Clinical Utility of Combidexin Various Cancers

Jelle O. Barentsz, MD

Professor of Radiology

University Medical Center Nijmegen, Netherlands

2

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

Primary Tumor Patients NodesBlinded Image Evaluation

Pre-Contrast Post-Contrast

Prostate

Harisinghani-NEJM-2003

80 334 X X

Bladder

Deserno-Radiology-2004

58 172 X X

Head and Neck

Mack-Radiology-2002

27 1029 X X

Breast

Michel-Radiology-2002

20 296 X

Post-Contrast Results –Published Studies

0

20

40

60

80

100

Sensitivity Specificity Accuracy

Prostate

Bladder

Head and Neck

Breast

5

Prostate Cancer

Current imaging has insufficient sensitivity for LN staging

Surgical LN Sampling – Samples only a limited area – 11–31% +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)

Prostate CancerImaging Performance – Patient Level

True

Positive

True

Negative

False

Positive

False

Negative

Pre-contrast

15 37 10 18

Post-contrast

33 45 2 0

NEJM 2003 Harisinghani

5/80 patients (6%)• Guided needle biopsy for solitary unenlarged (5–8 mm)

positive LN on Combidex MRI

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

All 5 confirmed positive

All 9 confirmed positive

Prostate CancerImpact on Treatment Planning

NEJM 2003 Harisinghani

8

7 mm partly metastatic node outside surgical field

Biopsy positive → Androgen ablationBiopsy positive → Androgen ablation

Prostate Cancer

91 mm metastasis in LN outside obturator fossa.

Possiblymetastatic

Prostate Cancer

10

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)

Bladder Cancer

Bladder CancerImaging Performance – Nodal Level

10/12 normal size positive LNs

seen on post-Combidex MRI only

Radiology 2004 Deserno

172 LN (58 patients)

Pre Post p-Value

Sensitivity

76% 96% <.001

Specificity

99% 95%

Accuracy 92% 95%

PPV 97% 89%

NPV 91% 98% <.01

12

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 (5–10 mm)

Radical neck dissection

– Commonly performed– Results in cosmetic deformity– Complication rate 36–54%

Head and Neck CancerImaging Performance – Nodal Level

Combidex MRI on LN level accurate in 26/27 (96%) patients 26% had reduced extent of surgery

Radiology 2002 Mack

1029 LN (27 Patients)

% Post

Sensitivity

86 59/69

Specificity

100 960/960

Accuracy 99 1019/1029

PPV 100 59/59

NPV 99 960/970

14

Head and Neck Cancer

Neck dissection could have been avoided

Normal

12 mm node

15

Breast Cancer

Sentinel Lymph Node Staging (SLN)

– 3–10% 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

Breast CancerImaging Performance – Nodal Level

Radiology 2002 Michel

Reader 1 Reader 2 Average

Sensitivity 83% (25/30) 73% (24/33) 78%

Specificity 97% (252/261) 96% (253/263) 96%

Accuracy 95% (277/291) 94% (277/296) 94%

PPV 74% (25/34) 71% (24/34) 72%

NPV 98% (252/257) 97% (253/262) 97%

296 LNs (18 Patients)

17

Breast Cancer

Metastatic

Normal

Sentinel node Sentinel node ++

PrimaryPrimary tumortumor

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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.

COMBIDEX®COMBIDEX®

(ferumoxtran-10)(ferumoxtran-10)