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  • 1. IMPLEMENTING BIOLOGIC TARGET VOLUMES (BTV) IN RADIATION THERAPY PLANNING SHERIEF H. GAMIE, MD, PhD VA Palo Alto Stanford University Health Care System
  • 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 Number PET or Author Year of PET/CT for Change in GTV With PET Comments Patients PET imaging Nishioka Sparing of the parotid in 71% 2002 21 PET increased in 1/21; decreased in 1/21 et al of pts with negative PET Ciernik et 2003 12 PET/CT increased in 2/12; decreased in 4/12 al In primary tumor increased in 3/21, Primary only positive with PET Heron et decreased in 14/21 2004 21 PET/CT in 3/21; distant metastases al In nodal stations increased in 7/21 and detected with PET in 3/21. decreased in 3/21 Scarfone 2004 6 PET Increased in 5/6 et al PET/CT based GTV not Paulino et included in the high-dose 2005 40 PET/CT Decreased in 30/40 and increased in 7/40 al IMRT area in 25% patients with CT-only based GTV. Mean contralateral parotid Not reported for individual patients; mean Schwartz and laryngeal cartilage dose 2005 20 PET PET/CT based GTV not significantly et al significantly smaller with different from CT only based GTV. 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 • Patient’s whose treatment would have included Brachytherapy
  • 8. GYN BRACHYTHERAPY INTRACAVITARY INTERSTITIAL (ICRT) (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 Bowel UB BM BM GTV R 3 D3% DVH
  • 21. GYN BRACHYTHERAPY INTRACAVITARY INTERSTITIAL (ICRT) (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 Beam’s 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 http://www.bcm.edu/oto/studs/anat/neck.html VI--Anterior compartment group
  • 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 PTV’s 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