MOLECULAR IMAGE VALIDATION UTILIZING THE CORRELATION OF HISTOPATHOLOGY AND MARKER PLACEMENT SYSTEM C

1
MOLECULAR IMAGE VALIDATION UTILIZING THE
CORRELATION OF HISTOPATHOLOGY AND MARKER
PLACEMENT SYSTEM (CHAMPSSM)

• Rodney J. Ellis1,2,3, Deborah A. Kaminsky1,
• Hang Zhou2, Martin I. Resnick2.
• 1Aultman Hospital, Department of Radiation
  Oncology, Canton, OH
• 2Case Western Reserve University, Department of
  Urology, Cleveland, OH.
• 3 Department of Radiology Northeastern Ohio
  Universities College of Medicine, Rootstown, OH

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Abstract

• Purpose/Objective(s) Based on experience gained
  through a clinical series
• of 239 men demonstrating selective
  intra-prostatic dose escalation to
• SPECT/CT Capromab Pendetide (ProstaScint)
  biological target volumes (BTV)
• a feasibility study was initiated to evaluate the
  ability of the CHAMPS protocol
• to pathologically validate regions of focal
  uptake on SPECT/CT ProstaScint
• images using uniquely identifiable biopsy site
  fiducial markers.
• Materials/Methods Five patients presenting to
  Radiation Oncology for
• definitive treatment of localized (T1cNxM0)
  biopsy-confirmed prostate cancer
• were evaluated by SPECT/CT ProstaScint prior to
  treatment planning. Eligible
• patients were selected from those scheduled for
  primary prostate cancer
• treatment with brachytherapy (with or without
  external beam) and in whom
• SPECT/CT identified definitive intra-prostatic
  focal uptake. Patients were
• prepared for brachytherapy per the BTV dose
  escalation protocol and were
• additionally consented for a biopsy procedure
  preceding treatment, with
• implantation of internal fiducial markers at each
  biopsy site, for improved post-
• operative dosimetry evaluation. Transperineal
  ultrasound guided biopsy tissue
• was collected at BTV regions identified by
  SPECT/CT and, in one patient,
• MRSi. Marked biopsy samples were sent to
  pathology on a blinded basis for

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SPECT/CT Histopathology Confirmation
SPECT
SPECT/CT Fusion
CT Scan
Post-prostatectomy serial section analysis has
confirmed pre-operative molecular studies. This
method and MRSi mapping require image warping
thereby limiting exact in-vivo tumor localization
for image guided radiation therapy (IGRT).
Direct, non-warped in-vivo validated pathology is
introduced using the Correlated Histopathology
and Marker Placement System (CHAMPS). CHAMPS
biopsy site fiducials are tracked in treatment
planning software using marked sites of pathology
validated-BTV for dose modulation using conformal
therapies such as Brachytherapy and IMRT
4
Identification of Intraprostatic Disease Enables
Dose Intensification to BTV

• Intraprostatic molecular imaging can identify
  areas of high tumor burden using, for example,
  SPECT with ProstaScint, MRI spectroscopy, and
  PET with Choline
• Molecular image registration to anatomic images
  sets (CT, MR) increases intraprostatic target
  delineation (SPECT/CT and PET/CT)
• CHAMPS biopsy procedures uniquely correlate
  pathology data for molecular image validation
  and discrete dose intensification targeting to
  tumor while sparing normal radiosensitive tissues
  (urethra, rectum, and neurovascular bundle) to
  decrease treatment related toxicity.

