1.IMPLEMENTING BIOLOGIC TARGET VOLUMES (BTV) IN RADIATION THERAPY PLANNING SHERIEF H. GAMIE, MD, PhD VA Palo Alto Health Care System Stanford University

2. SETUP PET-CT table is modified by - Addition of a radiation-planning couch planchet - Head holder secured to planchet - Patient in treatment-planning position Patient Laser Marker System 3. Proposed Utility of 18F-FDG PET For Radiation Therapy Treatment Planning Difference in PET vs. CT defined target volumes (45 - 50% PET SUV Threshold Values) Highlight the differences in intra-observer defined target volumes Differences in treatment-planning metrics, resulting from the inclusion of PET-defined targets and exclusion of PET negative areas Incorporating functional information derived from PET to optimize dose distribution Normal tissue sparing as a consequence of excluding CT suspicious PET negative regions from GTV Escalating the overall delivered dose to a precise GTV 4. AIMING TOWARDS TUMOR DOSE ESCALATION IMPROVED TUMOR CONTROL SPARING OF NORMAL SURROUNDING CRITICAL STRUCTURES 5. FDG PET in Radiation Therapy Planning Author Year Number of Patients PET or PET/CT for PET imaging Change in GTV With PET Comments Nishioka et al 2002 21 PET increased in 1/21; decreased in 1/21 Sparing of the parotid in 71% of pts with negative PET Ciernik et al 2003 12 PET/CT increased in 2/12; decreased in 4/12 Heron et al 2004 21 PET/CT In primary tumor increased in 3/21, decreased in 14/21 In nodal stations increased in 7/21 and decreased in 3/21 Primary only positive with PET in 3/21; distant metastases detected with PET in 3/21. Scarfone et al 2004 6 PET Increased in 5/6 Paulino et al 2005 40 PET/CT Decreased in 30/40 and increased in 7/40 PET/CT based GTV not included in the high-dose IMRT area in 25% patients with CT-only based GTV. Schwartz et al 2005 20 PET Not reported for individual patients; mean PET/CT based GTV not significantly different from CT only based GTV. Mean contralateral parotid and laryngeal cartilage dose significantly smaller with PET/CT based GTV. 6. GYNECOLOGIC BRACHYTHRAPY APPLICATIONS 7. INCLUSION CRITERIA Stage IIB IIIB Cx CA With radiologic evidence of residual disease following pelvic XRT Patients whose treatment would have included Brachytherapy 8. GYN BRACHYTHERAPY INTRACAVITARY (ICRT) INTERSTITIAL (ISBT) 9. ICRT TANDEM & OVOID AND FOLEY CATHETER 10. PET/CT-compatible phantom with tandem applicators 11. TANDEM & OVOID SIMULATION (a) Axial, (b) coronal, and (c) sagittal CT images of the phantom with superimposed colorwash PET images 12. METHODS Intraoperative placement of Tandem and Ovoids 15 mCi 18F - FDG, IV 20 40 mg IV Lasix; 20 25 min. later PET/CT of pelvis 30 - 45 minutes later Loading Fletcher-suit applicator with small tubes containing 2.5 mCi 18F FDG Repeat scan of pelvis 13. DEFINITIONS Gross Tumor Volume (GTV): Tumor and surrounding LN Clinical Target Volume (CTV): GTV + Areas of subclinical disease Planning Target Volume (PTV): CTV with 2 more layers: - Internal margin which considers organ movement - Possible setup errors Biologic Target Volume (BTV) ICRU report 62. Suppl to ICRU report 50; 1999 14. ICRT Dose Prescription Point A: 2 cm above the cervical os, and 2 cm lateral to the central uterine canal Point B: 2cm cephalad from central canal and 5cm lateral (transverse axis) Paracervical triangle of Tod and Meredith (Manchester System) showing Points A and B 15. Isodose Configuration Reference Volume Dose Distribution 16. Treatment Planning Simulation Applying 45 50% PET SUV Threshold Values ICRU report 62. Suppl to ICRU report 50; 1999 Axial PET image showing applicator, rectum, and bladder with Foley catheter 17. Treatment Planning Simulation Cont. Applying 45 50% PET SUV Threshold Values Axial image with target contour, rectum, and tandem applicator. 