Sauer, et al. German CAO/ARO/AIO 94. JCO, 2012 6
Overview of Current Treatment Strategy Preop T1 T2N0 Primary surgery If final path reveals T3 or N+ adjuvant chemo RT Preop T3 T4N0 or any N+ Preop chemo RT, followed by surgery and adjuvant chemo Debate remains between optimal fractionation (short vs long course) How Does Radiation Work? Invisible X rays damage DNA material of cells within the area being targeted Once a tumor cell gets damaged, it looses ability to survive/multiply 7
2D (outdated) Esophageal CA RT Treatment Field Types of Conventional RT Portal Fields T3 or N+ T4 cases Following APR 8
Current RT Treatment Design 1) Patient positioning 2) Placement of skin markers 3) Acquisition of CT images Optimal Positioning Techniques 9
CT Simulation for RT Planning MRI Fusion 10
PET CT Fusion Deformable Registrations 3D Planning: Defining Target Volumes 11
Gross Tumor Volume (GTV) Clinical Target Volume (CTV) 12
Clinical Target Volume (CTV) Clinical Target Volume (CTV) 13
Clinical Target Volume (CTV) Clinical Target Volume (CTV) 14
Boost Target Volume (CTV boost) Normal Tissues Contoured Male Pelvis RTOG Contouring Atlas 15
Normal Tissues Contoured Female Pelvis RTOG Contouring Atlas Prescribed Dose and Normal Tissue Constraints Typical PTV dose = 50.4 Gy in 28 fractions over 5.5 weeks with radiosensitizing 5 FU or capecitabine Small bowel: No volume should receive 50 Gy No more than 65 cc > 45 Gy No more than 100 cc > 40 Gy No more than 180 cc > 35 Gy Femoral heads: No more than 40% of volume > 40Gy No volume greater than 50 Gy Bladder: No more than 40% above 40 Gy No volume should receive 50 Gy RTOG 0822 protocol information 16
Dose Volume Histogram (DVH) PTV boost Bladder Small bowel Femoral heads Acute Side Effects: Pelvic RT General Fatigue Bone marrow suppression GI Rectal urgency, diarrhea Anorectal tenderness/pain Nausea, cramping GU Dysuria Increased urinary frequency 17
Acute Side Effects: Pelvic RT Dermatologic Transient erythema, pruritus Hyperpigmentation Skin dryness or desquamation Regionalized body hair loss Reproductive Azoospermia Ovarian dysfunction Vaginal dryness Late Term Effects: Pelvic RT GI Chronic rectal urgency, diarrhea Anastomotic stricturing Small bowel obstruction Rectal bleeding GU Bladder wall dysfunction RT induced cystitis Musculoskeletal Femoral head/neck injury 18
Late Term Effects: Pelvic RT Dermatologic Telangiectasias Pigmentation changes Skin thinning Soft tissue fibrosis Lymphatic Lower extremity lymphedema Reproductive Permanent sterility Vaginal dryness, vaginal canal stenosis RT induced Malignancies Beyond 3D Conformal: IMRT I Intensity M Modulated R Radiation T Therapy Modulation of RT beam to deliver highly conformal dose distributions to target(s) while minimizing doses to surrounding normal tissues 19
Implementation of IMRT Originated at Baylor College of Medicine Houston, TX 1992 1 st patient treated for Prostate ca IMRT vs 3D: Dose Distributions 20
Radiation TX Schedules Pre op: 50.4 Gy in 28 fx Or short course 25 Gy in 5 fx Post op: 54 Gy in 30 fractions 5 days per week Days off in between allow normal tissue cells to heal from radiation injury Average beam on time: VMAT IMRT 3D 2 min 5 min Varian Trilogy at CUMC Bergan Mercy 21
Computer-controlled Multileaf Collimator (MLC) Treatment Console MLC Monitor 22
LINAC TX: Rectal Ca Patient Setup IGRT Cone Beam CT (CBCT) 23
Volume Modulated Arc Therapy (VMAT): Rotational IMRT Volumetric Modulated ARC Therapy (VMAT) Advanced form of IMRT 24
Stereotactic Ablative Radiotherapy (SABR): Oligometastatic Disease Addressing Tumor Motion: 4D Gating 25
Stereotactic Radiosurgery (SRS) 26
Proton Therapy Uses protons rather than photons Minimal entrance dose and lack of exit dose compared to photons 27
Protons Versus IMRT Advantage of Protons Bragg Peak 28
Proton Therapy Centers in U.S. www.proton therapy.org Intraoperative RT (IORT) Mobile self shielded electron LINAC Energies: 6 12 MEV Dose Rate: 10 Gy/Min Applicator sizes: 3 10 cm Ideal candidates: T4 primaries with risk of R1/R2 resections Locally recurrent disease 29
Summary Points Most rectal ca pts with T3 T4 or LN+ tumors should receive chemo RT Preop chemo RT is the SOC due to higher LRC, increased sphincter preservation, and decreased toxicity Advances in imaging and RT delivery systems have enhanced ability to better protect normal tissues Future directions regarding selective use of RT, nonoperative management, and integration of immunologics will likely further enhance the therapeutic ratio Thank You 30