CHAMPS establishes pathology-validated BTV for
dose escalation, biopsy site tracking, and image
alignment
Urethra
Peripheral zone 100
rectum
Tumor 150
Prostatic Adenocarcinoma Gleason Grade 1-5
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The Validation of Molecular Images for Use in the
Definition of Pathology-Validated Treatment
Volumes are Unique to CHAMPS
Radiation Oncology IMRT plan prone position
Nuclear Medicine/Radiology SPECT/CT supine
position
Placement of markers at biopsy sites for use as
treatment planning coordinates of
pathology-validated regions of () and (-) tissue
Provides tracking regardless of change in
patient position and site of care (outpatient
imaging, radiation oncology and outpatient
surgical center).
6
Phantom Study of CHAMPS for Treatment Planning
An ultrasound phantom was used to place four 2
cm Visicoil markers back-to-back bilaterally in
the prostate prior to CT. Reconstruction
completed on a Variseed (Varian) treatment
planning computer. In-vivo correlation to biopsy
pathology and molecular images enhances the
ability to accurately define BTV for dose
escalation, by validating (or refuting)
uptake seen on molecular images.
Urethra
CHAMPS Markers
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Patient Characteristics
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Fluoroscopic CHAMPS BTV Localization
Foley Bulb
CHAMPS Markers
Rectal Ultrasound Probe
Patient example Fluoroscopic view of Visicoil
gold markers located at biopsy sites identified
by molecular imaging (e.g. SPECT/CT)
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CHAMPS Placement by Ultrasound Image
CHAMPS Marker
Needle
2cm Visicoil gold marker placed at BTV biopsy
site under transrectal ultrasound guidance prior
to prostate brachytherapy
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CHAMPS Guidance of Brachytherapy Source Placement
CHAMPS Marker
Pd-103 Seed
Pd-103 seed placed directly below Visicoil gold
marker used to help define Biological Target
Volume (BTV) at time of prostate brachytherapy
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CHAMPS Localization Post Brachytherapy
Foley Bulb
CHAMPS Markers
Fluoroscopic view after completion of Pd-103
brachytherapy of the prostate with Visicoil
markers placed at pathology validated BTV biopsy
sites
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SPECT/CT ProstaScint Fusion Showing CHAMPS and
Treatment Planning BTV Dose Escalation
A SPECT/CT ProstaScint was obtained pre-treatment
which demonstrated focal uptake in the mid left
gland defining a biologic target volume (BTV). A
SPECT/CT ProstaScint guided-biopsy was directed
to the BTV and with fiducial marker placement at
the biopsy at the time of seed implant.
Histopathology report validated the
molecular-image defined BTV site was positive
for Adenocarcinoma Gleason score 6 (33) in 5 of
core. The patient was treated patient with LDR
brachytherapy using I-125 to prescribe 145 Gy to
the prostate volume with BTV dose escalation to
150 of prescribed dose. The pathology confirmed
CHAMPS biopsy is retained should the patient
require EBRT.
Case Example Patient 1 78 year old male with
Adenocarcinoma of the prostate. PSA
15.5ng/ml. Biopsy reported bilateral disease
of low volume in unspecified locations
Gleason 6 (33)
CHAMPS Marker
BTV
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Pre-op Ultrasound Planning
Post-op CT Planning
3D
Pre-op DVH
CHAMPS Marker
2D
BTV Color wash
Post-op DVH
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Patient 2 - Case Example MIMvista Fused Image
of ProstaScint and CT Scan Showing Focal Activity
in High Anterior Right Base and Extending to the
Lateral Right Apex
Biopsy Confirmed Gleason 6(33)
Adenocarcinoma by CHAMPS at time of LDR
brachytherapy
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Pre and Post-operative Planning Images
BASE
APEX
3D
ProstaScint defined BTV
3D color wash with dose escalation to 150 of
prescription to CHAMPS pathology-validated BTV
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BTV IGRT Brachytherapy Outcomes Data
Compared-Biochemical Disease Free Survival by
ASTRO Consensus
1Quaranta BP, Marks LB, Anscher MS. Comparing
Radical Prostatectomy and Brachytherapy For
Localized Prostate Cancer. Oncology.
200418(10)1289-1302. 2 Ellis, RJ et al.
Seven-year biochemical disease-free survival
rates following permanent prostate brachytherapy
with dose escalation to biological tumor volumes
identified with SPECT/CT image fusion.
Brachytherapy. 20054(2)107 (P-88).
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Results and Conclusions
Results 14 biopsy cores were obtained from 7
SPECT/CT identified BTV sites in 5 patients.
Focal uptake on SPECT/CT was validated as
positive for adenocarcinoma in 4 of 5 patients
(80). Discordant findings in 1 patient was
significant for a report of bilateral disease on
the diagnostic-biopsy, while MRSi showed disease
limited to the left lateral apex and ProstaScint
uptake was found at the right mid gland biopsies
directed to both regions were negative. SPECT/CT
defined BTV dose-escalation targets were
validated with CHAMPS in 5 of 7 BTV (71.4).
Conclusions The CHAMPS protocol demonstrated
clinical feasibility as a validation method for
molecular imaging techniques such as SPECT/CT.
The process identified in-vivo histopathology
linked validated pathology to markers for
subsequent RT targeting confirmed initial
pathology findings with marked locations
identified and validated new regions of occult
disease not reported on the diagnostic-biopsy
and was found to benefit dosimetry evaluation to
ensure adequate dose coverage to
pathology-confirmed BTV. This study supports the
potential application of the CHAMPS protocol to
intensity-modulated therapies, and may provide an
efficient means to correlate genomic/proteomic
analysis for improved dose modulation.

• Author Disclosures
• CHAMPSSM is an applied patented technology of
  Advanced Clinical Solutions, Inc (ACSI) which is
  Co-owned by Drs Ellis and Kaminsky
• Dr. Ellis is on the speakers bureau and is a PI
  for an unrestricted Educational Research Grant
  sponsored by the Cytogen Corporation