18. (a) Reconstructed coronal PET image showing target, 65 cGy/h line, and 18 cGy/h line (b) Reconstructed sagittal PET image showing target, 65 cGy/h line, 18 cGy/h line, bladder, and rectum 19. 3D RENDERING VOLUME IMPLANT 3D target volume rendering with 65 cGy/h isodose line coverage. Also displayed are bladder, rectum, and 137Cs tubes in the tandem and ovoids 6.5-Gy isodose surface (green) for the initial implant, mid-implant, and final implant Bladder: yellow; Rectum: brown; Tumor: red 20. Image-Based Treatment Planning (CONT) PET/CT TP & DVH D3%3 BM BM Bowel UB GTV R DVH 21. GYN BRACHYTHERAPY INTRACAVITARY (ICRT) INTERSTITIAL (ISBT) 22. INTERSTITIAL BRACHYTHERAPY PET/CT TREATMENT PLANNING SYED NEBLETT TEMPLATE SYED-NEBLETT TEMPLATE 23. EXTERNAL BEAM RADIATION THERAPY 24. TREATMENT PORTALS FOR PELVIC XRT Standard Whole Pelvis PALN XRT 25. PET Positive Lesions Included as GTV Must @ A 45 50% Threshold Value Corresponds to an underlying CT abnormality A Lymph Node Have convincing intensity within a common site for disease, not explained by a benign process or artifact 26. ISODOSE DISTRIBUTION (a) Axial (b) Coronal (c) Sagittal through target (d) Coronal through midline IMRT dose distributions for PALN bed treatment plan. * Isodose lines are in 10% increments, starting with 10% (dark blue) isodose line. 27. Composite IMRT Dose Distribution Plan for PALN IMRT Technique Region 2: treated using IMRT to 59.4 Gy to GTV and 50.4 Gy to CTV with the isocenter placed as shown. Region 1: is treated (simultaneously) using conventional techniques to 50.4 Gy using the same isocenter position. 28. ACKNOWLEDGEMENT Dept. of Radiation Oncology Long Beach Memorial Medical Ctr. University of California Irvine 29. ACCURACY AND TIMING OF PET SCANNING 30. PULMONARY TREATMENT PLANNING 31. TARGET VOLUMES Gross Tumor Volume (GTV) : Tumor and surrounding LN Clinical Target Volume (CTV) : GTV + Areas of subclinical disease Planning Target Volume (PTV) : CTV with 2 more layers: - Internal margin which considers organ movement - Possible setup errors Biologic Target Volume (BTV) ICRU report 62. Suppl to ICRU report 50; 1999 32. CRITICAL STRUCTURES Beams eye View of 3D Rendering of a Four-field Conformal Treatment Plan 33. Discrepancies Avoided by PET/CT Treatment Planning Cont. Discrepancies in delineating: (a) Gross Tumor Volume (Blue) (b) Anatomic/Biologic Target Volume (Red) 34. Discrepancies avoided by PET/CT Treatment Planning Cont. FDG-PET/CT images with - Gross tumor volume (GTV) contour (Light Blue) - CT based Planning Target Volume (Green) - PET/CT based Planning Target Volume (PTV) (Red) 35. Discrepancies avoided by PET/CT Treatment Planning Cont. Discrepancies in delineating (a) Gross Tumor Volume (Light blue) (b) Anatomic Biologic Contour (Purple) 36. Geographic misses avoided by PET/CT Treatment Planning - (Left) FDG-avid subcarinal node anterior to a vertebral body, a node not detected on CT - (Right) The CT image showing the anterior and left anterior oblique beams of the plan based on CT only. * In this case, less