ROLE OF 18F-FDG-PET CT IN GYNAECOLOGICAL MALIGNANCIES

Dr Anju Sahdev Reader in Imaging and Consultant Uro-Gynae Radiologist

St Bartholomew’s Hospital, Bart’s Health

and

Queen Mary University of London

NECL Alliance Education meeting Feb 2020

BASIC PRINCIPLES: PET CT

Positron emission

tomography (PET)

Computerised

tomography (CT) +

Positron

emitters

18Flurorine 68Ga 11Carbon 15Oxygen

Unstable elements emitting positrons

which are neutralised by electrons.

This neutralization produces 2

annihilation photons of 511KeV.

These photons are detected and imaged

on bismuth, lutetium or gadolinium

detectors. +

Tracers

fluoro-2-

deoxy-D-

glucose

(FDG)

PSMA

DOTATE

Determines the imaging findings

E.g. FDG: glucose molecule taken up by glucose

utilizing cells

Ch: increased cell turnover

PSMA: prostate receptor specific,

DOTATE: somatostatin receptors

18F-FDG most commonly used due to its long half-life of 110

min which allows transportation from cyclotrons

Taken up by all tissue using glucose

Increased glucose use= increased tracer uptake

Cancers usually have increased glucose uptake = increased

tracer uptake

Infection and inflammation also has increased glucose and

therefore tracer uptake

THEREFORE NOT SPECIFIC

The uptake can be quantified and SUV (standardized uptake

value) is the most frequently used

OVARIAN CANCER

The role of FDG PET CT in ovarian cancer

includes:

lesion characterisation and diagnosis

staging

detection of recurrence

DIAGNOSIS AND CHARACTERISATION

Indeterminate lesions on TVUS: SUV >3

Sens 58%, spec 78% Reiber et al*

PPV 86% and NPV 76% **

False positives: dermoids and inflammatory masses

False negatives: borderline tumours

Combined with RMI>150

improves Sens 100% and Spec 92.5% ***

*Reiber et al. AJR Am J Roentgenol. 2001 Jul; 177(1):123-9

**Hubner et al. Gynecol Oncol. 1993 Nov; 51(2):197-204

*** Risum et al Gynecol Oncol. 2007 Apr; 105(1):145-9

Comparable

to

combination

of TVUS and

MRI

STAGING AND RECURRENCE

Study Setting Sens Spec

De Laco P et al

Eur J Radiol. 2011

staging 78% 68%

Hynninen J et al

Gynecol Oncol. 2013

Pre op

advanced dx

Overall 83%

FDG-PET/CT and CECT

poor for

subdiaphragmatic,

small bowel serosa

bowel mesentery and

right upper abdomen.

Zimny M et al

Gynecol Oncol. 2001

recurrence 83%

Rising to 94%

If CA125

83%

Bhosale P et al

Int J Gynecol Cancer.

2010

recurrence CECT 54%

PET CT 58% in normal CA125

not

unequivocally

superior to

CECT alone

In both staging and recurrence, unequivocally superior for:

nodal and distant metastases

supradiaphragmatic disease

results in stage migration

Limited change in management by the detection of additional

small volume abdominal or extra-abdominal disease

Small volume peritoneal and serosal disease

ADVANTAGES OF PET: RECURRENCE

ADVANTAGES OF PET

Borderline size

nodes

ADVANTAGES OF CT

Combined evaluation

of bowel

DIFFICULTIES ON PET

Cystic disease usually negative on PET

Borderline and low grade malignancy

DIFFICULTIES ON PET

DIFFICULTIES ON PET

Nodal metastases in low grade disease

CURRENT GUIDELINES: OVARIAN CANCER

RCR 2016 SIGN guidelines 2013 American NCCN 2017

• No role in primary

staging

• Rising CA125 with

negative or equivocal

cross-sectional imaging

Not routinely

recommended in the

diagnosis, staging,

surveillance or at

recurrence of epithelial

ovarian cancer

• Not routine for initial

adnexal masses, staging,

surveillance following

complete response

• Clinical relapse or Serially

rising CA-125 with or

without previous

chemotherapy

Evidence-based indications for the use of PET CT in the UK. Collaborative document 2016

American National Comprehensive Cancer Network

POTENTIAL ROLES

In patients with apparent solitary sites of

recurrence on CT prior to curative surgery

In patients with persistently raised CA125, high

RMI and normal TVUS?

Basu et al. PET and PET CT imaging of gynecological malignancies: present and

future. Expert Rev Anticancer Ther 2009;9:75-96

Prakash et al. Role of PET CT in ovarian cancer. AJR 2010 W464-470

CERVICAL CANCER

The role of FDG PET CT in cervical cancer includes:

Staging of locally advanced disease

• Extent of nodal and visceral metastases

• Microscopic metastases

• best performance with SCC, poor with adenoca

detection of recurrence

• Distinguishing between treatment effects and

recurrence locally

• Distant disease

Mapping the upper limit of

nodal metastases

Micro metastatic nodal metastases

PET CT PERFORMANCE

Stage dependent:

Early stage

Pooled data and meta analysis

PA node Sens 34% and Spec 97%

In early stage CaCx, mean size nodes 5mm*

Pelvic nodes Sens 53% (MRI 38%), Spec 90% (MRI 98%)

PA nodes Sens 25% and Spec 98%

*Wright et al Cancer. 2005 Dec 1; 104(11):2484-91

** Kang S et al J Nucl Med. 2010 Mar; 51(3):360-7

No added

benefit

over MRI

PET CT PERFORMANCE

Sens% Spec% PPV% NPV% Acc%

Sironi S Radiology 2006 (>1000 nodes)

72 99 81 99 99

Wright JD Cancer. 2005

25 98 50 93

Havrilesky LJ Gynecol Oncol. 2005

Pooled PA node data

79 96-99 Sensitivity of

detecting small

nodal metastases is

poor for all

modalities, 18F-FDG

PET CT offers the

best sensitivity in

advanced cervical

cancer.

