# Presentation: 866842

## Clinical Utility of Combidexin Various Cancers

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

## 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 ****significant****clinical**** ****benefit**

- Prostate
- Bladder
- Head and Neck
- Breast

## Published Studies

| Primary Tumor |  Patients | Nodes | Blinded 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

## 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 CancerImaging 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

## Prostate CancerImpact on Treatment Planning

- 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 Cancer****Impact on Treatment Planning**

- NEJM 2003 Harisinghani

## Prostate Cancer

**7 mm**** partly metastatic ****node ****outside ****surgical field**

**Biopsy positive → Androgen ablation**

**Prostate Cancer**

## Prostate Cancer

**1 mm metastasis in LN**** outside obturator fossa.**

**Possibly**
**metastatic**

**Prostate Cancer**

## 24% LN positive despite negative preoperative imaging 

Nodal metastases (N2-3, or >4) radically changestreatment 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)

- 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 CancerImaging 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 |

## 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 CancerImaging 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 |

**Head and Neck Cancer **

**Neck dissection ****could have been ****avoided**

**Normal**

**12 mm node**

## 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 CancerImaging 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)

## Breast Cancer

**Breast Cancer**

**Metastatic**

**Normal**

**Sentinel node +**

**Primary**** ****tumor**

## 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)

## 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)