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IMPLEMENTING BIOLOGIC TARGET
VOLUMES (BTV) IN RADIATION
THERAPY PLANNING
SHERIEF H. GAMIE, MD, PhD
VA Palo Alto
Health Car...
SETUP
• PET-CT table is modified by
- Addition of a radiation-planning couch
planchet
- Head holder secured to planchet
- ...
Proposed Utility of 18F-FDG PET For Radiation
Therapy Treatment Planning
• Difference in PET vs. CT defined target volumes...
AIMING TOWARDS……
• TUMOR DOSE ESCALATION
• IMPROVED TUMOR CONTROL
• SPARING OF NORMAL SURROUNDING
CRITICAL STRUCTURES
FDG – PET in Radiation Therapy Planning
Author Year
Number
of
Patients
PET or
PET/CT for
PET imaging
Change in GTV With PE...
GYNECOLOGIC
BRACHYTHRAPY
APPLICATIONS
INCLUSION CRITERIA
• Stage IIB – IIIB Cx CA
• With radiologic evidence of residual disease following
pelvic XRT
• Patient’...
GYN
BRACHYTHERAPY
INTRACAVITARY
(ICRT)
INTERSTITIAL
(ISBT)
ICRT
TANDEM & OVOID AND FOLEY CATHETER
PET/CT-compatible phantom with tandem applicators
TANDEM & OVOID SIMULATION
(a) Axial, (b) coronal, and (c) sagittal CT images of the phantom with superimposed
colorwash PE...
METHODS
• Intraoperative placement of Tandem and Ovoids
• 15 mCi 18F - FDG, IV
• 20 – 40 mg IV Lasix; 20 – 25 min. later
•...
DEFINITIONS
• Gross Tumor Volume (GTV): Tumor and surrounding LN
• Clinical Target Volume (CTV): GTV + Areas of subclinica...
ICRT – Dose Prescription
Point A: 2 cm above the cervical os,
and 2 cm lateral to the central
uterine canal
Point B: 2cm c...
Isodose Configuration
Reference Volume Dose Distribution
Treatment Planning Simulation
Applying 45 – 50% PET SUV Threshold Values
ICRU report 62. Suppl to ICRU report 50; 1999
Axi...
Treatment Planning Simulation Cont.
Applying 45 – 50% PET SUV Threshold Values
Axial image with target contour, rectum, an...
(a) Reconstructed coronal PET image showing
target, 65 cGy/h line, and 18 cGy/h line
(b) Reconstructed sagittal PET image ...
3D RENDERING
VOLUME IMPLANT
3D target volume rendering with 65 cGy/h isodose line coverage.
Also displayed are bladder, re...
Image-Based Treatment Planning (CONT)
PET/CT TP & DVH
D3%3
BM BM
Bowel
UB
GTV
R
DVH
GYN
BRACHYTHERAPY
INTRACAVITARY
(ICRT)
INTERSTITIAL
(ISBT)
INTERSTITIAL BRACHYTHERAPY PET/CT
TREATMENT PLANNING
SYED – NEBLETT TEMPLATE®
SYED-NEBLETT TEMPLATE®
EXTERNAL BEAM
RADIATION THERAPY
TREATMENT PORTALS FOR PELVIC XRT
Standard Whole Pelvis PALN XRT
PET Positive Lesions Included as GTV
Must @ A 45 – 50% Threshold Value
• Corresponds to an underlying CT
abnormality
• A L...
ISODOSE DISTRIBUTION
(a) Axial
(b) Coronal
(c) Sagittal through target
(d) Coronal through midline
IMRT dose distributions...
Composite IMRT Dose Distribution Plan for PALN
IMRT Technique
• Region 2: treated using IMRT to 59.4 Gy to GTV and 50.4 Gy...
ACKNOWLEDGEMENT
Dept. of Radiation Oncology
Long Beach Memorial Medical Ctr.
University of California Irvine
ACCURACY AND TIMING
OF PET SCANNING
PULMONARY TREATMENT
PLANNING
TARGET VOLUMES
• Gross Tumor Volume (GTV) : Tumor and surrounding LN
• Clinical Target Volume (CTV) : GTV + Areas of subcl...
CRITICAL STRUCTURES
Beam’s eye View of 3D Rendering of a
Four-field Conformal Treatment Plan
Discrepancies Avoided by PET/CT Treatment Planning Cont.
Discrepancies in delineating:
(a) Gross Tumor Volume (Blue)
(b) A...
Discrepancies avoided by PET/CT Treatment Planning Cont.
FDG-PET/CT images with
- Gross tumor volume (GTV) contour (Light ...
Discrepancies avoided by PET/CT Treatment Planning Cont.
Discrepancies in delineating
(a) Gross Tumor Volume
(Light blue)
...
Geographic misses avoided by PET/CT
Treatment Planning
- (Left) FDG-avid subcarinal node anterior to a vertebral body, a n...
