2011 ACRIN Annual Meeting

ACRIN 6671ACRIN 6671//GOG 0233GOG 0233

FERUMOXTRAN-10 MRI REVIEW REVIEW RESULTSRESULTS

ACRIN PI: M. ATRIACRIN PI: M. ATRIGOG PI: M. GOLDGOG PI: M. GOLD

Zhang Z, Marques H, Gorelick J, Harisinghani M, Sohaib A, Zhang Z, Marques H, Gorelick J, Harisinghani M, Sohaib A, Koh DM, Raman S, Gee M, Choi H, Landrum L, Manne R, Koh DM, Raman S, Gee M, Choi H, Landrum L, Manne R,

Chuang L, Yu J, McCourt CChuang L, Yu J, McCourt C

2011 ACRIN Annual Meeting

• Ferumoxtran-10 nanoparticle, an ultra-small Ferumoxtran-10 nanoparticle, an ultra-small particle iron oxide (USPIO) agent improves particle iron oxide (USPIO) agent improves sensitivity/specificity of MRI to detect metastatic sensitivity/specificity of MRI to detect metastatic lymphadenopathylymphadenopathy

• Harisinghani et al. showed a per patient Harisinghani et al. showed a per patient sensitivity/specificity of 100%/96% for LN detection sensitivity/specificity of 100%/96% for LN detection in 80 prostate cancer patientsin 80 prostate cancer patients

• Rockall et al. showed significantly higher Rockall et al. showed significantly higher sensitivity than size criteria without compromise of sensitivity than size criteria without compromise of specificity in 44 endometrial and cervical cancer specificity in 44 endometrial and cervical cancer patientspatients

INTRODUCTIONINTRODUCTION

2011 ACRIN Annual Meeting

• To determine efficacy of f-10 in the evaluation of LN metastasis from loco-regionally advanced cervical cancer

OBJECTIVEOBJECTIVE

2011 ACRIN Annual Meeting

STUDY DESIGNSTUDY DESIGN

• Loco-regionally advanced CALoco-regionally advanced CA• Pre-operative MRI 24-36hrs post f-10Pre-operative MRI 24-36hrs post f-10• Extra-peritoneal/laparoscopic abdominal & Extra-peritoneal/laparoscopic abdominal &

pelvic lymph node samplingpelvic lymph node sampling• Per regionPer region comparison of lymphadenectomy comparison of lymphadenectomy

and f-10 MRI for 8 regions:and f-10 MRI for 8 regions:• Rt. & Lt. para-aortic Rt. & Lt. para-aortic • Rt. & Lt. common iliac Rt. & Lt. common iliac • Rt. & Lt. external iliacRt. & Lt. external iliac• Rt. & Lt. obturator Rt. & Lt. obturator

ABDOMENABDOMEN

PELVISPELVIS

2011 ACRIN Annual Meeting

STUDY POPULATIONSTUDY POPULATION

• 33 women• 30 – 67 year (mean 49 ±11)• Primary tumor: 5.4 cm ±1.5 cm• Disease Stage: IB2:12, IIA:3, IIB:15,

IIIB:3• Pathology: Squamous cell;29,

Adenoca;3, Rhabdomyosarcoma;1• Grade: 1 (1), grade 2 (20), grade 3 (12)

2011 ACRIN Annual Meeting

• 1.5 Tesla MRI, pelvic phased array coil1.5 Tesla MRI, pelvic phased array coil

• Coverage from IMA origin to symphysis Coverage from IMA origin to symphysis pubispubis

• 2.6 mg/kg of f-10 diluted in 100 ML of 2.6 mg/kg of f-10 diluted in 100 ML of normal saline (IND agent, IND held by normal saline (IND agent, IND held by NCI) (provided by AMAG Inc.) NCI) (provided by AMAG Inc.)

• Infused over 30 minutesInfused over 30 minutes

• T1W, T2W, and T2*GRE sequencesT1W, T2W, and T2*GRE sequences

MRI EXAMINATIONMRI EXAMINATION

2011 ACRIN Annual Meeting

• Independent review by seven readers• 1st Review: All sequences excluding T2*

GRE sequence • Lymph node positive:Lymph node positive:

• short axis > 8mm for a node with short axis > half of longshort axis > 8mm for a node with short axis > half of long• short axis > 10mm for a node with short axis < half of longshort axis > 10mm for a node with short axis < half of long

• 2nd. Review: All sequences including T2* GRE sequence• Lymph node positive:Lymph node positive:

• High signal LN or high signal foci within LN

MRI REVIEW PROCESSMRI REVIEW PROCESS

2011 ACRIN Annual Meeting

• Institutional pathology review

• Presence/absence of LN metastasis, size of the largest focus of metastasis/region, size of the largest positive LN/region recorded

PATHOLOGY REVIEWPATHOLOGY REVIEW

2011 ACRIN Annual Meeting

• Degree of suspicion of LN metastasis recorded on a 6 point scale

• Test result dichotomized to positive/negative using top or bottom 3 scores to calculate sensitivity/specificity

• Abdomen or pelvis positive if one or more region was positive in abdomen or pelvis on the same side on MRI and surgery

STATISTICAL ANALYSISSTATISTICAL ANALYSIS

2011 ACRIN Annual Meeting

• Prevalence of LN metastasis Prevalence of LN metastasis Abdomen: 36% (12/33) Abdomen: 36% (12/33)

Pelvis: 64% (21/33)Pelvis: 64% (21/33)• Median size of the largest focus of cancer Median size of the largest focus of cancer

18mm (range 2–50mm) 18mm (range 2–50mm)• Mean size of the largest focus Mean size of the largest focus

