Clinical Utility of Combidex in Various Cancers

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Clinical Utility of Combidexin Various Cancers

• Jelle O. Barentsz, MD
• Professor of Radiology
• University Medical Center Nijmegen, Netherlands

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Clinical Utility in Cancer

• Post-Phase III peer reviewed publications
• NEJM, Radiology
• Blinded post-contrast image evaluation with
  histopathology
  
• Impact on treatment planning
• Areas where Combidex MRI provides
  significantclinical benefit

• Prostate
• Bladder
• Head and Neck
• Breast

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Published Studies
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Post-Contrast Results Published Studies
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Prostate Cancer

• Current imaging has insufficient sensitivity for
  LN staging
  
• Surgical LN Sampling
• Samples only a limited area
• 1131 LN outside sampled area
• Complications 22 (open), 5 (lap)
• Lymphocele, lymphedema, DVT, PE, nerve
  damage, blood loss

• Extended LN dissection detects more LN
• but increases morbidity
• Zincke (Mayo), Walsh (JHH), Burkhard (Bern)

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Prostate CancerImaging Performance Patient
Level
NEJM 2003 Harisinghani
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Prostate CancerImpact on Treatment Planning

• 5/80 patients (6)
• Guided needle biopsy for solitary unenlarged (58
  mm) positive LN on Combidex MRI

• All 5 confirmed positive

• 9/80 patients (11)
• PLND extended outside usual field due to
  positive LN on Combidex images

• All 9 confirmed positive

NEJM 2003 Harisinghani
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Prostate Cancer
7 mm partly metastatic node outside surgical field
Biopsy positive ? Androgen ablation
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Prostate Cancer
Possibly metastatic
1 mm metastasis in LN outside obturator fossa.
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Bladder Cancer

• 24 LN positive despite negative preoperative
  imaging
  
• Nodal metastases (N2-3, or 4) radically
  changestreatment options
  
• Extended LN dissection
• Detects more LN
• Increases survival for minimal disease
• Does not sample all areas of LN
• Increases morbidity
• Studer (Switzerland) Skinner
  (USC) Ghoneim (Egypt)

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Bladder CancerImaging Performance Nodal Level
172 LN (58 patients)

• 10/12 normal size positive LNs
• seen on post-Combidex MRI only
• Radiology 2004 Deserno

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Head and Neck Cancer

• 5 yr survival 91 (localized) and 63 (regional
  LN)
  
• Status of cervical LN is vital for choice of
  therapy
  
• 25 LN positive despite negative preoperative
  imaging (contrast CT) as metastatic nodes are
  small (510 mm)
  
• Radical neck dissection
• Commonly performed Results in cosmetic
  deformity Complication rate 3654

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Head and Neck CancerImaging Performance Nodal
Level
1029 LN (27 Patients)

• Combidex MRI on LN level accurate in 26/27 (96)
  patients
  
• 26 had reduced extent of surgery
• Radiology 2002 Mack

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Head and Neck Cancer
12 mm node
Normal
Neck dissection could have been avoided
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Breast Cancer

• Sentinel Lymph Node Staging (SLN)
• 310 false negative
• The Sentinel Node is the only positive node in
  61 of patients with positive LNs
  
• These patients all undergo axillary
  dissection High rate of clinically significant
  complications
  

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Breast CancerImaging Performance Nodal Level
296 LNs (18 Patients)

• Radiology 2002 Michel

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Breast Cancer
Normal
Metastatic
Sentinel node
Primary tumor
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Summary Clinical Relevance

• Current techniques to detect positive LNs in
  prostate, bladder, head and neck, and breast
  cancer havesignificant limitations
  
• Combidex MRI shows high sensitivity and
  specificityin these tumors
  
• Combidex MRI may reduce the extent of surgeryand
  morbidity
  
• Combidex MRI identifies additional positive LNs
  for biopsy or image-guided extended dissection
  (improve staging)

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Indication

• Combidex (ferumoxtran-10) is for intravenous
  administration as a contrast agent for use with
  magnetic resonance imaging (MRI). Combidex can
  assist in the differentiation of metastatic and
  non-metastatic lymph nodes in patients with
  confirmed primary cancer who are at risk for
  lymph node metastases.
• The information provided by Combidex should be
  considered in conjunction with other diagnostic
  information and lymph node findings from Combidex
  images should be pathologically confirmed unless
  medically contraindicated.

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COMBIDEX
(ferumoxtran-10)