than 70% of PTV/CT/FDG (light blue) would have received at least 90% of the prescribed dose on a plan based on CT only 37. RESPIRATORY GATING 38. Achieving Tumor Definition by Respiratory Gating About 2.0 - 2.5 cm difference with tidal breathing When the radiation beam is activated in synchronization with a patient's respiratory pattern, it targets the tumor only when it is in the optimal position and prevents the radiation beam to treat healthy tissues. Using the data from respiratory-gated PET/CT Lung-tumor immobilization using self-gated breath-holding at extremes of inspiration has been validated clinically, and is associated with improved lung-outcome predictors Caldwell et al. Int J Rad Oncol Biol Phys, 5; 2003 39. CT images of a patient at different gating phases with corresponding GTV and PTV delineated. (a) Gated at the expiration phase (b) Gated at middle phase (c) gated at inpiration phase (d) a regular spiral scan Caldwell et al. Int J Rad Oncol Biol Phys, 5; 2003 40. Coronal plane view of the PET images of a patient with the contours of GTV of CT images at different phases superimposed Caldwell et al. Int J Rad Oncol Biol Phys, 5; 2003 41. HEAD & NECK 42. HEAD AND NECK ANATOMY I--Submental and submandibular nodes II--Upper jugulodigastric group III--Middle jugular nodes draining the naso- and oropharynx, oral cavity, hypopharynx, larynx. IV--Inferior jugular nodes draining the hypopharynx, subglottic larynx, thyroid, and esophagus. V-- Posterior triangle group VI--Anterior compartment group http://www.bcm.edu/oto/studs/anat/neck.html 43. Discrepancies avoided by PET/CT Treatment Planning Cont. Computed tomography (CT) and positron emission tomography (PET) contours for nodal areas depicting anatomic and functional abnormalities ABNc = abnormal nodal region on CT ABNp = abnormal nodal region on PET 44. Discrepancies avoided by PET/CT Treatment Planning Cont. PET/CT contours for nodal areas depicting anatomic and functional abnormalities GTV = gross tumor volume on CT by CT (Light Blue) GTV = gross tumor volume on PET (Yellow) 45. Transverse cut of patient with left tonsillar tumor - Gross tumor volume (CT-GTV) (blue line) encompassed positron emission tomography (PET-GTV) (red shaded area) Sagittal cut of same patient PET-GTV (red shaded area) well- contained in CT-GTV (blue line). 46. PRELIMINARY OBSERVATIONS PET: 77% ACCURACY AND 23% INACCURACY IN GENERATING REPORDUCIBLE PTVs Volume definition depends on Threshold values, while FDG uptake varies from patient to patient PET resolution poor for lesions < 5mm SOLUTION: 4D-CT images fused with PET 47. IMPROVING PET FOR TREATMENT PLANNING HIGHER SPATIAL RESOLUTION OF PET BETTER TRACKING OF TUMOR MOTION MORE TUMOR SPECIFIC RADIOTRACERS 48. TIMING OF POST TREATMENT 18FDG - PET IMAGING 49. TIMING OF PET Muskuloskeletal Tumors: USC Experience Recommendations of a 4 6 wk interval most optimal Jadvar H, Gamie S. Musculoskeletal System. SEMINAR IN NUCLEAR MEDICINE: 06/2004; 254-260 50. TIMING OF PET cont. Goerrs et al: 26 pts with H&N tumors Treated by RT + CT PET scan 4 8 wks post treatment Assessment - visual Sensitivity: 91 % Specificity: 93 % Arch Otoloaryngel Head Neck Surg 130:2004 Nam et al: 24 patients with H&N tumors treated by RT PET scan 4 wks post treatment Assessment - SUVmax of 3.0 Accuracy: 14% Cancer 101:2004 Bujenovic et al: Recommend 6wk 3 4 mo. interval Seminars in Nuclear Medicine 3;2003 51. THANK YOU