Abdomen (13.7mm) Abdomen (13.7mm) Pelvis (18.8mm) Pelvis (18.8mm)

P valueP value (0.018)(0.018)

RESULTSRESULTS

2011 ACRIN Annual Meeting

RESULTSRESULTS

MRI Accuracy Values

T2* Insensitive Sequences

All

Sequences

P Value

Range Average Range Average

P

E

L

V

I

S

Sensitivity 0.76-0.81 0.78 (0.70-0.84) 0.71-0.90 0.83 (0.76-0.88) 0.243

Specificity 0.56-0.89 0.75 (0.62-0.84) 0.22-0.67 0.48 (0.35-0.61) 0.003

NPV 0.50-0.64 0.59 (0.48-0.69) 0.25-0.67 0.55 (0.41-0.67) 0.629

PPV 0.80-1.00 0.88 (0.81-0.92) 0.68-0.85 0.79 (0.72-0.84) 0.049

Accuracy 0.70-0.80 0.77 (0.70-0.82) 0.57-0.77 0.72 (0.66-0.78) 0.315

A

B

D

O

M

E

N

Sensitivity 0.50-0.58 0.54 (0.43-0.64) 0.50-0.75 0.60 (0.49-0.70) 0.438

Specificity 0.68-0.89 0.83 (0.75-0.88) 0.58-0.89 0.75 (0.67-0.82) 0.136

NPV 0.70-0.76 0.74 (0.66-0.80) 0.69-0.83 0.75 (0.67-0.81) 0.878

PPV 0.54-0.75 0.66 (0.54-0.76) 0.47-0.75 0.60 (0.49-0.70) 0.454

Accuracy 0.65-0.74 0.71 (0.65-0.77) 0.58-0.77 0.69 (0.63-0.75 ) 0.600

2011 ACRIN Annual Meeting

RESULTSRESULTS

MRI Accuracy Values

T2* Insensitive Sequences

All

Sequences

P Value

Range Average Range Average

P

E

L

V

I

S

Sensitivity 0.76-0.81 0.78 (0.70-0.84) 0.71-0.90 0.83 (0.76-0.88) 0.243

Specificity 0.56-0.89 0.75 (0.62-0.84) 0.22-0.67 0.48 (0.35-0.61) 0.003

NPV 0.50-0.64 0.59 (0.48-0.69) 0.25-0.67 0.55 (0.41-0.67) 0.629

PPV 0.80-1.00 0.88 (0.81-0.92) 0.68-0.85 0.79 (0.72-0.84) 0.049

Accuracy 0.70-0.80 0.77 (0.70-0.82) 0.57-0.77 0.72 (0.66-0.78) 0.315

A

B

D

O

M

E

N

Sensitivity 0.50-0.58 0.54 (0.43-0.64) 0.50-0.75 0.60 (0.49-0.70) 0.438

Specificity 0.68-0.89 0.83 (0.75-0.88) 0.58-0.89 0.75 (0.67-0.82) 0.136

NPV 0.70-0.76 0.74 (0.66-0.80) 0.69-0.83 0.75 (0.67-0.81) 0.878

PPV 0.54-0.75 0.66 (0.54-0.76) 0.47-0.75 0.60 (0.49-0.70) 0.454

Accuracy 0.65-0.74 0.71 (0.65-0.77) 0.58-0.77 0.69 (0.63-0.75 ) 0.600

2011 ACRIN Annual Meeting

MRI Accuracy Values

T2* Insensitive

Sequences

All

Sequences

P Value

Range Average Range Average

C

O

M

B

I

N

E

D

Sensitivity 0.78-0.83 0.80 (0.73-0.85) 0.78-0.96 0.86 (0.79-0.90) 0.144

Specificity 0.63-0.88 0.73 (0.60-0.83) 0.25-0.63 0.43 (0.30-0.56) 0.002

NPV 0.50-0.60 0.55 (0.44-0.66) 0.29-0.67 0.51 (0.37-0.65) 0.642

PPV 0.86-0.95 0.90 (0.83-0.94) 0.75-0.87 0.81 (0.75-0.86) 0.043

Accuracy 0.74-0.81 0.78 (0.72-0.83) 0.65-0.81 0.75 (0.68-0.80) 0.430

RESULTSRESULTS

2011 ACRIN Annual Meeting

INTER-OBSERVER AGREEMENTINTER-OBSERVER AGREEMENT

Comparison

of All Readers

T2* Insensitive Sequences

All

SequencesKappa P Value Kappa P Value

Abdomen 0.74 < 0.0001 0.54 < 0.0001

Pelvis 0.84 < 0.0001 0.52 < 0.0001

Combined 0.89 < 0.0001 0.46 < 0.0001

2011 ACRIN Annual Meeting

T2W

T2*

2011 ACRIN Annual Meeting

T2W

T2*

2011 ACRIN Annual Meeting

T2*

T2W

2011 ACRIN Annual Meeting

• Results of this study suggests higher Results of this study suggests higher sensitivity of ferumoxtran-10 MRI over sensitivity of ferumoxtran-10 MRI over standard MRI that did not reach statistical standard MRI that did not reach statistical significancesignificance

• Specificity of ferumoxtran-10 MRI was Specificity of ferumoxtran-10 MRI was significantly lower than standard MRIsignificantly lower than standard MRI

• Lower specificity may be due to issues Lower specificity may be due to issues related to mismatching of metastatic LNs on related to mismatching of metastatic LNs on MRI and surgery and lack of removal of MRI and surgery and lack of removal of involved LNsinvolved LNs

SUMMARY