N A GRADING SCHEME FOR COMBINED SOMATOSTATIN RECEPTOR (SSR) & FDG IMAGING Dale L Bailey David LH Chan Geoffrey P Schembri Elizabeth J Bernard Nick Pavlakis

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A GRADING SCHEME FOR COMBINED SOMATOSTATIN

RECEPTOR (SSR) & FDG IMAGING

Dale L BaileyDavid LH ChanGeoffrey P SchembriElizabeth J BernardNick PavlakisPaul J Roach

ANZNET

Departments of Nuclear Medicine & Medical Oncology Royal North Shore HospitalFaculty of Health Sciences & Sydney Medical School University of Sydney

Sydney Vital (Northern Translational Cancer Research Centre)Sydney AUSTRALIA

ANZNET[68Ga]-DOTA-Octreotate

(“DOTATATE”)[18F]-FDG

COMBINED SSR & FDG PETSCANNING IN NETs

ANZNET

[18F]-FDG

EXAMPLE SCAN REPORTS

SCANNED 1 DAY APART

REPORTED BY SAME SPECIALIST

NO MENTION OF OTHER SCAN IN EITHER REPORT

NO INDICATION IF THE SAME LESIONS ARE BEING CONSIDERED

NO MENTION OF HOW UPTAKE CORRELATES SPATIALLY

REPORT SUGGESTIVE OF PARTIAL RESPONSE - IS THE DISEASE CHANGING?

[68Ga]-DOTA-Octreotate(“DOTATATE”)

ANZNET

COMBINED SSR & FDG IMAGING

SSR (DOTATATE) +ve IMAGING

• Reflects well-differentiated disease

• Well suited to targetting with radiolabelled SSR therapy

• What is the significance of the degree of uptake (e.g., SUVmax)?

• What is the reproducibility of uptake?

• Is uptake affected by competing agents?

• Role in reflecting likely rate of disease progression?

FDG +ve IMAGING

• Reflects degree of de-differentiation / Ki67

• Often invoked when Ki67 from the primary lesion or a biopsy exceeds a threshold (3%, 5%, 10%, 20%, etc) – based on NET Grading (G1, G2, G3)

• High FDG uptake with low SSR uptake indicates disease may be less amenable to radiolabelled SSR therapy - chemo/biologics may be more suitable

• Represents more aggressive disease & poorer prognosis

• Pathology may not reflect varying disease differentiation throughout the body

ANZNET

The NETPET Grading Scheme - AIMS

› To summarise the results of the two scans in a single score which captures the joint information available – especially to assist referrers;

› To grade the scans by spatial concordance and relative uptake;

› To develop a grading scheme for combined SSR and FDG PET imaging that gives an indication of the subject’s suitability for radionuclide SSR-based therapy based on the scan findings;

› To try to improve consistency and standardisation of reporting of the two scans:- between contemporaneous SSR and FDG scans;- over time;

› To recognise the complementary intrinsic biological signals present in each scan;

› To allow for easier summarising of scan results for data mining in translational research;

› To see whether the grading scheme has a role in prognosis.

NETPET Grading Scheme*

P0 P1 P2 P3 P4 P5

SSR -ve

FDG -ve

SSR +ve

FDG -ve

SSR -ve

FDG +ve

SSR +ve

FDG +ve

FDG uptake < SSR uptake

FDG uptake SSR uptake

FDG uptake > SSR uptake

SSR +ve

FDG +ve

SSR +ve

FDG +ve

ANZNET

*With image display thresholds set at: SUVmax(DOTATATE) = 15SUVmax(FDG) = 7

ANZNETANZNET

ANZNETANZNET

METHODS

› In the period 2011-2015 we performed n=186 [68Ga]-DOTATATE and [18F]-FDG scans on the same individuals (n=125) within 28 days;

› All scans acquired on Siemens Biograph mCT with Time-of-Flight capability and resolution recovery software using an iterative OSEM reconstruction;

› A cohort of subjects diagnosed as having primary pancreatic NET (pNET) were selected for pilot evaluation (n=30):

- these are the results being presented today;

› Two experienced NM physicians independently scored the DOTATATE/FDG scan pairs, with all clinical information available, & graded them according to the flowchart;

› After the scans were read independently the two reporters conferred to check each other’s gradings.

[68Ga]-DOTA-Octreotate [18F]-FDG

RS 1578506

P1 P2 P3 P4 P5P0

SSR -ve

FDG -ve


SB 1624411

P1 P2 P3 P4 P5P0

SSR +ve

FDG -ve

More likely to benefit from

Lutate Rx


LB 0393073

SSR -ve

FDG +ve

Less likely to benefit from

Lutate Rx


MU 1694996

P1 P2 P3 P4 P5P0

P2aFDG uptake < SSR uptake

1-2 lesionsFDG < SSR


Lutate Rx


SF 0351903

P2b3 lesions

FDG < SSR


Lutate Rx

SSR scan +veFDG scan +ve

No lesionsFDG +veSSR -ve


DC 1687299

P1 P2 P3 P4 P5P0

P3aFDG uptake SSR uptake

1-2 lesionsFDG SSR


Lutate Rx


RB 1678868

P3b3 lesions

FDG SSR


Lutate Rx




GM 1062450

P1 P2 P3 P4 P5P0

P4aFDG uptake > SSR uptake

1-2 lesionsFDG > SSR


Lutate Rx


XW 1644491

P4b3 lesions

FDG > SSR


Lutate Rx




P1 P2 P3 P4 P5P0

JP 0314628

2 lesionsFDG +ve / SSR -ve

Lesions present includeFDG +veDOTA -ve


Lutate Rx

RESULTS – pNETs ONLY

Grade Number Lutate Rx?

P0 4 0

P1 3 0

P2a 2 0

P2b 9 1

P3a 2 1

P3b 1 1

P4a 3 2

P4b 2 1

P5 4 0

TOTAL 30 6

(XW)

RESULTS – pNETs ONLY

n=4

n=22

n=4

Survival (months)0 16 32 48

P=0.014 by logrank test for trend (Bland JM & Altman DG. The logrank test. BMJ. 2004;328:1073)

Grade Changing

[68Ga]-DOTA-Octreotate [18F]-FDG [68Ga]-DOTA-Octreotate [18F]-FDG

Mar 2015 - P4a July 2015 - P2a 2 cycles Lutate

KG 1487636

DISCUSSION

› Only small numbers to date and limited follow-up period;

› Does the grading scheme adequately reflect the burden of disease?;

› Do we know the significance of SUV (or uptake level) for SSR imaging?:

- for the present should [68Ga]-DOTATATE be graded with a binary score (Y/N)?;

› Do we need to add more information regarding the bulk of disease for the primary lesion? Or perhaps include a TNM system?

ACKNOWLEDGEMENTS• David Chan is a research fellow funded in part by Sydney Vital (Cancer Institute NSW);• Nick Pavlakis & Dale Bailey are co-leaders of the “NETwork” flagship project of Sydney Vital which receives funding from Cancer Institute NSW.

› How to deal with intra-lesional heterogeneity;

› Dos the classification scheme predict for Lutate efficacy?

› Will the classification scheme have prognostic value?

› How will the classification compare with other grading schema?

FDG

DOTATATE

GM 1062450

Documents

N A GRADING SCHEME FOR COMBINED SOMATOSTATIN RECEPTOR (SSR) & FDG IMAGING Dale L Bailey David LH Chan Geoffrey P Schembri Elizabeth J Bernard Nick Pavlakis