RESPIRATORY GATING
Achieving Tumor Definition by Respiratory Gating
About 2.0 - 2.5 cm difference with tidal breathing
• When the radiation b...
CT images of a patient at different gating
phases with corresponding GTV and PTV
delineated.
• (a) Gated at the expiration...
Coronal plane view of the PET images of a patient with the contours of GTV of
CT images at different phases superimposed
C...
HEAD & NECK
HEAD AND NECK ANATOMY
I--Submental and submandibular nodes
II--Upper jugulodigastric group
III--Middle jugular nodes drain...
Discrepancies avoided by PET/CT Treatment Planning Cont.
Computed tomography (CT) and positron emission tomography (PET) c...
Discrepancies avoided by PET/CT Treatment Planning Cont.
PET/CT contours for nodal areas depicting anatomic and functional...
• Transverse cut of patient with left tonsillar
tumor
- Gross tumor volume (CT-GTV) (blue
line) encompassed positron emiss...
PRELIMINARY OBSERVATIONS
• PET: 77% ACCURACY AND 23% INACCURACY
IN GENERATING REPORDUCIBLE PTV’s
Volume definition depends...
IMPROVING PET FOR TREATMENT
PLANNING
• HIGHER SPATIAL RESOLUTION OF PET
• BETTER TRACKING OF TUMOR MOTION
• MORE TUMOR SPE...
TIMING OF POST TREATMENT
18FDG - PET IMAGING
TIMING OF PET
Muskuloskeletal Tumors: USC Experience
• Recommendations of a 4 – 6 wk interval
most optimal
Jadvar H, Gamie...
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...
THANK YOU
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  1. 1. IMPLEMENTING BIOLOGIC TARGET VOLUMES (BTV) IN RADIATION THERAPY PLANNING SHERIEF H. GAMIE, MD, PhD VA Palo Alto Health Care System Stanford University
  2. 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. 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. 4. AIMING TOWARDS…… • TUMOR DOSE ESCALATION • IMPROVED TUMOR CONTROL • SPARING OF NORMAL SURROUNDING CRITICAL STRUCTURES
  5. 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. 6. GYNECOLOGIC BRACHYTHRAPY APPLICATIONS
  7. 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. 8. GYN BRACHYTHERAPY INTRACAVITARY (ICRT) INTERSTITIAL (ISBT)
  9. 9. ICRT TANDEM & OVOID AND FOLEY CATHETER
  10. 10. PET/CT-compatible phantom with tandem applicators
  11. 11. TANDEM & OVOID SIMULATION (a) Axial, (b) coronal, and (c) sagittal CT images of the phantom with superimposed colorwash PET images
  12. 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. 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. 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. 15. Isodose Configuration Reference Volume Dose Distribution
  16. 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. 17. Treatment Planning Simulation Cont. Applying 45 – 50% PET SUV Threshold Values Axial image with target contour, rectum, and tandem applicator.
  18. 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. 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. 20. Image-Based Treatment Planning (CONT) PET/CT TP & DVH D3%3 BM BM Bowel UB GTV R DVH
  21. 21. GYN BRACHYTHERAPY INTRACAVITARY (ICRT) INTERSTITIAL (ISBT)
  22. 22. INTERSTITIAL BRACHYTHERAPY PET/CT TREATMENT PLANNING SYED – NEBLETT TEMPLATE® SYED-NEBLETT TEMPLATE®
  23. 23. EXTERNAL BEAM RADIATION THERAPY
  24. 24. TREATMENT PORTALS FOR PELVIC XRT Standard Whole Pelvis PALN XRT
  25. 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. 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. 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. 28. ACKNOWLEDGEMENT Dept. of Radiation Oncology Long Beach Memorial Medical Ctr. University of California Irvine
  29. 29. ACCURACY AND TIMING OF PET SCANNING
  30. 30. PULMONARY TREATMENT PLANNING
  31. 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. 32. CRITICAL STRUCTURES Beam’s eye View of 3D Rendering of a Four-field Conformal Treatment Plan
  33. 33. Discrepancies Avoided by PET/CT Treatment Planning Cont. Discrepancies in delineating: (a) Gross Tumor Volume (Blue) (b) Anatomic/Biologic Target Volume (Red)
  34. 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. 35. Discrepancies avoided by PET/CT Treatment Planning Cont. Discrepancies in delineating (a) Gross Tumor Volume (Light blue) (b) Anatomic Biologic Contour (Purple)
  36. 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. 37. RESPIRATORY GATING
  38. 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. 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. 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. 41. HEAD & NECK
  42. 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. 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. 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. 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. 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. 47. IMPROVING PET FOR TREATMENT PLANNING • HIGHER SPATIAL RESOLUTION OF PET • BETTER TRACKING OF TUMOR MOTION • MORE TUMOR SPECIFIC RADIOTRACERS
  48. 48. TIMING OF POST TREATMENT 18FDG - PET IMAGING
  49. 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. 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. 51. THANK YOU
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