Advanced stage

RECURRENT DISEASE

PET CT, by RCR and ANCCN guidelines, has been advocated in

the detection of clinically suspected recurrent disease when

cross-sectional imaging is equivocal

• early detection loco-regional treatment failure suitable for

salvage therapy

• to identify unsuspected asymptomatic distant metastatic

disease

Grigsby PW. Gynecol Oncol. 2007. (Suppl 1):S27-9.

Chung HH et al. Gynecol Oncol 2006

Distinguishes

between

residual or

recurrent

disease and post

tx changes

LOCAL RECURRENCE VS RT CHANGES

Pre Post

Small local recurrence

10 months post CRT

DISTANT DISEASE RECURRENCE

>90% are pelvic or para-aortic nodal recurrences

Findings

Kitajima et al Eur J Nucl Med Mol Imaging.

2010 Aug; 37(8):1490-8.

Sens 92% and Spec 93%

Chu Y et al Nucl Med Commun. 2014 Feb;

35(2):144-50.

Meta-analysis

Sens 94% and Spec 84%

Scarsbrook et al Eur J Nucl Med Mol Imaging.

2017 Apr; 44(4):581-588.

Sens 94% , NPV 95%

Spec 62%, PPV 59% *, Acc 74%

* PET CT 8-16 wks after CRT False –ve

<10mm PA

nodes

False +ve

mediastinal

nodes

EMERGING APPLICATIONS

Improve delineation of metabolic tumour volume (MTV) defined with PET CT/PET MRI

cervical primary and pelvic and PA nodes

False –ve 12% PA nodes

Herrera FG et al. Front Oncol. 2013

*Burger IA Gynecol oncol 2013

Assesses treatment response and predict survival outcome Persistent FDG uptake at the end of treatment with chemo radiotherapy

confers a poor 5-year survival outcome * 46%

No residual uptake 5-year survival 92%

Development of new uptake 5- year survival 0%

Higher pre-treatment SUV of the primary tumour and nodes predicts higher

likelihood of persistent FDG uptake at EOT ** and higher risk of nodal

metastases *Grigsby et al J Clin Oncol. 2004 Jun 1;

22(11):2167-71

**Kidd EA, Siegel BA, Dehdashti F, Grigsby PW

Cancer. 2007 Oct 15; 110(8):1738-44.

KEY POINTS IN CERVICAL CANCER

Improves detection of distant nodal disease in

ADVANCED disease

High sensitivity for distant recurrent disease detection

making is suitable for use in treatment planning

including exenterative surgery

SUV max values are biomarkers for response, survival

and predicting recurrence

ENDOMETRIAL CANCER

The role of FDG PET CT in endometrial cancer is limited:

physiological uptake of endometrium, limited use to detect EC

Poor spatial resolution for local myoinvasion compared to MRI

Need and importance of detecting microscopic nodal or distant

disease for patient management is controversial.

PET CT continues to provide only modest improvement in the

detection of microscopic nodal metastasis even in patients with

high-risk endometrial cancer

Useful adjunct to conventional imaging in detection of unexpected

nodal or distant disease in young patients being considered for

pelvic exenterative surgery for central recurrence of endometrial

cancer

Bollineni et al

J Nucl Med. 2016 Jun;

57(6):879-85

Meta-analysis

Sens 95% and Spec 91% in detection of

recurrence

Kadkhodayan et al

Gynecol Oncol. 2013 Feb;

128(2):397-404.

Meta-analysis

Sens 96% and Spec 93% in detection of

recurrence

* No mandatory histological

confirmation

CURRENT GUIDELINES: ENDOMETRIAL CANCER

RCR 2016 SIGN guidelines 2013 American NCCN 2017

• No role in primary

staging

• Patients being considered

for exenterative surgery

• Suspected recurrence

with equivocal cross-

sectional imaging

Does not recommend PET

CT at initial diagnosis or

staging of endometrial

cancer

PET CT at initial staging or

at suspected recurrence if

metastatic disease is

suspected in select patients

Evidence-based indications for the use of PET CT in the UK. Collaborative document 2016

American National Comprehensive Cancer Network 2017

THE FUTURE?

PET CT

Long half life emitters using

(89)Zr, (124)I, and (90)Y

Tumour specific tracers and

ligands

PET MRI

One stop shop for all

gynae/pelvic cancers

Staging: local + distant disease

Tx Planning

Biomaker functionality

recurrence and tx planning

• Decreased dose

• Improved spatial and tissue

resolution

• ?Improve CRT

Thank You